Low energy dipole strength from large scale shell model calculations

NASA Astrophysics Data System (ADS)

Sieja, Kamila

2017-09-01

Low energy enhancement of radiative strength functions has been deduced from experiments in several mass regions of nuclei. Such an enhancement is believed to impact the calculated neutron capture rates which are crucial input for reaction rates of astrophysical interest. Recently, shell model calculations have been performed to explain the upbend of the γ-strength as due to the M1 transitions between close-lying states in the quasi-continuum in Fe and Mo nuclei. Beyond mean-↓eld calculations in Mo suggested, however, a non-negligible role of electric dipole in the low energy enhancement. So far, no calculations of both dipole components within the same theoretical framework have been presented in this context. In this work we present newly developed large scale shell model appraoch that allows to treat on the same footing natural and non-natural parity states. The calculations are performed in a large sd - pf - gds model space, allowing for 1p{1h excitations on the top of the full pf-shell con↓guration mixing. We restrict the discussion to the magnetic part of the dipole strength, however, we calculate for the ↓rst time the magnetic dipole strength between states built of excitations going beyond the classical shell model spaces. Our results corroborate previous ↓ndings for the M1 enhancement for the natural parity states while we observe no enhancement for the 1p{1h contributions. We also discuss in more detail the e↑ects of con↓guration mixing limitations on the enhancement coming out from shell model calculations.

Inner-shell excitation and ionic fragmentation of molecules

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

Hitchcock, A.P.; Tyliszczak, T.; Cavell, R.G.

1997-04-01

Inner-shell excitation and associated decay spectroscopies are site specific probes of electronic and geometrical structure and photoionization dynamics. X-ray absorption probes the geometric and electronic structure, while time-of-flight mass spectrometry with multi-coincidence detection provides information on the photofragmentation dynamics of the initially produced inner-shell state. Auger decay of inner-shell excited and ionised states is an efficient source of multiply charged ions. The charge separation and fragmentation of these species, studied by photoelectron-photoion-photoion coincidence (also called charge separation mass spectrometry) gives insights into bonding and electronic structure. In molecules, the dependence of the fragmentation process on the X-ray energy can revealmore » cases of site and/or state selective fragmentation. At the ALS the authors have examined the soft X-ray spectroscopy and ionic fragmentation of a number of molecules, including carboranes, silylenes, phosphorus halides, SF{sub 6} and CO{sub 2}. Their work is illustrated using results from the carborane and PF{sub 3} studies.« less

Li+ solvation and kinetics of Li+-BF4-/PF6- ion pairs in ethylene carbonate. A molecular dynamics study with classical rate theories

NASA Astrophysics Data System (ADS)

Chang, Tsun-Mei; Dang, Liem X.

2017-10-01

Using our polarizable force-field models and employing classical rate theories of chemical reactions, we examine the ethylene carbonate (EC) exchange process between the first and second solvation shells around Li+ and the dissociation kinetics of ion pairs Li+-[BF4] and Li+-[PF6] in this solvent. We calculate the exchange rates using transition state theory and correct them with transmission coefficients computed by the reactive flux, Impey, Madden, and McDonald approaches, and Grote-Hynes theory. We found that the residence times of EC around Li+ ions varied from 60 to 450 ps, depending on the correction method used. We found that the relaxation times changed significantly from Li+-[BF4] to Li+-[PF6] ion pairs in EC. Our results also show that, in addition to affecting the free energy of dissociation in EC, the anion type also significantly influences the dissociation kinetics of ion pairing.

Coulomb energy differences in isobaric multiplets

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

Lenzi, S. M.; Farnea, E.; Bazzacco, D.

2007-02-12

By comparing the excitation energies of analogue states in isobaric multiplets, several nuclear structure properties can be studied as a function of the angular momentum up to high spin states. In particular, the mirror nuclei 35Ar and 35Cl show large differences between the excitation energies of analogue negative-parity states at high spin, confirming the important contribution of the relativistic electromagnetic spin-orbit interaction to the Coulomb energy. The single-particle character of the configuration of these states is reproduced with very good accuracy by shell model calculations in the sd and pf shells valence space. In addition, evidence of isospin mixing ismore » deduced from the El transitions linking positive and negative parity states.« less

Li + solvation and kinetics of Li +–BF 4 -/PF 6 - ion pairs in ethylene carbonate. A molecular dynamics study with classical rate theories

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

Chang, Tsun-Mei; Dang, Liem X.

Using our polarizable force-field models and employing classical rate theories of chemical reactions, we examine in this paper the ethylene carbonate (EC) exchange process between the first and second solvation shells around Li + and the dissociation kinetics of ion pairs Li +–[BF 4] and Li +–[PF 6] in this solvent. We calculate the exchange rates using transition state theory and correct them with transmission coefficients computed by the reactive flux, Impey, Madden, and McDonald approaches, and Grote-Hynes theory. We found that the residence times of EC around Li + ions varied from 60 to 450 ps, depending on themore » correction method used. We found that the relaxation times changed significantly from Li +–[BF 4] to Li +–[PF 6] ion pairs in EC. Finally, our results also show that, in addition to affecting the free energy of dissociation in EC, the anion type also significantly influences the dissociation kinetics of ion pairing.« less

Li + solvation and kinetics of Li +–BF 4 -/PF 6 - ion pairs in ethylene carbonate. A molecular dynamics study with classical rate theories

DOE PAGES

Chang, Tsun-Mei; Dang, Liem X.

2017-07-19

Using our polarizable force-field models and employing classical rate theories of chemical reactions, we examine in this paper the ethylene carbonate (EC) exchange process between the first and second solvation shells around Li + and the dissociation kinetics of ion pairs Li +–[BF 4] and Li +–[PF 6] in this solvent. We calculate the exchange rates using transition state theory and correct them with transmission coefficients computed by the reactive flux, Impey, Madden, and McDonald approaches, and Grote-Hynes theory. We found that the residence times of EC around Li + ions varied from 60 to 450 ps, depending on themore » correction method used. We found that the relaxation times changed significantly from Li +–[BF 4] to Li +–[PF 6] ion pairs in EC. Finally, our results also show that, in addition to affecting the free energy of dissociation in EC, the anion type also significantly influences the dissociation kinetics of ion pairing.« less

Strongly screening corrections to antineutrino energy loss by β --decay of nuclides 53Fe, 54Fe, 55Fe, and 56Fe in supernova

NASA Astrophysics Data System (ADS)

Liu, Jing-Jing; Liu, Dong-Mei

2018-06-01

Based on the p-f shell-model, we discuss and calculate β--decay half-lives of neutron-rich nuclei, with a consideration of shell and pair effects, the decay energy, and the nucleon numbers. According to the linear response theory model, we study the effect of electron screening on the electron energy, beta-decay threshold energy, and the antineutrino energy loss rate by β--decay of some iron isotopes. We find that the electron screening antineutrino energy loss rates increase by about two orders of magnitude due to the shell effects and the pairing effect. Beta-decay rates with Q-value corrections due to strong electron screening are higher than those without the Q-value corrections by more than two orders of magnitude. Our conclusions may be helpful for the research on numerical simulations of the cooling of stars.

Coulomb Excitation of the 64Ni Nucleus and Application of Inverse Kinematics

NASA Astrophysics Data System (ADS)

Greaves, Beau; Muecher, Dennis; Ali, Fuad A.; Drake, Tom; Bildstein, Vinzenz; Berner, Christian; Gernhaeuser, Roman; Nowak, K.; Hellgartner, S.; Lutter, R.; Reichert, S.

2017-09-01

In this contribution, we present new data on the semi-magic 64Ni nucleus, close to the N =40 harmonic oscillator shell gap. Recent studies suggest a complicated existence of shape coexistence in 68Ni, likely caused by type-II shell evolutions. The region studied here thus might define the ``shore'' of the region of more deformed nuclei in the Island of Inversion below 68Ni. At the Maier-Leibnitz-Laboratory (MLL) in Munich, a beam of 64Ni was excited using Coulomb excitation. The high-granularity MINIBALL HPGe array and a segmented silicon strip detector were used to identify gamma decays in 64Ni. Doppler-shifted attenuation method (DSAM) analysis was applied to the experimental data acquired to resolve the low-lying excited states and acquire a lifetime measurement based on Geant4 simulations of the first excited 2 + state, clarifying the previously conflicting results. Furthermore, we show DSAM data following transfer reactions in inverse kinematics. This new method has the potential to provide insight into tests of ab-initio shell model calculations in the sd-pf shell and for the study of nuclear reaction rates. Supported under NSERC SAPIN-2016-00030.

A two-pronged structural analysis of retroviral maturation indicates that core formation proceeds by a disassembly-reassembly pathway rather than a displacive transition.

PubMed

Keller, Paul W; Huang, Rick K; England, Matthew R; Waki, Kayoko; Cheng, Naiqian; Heymann, J Bernard; Craven, Rebecca C; Freed, Eric O; Steven, Alasdair C

2013-12-01

Retrovirus maturation involves sequential cleavages of the Gag polyprotein, initially arrayed in a spherical shell, leading to formation of capsids with polyhedral or conical morphology. Evidence suggests that capsids assemble de novo inside maturing virions from dissociated capsid (CA) protein, but the possibility persists of a displacive pathway in which the CA shell remains assembled but is remodeled. Inhibition of the final cleavage between CA and spacer peptide SP1/SP blocks the production of mature capsids. We investigated whether retention of SP might render CA assembly incompetent by testing the ability of Rous sarcoma virus (RSV) CA-SP to assemble in vitro into icosahedral capsids. Capsids were indeed assembled and were indistinguishable from those formed by CA alone, indicating that SP was disordered. We also used cryo-electron tomography to characterize HIV-1 particles produced in the presence of maturation inhibitor PF-46396 or with the cleavage-blocking CA5 mutation. Inhibitor-treated virions have a shell that resembles the CA layer of the immature Gag shell but is less complete. Some CA protein is generated but usually not enough for a mature core to assemble. We propose that inhibitors like PF-46396 bind to the Gag lattice where they deny the protease access to the CA-SP1 cleavage site and prevent the release of CA. CA5 particles, which exhibit no cleavage at the CA-SP1 site, have spheroidal shells with relatively thin walls. It appears that this lattice progresses displacively toward a mature-like state but produces neither conical cores nor infectious virions. These observations support the disassembly-reassembly pathway for core formation.

Plate/shell structure topology optimization of orthotropic material for buckling problem based on independent continuous topological variables

NASA Astrophysics Data System (ADS)

Ye, Hong-Ling; Wang, Wei-Wei; Chen, Ning; Sui, Yun-Kang

2017-10-01

The purpose of the present work is to study the buckling problem with plate/shell topology optimization of orthotropic material. A model of buckling topology optimization is established based on the independent, continuous, and mapping method, which considers structural mass as objective and buckling critical loads as constraints. Firstly, composite exponential function (CEF) and power function (PF) as filter functions are introduced to recognize the element mass, the element stiffness matrix, and the element geometric stiffness matrix. The filter functions of the orthotropic material stiffness are deduced. Then these filter functions are put into buckling topology optimization of a differential equation to analyze the design sensitivity. Furthermore, the buckling constraints are approximately expressed as explicit functions with respect to the design variables based on the first-order Taylor expansion. The objective function is standardized based on the second-order Taylor expansion. Therefore, the optimization model is translated into a quadratic program. Finally, the dual sequence quadratic programming (DSQP) algorithm and the global convergence method of moving asymptotes algorithm with two different filter functions (CEF and PF) are applied to solve the optimal model. Three numerical results show that DSQP&CEF has the best performance in the view of structural mass and discretion.

A high-performance Fortran code to calculate spin- and parity-dependent nuclear level densities

NASA Astrophysics Data System (ADS)

Sen'kov, R. A.; Horoi, M.; Zelevinsky, V. G.

2013-01-01

A high-performance Fortran code is developed to calculate the spin- and parity-dependent shell model nuclear level densities. The algorithm is based on the extension of methods of statistical spectroscopy and implies exact calculation of the first and second Hamiltonian moments for different configurations at fixed spin and parity. The proton-neutron formalism is used. We have applied the method for calculating the level densities for a set of nuclei in the sd-, pf-, and pf+g- model spaces. Examples of the calculations for 28Si (in the sd-model space) and 64Ge (in the pf+g-model space) are presented. To illustrate the power of the method we estimate the ground state energy of 64Ge in the larger model space pf+g, which is not accessible to direct shell model diagonalization due to the prohibitively large dimension, by comparing with the nuclear level densities at low excitation energy calculated in the smaller model space pf. Program summaryProgram title: MM Catalogue identifier: AENM_v1_0 Program summary URL:http://cpc.cs.qub.ac.uk/summaries/AENM_v1_0.html Program obtainable from: CPC Program Library, Queen's University, Belfast, N. Ireland Licensing provisions: Standard CPC licence, http://cpc.cs.qub.ac.uk/licence/licence.html No. of lines in distributed program, including test data, etc.: 193181 No. of bytes in distributed program, including test data, etc.: 1298585 Distribution format: tar.gz Programming language: Fortran 90, MPI. Computer: Any architecture with a Fortran 90 compiler and MPI. Operating system: Linux. RAM: Proportional to the system size, in our examples, up to 75Mb Classification: 17.15. External routines: MPICH2 (http://www.mcs.anl.gov/research/projects/mpich2/) Nature of problem: Calculating of the spin- and parity-dependent nuclear level density. Solution method: The algorithm implies exact calculation of the first and second Hamiltonian moments for different configurations at fixed spin and parity. The code is parallelized using the Message Passing Interface and a master-slaves dynamical load-balancing approach. Restrictions: The program uses two-body interaction in a restricted single-level basis. For example, GXPF1A in the pf-valence space. Running time: Depends on the system size and the number of processors used (from 1 min to several hours).

Lifetime Measurement of Nickel-58 Using RDM with GRETINA

NASA Astrophysics Data System (ADS)

Loelius, Charles

2014-09-01

The structure of nuclei near the doubly magic 56Ni has provided a sensitive probe of configuration mixing across the N=Z=28 shell gap. The shell model description of nuclei in this region is well established, with the gxpf1 interaction accurately reproducing the energy levels and transition strengths of Nuclei in the vicinity of 56Ni. However, there remain open questions as to the effects of higher lying orbitals beyond the pf shell. These can be addressed by a study of the B(E2)'s of nuclei in near the shell gap, particularly the B(E2;4+ -->2+) where effects of high l orbitals may be enhanced. 58Ni provides a strong candidate for study, as the only previous B(E2;4+ -->2+) measurement using the Doppler Shift Attenuation Method resulted in a B(E2) three times larger than that predicted by theory. In order to determine the possible effects of higher lying orbitals, a second measurement of the lifetime of 58Ni was undertaken at the National Superconducting Cyclotron Laboratory using the the Gamma-Ray Energy Tracking in Beam Nuclear Array (GRETINA) and the Recoil Distance Method (RDM). Preliminary results of this measurement will be presented.

Planktonic Foraminifera Proxies Calibration Off the NW Iberian Margin: Nutrients Approach

NASA Astrophysics Data System (ADS)

Salgueiro, E.; Castro, C. G.; Zuniga, D.; Martin, P. A.; Groeneveld, J.; de la Granda, F.; Villaceiros-Robineau, N.; Alonso-Perez, F.; Alberto, A.; Rodrigues, T.; Rufino, M. M.; Abrantes, F. F. G.; Voelker, A. H. L.

2014-12-01

Planktonic foraminifera (PF) shells preserved in marine sediments are a useful tool to reconstruct productivity conditions at different geological timescales. However, the accuracy of these paleoreconstructions depends on the data set and calibration quality. Several calibration works have been defining and improving the use of proxies for productivity and nutrient cycling parameters. Our contribution is centred on a multi-proxy calibration at a regional coastal upwelling system. To minimize the existing uncertainties affecting the use of trace elements and C stable isotopes as productivity proxy in the high productivity upwelling areas, we investigate the content and distribution of Ba/Ca and δ13C in the water column, its transference into the planktonic foraminifera shells, and, how the living planktonic foraminifera Ba/Ca and δ13C signal is related to the same planktonic foraminiferal species preserved in the sediment record. This study is based on a large data set from two stations (RAIA - 75m water depth, and CALIBERIA - 350m water depth) located off the NW Iberian margin (41.5-42.5ºN; 9-10ºW), and includes: i) two year monthly water column data (temperature, salinity, nutrients, chlorophyll a, Ba/Ca, and δ13C-DIC); ii) seasonal Ba/Ca, δ13C in several living PF species at both stations; and iii) Ba/Ca and δ13C in several PF species from a large set of core-top sediment samples in the study region. Additionally, total organic carbon and total alkenones were also measured in the sediment. Our results showed the link between productivity proxies in the surface sediment foraminifera assemblage and the processes regulating the actual phytoplankton dynamics in an upwelling area. The understanding of this relationship has special relevance since it gives fundamental information related to the past oceanic biogeochemistry and/or climate and improves the prevision of future changes against possible climate variability due to anthropogenic forcing.

A nucleon-pair and boson coexistent description of nuclei

NASA Astrophysics Data System (ADS)

Dai, Lianrong; Pan, Feng; Draayer, J. P.

2017-07-01

We study a mixture of s-bosons and like-nucleon pairs with the standard pairing interaction outside an inert core. Competition between the nucleon-pairs and s-bosons is investigated in this scenario. The robustness of the BCS-BEC coexistence and crossover phenomena are examined through an analysis of pf-shell nuclei with realistic single-particle energies, in which two configurations with Pauli blocking of nucleon-pair orbits due to the formation of the s-bosons is taken into account. When the nucleon-pair orbits are considered to be independent of the s-bosons, the BCS-BEC crossover becomes smooth, with the number of the s-bosons noticeably more than that of the nucleon-pairs near the half-shell point, a feature that is demonstrated in the pf-shell for several values of the standard pairing interaction strength. As a further test of the robustness of the BCS-BEC coexistence and crossover phenomena in nuclei, results are given for values of even-even 102-130Sn with 100Sn taken as a core and valence neutron pairs confined within the 1d 5/2, 0g 7/2, 1d 3/2, 2s 1/2, 1h 11/2 orbits in the nucleon-pair orbit and the s-boson independent approximation. The results indicate that the B(E2) values are reproduced well. Supported by National Natural Science Foundation of China (11375080, 11675071), the U.S. National Science Foundation (OCI-0904874 and ACI-1516338), U. S. Department of Energy (DE-SC0005248), the Southeastern Universities Research Association, the China-U. S. Theory Institute for Physics with Exotic Nuclei (CUSTIPEN) (DE-SC0009971), and the LSU-LNNU joint research program (9961) is acknowledged

Li + solvation and kinetics of Li +–BF 4 -/PF 6 - ion pairs in ethylene carbonate. A molecular dynamics study with classical rate theories

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

Chang, Tsun-Mei; Dang, Liem X.

Using our polarizable force-field models and employing classical rate theories of chemical reactions, we examine the ethylene carbonate (EC) exchange process between the first and second solvation shells around Li+ and the dissociation kinetics of ion pairs Li+-[BF4] and Li+-[PF6] in this solvent. We calculate the exchange rates using transition state theory and correct them with transmission coefficients computed by the reactive flux; Impey, Madden, and McDonald approaches; and Grote-Hynes theory. We found the residence times of EC around Li+ ions varied from 70 to 450 ps, depending on the correction method used. We found the relaxation times changed significantlymore » from Li+-[BF4] to Li+-[PF6] ion pairs in EC. Our results also show that, in addition to affecting the free energy of dissociation in EC, the anion type also significantly influence the dissociation kinetics of ion pairing. This work was supported by the U.S. Department of Energy, Office of Science, Office of Basic Energy Sciences, Division of Chemical Sciences, Geosciences, and Biosciences. The calculations were carried out using computer resources provided by the Office of Basic Energy Sciences.« less

Type II shell evolution in A = 70 isobars from the N ≥ 40 island of inversion

NASA Astrophysics Data System (ADS)

Morales, A. I.; Benzoni, G.; Watanabe, H.; Tsunoda, Y.; Otsuka, T.; Nishimura, S.; Browne, F.; Daido, R.; Doornenbal, P.; Fang, Y.; Lorusso, G.; Patel, Z.; Rice, S.; Sinclair, L.; Söderström, P.-A.; Sumikama, T.; Wu, J.; Xu, Z. Y.; Yagi, A.; Yokoyama, R.; Baba, H.; Avigo, R.; Bello Garrote, F. L.; Blasi, N.; Bracco, A.; Camera, F.; Ceruti, S.; Crespi, F. C. L.; de Angelis, G.; Delattre, M.-C.; Dombradi, Zs.; Gottardo, A.; Isobe, T.; Kojouharov, I.; Kurz, N.; Kuti, I.; Matsui, K.; Melon, B.; Mengoni, D.; Miyazaki, T.; Modamio-Hoybjor, V.; Momiyama, S.; Napoli, D. R.; Niikura, M.; Orlandi, R.; Sakurai, H.; Sahin, E.; Sohler, D.; Schaffner, H.; Taniuchi, R.; Taprogge, J.; Vajta, Zs.; Valiente-Dobón, J. J.; Wieland, O.; Yalcinkaya, M.

2017-02-01

The level structures of 70Co and 70Ni, populated from the β decay of 70Fe, have been investigated using β-delayed γ-ray spectroscopy following in-flight fission of a 238U beam. The experimental results are compared to Monte-Carlo Shell-Model calculations including the pf +g9/2 +d5/2 orbitals. The strong population of a (1+) state at 274 keV in 70Co is at variance with the expected excitation energy of ∼1 MeV from near spherical single-particle estimates. This observation indicates a dominance of prolate-deformed intruder configurations in the low-lying levels, which coexist with the normal near spherical states. It is shown that the β decay of the neutron-rich A = 70 isobars from the new island of inversion to the Z = 28 closed-shell regime progresses in accordance with a newly reported type of shell evolution, the so-called Type II, which involves many particle-hole excitations across energy gaps.

Probing the N = 14 subshell closure: g factor of the 26Mg (21+) state

NASA Astrophysics Data System (ADS)

McCormick, B. P.; Stuchbery, A. E.; Kibédi, T.; Lane, G. J.; Reed, M. W.; Eriksen, T. K.; Hota, S. S.; Lee, B. Q.; Palalani, N.

2018-04-01

The first-excited state g factor of 26Mg has been measured relative to the g factor of the 24Mg (21+) state using the high-velocity transient-field technique, giving g = + 0.86 ± 0.10. This new measurement is in strong disagreement with the currently adopted value, but in agreement with the sd-shell model using the USDB interaction. The newly measured g factor, along with E (21+) and B (E 2) systematics, signal the closure of the νd5/2 subshell at N = 14. The possibility that precise g-factor measurements may indicate the onset of neutron pf admixtures in first-excited state even-even magnesium isotopes below 32Mg is discussed and the importance of precise excited-state g-factor measurements on sd shell nuclei with N ≠ Z to test shell-model wavefunctions is noted.

IMPACT OF NEW GAMOW–TELLER STRENGTHS ON EXPLOSIVE TYPE IA SUPERNOVA NUCLEOSYNTHESIS

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

Mori, Kanji; Famiano, Michael A.; Kajino, Toshitaka

2016-12-20

Recent experimental results have confirmed a possible reduction in the Gamow–Teller (GT{sub +}) strengths of pf-shell nuclei. These proton-rich nuclei are of relevance in the deflagration and explosive burning phases of SNe Ia. While prior GT strengths result in nucleosynthesis predictions with a lower-than-expected electron fraction, a reduction in the GT{sub +} strength can result in a slightly increased electron fraction compared to previous shell model predictions, though the enhancement is not as large as previous enhancements in going from rates computed by Fuller, Fowler, and Newman based on an independent particle model. A shell model parametrization has been developed thatmore » more closely matches experimental GT strengths. The resultant electron-capture rates are used in nucleosynthesis calculations for carbon deflagration and explosion phases of SNe Ia, and the final mass fractions are compared to those obtained using more commonly used rates.« less

Impact of New Gamow-Teller Strengths on Explosive Type Ia Supernova Nucleosynthesis

NASA Astrophysics Data System (ADS)

Mori, Kanji; Famiano, Michael A.; Kajino, Toshitaka; Suzuki, Toshio; Hidaka, Jun; Honma, Michio; Iwamoto, Koichi; Nomoto, Ken'ichi; Otsuka, Takaharu

2016-12-01

Recent experimental results have confirmed a possible reduction in the Gamow-Teller (GT+) strengths of pf-shell nuclei. These proton-rich nuclei are of relevance in the deflagration and explosive burning phases of SNe Ia. While prior GT strengths result in nucleosynthesis predictions with a lower-than-expected electron fraction, a reduction in the GT+ strength can result in a slightly increased electron fraction compared to previous shell model predictions, though the enhancement is not as large as previous enhancements in going from rates computed by Fuller, Fowler, and Newman based on an independent particle model. A shell model parametrization has been developed that more closely matches experimental GT strengths. The resultant electron-capture rates are used in nucleosynthesis calculations for carbon deflagration and explosion phases of SNe Ia, and the final mass fractions are compared to those obtained using more commonly used rates.

Lithium ion solvation and diffusion in bulk organic electrolytes from first-principles and classical reactive molecular dynamics.

PubMed

Ong, Mitchell T; Verners, Osvalds; Draeger, Erik W; van Duin, Adri C T; Lordi, Vincenzo; Pask, John E

2015-01-29

Lithium-ion battery performance is strongly influenced by the ionic conductivity of the electrolyte, which depends on the speed at which Li ions migrate across the cell and relates to their solvation structure. The choice of solvent can greatly impact both the solvation and diffusivity of Li ions. In this work, we used first-principles molecular dynamics to examine the solvation and diffusion of Li ions in the bulk organic solvents ethylene carbonate (EC), ethyl methyl carbonate (EMC), and a mixture of EC and EMC. We found that Li ions are solvated by either carbonyl or ether oxygen atoms of the solvents and sometimes by the PF6(-) anion. Li(+) prefers a tetrahedrally coordinated first solvation shell regardless of which species are involved, with the specific preferred solvation structure dependent on the organic solvent. In addition, we calculated Li diffusion coefficients in each electrolyte, finding slightly larger diffusivities in the linear carbonate EMC compared to the cyclic carbonate EC. The magnitude of the diffusion coefficient correlates with the strength of Li(+) solvation. Corresponding analysis for the PF6(-) anion shows greater diffusivity associated with a weakly bound, poorly defined first solvation shell. These results can be used to aid in the design of new electrolytes to improve Li-ion battery performance.

Rate theory of solvent exchange and kinetics of Li(+) - BF4 (-)/PF6 (-) ion pairs in acetonitrile.

PubMed

Dang, Liem X; Chang, Tsun-Mei

2016-09-07

In this paper, we describe our efforts to apply rate theories in studies of solvent exchange around Li(+) and the kinetics of ion pairings in lithium-ion batteries (LIBs). We report one of the first computer simulations of the exchange dynamics around solvated Li(+) in acetonitrile (ACN), which is a common solvent used in LIBs. We also provide details of the ion-pairing kinetics of Li(+)-[BF4] and Li(+)-[PF6] in ACN. Using our polarizable force-field models and employing classical rate theories of chemical reactions, we examine the ACN exchange process between the first and second solvation shells around Li(+). We calculate exchange rates using transition state theory and weighted them with the transmission coefficients determined by the reactive flux, Impey, Madden, and McDonald approaches, and Grote-Hynes theory. We found the relaxation times changed from 180 ps to 4600 ps and from 30 ps to 280 ps for Li(+)-[BF4] and Li(+)-[PF6] ion pairs, respectively. These results confirm that the solvent response to the kinetics of ion pairing is significant. Our results also show that, in addition to affecting the free energy of solvation into ACN, the anion type also should significantly influence the kinetics of ion pairing. These results will increase our understanding of the thermodynamic and kinetic properties of LIB systems.

Rate theory of solvent exchange and kinetics of Li+ - BF4-/PF6- ion pairs in acetonitrile

NASA Astrophysics Data System (ADS)

Dang, Liem X.; Chang, Tsun-Mei

2016-09-01

In this paper, we describe our efforts to apply rate theories in studies of solvent exchange around Li+ and the kinetics of ion pairings in lithium-ion batteries (LIBs). We report one of the first computer simulations of the exchange dynamics around solvated Li+ in acetonitrile (ACN), which is a common solvent used in LIBs. We also provide details of the ion-pairing kinetics of Li+-[BF4] and Li+-[PF6] in ACN. Using our polarizable force-field models and employing classical rate theories of chemical reactions, we examine the ACN exchange process between the first and second solvation shells around Li+. We calculate exchange rates using transition state theory and weighted them with the transmission coefficients determined by the reactive flux, Impey, Madden, and McDonald approaches, and Grote-Hynes theory. We found the relaxation times changed from 180 ps to 4600 ps and from 30 ps to 280 ps for Li+-[BF4] and Li+-[PF6] ion pairs, respectively. These results confirm that the solvent response to the kinetics of ion pairing is significant. Our results also show that, in addition to affecting the free energy of solvation into ACN, the anion type also should significantly influence the kinetics of ion pairing. These results will increase our understanding of the thermodynamic and kinetic properties of LIB systems.

Lithium Ion Solvation and Diffusion in Bulk Organic Electrolytes from First-Principles and Classical Reactive Molecular Dynamics

DOE PAGES

Ong, Mitchell T.; Verners, Osvalds; Draeger, Erik W.; ...

2014-12-19

We report that lithium-ion battery performance is strongly influenced by the ionic conductivity of the electrolyte, which depends on the speed at which Li ions migrate across the cell and relates to their solvation structure. The choice of solvent can greatly impact both the solvation and diffusivity of Li ions. In this work, we used first-principles molecular dynamics to examine the solvation and diffusion of Li ions in the bulk organic solvents ethylene carbonate (EC), ethyl methyl carbonate (EMC), and a mixture of EC and EMC. We found that Li ions are solvated by either carbonyl or ether oxygen atoms of the solvents and sometimes by the PF more » $$\\bar{6}$$ anion. Li + prefers a tetrahedrally coordinated first solvation shell regardless of which species are involved, with the specific preferred solvation structure dependent on the organic solvent. In addition, we calculated Li diffusion coefficients in each electrolyte, finding slightly larger diffusivities in the linear carbonate EMC compared to the cyclic carbonate EC. The magnitude of the diffusion coefficient correlates with the strength of Li + solvation. Corresponding analysis for the PF $$\\bar{6}$$ anion shows greater diffusivity associated with a weakly bound, poorly defined first solvation shell. In conclusion, these results can be used to aid in the design of new electrolytes to improve Li-ion battery performance.« less

MD simulations of the formation of stable clusters in mixtures of alkaline salts and imidazolium-based ionic liquids.

PubMed

Méndez-Morales, Trinidad; Carrete, Jesús; Bouzón-Capelo, Silvia; Pérez-Rodríguez, Martín; Cabeza, Óscar; Gallego, Luis J; Varela, Luis M

2013-03-21

Structural and dynamical properties of room-temperature ionic liquids containing the cation 1-butyl-3-methylimidazolium ([BMIM](+)) and three different anions (hexafluorophosphate, [PF6](-), tetrafluoroborate, [BF4](-), and bis(trifluoromethylsulfonyl)imide, [NTf2](-)) doped with several molar fractions of lithium salts with a common anion at 298.15 K and 1 atm were investigated by means of molecular dynamics simulations. The effect of the size of the salt cation was also analyzed by comparing these results with those for mixtures of [BMIM][PF6] with NaPF6. Lithium/sodium solvation and ionic mobilities were analyzed via the study of radial distribution functions, coordination numbers, cage autocorrelation functions, mean-square displacements (including the analysis of both ballistic and diffusive regimes), self-diffusion coefficients of all the ionic species, velocity and current autocorrelation functions, and ionic conductivity in all the ionic liquid/salt systems. We found that lithium and sodium cations are strongly coordinated in two different positions with the anion present in the mixture. Moreover, [Li](+) and [Na](+) cations were found to form bonded-like, long-lived aggregates with the anions in their first solvation shell, which act as very stable kinetic entities within which a marked rattling motion of salt ions takes place. With very long MD simulation runs, this phenomenon is proved to be on the basis of the decrease of self-diffusion coefficients and ionic conductivities previously reported in experimental and computational results.

Projection of angular momentum via linear algebra

DOE PAGES

Johnson, Calvin W.; O'Mara, Kevin D.

2017-12-01

Projection of many-body states with good angular momentum from an initial state is usually accomplished by a three-dimensional integral. Here, we show how projection can instead be done by solving a straightforward system of linear equations. We demonstrate the method and give sample applications tomore » $$^{48}$$Cr and $$^{60}$$Fe in the $pf$ shell. This new projection scheme, which is competitive against the standard numerical quadrature, should also be applicable to other quantum numbers such as isospin and particle number.« less

Projection of angular momentum via linear algebra

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

Johnson, Calvin W.; O'Mara, Kevin D.

Projection of many-body states with good angular momentum from an initial state is usually accomplished by a three-dimensional integral. Here, we show how projection can instead be done by solving a straightforward system of linear equations. We demonstrate the method and give sample applications tomore » $$^{48}$$Cr and $$^{60}$$Fe in the $pf$ shell. This new projection scheme, which is competitive against the standard numerical quadrature, should also be applicable to other quantum numbers such as isospin and particle number.« less

Free energy force field (FEFF) 3D-QSAR analysis of a set of Plasmodium falciparum dihydrofolate reductase inhibitors

NASA Astrophysics Data System (ADS)

Santos-Filho, Osvaldo A.; Mishra, Rama K.; Hopfinger, A. J.

2001-09-01

Free energy force field (FEFF) 3D-QSAR analysis was used to construct ligand-receptor binding models for a set of 18 structurally diverse antifolates including pyrimethamine, cycloguanil, methotrexate, aminopterin and trimethoprim, and 13 pyrrolo[2,3-d]pyrimidines. The molecular target (`receptor') used was a 3D-homology model of a specific mutant type of Plasmodium falciparum (Pf) dihydrofolate reductase (DHFR). The dependent variable of the 3D-QSAR models is the IC50 inhibition constant for the specific mutant type of PfDHFR. The independent variables of the 3D-QSAR models (the descriptors) are scaled energy terms of a modified first-generation AMBER force field combined with a hydration shell aqueous solvation model and a collection of 2D-QSAR descriptors often used in QSAR studies. Multiple temperature molecular dynamics simulation (MDS) and the genetic function approximation (GFA) were employed using partial least square (PLS) and multidimensional linear regressions as the fitting functions to develop FEFF 3D-QSAR models for the binding process. The significant FEFF energy terms in the best 3D-QSAR models include energy contributions of the direct ligand-receptor interaction. Some changes in conformational energy terms of the ligand due to binding to the enzyme are also found to be important descriptors. The FEFF 3D-QSAR models indicate some structural features perhaps relevant to the mechanism of resistance of the PfDHFR to current antimalarials. The FEFF 3D-QSAR models are also compared to receptor-independent (RI) 4D-QSAR models developed in an earlier study and subsequently refined using recently developed generalized alignment rules.

Protein-protein interaction studies reveal the Plasmodium falciparum merozoite surface protein-1 region involved in a complex formation that binds to human erythrocytes.

PubMed

Paul, Gourab; Deshmukh, Arunaditya; Kumar Chourasia, Bishwanath; Kalamuddin, Md; Panda, Ashutosh; Kumar Singh, Susheel; Gupta, Puneet K; Mohmmed, Asif; Chauhan, Virender S; Theisen, Michael; Malhotra, Pawan

2018-03-29

Plasmodium falciparum merozoite surface protein (PfMSP) 1 has been studied extensively as a vaccine candidate antigen. PfMSP-1 undergoes proteolytic processing into four major products, such as p83, p30, p38, and p42, that are associated in the form of non-covalent complex(s) with other MSPs. To delineate MSP1 regions involved in the interaction with other MSPs, here we expressed recombinant proteins (PfMSP-1 65 ) encompassing part of p38 and p42 regions and PfMSP-1 19 PfMSP-1 65 interacted strongly with PfMSP-3, PfMSP-6, PfMSP-7, and PfMSP-9, whereas PfMSP-1 19 did not interact with any of these proteins. Since MSP-1 complex binds human erythrocytes, we examined the ability of these proteins to bind human erythrocyte. Among the proteins of MSP-1 complex, PfMSP-6 and PfMSP-9 bound to human erythrocytes. Serological studies showed that PfMSP-1 65 was frequently recognized by sera from malaria endemic regions, whereas this was not the case for PfMSP-1 19 In contrast, antibodies against PfMSP-1 19 showed much higher inhibition of merozoite invasion compared with antibodies against the larger PfMSP-1 65 fragment. Importantly, anti-PfMSP-1 19 antibodies recognized both recombinant proteins, PfMSP-1 19 and PfMSP-1 65 ; however, anti-PfMSP-1 65 antibody failed to recognize the PfMSP-1 19 protein. Taken together, these results demonstrate that PfMSP-1 sequences upstream of the 19 kDa C-terminal region are involved in molecular interactions with other MSPs, and these sequences may probably serve as a smoke screen to evade antibody response to the membrane-bound C-terminal 19 kDa region. © 2018 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.

Pteropods in Southern Ocean ecosystems

NASA Astrophysics Data System (ADS)

Hunt, B. P. V.; Pakhomov, E. A.; Hosie, G. W.; Siegel, V.; Ward, P.; Bernard, K.

2008-09-01

To date, little research has been carried out on pelagic gastropod molluscs (pteropods) in Southern Ocean ecosystems. However, recent predictions are that, due to acidification resulting from a business as usual approach to CO 2 emissions (IS92a), Southern Ocean surface waters may begin to become uninhabitable for aragonite shelled thecosome pteropods by 2050. To gain insight into the potential impact that this would have on Southern Ocean ecosystems, we have here synthesized available data on pteropod distributions and densities, assessed current knowledge of pteropod ecology, and highlighted knowledge gaps and directions for future research on this zooplankton group. Six species of pteropod are typical of the Southern Ocean south of the Sub-Tropical Convergence, including the four Thecosomes Limacina helicina antarctica, Limacina retroversa australis, Clio pyramidata, and Clio piatkowskii, and two Gymnosomes Clione limacina antarctica and Spongiobranchaea australis. Limacina retroversa australis dominated pteropod densities north of the Polar Front (PF), averaging 60 ind m -3 (max = 800 ind m -3) and 11% of total zooplankton at the Prince Edward Islands. South of the PF L. helicina antarctica predominated, averaging 165 ind m -3 (max = 2681 ind m -3) and up to >35% of total zooplankton at South Georgia, and up to 1397 ind m -3 and 63% of total zooplankton in the Ross Sea. Combined pteropods contributed <5% to total zooplankton in the Lazarev Sea, but 15% (max = 93%) to macrozooplankton in the East Antarctic. In addition to regional density distributions we have synthesized data on vertical distributions, seasonal cycles, and inter-annual density variation. Trophically, gymnosome are specialist predators on thecosomes, while thecosomes are considered predominantly herbivorous, capturing food with a mucous web. The ingestion rates of L. retroversa australis are in the upper range for sub-Antarctic mesozooplankton (31.2-4196.9 ng pig ind -1 d -1), while those of L. helicina antarctica and C. pyramidata are in the upper range for all Southern Ocean zooplankton, in the latter species reaching 27,757 ng pig ind -1 d -1 and >40% of community grazing impact. Further research is required to quantify diet selectivity, the effect of phytoplankton composition on growth and reproductive success, and the role of carnivory in thecosomes. Life histories are a significant knowledge gap for Southern Ocean pteropods, a single study having been completed for L. retroversa australis, making population studies a priority for this group. Pteropods appear to be important in biogeochemical cycling, thecosome shells contributing >50% to carbonate flux in the deep ocean south of the PF. Pteropods may also contribute significantly to organic carbon flux through the production of fast sinking faecal pellets and mucous flocs, and rapid sinking of dead animals ballasted by their aragonite shells. Quantification of these contributions requires data on mucous web production rates, egestion rates, assimilation efficiencies, metabolic rates, and faecal pellet morphology for application to sediment trap studies. Based on the available data, pteropods are regionally significant components of the Southern Ocean pelagic ecosystem. However, there is an urgent need for focused research on this group in order to quantify how a decline in pteropod densities may impact on Southern Ocean ecosystems.

Lithostratigraphy, biostratigraphy and chemostratigraphy of Upper Cretaceous and Paleogene sediments from southern Tanzania: Tanzania Drilling Project Sites 27-35

NASA Astrophysics Data System (ADS)

Jimènez Berrocoso, Àlvaro; Huber, Brian T.; MacLeod, Kenneth G.; Petrizzo, Maria Rose; Lees, Jacqueline A.; Wendler, Ines; Coxall, Helen; Mweneinda, Amina K.; Falzoni, Francesca; Birch, Heather; Singano, Joyce M.; Haynes, Shannon; Cotton, Laura; Wendler, Jens; Bown, Paul R.; Robinson, Stuart A.; Gould, Jeremy

2012-07-01

The 2008 Tanzania Drilling Project (TDP) expedition recovered common planktonic foraminifera (PF), calcareous nannofossils (CN) and calcareous dinoflagellates with extraordinary shell preservation at multiple Cenomanian-Campanian sites that will be used for paleoclimatic, paleoceanographic, and biostratigraphic studies. New cores confirm the existence of a more expanded and continuous Upper Cretaceous sequence than had previously been documented in the Lindi and Kilwa regions of southeastern coastal Tanzania. This TDP expedition cored 684.02 m at eight Upper Cretaceous sites (TDP Sites 28-35) and a thin Paleocene section (TDP Site 27). TDP Sites 29, 30, 31 and 34 together span the lowermost Turonian to Coniacian (PF Whiteinella archaeocretacea to Dicarinella concavata Zones and CN Zones UC6a-9b), with TDP Site 31 being the most biostratigraphically complete Turonian section found during TDP drilling. A discontinuous section from the Santonian-upper Campanian (PF D. asymetrica to Radotruncana calcarata Zones and CN Zones UC12-16) was collectively recovered at TDP Sites 28, 32 and 35, while thin sequences of the lower Cenomanian (PF Thalmanninella globotruncanoides Zone and CN subzones UC3a-b) and middle Paleocene (Selandian; PF Zone P3a and CN Zone NP5) were cored in TDP Sites 33 and 27, respectively. Records of δ13Corg and δ13Ccarb from bulk sediments generated for all the Cretaceous sites show largely stable values through the sections. Only a few parallel δ13Corg and δ13Ccarb shifts have been found and they are interpreted to reflect local processes. The δ18Ocarb record, however, is consistent with Late Cretaceous cooling trends from the Turonian into the Campanian. Lithologies of these sites include thick intervals of claystones and siltstones with locally abundant, finely-laminated fabrics, irregular occurrences of thin sandstone layers, and sporadic bioclastic debris (e.g., inoceramids, ammonites). Minor lithologies represent much thinner units of up to medium-grained, massive sandstones. The %CaCO3 (∼5-40%) and %Corg (∼0.1-2%) are variable, with the highest %CaCO3 in the lower Campanian and the highest %Corg in the Turonian. Lithofacies analysis suggests that deposition of these sediments occurred in outer shelf-upper slope, a setting that agrees well with inferences from benthic foraminifera and calcareous dinoflagellates.

Impact of bisphenol A (BPA) on early embryo development in the marine mussel Mytilus galloprovincialis: Effects on gene transcription.

PubMed

Balbi, Teresa; Franzellitti, Silvia; Fabbri, Rita; Montagna, Michele; Fabbri, Elena; Canesi, Laura

2016-11-01

Bisphenol A (BPA), a monomer used in plastic manufacturing, is weakly estrogenic and a potential endocrine disruptor in mammals. Although it degrades quickly, it is pseudo-persistent in the environment because of continual inputs, with reported concentrations in aquatic environments between 0.0005 and 12 μg/L. BPA represents a potential concern for aquatic ecosystems, as shown by its reproductive and developmental effects in aquatic vertebrates. In invertebrates, endocrine-related effects of BPA were observed in different species and experimental conditions, with often conflicting results, indicating that the sensitivity to this compound can vary considerably among related taxa. In the marine mussel Mytilus galloprovincialis BPA was recently shown to affect early development at environmental concentrations. In this work, the possible effects of BPA on mussel embryos were investigated at the molecular level by evaluating transcription of 13 genes, selected on the basis of their biological functions in adult mussels. Gene expression was first evaluated in trocophorae and D-veligers (24 and 48 h post fertilization) grown in physiological conditions, in comparison with unfertilized eggs. Basal expressions showed a general up-regulation during development, with distinct transcript levels in trocophorae and D-veligers. Exposure of fertilized eggs to BPA (10 μg/L) induced a general upregulation at 24 h pf, followed by down regulation at 48 h pf. Mytilus Estrogen Receptors, serotonin receptor and genes involved in biomineralization (Carbonic Anydrase and Extrapallial Protein) were the most affected by BPA exposure. At 48 h pf, changes in gene expression were associated with irregularities in shell formation, as shown by scanning electron microscopy (SEM), indicating that the formation of the first shelled embryo, a key step in mussel development, represents a sensitive target for BPA. Similar results were obtained with the natural estrogen 17β-estradiol. The results demonstrate that BPA and E 2 can affect Mytilus early development through dysregulation of gene transcription. Copyright © 2016 Elsevier Ltd. All rights reserved.

Symmetry energies for A =24 and 48 and the USD and KB3 shell model Hamiltonians

NASA Astrophysics Data System (ADS)

Kingan, A.; Neergârd, K.; Zamick, L.

2017-12-01

Calculations in the sd and pf shells reported some time ago by Satuła et al. [Phys. Lett. B 407, 103 (1997), 10.1016/S0370-2693(97)00711-9] are redone for an extended analysis of the results. As in the original work, we do calculations for one mass number in each shell and consider in each case the sequence of lowest energies for isospins 0, 2, and 4, briefly the symmetry spectrum. Following further the original work, we study how this spectrum changes when parts of the two-nucleon interaction are turned off. The variation of its width is explored in detail. A differential combination ɛW of the three energies was taken in the original work as a measure of the so-called Wigner term in semiempirical mass formulas, and it was found to decrease drastically when the two-nucleon interaction in the channel of zero isospin is turned off. Our analysis shows that the width of the symmetry spectrum experiences an equally drastic decrease, which can be explained qualitatively in terms of schematic approximations. We therefore suggest that the decrease of ɛW be seen mainly as a side effect of a narrowing of the symmetry spectrum rather than an independent manifestation of the two-nucleon interaction in the channel of zero isospin.

Unpacking personalized feedback: an exploratory study of the impact of its components and the reactions it elicits among problem drinking men who have sex with men.

PubMed

Kuerbis, Alexis Noel; Schaumberg, Katherine; Davis, Christine M; Hail, Lisa; Morgenstern, Jon

2014-03-01

Personalized feedback (PF) has demonstrated effectiveness in reducing drinking. Few studies have examined its effectiveness with adult problem drinkers or its potential mediators or moderators, including developing discrepancy. This study aimed to identify potential mediators and moderators of PF provided to adult problem drinking men who have sex with men (PDMSM). An exploratory analysis of PF provided to PDMSM in the context of modified behavioral self-control therapy (N = 90). The association of individual items of PF, severity of PF, and independently rated, in-session participant reactions to PF with drinking outcomes (mean drinks per drinking day, MDDD) were examined using correlations and logistic and linear regression. Significant pre-post differences in MDDD emerged. Other drug risk, family risk, and having an abnormal liver enzyme test result were significantly associated with proxies for developed discrepancy in expected directions; however, no PF item or reaction to PF predicted drinking outcomes. Severity of PF was not associated with participant reactions or drinking outcome. PF may be an effective intervention for PDMSM. Further research is needed to identify potential mediators and moderators of PF among adults.

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

Dang, Liem X.; Chang, Tsun-Mei

In this paper, we describe our efforts to apply rate theories in studies of solvent exchange around Li +(aq) and the kinetics of ion pairings in lithium-ion batteries (LIB). We report one of the first computer simulations of the exchange dynamics around hydrated Li + in acetonitrile (ACN), which is common solvent used in LIBs. We also provide details of the ion-pairing kinetics of Li +-[BF 4] and Li +-[PF 6] in ACN. Using our polarizable force-field models and employing classical rate theories of chemical reactions, we examine the ACN exchange process between the first and second solvation shells aroundmore » Li +(aq). We calculate exchange rates using transition state theory and weighted them with transmission coefficients determined by the reactive flux and Impey, Madden, and McDonald approaches and Grote-Hynes theory. We found the relaxation times changed from 180 ps to 4600 ps and from 30 ps to 280 ps for Li +-[BF 4] and Li +-[PF 6] ion pairs, respectively. These results confirm that the solvent response to the kinetics of ion pairing is significant. Our results also show that, in addition to affecting the free energy of solvation into ACN, the anion type also should significantly influence the kinetics of ion pairing. These results will increase our understanding of the thermodynamic and kinetic properties of LIB systems.« less

Investigation of the combined effect of MgO and PEG on the release profile of mefenamic acid prepared via hot-melt extrusion techniques.

PubMed

Alshehri, Sultan M; Tiwari, Roshan V; Alsulays, Bader B; Ashour, Eman A; Alshetaili, Abdullah S; Almutairy, Bjad; Park, Jun-Bom; Morott, Joseph; Sandhu, Bhupinder; Majumdar, Soumyajit; Repka, Michael A

2017-09-01

This study aimed to investigate the combined effect of magnesium oxide (MgO) as an alkalizer and polyethylene glycol (PEG) as a plasticizer and wetting agent in the presence of Kollidon® 12 PF and 17 PF polymer carriers on the release profile of mefenamic acid (MA), which was prepared via hot-melt extrusion technique. Various drug loads of MA and various ratios of the polymers, PEG 3350 and MgO were blended using a V-shell blender and extruded using a twin-screw extruder (16-mm Prism EuroLab, ThermoFisher Scientific, Carlsbad, CA) at different screw speeds and temperatures to prepare a solid dispersion system. Differential scanning calorimetry and X-ray diffraction data of the extruded material confirmed that the drug existed in the amorphous form, as evidenced by the absence of corresponding peaks. MgO and PEG altered the micro-environmental pH to be more alkaline (pH 9) and increased the hydrophilicity and dispersibility of the extrudates to enhance MA solubility and release, respectively. The in vitro release study demonstrated an immediate release for 2 h with more than 80% drug release within 45 min in matrices containing MgO and PEG in combination with polyvinylpyrrolidone when compared to the binary mixture, physical mixture and pure drug.

Plasmodium falciparum Hop (PfHop) Interacts with the Hsp70 Chaperone in a Nucleotide-Dependent Fashion and Exhibits Ligand Selectivity.

PubMed

Zininga, Tawanda; Makumire, Stanely; Gitau, Grace Wairimu; Njunge, James M; Pooe, Ofentse Jacob; Klimek, Hanna; Scheurr, Robina; Raifer, Hartmann; Prinsloo, Earl; Przyborski, Jude M; Hoppe, Heinrich; Shonhai, Addmore

2015-01-01

Heat shock proteins (Hsps) play an important role in the development and pathogenicity of malaria parasites. One of the most prominent functions of Hsps is to facilitate the folding of other proteins. Hsps are thought to play a crucial role when malaria parasites invade their host cells and during their subsequent development in hepatocytes and red blood cells. It is thought that Hsps maintain proteostasis under the unfavourable conditions that malaria parasites encounter in the host environment. Although heat shock protein 70 (Hsp70) is capable of independent folding of some proteins, its functional cooperation with heat shock protein 90 (Hsp90) facilitates folding of some proteins such as kinases and steroid hormone receptors into their fully functional forms. The cooperation of Hsp70 and Hsp90 occurs through an adaptor protein called Hsp70-Hsp90 organising protein (Hop). We previously characterised the Hop protein from Plasmodium falciparum (PfHop). We observed that the protein co-localised with the cytosol-localised chaperones, PfHsp70-1 and PfHsp90 at the blood stages of the malaria parasite. In the current study, we demonstrated that PfHop is a stress-inducible protein. We further explored the direct interaction between PfHop and PfHsp70-1 using far Western and surface plasmon resonance (SPR) analyses. The interaction of the two proteins was further validated by co-immunoprecipitation studies. We observed that PfHop and PfHsp70-1 associate in the absence and presence of either ATP or ADP. However, ADP appears to promote the association of the two proteins better than ATP. In addition, we investigated the specific interaction between PfHop TPR subdomains and PfHsp70-1/ PfHsp90, using a split-GFP approach. This method allowed us to observe that TPR1 and TPR2B subdomains of PfHop bind preferentially to the C-terminus of PfHsp70-1 compared to PfHsp90. Conversely, the TPR2A motif preferentially interacted with the C-terminus of PfHsp90. Finally, we observed that recombinant PfHop occasionally eluted as a protein species of twice its predicted size, suggesting that it may occur as a dimer. We conducted SPR analysis which suggested that PfHop is capable of self-association in presence or absence of ATP/ADP. Overall, our findings suggest that PfHop is a stress-inducible protein that directly associates with PfHsp70-1 and PfHsp90. In addition, the protein is capable of self-association. The findings suggest that PfHop serves as a module that brings these two prominent chaperones (PfHsp70-1 and PfHsp90) into a functional complex. Since PfHsp70-1 and PfHsp90 are essential for parasite growth, findings from this study are important towards the development of possible antimalarial inhibitors targeting the cooperation of these two chaperones.

The Colletotrichum acutatum species complex

PubMed Central

Damm, U.; Cannon, P.F.; Woudenberg, J.H.C.; Crous, P.W.

2012-01-01

Colletotrichum acutatum is known as an important anthracnose pathogen of a wide range of host plants worldwide. Numerous studies have reported subgroups within the C. acutatum species complex. Multilocus molecular phylogenetic analysis (ITS, ACT, TUB2, CHS-1, GAPDH, HIS3) of 331 strains previously identified as C. acutatum and other related taxa, including strains from numerous hosts with wide geographic distributions, confirmed the molecular groups previously recognised and identified a series of novel taxa. Thirty-one species are accepted, of which 21 have not previously been recognised. Colletotrichum orchidophilum clusters basal to the C. acutatum species complex. There is a high phenotypic diversity within this complex, and some of the species appear to have preferences to specific hosts or geographical regions. Others appear to be plurivorous and are present in multiple regions. In this study, only C. salicis and C. rhombiforme formed sexual morphs in culture, although sexual morphs have been described from other taxa (especially as laboratory crosses), and there is evidence of hybridisation between different species. One species with similar morphology to C. acutatum but not belonging to this species complex was also described here as new, namely C. pseudoacutatum. Taxonomic novelties: New combinations - Colletotrichum limetticola (R.E. Clausen) Damm, P.F. Cannon & Crous, C. lupini (Bondar) Damm, P.F. Cannon & Crous, C. salicis (Fuckel) Damm, P.F. Cannon & Crous. New species - C. acerbum Damm, P.F. Cannon & Crous, C. australe Damm, P.F. Cannon & Crous, C. brisbanense Damm, P.F. Cannon & Crous, C. cosmi Damm, P.F. Cannon & Crous, C. costaricense Damm, P.F. Cannon & Crous, C. cuscutae Damm, P.F. Cannon & Crous, C. guajavae Damm, P.F. Cannon & Crous, C. indonesiense Damm, P.F. Cannon & Crous, C. johnstonii Damm, P.F. Cannon & Crous, C. kinghornii Damm, P.F. Cannon & Crous, C. laticiphilum Damm, P.F. Cannon & Crous, C. melonis Damm, P.F. Cannon & Crous, C. orchidophilum Damm, P.F. Cannon & Crous, C. paxtonii Damm, P.F. Cannon & Crous, C. pseudoacutatum Damm, P.F. Cannon & Crous C. pyricola Damm, P.F. Cannon & Crous, C. rhombiforme Damm, P.F. Cannon & Crous, C. scovillei Damm, P.F. Cannon & Crous, C. sloanei Damm, P.F. Cannon & Crous, C. tamarilloi Damm, P.F. Cannon & Crous, C. walleri Damm, P.F. Cannon & Crous. Typifications: Epitypifications - C. acutatum J.H. Simmonds, C. limetticola (R.E. Clausen) Damm, P.F. Cannon & Crous, C. nymphaeae (Pass.) Aa, C. phormii (Henn.) D.F. Farr & Rossman, C. salicis (Fuckel) Damm, P.F. Cannon & Crous. Lectotypifications - C. nymphaeae (Pass.) Aa, C. orchidearum Allesch. PMID:23136458

Comparative study of flexural strength test methods on CAD/CAM Y-TZP dental ceramics

PubMed Central

Xu, Yongxiang; Han, Jianmin; Lin, Hong; An, Linan

2015-01-01

Clinically, fractures are the main cause of computer-aided design and computer-aided manufacturing (CAD/CAM) 3 mol%-yttria-stabilized tetragonal zirconia polycrystal (Y-TZP) all-ceramic dental restorations failure because of repetitive occlusal loading. The goal of this work is to study the effect of test methods and specimen’s size on the flexural strength of five ceramic products. Both bi-axial flexure test (BI) and uni-axial flexure tests (UNI), including three-point flexure test (3PF) and four-point flexure test (4PF), are used in this study. For all five products, the flexural strength is as follows: BI > 3PF > 4PF. Furthermore, specimens with smaller size (3PF-s) have higher values than the bigger ones (3PF). The difference between BI and UNI resulted from the edge flaws in ceramic specimens. The relationship between different UNI (including 3PF-s, 3PF and 4PF) can be explained according to Weibull statistical fracture theory. BI is recommended to evaluate the flexural strength of CAD/CAM Y-TZP dental ceramics. PMID:26816646

A secretory multifunctional serine protease, DegP of Plasmodium falciparum, plays an important role in thermo-oxidative stress, parasite growth and development.

PubMed

Sharma, Shweta; Jadli, Mohit; Singh, Anu; Arora, Kavita; Malhotra, Pawan

2014-03-01

Plasmodium falciparum heat shock proteins and proteases are known for their indispensable roles in parasite virulence and survival in the host cell. They neutralize various host-derived stress responses that are deleterious for parasite growth and invasion. We report identification and functional characterization of the first DegP from an apicomplexan (P. falciparum). To determine the molecular identity and functions of the parasite-encoded DegP, we complemented the Escherichia coli degP null mutant with a putative PfdegP gene, and the results showed that PfDegP complements the growth defect of the temperature sensitive DegP-deficient mutant and imparts resistance to non-permissive temperatures and oxidative stress. Molecular interaction studies showed that PfDegP exists as a complex with parasite-encoded heat shock protein 70, iron superoxide dismutase and enolase. DegP expression is significantly induced in parasite culture upon heat shock/oxidative stress. Our data suggest that the PfDegP protein may play a role in the growth and development of P. falciparum through its ability to confer protection against thermal/oxidative stress. Antibody against DegP showed anti-plasmodial activity against blood-stage parasites in vitro, suggesting that PfDegP and its associated complex may be a potential focus for new anti-malarial therapies. ●PfDegP physically interacts with PfHsp70 and PfEno by anti-bait co-immunoprecipitation (View interaction) ●PfDegP physically interacts with PfEno, PfSod, PfOat, PfHsp70, PfLDH and PfGpi by anti-bait co-immunoprecipitation (View interaction) ●PfHsp-70 and PfDegP co-localize by fluorescence microscopy (View interaction) ●PfDegP physically interacts with PfOat, PfHsp70, PfEno, PfSod, PfGpi and PfLDH by surface plasmon resonance (View interaction) ●PfEno and PfDegP co-localize by fluorescence microscopy (View interaction) ●PfDegP and PfHsp70 co-localize by co-sedimentation through density gradient (View interaction). © 2014 FEBS.

Application of thermogravimetric studies for optimization of lithium hexafluorophosphate production

NASA Astrophysics Data System (ADS)

Smagin, A. A.; Matyukha, V. A.; Korobtsev, V. P.

Lithium hexafluorophosphate, isolated from hydrogen fluoride solution (anhydrous) by decanting and filtering, is an adduct of composition LiPF 6*HF. By thermogravimetric investigations the dynamics of HF removal from LiPF 6 by LiPF 6*HF thermal decomposition was studied. Based on the experimental data the constants entering into the equations as C = C0*exp( t*K0* exp(- E/RT)) were calculated, explaining the thermal decomposition processes of LiPF 6*HF and LiPF 6.

Paeoniflorin protects against ischemia-induced brain damages in rats via inhibiting MAPKs/NF-κB-mediated inflammatory responses.

PubMed

Guo, Ruo-Bing; Wang, Guo-Feng; Zhao, An-Peng; Gu, Jun; Sun, Xiu-Lan; Hu, Gang

2012-01-01

Paeoniflorin (PF), the principal component of Paeoniae Radix prescribed in traditional Chinese medicine, has been reported to exhibit many pharmacological effects including protection against ischemic injury. However, the mechanisms underlying the protective effects of PF on cerebral ischemia are still under investigation. The present study showed that PF treatment for 14 days could significantly inhibit transient middle cerebral artery occlusion (MCAO)-induced over-activation of astrocytes and microglia, and prevented up-regulations of pro-inflamamtory mediators (TNFα, IL-1β, iNOS, COX(2) and 5-LOX) in plasma and brain. Further study demonstrated that chronic treatment with PF suppressed the activations of JNK and p38 MAPK, but enhanced ERK activation. And PF could reverse ischemia-induced activation of NF-κB signaling pathway. Moreover, our in vitro study revealed that PF treatment protected against TNFα-induced cell apoptosis and neuronal loss. Taken together, the present study demonstrates that PF produces a delayed protection in the ischemia-injured rats via inhibiting MAPKs/NF-κB mediated peripheral and cerebral inflammatory response. Our study reveals that PF might be a potential neuroprotective agent for stroke.

Paeoniflorin, a Monoterpene Glycoside, Protects the Brain from Cerebral Ischemic Injury via Inhibition of Apoptosis.

PubMed

Zhang, Yuqin; Li, Huang; Huang, Mingqing; Huang, Mei; Chu, Kedan; Xu, Wei; Zhang, Shengnan; Que, Jinhua; Chen, Lidian

2015-01-01

Paeoniflorin (PF) is a principal bioactive component, which exhibits many pharmacological effects, including protection against ischemic injury. This paper aimed to investigate the protective effect of PF both in vivo and in vitro. Middle cerebral artery occlusion (MCAO) was performed on male Sprague-Dawley (SD) rat for 2 h, and different doses of PF or vehicle were administered 2 h after reperfusion. Rats were sacrificed after 7 days treatment of PF/vehicle. PF treatment for 7 days ameliorated MCAO-induced neurological deficit and decreased the infarct area. Further study demonstrated that PF inhibited the over-activation of astrocytes and apoptosis of neurons, and PF promoted up-regulation of neuronal specific marker neuron-specific nuclear (NeuN) and microtubule-associated protein 2 (MAP-2) in brain. Moreover, NMDA-induced neuron apoptosis was employed. The in vitro study revealed that PF treatment protected against NMDA-induced cell apoptosis and neuronal loss via up-regulation of neuronal specific marker NeuN, MAP-2 and Bcl-2 and the down-regulation Bax. Taken together, the present study demonstrates that PF produces its protective effect by inhibiting the over-activation of astrocytes, apoptosis of neurons and up-regulation of neuronal specific marker NeuN, MAP-2, and B-cell lymphoma-2 (Bcl-2), and down-regulation Bax. Our study reveals that PF may be a potential neuroprotective agent for stroke and can provide basic data for clinical use.

Deciphering the key residues in Plasmodium falciparum beta-ketoacyl acyl carrier protein reductase responsible for interactions with Plasmodium falciparum acyl carrier protein.

PubMed

Karmodiya, Krishanpal; Modak, Rahul; Sahoo, Nirakar; Sajad, Syed; Surolia, Namita

2008-10-01

The type II fatty acid synthase (FAS) pathway of Plasmodium falciparum is a validated unique target for developing novel antimalarials, due to its intrinsic differences from the typeI pathway operating in humans. beta-Ketoacyl acyl carrier protein (ACP) reductase (FabG) performs the NADPH-dependent reduction of beta-ketoacyl-ACP to beta-hydroxyacyl-ACP, the first reductive step in the elongation cycle of fatty acid biosynthesis. In this article, we report intensive studies on the direct interactions of Plasmodium FabG and Plasmodium ACP in solution, in the presence and absence of its cofactor, NADPH, by monitoring the change in intrinsic fluorescence of P.falciparum FabG (PfFabG) and by surface plasmon resonance. To address the issue of the importance of the residues involved in strong, specific and stoichiometric binding of PfFabG to P.falciparum ACP (PfACP), we mutated Arg187, Arg190 and Arg230 of PfFabG. The activities of the mutants were assessed using both an ACP-dependent and an ACP-independent assay. The affinities of all the PfFabG mutants for acetoacetyl-ACP (the physiological substrate) were reduced to different extents as compared to wild-type PfFabG, but were equally active in biochemical assays with the substrate analog acetoacetyl-CoA. Kinetic analysis and studies of direct binding between PfFabG and PfACP confirmed the identification of Arg187 and Arg230 as critical residues for the PfFabG-PfACP interactions. Our studies thus reveal the significance of the positively charged/hydrophobic patch located adjacent to the active site cavities of PfFabG for interactions with PfACP.

Physical Activity, Physical Fitness and Leukocyte Telomere Length: the Cardiovascular Health Study.

PubMed Central

Soares-Miranda, Luisa; Imamura, Fumiaki; Siscovick, David; Jenny, Nancy Swords; Fitzpatrick, Annette L; Mozaffarian, Dariush

2015-01-01

Introduction The influence of physical activity (PA) and physical fitness (PF) at older ages on changes in telomere length (TL), repetitive DNA sequences that may mark biologic aging, is not well-established. Few prior studies have been conducted in older adults, these were mainly cross-sectional, and few evaluated PF. Methods We investigated cross-sectional and prospective associations of PA and PF with leukocyte TL among 582 older adults (age 73±5 y at baseline) in the Cardiovascular Health Study, having serial TL measures and PA and PF assessed multiple times. Cross-sectional associations were assessed using multivariable repeated-measures regression, in which cumulatively averaged PA and PF measures were related to TL. Longitudinal analyses assessed cumulatively averaged PA and PF against later changes in TL; and changes in cumulatively averaged PA and PF against changes in TL. Results Cross-sectionally, greater walking distance and chair test performance, but not other PA and PF measures, were each associated with longer TL (p-trend=0.007, 0.04 respectively). In longitudinal analyses, no significant associations of baseline PA and PF with change in TL were observed. In contrast, changes in leisure-time activity and chair test performance were each inversely associated with changes in TL. Conclusions Cross-sectional analyses suggest that greater PA and PF are associated with longer TL. Prospective analyses show that changes in PA and PF are associated with differences in changes in TL. Even later in life, changes in certain PA and PF measures are associated with changes in TL, suggesting that leisure-time activity and fitness could reduce leukocyte telomere attrition among older adults. PMID:26083773

PROMIS Physical Function Computer Adaptive Test Compared With Other Upper Extremity Outcome Measures in the Evaluation of Proximal Humerus Fractures in Patients Older Than 60 Years.

PubMed

Morgan, Jordan H; Kallen, Michael A; Okike, Kanu; Lee, Olivia C; Vrahas, Mark S

2015-06-01

To compare the PROMIS Physical Function Computer Adaptive Test (PROMIS PF CAT) to commonly used traditional PF measures for the evaluation of patients with proximal humerus fractures. Prospective. Two Level I trauma centers. Forty-seven patients older than 60 years with displaced proximal humerus fractures treated between 2006 and 2009. Evaluation included completion of the PROMIS PF CAT, the Constant Shoulder Score, the Disabilities of the Arm, Shoulder, and Hand (DASH) and the Short Musculoskeletal Functional Assessment (SMFA). Observed correlations among the administered PF outcome measures. On average, patients responded to 86 outcome-related items for this study: 4 for the PROMIS PF CAT (range: 4-8 items), 6 for the Constant Shoulder Score, 30 for the DASH, and 46 for the SMFA. Time to complete the PROMIS PF CAT (median completion time = 98 seconds) was significantly less than that for the DASH (median completion time = 336 seconds, P < 0.001) and for the SMFA (median completion time = 482 seconds, P < 0.001). PROMIS PF CAT scores correlated statistically significantly and were of moderate-to-high magnitude with all other PF outcome measure scores administered. This study suggests using the PROMIS PF CAT as a sole PF outcome measure can yield an assessment of upper extremity function similar to those provided by traditional PF measures, while substantially reducing patient assessment time.

Risk factors and outcomes of postoperative pancreatic fistula after pancreatico-duodenectomy: an audit of 532 consecutive cases.

PubMed

Fu, Shun-Jun; Shen, Shun-Li; Li, Shao-Qiang; Hu, Wen-Jie; Hua, Yun-Peng; Kuang, Ming; Liang, Li-Jian; Peng, Bao-Gang

2015-03-26

Pancreatic fistula (PF) remains the most challenging complication after pancreaticoduodenectomy (PD). The purpose of this study was to identify the risk factors of PF and delineate its impact on patient outcomes. We retrospectively reviewed clinical data of 532 patients who underwent PD and divided them into PF group and no PF group. Risk factors and outcomes of PF following PD were examined. PF was found in 65 (12.2%) cases, of whom 11 were classified into ISGPF grade A, 42 grade B, and 12 grade C. Clinically serious postoperative complications in the PF versus no PF group were mortality, abdominal bleeding, bile leak, intra-abdominal abscess and pneumonia. Univariate and multivariate analysis showed that blood loss ≥ 500 ml, pancreatic duct diameter ≤ 3 mm and pancreaticojejunostomy type were independent risk factors of PF after PD. Blood loss ≥ 500 ml, pancreatic duct diameter ≤ 3 mm and pancreatico-jejunostomy type were independent risk factors of PF after PD. PF was related with higher mortality rate, longer hospital stay, and other complications.

Baking loss of bread with special emphasis on increasing water holding capacity.

PubMed

Kotoki, D; Deka, S C

2010-01-01

Potato flour (PF), hydroxypropyl methylcellulose (HPMC) and honey were used as baking agents and their effects on baking loss and sensory quality were studied. PF at 1, 2 and 4% levels decreased baking loss followed by HPMC and honey. Water absorption was substantially high with the HPMC (70.8-80.8%) and PF (61.7-71.7%) compared to honey and normal standard bread. PF incorporation increased shelf-life (6-7 days) as compared to HPMC and honey. HPMC incorporated bread had higher moisture content (36.8-38.0%) followed by PF (34.5-35.8%) and honey (34.7%). The ash content was in the order of PF (1%) > honey (4%) > PF (2%) > normal bread > HPMC (0.5 g) > PF (4%) > HPMC (1 g) > HPMC (1.5 g). PF incorporated bread had sensorily highest acceptance followed by HPMC and honey.

A Phase 1 study of PF-04929113 (SNX-5422), an orally bioavailable heat shock protein 90 inhibitor in patients with refractory solid tumor malignancies and lymphomas

PubMed Central

Rajan, Arun; Kelly, Ronan J.; Trepel, Jane B.; Kim, Yeong Sang; Alarcon, Sylvia V.; Kummar, Shivaani; Gutierrez, Martin; Crandon, Sonja; Zein, Wadih M.; Jain, Lokesh; Mannargudi, Baskar; Figg, William D.; Houk, Brett E.; Shnaidman, Michael; Brega, Nicoletta; Giaccone, Giuseppe

2011-01-01

Purpose To determine the maximum tolerated dose (MTD), toxicities, and pharmacokinetic-pharmacodynamic profile of the heat shock protein 90 (Hsp90) inhibitor PF-04929113 (SNX-5422) in patients with advanced solid tumors and lymphomas. Methods This was a single institution, phase I, dose-escalation study of PF-04929113 dosed twice-weekly. Endpoints included determination of dose-limiting toxicities (DLT), MTD, the safety profile of PF-04929113, pharmacodynamic assessment of PF-04929113 on Hsp70 induction, pharmacokinetic (PK) analysis of PF 04928473 (SNX-2112) and its prodrug PF-04929113 and assessment of response. Results Thirty three patients with advanced malignancies were treated. Dose escalation was continued up to 177 mg/m2 administered orally twice a week. One DLT (non-septic arthritis) was noted. No grade 4 adverse events (AEs) were seen; grade 3 AEs included diarrhea (9%), non-septic arthritis (3%), AST elevation (3%) and thrombocytopenia (3%). No objective responses were seen in 32 evaluable patients. Fifteen patients (47%) had stable disease; 17 patients (53%) had progressive disease. PK data revealed rapid absorption, hepatic and extra-hepatic clearance, extensive tissue binding and almost linear pharmacokinetics of the active drug PF 04928473. PD studies confirmed inhibition of Hsp90 and a linear correlation between PK parameters and Hsp70 induction. Conclusions PF-04929113 administered orally twice weekly is well tolerated and inhibits its intended target Hsp90. No objective responses were seen but long lasting stabilizations were obtained. Although no clinically significant drug-related ocular toxicity was seen in this study the development of PF-04929113 has been discontinued due to ocular toxicity seen in animal models and in a separate phase I study. PMID:21908572

The influence of transection site on the development of pancreatic fistula in patients undergoing distal pancreatectomy: A review of 294 consecutive cases.

PubMed

Sell, Naomi M; Pucci, Michael J; Gabale, Salil; Leiby, Benjamin E; Rosato, Ernest L; Winter, Jordan M; Yeo, Charles J; Lavu, Harish

2015-06-01

Pancreatic fistula (PF) is a significant cause of morbidity in patients undergoing distal pancreatectomy (DP), with an incidence of 15-40%. It remains unclear if the location of pancreatic transection affects the rate of PF occurrence. This study examines the correlation between the transection site of the pancreas during DP and the incidence of PF. All cases of DP from October 2005 to January 2012 were reviewed retrospectively from an institutional review board-approved database at the Thomas Jefferson University Hospital. Patient demographics and perioperative outcomes were analyzed. The pancreatic transection location was determined by review of operative reports, and then dichotomized into 2 groups: neck/body or tail. PF were graded following the International Study Group on Pancreatic Fistula guidelines. During the study period, 294 DP were performed with 244 pancreas transections at the neck/body and 50 at the tail. Of the 294 patients, 52 (17.7%) developed a postoperative PF. The incidence of PF after transection at the tail of the pancreas was higher (28%) when compared with transection at the neck/body (15.6%; P = .04). When stratified by PF grade, grade A PF occurred more commonly when transection of the gland was at the tail (22% tail vs 8.2% neck/body; P = .007); however, no difference was found for grade B/C PF (6% tail vs 7.4% neck/body; P = 1). Our data suggest that PF occurs more often when the tail is transected during DP, although the majority are low grade and of minimal clinical significance. More severe PF occurred equally between the transection sites. Copyright © 2015 Elsevier Inc. All rights reserved.

Novel mucus-penetrating liposomes as a potential oral drug delivery system: preparation, in vitro characterization, and enhanced cellular uptake

PubMed Central

Li, Xiuying; Chen, Dan; Le, Chaoyi; Zhu, Chunliu; Gan, Yong; Hovgaard, Lars; Yang, Mingshi

2011-01-01

Background The aim of this study was to investigate the intestinal mucus-penetrating properties and intestinal cellular uptake of two types of liposomes modified by Pluronic F127 (PF127). Methods The two types of liposomes, ie, PF127-inlaid liposomes and PF127-adsorbed liposomes, were prepared by a thin-film hydration method followed by extrusion, in which coumarin 6 was loaded as a fluorescence marker. A modified Franz diffusion cell mounted with the intestinal mucus of rats was used to study the diffusion characteristics of the two types of PF127 liposomes. Cell uptake studies were conducted in Caco-2 cells and analyzed using confocal laser scanning microcopy as well as flow cytometry. Results The diffusion efficiency of the two types of PF127-modified liposomes through intestinal rat mucus was 5–7-fold higher than that of unmodified liposomes. Compared with unmodified liposomes, PF127-inlaid liposomes showed significantly higher cellular uptake of courmarin 6. PF127-adsorbed liposomes showed a lower cellular uptake. Moreover, and interestingly, the two types of PF127-modified liposomes showed different cellular uptake mechanisms in Caco-2 cells. Conclusion PF127-inlaid liposomes with improved intestinal mucus-penetrating ability and enhanced cellular uptake might be a potential carrier candidate for oral drug delivery. PMID:22163166

Development of a copula-based particle filter (CopPF) approach for hydrologic data assimilation under consideration of parameter interdependence

NASA Astrophysics Data System (ADS)

Fan, Y. R.; Huang, G. H.; Baetz, B. W.; Li, Y. P.; Huang, K.

2017-06-01

In this study, a copula-based particle filter (CopPF) approach was developed for sequential hydrological data assimilation by considering parameter correlation structures. In CopPF, multivariate copulas are proposed to reflect parameter interdependence before the resampling procedure with new particles then being sampled from the obtained copulas. Such a process can overcome both particle degeneration and sample impoverishment. The applicability of CopPF is illustrated with three case studies using a two-parameter simplified model and two conceptual hydrologic models. The results for the simplified model indicate that model parameters are highly correlated in the data assimilation process, suggesting a demand for full description of their dependence structure. Synthetic experiments on hydrologic data assimilation indicate that CopPF can rejuvenate particle evolution in large spaces and thus achieve good performances with low sample size scenarios. The applicability of CopPF is further illustrated through two real-case studies. It is shown that, compared with traditional particle filter (PF) and particle Markov chain Monte Carlo (PMCMC) approaches, the proposed method can provide more accurate results for both deterministic and probabilistic prediction with a sample size of 100. Furthermore, the sample size would not significantly influence the performance of CopPF. Also, the copula resampling approach dominates parameter evolution in CopPF, with more than 50% of particles sampled by copulas in most sample size scenarios.

Fluorimetric study on the interaction between Norfloxacin and Proflavine hemisulphate.

PubMed

More, Vishalkumar R; Anbhule, Prashant V; Lee, Sang H; Patil, Shivajirao R; Kolekar, Govind B

2011-07-01

The interaction between Norfloxacin (NF) and Proflavine hemisulphate (PF) was investigated by spectroscopic tools like UV-VIS absorption and Fluorescence spectroscopy. It was proved that fluorescence quenching of NF by PF is due to the formation of NF-PF complex which was supported by UV-VIS absorption study. The study of thermodynamic parameters suggested that the key interacting forces are hydrogen bond and van der Waal's interactions and the binding interaction was spontaneous. The distance r between NF and PF was obtained according to the Förster's theory of non-radiative energy transfer. The fluorescence quenching mechanism was applied to estimate PF directly from pharmaceutical samples. © Springer Science+Business Media, LLC 2011

Anti-Plasmodium falciparum invasion ligand antibodies in a low malaria transmission region, Loreto, Peru

PubMed Central

2012-01-01

Background Erythrocyte invasion by Plasmodium falciparum is a complex process that involves two families; Erythrocyte Binding-Like (EBL) and the Reticulocyte Binding-Like (PfRh) proteins. Antibodies that inhibit merozoite attachment and invasion are believed to be important in mediating naturally acquired immunity and immunity generated by parasite blood stage vaccine candidates. The hypotheses tested in this study were 1) that antibody responses against specific P. falciparum invasion ligands (EBL and PfRh) differ between symptomatic and asymptomatic individuals living in the low-transmission region of the Peruvian Amazon and 2), such antibody responses might have an association, either direct or indirect, with clinical immunity observed in asymptomatically parasitaemic individuals. Methods ELISA was used to assess antibody responses (IgG, IgG1 and IgG3) against recombinant P. falciparum invasion ligands of the EBL (EBA-175, EBA-181, EBA-140) and PfRh families (PfRh1, PfRh2a, PfRh2b, PfRh4 and PfRh5) in 45 individuals infected with P. falciparum from Peruvian Amazon. Individuals were classified as having symptomatic malaria (N=37) or asymptomatic infection (N=8). Results Antibody responses against both EBL and PfRh family proteins were significantly higher in asymptomatic compared to symptomatic individuals, demonstrating an association with clinical immunity. Significant differences in the total IgG responses were observed with EBA-175, EBA-181, PfRh2b, and MSP119 (as a control). IgG1 responses against EBA-181, PfRh2a and PfRh2b were significantly higher in the asymptomatic individuals. Total IgG antibody responses against PfRh1, PfRh2a, PfRh2b, PfRh5, EBA-175, EBA-181 and MSP119 proteins were negatively correlated with level of parasitaemia. IgG1 responses against EBA-181, PfRh2a and PfRh2b and IgG3 response for PfRh2a were also negatively correlated with parasitaemia. Conclusions These data suggest that falciparum malaria patients who develop clinical immunity (asymptomatic parasitaemia) in a low transmission setting such as the Peruvian Amazon have antibody responses to defined P. falciparum invasion ligand proteins higher than those found in symptomatic (non-immune) patients. While these findings will have to be confirmed by larger studies, these results are consistent with a potential role for one or more of these invasion ligands as a component of an anti-P. falciparum vaccine in low-transmission malaria-endemic regions. PMID:23110555

Interaction of apicoplast-encoded elongation factor (EF) EF-Tu with nuclear-encoded EF-Ts mediates translation in the Plasmodiumfalciparum plastid.

PubMed

Biswas, Subir; Lim, Erin E; Gupta, Ankit; Saqib, Uzma; Mir, Snober S; Siddiqi, Mohammad Imran; Ralph, Stuart A; Habib, Saman

2011-03-01

Protein translation in the plastid (apicoplast) of Plasmodium spp. is of immense interest as a target for potential anti-malarial drugs. However, the molecular data on apicoplast translation needed for optimisation and development of novel inhibitors is lacking. We report characterisation of two key translation elongation factors in Plasmodium falciparum, apicoplast-encoded elongation factor PfEF-Tu and nuclear-encoded PfEF-Ts. Recombinant PfEF-Tu hydrolysed GTP and interacted with its presumed nuclear-encoded partner PfEF-Ts. The EF-Tu inhibitor kirromycin affected PfEF-Tu activity in vitro, indicating that apicoplast EF-Tu is indeed the target of this drug. The predicted PfEF-Ts leader sequence targeted GFP to the apicoplast, confirming that PfEF-Ts functions in this organelle. Recombinant PfEF-Ts mediated nucleotide exchange on PfEF-Tu and homology modeling of the PfEF-Tu:PfEF-Ts complex revealed PfEF-Ts-induced structural alterations that would expedite GDP release from PfEF-Tu. Our results establish functional interaction between two apicoplast translation factors encoded by genes residing in different cellular compartments and highlight the significance of their sequence/structural differences from bacterial elongation factors in relation to inhibitor activity. These data provide an experimental system to study the effects of novel inhibitors targeting PfEF-Tu and PfEF-Tu.PfEF-Ts interaction. Our finding that apicoplast EF-Tu possesses chaperone-related disulphide reductase activity also provides a rationale for retention of the tufA gene on the plastid genome. Copyright © 2010 Australian Society for Parasitology Inc. All rights reserved.

Low levels of circulating platelet factor 4 (PF4, CXCL4) in subclinically hypothyroid autoimmune thyroiditis.

PubMed

Görar, S; Ademoğlu, E; Çarlıoğlu, A; Alioğlu, B; Bekdemir, H; Sağlam, B; Candan, Z; Üçler, R; Culha, C; Aral, Y

2016-02-01

Chemokines play an important role in the pathogenesis of autoimmune thyroid diseases. Platelet factor 4 (PF4, CXCL4) released from activated platelets is a chemokine. However, its clinical importance in autoimmune thyroiditis remains unknown. This study is intended to determine circulating levels of PF4 levels in patients with autoimmune thyroiditis (AIT). Circulating levels of PF4 were measured in 34 consecutive patients with newly diagnosed AIT and 18 euthyroid controls. Among AIT group, 16 patients were euthyroid and 18 had subclinic hypothyroidism. Controls and individuals with AIT were similar in terms of age. Serum levels of PF4 were comparable in patients with AIT and in controls. Among patients with AIT, PF4 was significantly lower in those with subclinical hypothyroidism than in euthyroid individuals (p = 0.001). In correlation analysis, PF4 was negatively correlated with TSH (r = -0.663, p = 0.000) and positively correlated with free T4 (r = 0.428, p = 0.012). There was not any significant correlation between PF4 and AbTPO, AbTg. The present study demonstrated for the first time that circulating PF4 levels are decreased in subclinically hypothyroid AIT. This result draws attention to the circulating PF4 levels in subclinically hypothyroid AIT and may shed light on further researches at this topic.

Pf155/RESA protein influences the dynamic microcirculatory behavior of ring-stage Plasmodium falciparum infected red blood cells

PubMed Central

Diez-Silva, Monica; Park, YongKeun; Huang, Sha; Bow, Hansen; Mercereau-Puijalon, Odile; Deplaine, Guillaume; Lavazec, Catherine; Perrot, Sylvie; Bonnefoy, Serge; Feld, Michael S.; Han, Jongyoon; Dao, Ming; Suresh, Subra

2012-01-01

Proteins exported by Plasmodium falciparum to the red blood cell (RBC) membrane modify the structural properties of the parasitized RBC (Pf-RBC). Although quasi-static single cell assays show reduced ring-stage Pf-RBCs deformability, the parameters influencing their microcirculatory behavior remain unexplored. Here, we study the dynamic properties of ring-stage Pf-RBCs and the role of the parasite protein Pf155/Ring-Infected Erythrocyte Surface Antigen (RESA). Diffraction phase microscopy revealed RESA-driven decreased Pf-RBCs membrane fluctuations. Microfluidic experiments showed a RESA-dependent reduction in the Pf-RBCs transit velocity, which was potentiated at febrile temperature. In a microspheres filtration system, incubation at febrile temperature impaired traversal of RESA-expressing Pf-RBCs. These results show that RESA influences ring-stage Pf-RBCs microcirculation, an effect that is fever-enhanced. This is the first identification of a parasite factor influencing the dynamic circulation of young asexual Pf-RBCs in physiologically relevant conditions, offering novel possibilities for interventions to reduce parasite survival and pathogenesis in its human host. PMID:22937223

Pf155/RESA protein influences the dynamic microcirculatory behavior of ring-stage Plasmodium falciparum infected red blood cells

NASA Astrophysics Data System (ADS)

Diez-Silva, Monica; Park, Yongkeun; Huang, Sha; Bow, Hansen; Mercereau-Puijalon, Odile; Deplaine, Guillaume; Lavazec, Catherine; Perrot, Sylvie; Bonnefoy, Serge; Feld, Michael S.; Han, Jongyoon; Dao, Ming; Suresh, Subra

2012-08-01

Proteins exported by Plasmodium falciparum to the red blood cell (RBC) membrane modify the structural properties of the parasitized RBC (Pf-RBC). Although quasi-static single cell assays show reduced ring-stage Pf-RBCs deformability, the parameters influencing their microcirculatory behavior remain unexplored. Here, we study the dynamic properties of ring-stage Pf-RBCs and the role of the parasite protein Pf155/Ring-Infected Erythrocyte Surface Antigen (RESA). Diffraction phase microscopy revealed RESA-driven decreased Pf-RBCs membrane fluctuations. Microfluidic experiments showed a RESA-dependent reduction in the Pf-RBCs transit velocity, which was potentiated at febrile temperature. In a microspheres filtration system, incubation at febrile temperature impaired traversal of RESA-expressing Pf-RBCs. These results show that RESA influences ring-stage Pf-RBCs microcirculation, an effect that is fever-enhanced. This is the first identification of a parasite factor influencing the dynamic circulation of young asexual Pf-RBCs in physiologically relevant conditions, offering novel possibilities for interventions to reduce parasite survival and pathogenesis in its human host.

Patellar maltracking is prevalent among patellofemoral pain subjects with patella alta: an upright, weightbearing MRI study

PubMed Central

Pal, Saikat; Besier, Thor F.; Beaupre, Gary S.; Fredericson, Michael; Delp, Scott L.; Gold, Garry E.

2012-01-01

The purpose of this study is to determine if patellar maltracking is more prevalent among patellofemoral (PF) pain subjects with patella alta compared to subjects with normal patella height. We imaged 37 PF pain and 15 pain free subjects in an open-configuration magnetic resonance imaging scanner while they stood in a weightbearing posture. We measured patella height using the Caton-Deschamps, Blackburne-Peel, Insall-Salvati, Modified Insall-Salvati, and Patellotrochlear indices, and classified the subjects into patella alta and normal patella height groups. We measured patella tilt and bisect offset from oblique-axial plane images, and classified the subjects into maltracking and normal tracking groups. Patellar maltracking was more prevalent among PF pain subjects with patella alta compared to PF pain subjects with normal patella height (two-tailed Fisher’s exact test, p < 0.050). Using the Caton-Deschamps index, 67% (8/12) of PF pain subjects with patella alta were maltrackers, whereas only 16% (4/25) of PF pain subjects with normal patella height were maltrackers. Patellofemoral pain subjects classified as maltrackers displayed a greater patella height compared to the pain free and PF pain subjects classified as normal trackers (two-tailed unpaired t-tests with Bonferroni correction, p < 0.017). This study adds to our understanding of PF pain in two ways - 1) we demonstrate that patellar maltracking is more prevalent in PF pain subjects with patella alta compared to subjects with normal patella height; and 2) we show greater patella height in PF pain subjects compared to pain free subjects using four indices commonly used in clinics. PMID:23165335

Solvate Structures and Computational/Spectroscopic Characterization of LiPF6 Electrolytes

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

Han, Sang D.; Yun, Sung-Hyun; Borodin, Oleg

2015-04-23

Raman spectroscopy is a powerful method for identifying ion-ion interactions, but only if the vibrational band signature for the anion coordination modes can be accurately deciphered. The present study characterizes the PF6- anion P-F Raman symmetric stretching vibrational band for evaluating the PF6-...Li+ cation interactions within LiPF6 crystalline solvates to create a characterization tool for liquid electrolytes. To facilitate this, the crystal structures for two new solvates—(G3)1:LiPF6 and (DEC)2:LiPF6 with triglyme and diethyl carbonate, respectively—are reported. The information obtained from this analysis provides key guidance about the ionic association information which may be obtained from a Raman spectroscopic evaluation ofmore » electrolytes containing the LiPF6 salt and aprotic solvents. Of particular note is the overlap of the Raman bands for both solvent-separated ion pair (SSIP) and contact ion pair (CIP) coordination in which the PF6- anions are uncoordinated or coordinated to a single Li+ cation, respectively.« less

Study of the interrelation between the electrotechnical parameters of the plasma focus discharge circuit and the plasma compression dynamics on the PF-3 and PF-1000 facilities

NASA Astrophysics Data System (ADS)

Mitrofanov, K. N.; Krauz, V. I.; Grabovski, E. V.; Myalton, V. V.; Vinogradov, V. P.; Paduch, M.; Scholz, M.; Karpiński, L.

2015-05-01

The main stages of the plasma current sheath (PCS) dynamics on two plasma focus (PF) facilities with different geometries of the electrode system, PF-3 (Filippov type) and PF-1000 (Mather type), were studied by analyzing the results of the current and voltage measurements. Some dynamic characteristics, such as the PCS velocity in the acceleration phase in the Mather-type facility (PF-1000), the moment at which the PCS reaches the anode end, and the plasma velocity in the radial stage of plasma compression in the PF-3 Filippov-type facility, were determined from the time dependence of the inductance of the discharge circuit with a dynamic plasma load. The energy characteristics of the discharge circuit of the compressing PCS were studied for different working gases (deuterium, argon, and neon) at initial pressures of 1.5-3 Torr in discharges with energies of 0.3-0.6 MJ. In experiments with deuterium, correlation between the neutron yield and the electromagnetic energy deposited directly in the compressed PCS was investigated.

Moxifloxacin pharmacokinetics and pleural fluid penetration in patients with pleural effusion.

PubMed

Chatzika, Kalliopi; Manika, Katerina; Kontou, Paschalina; Pitsiou, Georgia; Papakosta, Despina; Zarogoulidis, Konstantinos; Kioumis, Ioannis

2014-01-01

The aim of this study was to evaluate the pharmacokinetics and penetration of moxifloxacin (MXF) in patients with various types of pleural effusion. Twelve patients with empyema/parapneumonic effusion (PPE) and 12 patients with malignant pleural effusion were enrolled in the study. A single-dose pharmacokinetic study was performed after intravenous administration of 400 mg MXF. Serial plasma (PL) and pleural fluid (PF) samples were collected during a 24-h time interval after drug administration. The MXF concentration in PL and PF was determined by high-performance liquid chromatography, and main pharmacokinetic parameters were estimated. Penetration of MXF in PF was determined by the ratio of the area under the concentration-time curve from time zero to 24 h (AUC24) in PF (AUC24PF) to the AUC24 in PL. No statistically significant differences in the pharmacokinetics in PL were observed between the two groups, despite the large interindividual variability in the volume of distribution, clearance, and elimination half-life. The maximum concentration in PF (CmaxPF) in patients with empyema/PPE was 2.23±1.31 mg/liter, and it was detected 7.50±2.39 h after the initiation of the infusion. In patients with malignant effusion, CmaxPF was 2.96±1.45 mg/liter, but it was observed significantly earlier, at 3.58±1.38 h (P<0.001). Both groups revealed similar values of AUC24PF (31.83±23.52 versus 32.81±12.66 mg·h/liter). Penetration of MXF into PF was similarly good in both patient groups (1.11±0.74 versus 1.17±0.39). Despite similar plasma pharmacokinetics, patients with empyema/parapneumonic effusion showed a significant delay in achievement of PF maximum MXF levels compared to those with malignant effusion. However, in both groups, the degree of MXF PF penetration and the on-site drug exposure, expressed by AUC24PF, did not differ according to the type of pleural effusion.

Preparation and Characterization of Pyrotechnics Binder-Coated Nano-Aluminum Composite Particles

NASA Astrophysics Data System (ADS)

Ye, Mingquan; Zhang, Shuting; Liu, Songsong; Han, Aijun; Chen, Xin

2017-07-01

The aim of this article is to protect the activity of nano-aluminum (Al) particles in solid rocket propellants and pyrotechnics. The morphology, structure, active aluminum content, and thermal and catalytic properties of the coated samples were characterized by scanning electron microscopy (SEM), transmission electron microscopy (TEM), Fourier transform infrared spectroscopy (FTIR), thermogravimetry-differential scanning calorimetry (TG-DSC), and oxidation-reduction titration methods. The results indicated that nano-Al particles could be effectively coated with phenolic resin (PF), fluororubber (Viton B), and shellac through a solvent/nonsolvent method. The energetic composite particles have core-shell structures and the thickness of the coating film is about 5-15 nm. Analysis of the active Al content revealed that Viton B coating had a much better protective effect. The TG-DSC results showed that the energy amount and energy release rate of PF-, Viton B-, and shellac-coated Al particles were larger than those of the raw nano-Al particles. The catalytic effects of coated Al particles on the thermal decomposition of ammonium perchlorate (AP) were better than those of raw nano-Al particles, and the effect of shellac-coated Al particles was significantly better than that of Viton B-coated Al particles.

In vitro, ex vivo and in vivo characterization of PLGA nanoparticles loading pranoprofen for ocular administration.

PubMed

Cañadas, Cristina; Alvarado, Helen; Calpena, Ana C; Silva, Amélia M; Souto, Eliana B; García, Maria L; Abrego, Guadalupe

2016-09-25

Pranoprofen (PF) is a NSAID considered as a safe anti-inflammatory treatment for strabismus and/or cataract surgery. The drug has been formulated in poly (lactic/glycolic) acid (PLGA) nanoparticles (PF-F1NPs with cPF 1.5mg/mL, PF-F2NPs with cPF 1mg/mL) produced by solvent displacement technique and tested the in vitro cytotoxicity, ex vivo corneal permeation, in vivo ocular tolerance and in vivo anti-inflammatory efficacy of PF-F1NPs, PF-F2NPs, in comparison to eye drops conventional dosage form (Oftalar(®), PF 1mg/mL) and free drug solution (PF dissolved in PBS, 1.5mg/mL). The mean particle size of both formulations was around 350nm, with polydispersity index below 0.1, and a net negative charge of -7.41mV and -8.5mV for PF-F1NPs and PF-F2NPs, respectively. Y-79 human retinoblastoma cell line was used to evaluate the cytotoxicity of PF-F1NPs and PF-F2NPs, which were compared to blank NPs and free drug solution (PF dissolved in PBS, 1.5mg/mL). Concentrations up to 75μg/mL exhibited no toxicity to Y-79 cells, whereas at 150μg/mL a decrease of about 80% on the cell viability was observed after exposing the cells to PF-F1NPs. When treating the Y-79 cells with concentrations of PF-F2NPs between 1μg/mL to 100μg/mL, the cell viability was similar to control values after 24h and 48h of exposure. An ex vivo corneal permeation study was carried out in New Zealand rabbits. A very similar profile has been observed for the permeation of PF through the cornea when administered as eye drops and as free drug solution, which was kept much lower in comparison to PF-NPs formulations. The permeated amount of PF from the PF-F1NPs was slightly smaller than from PF-F2NPs, attributed to the increase of viscosity of the formulations with the increase of cPVA concentration. New Zealand white rabbits were also used to evaluate the irritancy of PF-F1NPs and PF-F2NPs, which demonstrated to be well-tolerated to the eye (i.e. the mean total score (MTS) was 0). PF-F2NPs exhibited the highest QP (amounts of PF permeated in the cornea) and significantly reduced the ocular edema compared to the tested formulations. The QR (amounts of PF retained in the cornea) of the PF-F1NPs was greater than that obtained for PF-F2NPs. Copyright © 2016 Elsevier B.V. All rights reserved.

Pleural effusion levels of DJ-1 are increased in elderly lung cancer patients with malignant pleural effusions.

PubMed

Vavougios, George; Kerenidi, Theodora; Tsilioni, Irene; Zarogiannis, Sotirios G; Gourgoulianis, Konstantinos I

2015-01-01

DJ-1 is a multifunctional protein implicated in redox dependent cell fate decisions. The aim of our study was to determine the pleural fluid (PF) levels of DJ-1 in malignant pleural effusions (MPEs) secondary to lung cancer. Additionally, we opted to assess potential correlations of DJ-1 PF levels with the PF levels of superoxide dismutase-1 (SOD1) and 8-isoprostane that are known antioxidant enzymes and have been previously reported in MPEs. Forty lung cancer patients with cytological proof of MPE were enrolled in this study. The PF levels of DJ-1, SOD1, and 8-isoprostane were measured by means of enzyme-linked immunosorbent assay. The median PF levels of DJ-1 were 826 ng/mL (interquartile range, IQR: 482-1010 ng/mL). DJ-1 PF levels significantly correlated with PF Cu/Zn-SOD1 and PF 8-isoprostane levels (Spearman's rho, r; r = -0.476, P = 0.002 and r = -0.264, P = 0.033, respectively), PF lactate dehydrogenase (r = -0.497, P = 0.001) and total PF cell counts (r = -0.325, P = 0.041). Finally, in patients aged over 65 the PF DJ-1 levels were significantly higher than patients aged less than 65 (875 ng/mL vs. 607 ng/mL, respectively, P = 0.037). To our knowledge, this is the first report to determine DJ-1's levels in MPEs due to lung cancer. The negative correlations between DJ-1, SOD1, and 8-isorpostane warrant further investigation regarding the altered redox regulation associated with MPEs.

Enhanced Oral Bioavailability of Pueraria Flavones by a Novel Solid Self-microemulsifying Drug Delivery System (SMEDDS) Dropping Pills.

PubMed

Guan, Qingxiang; Zhang, Guangyuan; Sun, Shilin; Fan, Hongbo; Sun, Cheng; Zhang, Shaoyuan

2016-05-01

To improve bioavailability of pueraria flavones (PF), a self-microemulsifying drug delivery system (SMEDDS) dropping pills composed of PF, Crodamol GTCC, Maisine 35-1, Cremophor RH 40, 1,2-propylene glycol and polyethylene glycol 6000 (PEG6000) was developed. Particle size, zeta potential, morphology and in vitro drug release were investigated, respectively. Pharmacokinetics, bioavailability of PF-SMEDDS dropping pills and commercial Yufengningxin dropping pills were also evaluated and compared in rats. Puerarin treated as the representative component of PF was analyzed. Dynamic light scattering showed the ability of PF-SMEDDS dropping pills to form a nanoemulsion droplet size in aqueous media. The type of media showed no significant effects on the release rate of PF. PF-SMEDDS dropping pills were able to improve the in vitro release rate of PF, and the in vitro release of these dropping pills was significantly faster than that of Yufengningxin dropping pills. There was a dramatic difference between the mean value of t1/2, peak concentration (Cmax), the area of concentration-time curve from 0 to 6 h (AUC0-6 h) of PF-SMEDDS dropping pills and that of commercial Yufengningxin dropping pills. A pharmacokinetic study showed that the bioavailability of PF was greatly enhanced by PF-SMEDDS dropping pills. The value of Cmax and relative bioavailability of PF-SMEDDS dropping pills were dramatically improved by an average of 1.69- and 2.36-fold compared with that of Yufengningxin dropping pills after gavage administration, respectively. It was concluded that bioavailability of PF was greatly improved and that PF-SMEDDS dropping pills might be an encouraging strategy to enhance the oral bioavailability of PF.

A Chimeric Plasmodium falciparum Merozoite Surface Protein Vaccine Induces High Titers of Parasite Growth Inhibitory Antibodies

PubMed Central

Alaro, James R.; Partridge, Andrea; Miura, Kazutoyo; Diouf, Ababacar; Lopez, Ana M.; Angov, Evelina; Long, Carole A.

2013-01-01

The C-terminal 19-kDa domain of Plasmodium falciparum merozoite surface protein 1 (PfMSP119) is an established target of protective antibodies. However, clinical trials of PfMSP142, a leading blood-stage vaccine candidate which contains the protective epitopes of PfMSP119, revealed suboptimal immunogenicity and efficacy. Based on proof-of-concept studies in the Plasmodium yoelii murine model, we produced a chimeric vaccine antigen containing recombinant PfMSP119 (rPfMSP119) fused to the N terminus of P. falciparum merozoite surface protein 8 that lacked its low-complexity Asn/Asp-rich domain, rPfMSP8 (ΔAsn/Asp). Immunization of mice with the chimeric rPfMSP1/8 vaccine elicited strong T cell responses to conserved epitopes associated with the rPfMSP8 (ΔAsn/Asp) fusion partner. While specific for PfMSP8, this T cell response was adequate to provide help for the production of high titers of antibodies to both PfMSP119 and rPfMSP8 (ΔAsn/Asp) components. This occurred with formulations adjuvanted with either Quil A or with Montanide ISA 720 plus CpG oligodeoxynucleotide (ODN) and was observed in both inbred and outbred strains of mice. PfMSP1/8-induced antibodies were highly reactive with two major alleles of PfMSP119 (FVO and 3D7). Of particular interest, immunization with PfMSP1/8 elicited higher titers of PfMSP119-specific antibodies than a combined formulation of rPfMSP142 and rPfMSP8 (ΔAsn/Asp). As a measure of functionality, PfMSP1/8-specific rabbit IgG was shown to potently inhibit the in vitro growth of blood-stage parasites of the FVO and 3D7 strains of P. falciparum. These data support the further testing and evaluation of this chimeric PfMSP1/8 antigen as a component of a multivalent vaccine for P. falciparum malaria. PMID:23897613

Population genetic structure and natural selection of Plasmodium falciparum apical membrane antigen-1 in Myanmar isolates.

PubMed

Kang, Jung-Mi; Lee, Jinyoung; Moe, Mya; Jun, Hojong; Lê, Hương Giang; Kim, Tae Im; Thái, Thị Lam; Sohn, Woon-Mok; Myint, Moe Kyaw; Lin, Khin; Shin, Ho-Joon; Kim, Tong-Soo; Na, Byoung-Kuk

2018-02-07

Plasmodium falciparum apical membrane antigen-1 (PfAMA-1) is one of leading blood stage malaria vaccine candidates. However, genetic variation and antigenic diversity identified in global PfAMA-1 are major hurdles in the development of an effective vaccine based on this antigen. In this study, genetic structure and the effect of natural selection of PfAMA-1 among Myanmar P. falciparum isolates were analysed. Blood samples were collected from 58 Myanmar patients with falciparum malaria. Full-length PfAMA-1 gene was amplified by polymerase chain reaction and cloned into a TA cloning vector. PfAMA-1 sequence of each isolate was sequenced. Polymorphic characteristics and effect of natural selection were analysed with using DNASTAR, MEGA4, and DnaSP programs. Polymorphic nature and natural selection in 459 global PfAMA-1 were also analysed. Thirty-seven different haplotypes of PfAMA-1 were identified in 58 Myanmar P. falciparum isolates. Most amino acid changes identified in Myanmar PfAMA-1 were found in domains I and III. Overall patterns of amino acid changes in Myanmar PfAMA-1 were similar to those in global PfAMA-1. However, frequencies of amino acid changes differed by country. Novel amino acid changes in Myanmar PfAMA-1 were also identified. Evidences for natural selection and recombination event were observed in global PfAMA-1. Among 51 commonly identified amino acid changes in global PfAMA-1 sequences, 43 were found in predicted RBC-binding sites, B-cell epitopes, or IUR regions. Myanmar PfAMA-1 showed similar patterns of nucleotide diversity and amino acid polymorphisms compared to those of global PfAMA-1. Balancing natural selection and intragenic recombination across PfAMA-1 are likely to play major roles in generating genetic diversity in global PfAMA-1. Most common amino acid changes in global PfAMA-1 were located in predicted B-cell epitopes where high levels of nucleotide diversity and balancing natural selection were found. These results highlight the strong selective pressure of host immunity on the PfAMA-1 gene. These results have significant implications in understanding the nature of Myanmar PfAMA-1 along with global PfAMA-1. They also provide useful information for the development of effective malaria vaccine based on this antigen.

Weak-interaction rates in stellar conditions

NASA Astrophysics Data System (ADS)

Sarriguren, Pedro

2018-05-01

Weak-interaction rates, including β-decay and electron captures, are studied in several mass regions at various densities and temperatures of astrophysical interest. In particular, we study odd-A nuclei in the pf-shell region, which are involved in presupernova formations. Weak rates are relevant to understand the late stages of the stellar evolution, as well as the nucleosynthesis of heavy nuclei. The nuclear structure involved in the weak processes is studied within a quasiparticle proton-neutron random-phase approximation with residual interactions in both particle-hole and particle-particle channels on top of a deformed Skyrme Hartree-Fock mean field with pairing correlations. First, the energy distributions of the Gamow-Teller strength are discussed and compared with the available experimental information, measured under terrestrial conditions from charge-exchange reactions. Then, the sensitivity of the weak-interaction rates to both astrophysical densities and temperatures is studied. Special attention is paid to the relative contribution to these rates of thermally populated excited states in the decaying nucleus and to the electron captures from the degenerate electron plasma.

Expansion of a physical function item bank and development of an abbreviated form for clinical research.

PubMed

Bode, Rita K; Lai, Jin-shei; Dineen, Kelly; Heinemann, Allen W; Shevrin, Daniel; Von Roenn, Jamie; Cella, David

2006-01-01

We expanded an existing 33-item physical function (PF) item bank with a sufficient number of items to enable computerized adaptive testing (CAT). Ten items were written to expand the bank and the new item pool was administered to 295 people with cancer. For this analysis of the new pool, seven poorly performing items were identified for further examination. This resulted in a bank with items that define an essentially unidimensional PF construct, cover a wide range of that construct, reliably measure the PF of persons with cancer, and distinguish differences in self-reported functional performance levels. We also developed a 5-item (static) assessment form ("BriefPF") that can be used in clinical research to express scores on the same metric as the overall bank. The BriefPF was compared to the PF-10 from the Medical Outcomes Study SF-36. Both short forms significantly differentiated persons across functional performance levels. While the entire bank was more precise across the PF continuum than either short form, there were differences in the area of the continuum in which each short form was more precise: the BriefPF was more precise than the PF-10 at the lower functional levels and the PF-10 was more precise than the BriefPF at the higher levels. Future research on this bank will include the development of a CAT version, the PF-CAT.

Nematicidal protease genes screened from a soil metagenomic library to control Radopholus similis mediated by Pseudomonas fluorescens pf36.

PubMed

Chen, Deqiang; Wang, Dongwei; Xu, Chunling; Chen, Chun; Li, Junyi; Wu, Wenjia; Huang, Xin; Xie, Hui

2018-04-01

Controlling Radopholus similis, an important phytopathogenic nematode, is a challenge worldwide. Herein, we constructed a metagenomic fosmid library from the rhizosphere soil of banana plants, and six clones with protease activity were obtained by functionally screening the library. Furthermore, subclones were constructed using the six clones, and three protease genes with nematicidal activity were identified: pase1, pase4, and pase6. The pase4 gene was successfully cloned and expressed, demonstrating that the protease PASE4 could effectively degrade R. similis tissues and result in nematode death. Additionally, we isolated a predominant R. similis-associated bacterium, Pseudomonas fluorescens (pf36), from 10 R. similis populations with different hosts. The pase4 gene was successfully introduced into the pf36 strain by vector transformation and conjugative transposition, and two genetically modified strains were obtained: p4MCS-pf36 and p4Tn5-pf36. p4MCS-pf36 had significantly higher protease expression and nematicidal activity (p < 0.05) than p4Tn5-pf36 in a microtiter plate assay, whereas p4Tn5-pf36 was superior to p4MCS-pf36 in terms of genetic stability and controlling R. similis in growth pot tests. This study confirmed that R. similis is inhibited by the associated bacterium pf36-mediated expression of nematicidal proteases. Herein, a novel approach is provided for the study and development of efficient, environmentally friendly, and sustainable biocontrol techniques against phytonematodes.

Immune complexes formed following the binding of anti-platelet factor 4 (CXCL4) antibodies to CXCL4 stimulate human neutrophil activation and cell adhesion.

PubMed

Xiao, Zhihua; Visentin, Gian P; Dayananda, Kannayakanahalli M; Neelamegham, Sriram

2008-08-15

We tested the possibility that immune complexes formed following platelet factor 4 (PF4/CXCL4) binding to anti-PF4 antibody can stimulate neutrophil activation, similar to previous reports with platelets. Monoclonal Abs against PF4 and IgG from a heparin-induced thrombocytopenia (HIT) patient were applied. We observed that although PF4 or anti-PF4 antibody alone did not alter neutrophil function, costimulation with both reagents resulted in approximately 3-fold increase in cell surface Mac-1 expression, enhanced cell adhesion via L-selectin and CD18 integrins, and degranulation of secondary and tertiary granules. The level of Mac-1 up-regulation peaked at an intermediate PF4 dose, suggesting that functional response varies with antigen-antibody stoichiometry. PF4 binding to neutrophils was blocked by chondroitinase ABC. Cell activation was inhibited by both chondroitinase ABC and anti-CD32/FcgammaRII blocking mAb, IV.3. Confocal microscopy demonstrated that immune complexes colocalize with CD32a. Studies with HIT IgG demonstrated that neutrophils could be activated in the absence of exogenous heparin. These data, together, show that leukocyte surface chondroitin sulfates promote neutrophil activation by enhancing immune-complex binding to CD32a. Studies with recombinant PF4 suggest a role for arginine 49 in stabilizing PF4-chondroitin binding. Neutrophils activated via this mechanism may contribute to thrombosis and inflammation in patients mounting an immune response to PF4-heparin.

The Malaria Parasite Cyclin H Homolog PfCyc1 Is Required for Efficient Cytokinesis in Blood-Stage Plasmodium falciparum.

PubMed

Robbins, Jonathan A; Absalon, Sabrina; Streva, Vincent A; Dvorin, Jeffrey D

2017-06-13

All well-studied eukaryotic cell cycles are driven by cyclins, which activate cyclin-dependent kinases (CDKs), and these protein kinase complexes are viable drug targets. The regulatory control of the Plasmodium falciparum cell division cycle remains poorly understood, and the roles of the various CDKs and cyclins remain unclear. The P. falciparum genome contains multiple CDKs, but surprisingly, it does not contain any sequence-identifiable G 1 -, S-, or M-phase cyclins. We demonstrate that P. falciparum Cyc1 (PfCyc1) complements a G 1 cyclin-depleted Saccharomyces cerevisiae strain and confirm that other identified malaria parasite cyclins do not complement this strain. PfCyc1, which has the highest sequence similarity to the conserved cyclin H, cannot complement a temperature-sensitive yeast cyclin H mutant. Coimmunoprecipitation of PfCyc1 from P. falciparum parasites identifies PfMAT1 and PfMRK as specific interaction partners and does not identify PfPK5 or other CDKs. We then generate an endogenous conditional allele of PfCyc1 in blood-stage P. falciparum using a destabilization domain (DD) approach and find that PfCyc1 is essential for blood-stage proliferation. PfCyc1 knockdown does not impede nuclear division, but it prevents proper cytokinesis. Thus, we demonstrate that PfCyc1 has a functional divergence from bioinformatic predictions, suggesting that the malaria parasite cell division cycle has evolved to use evolutionarily conserved proteins in functionally novel ways. IMPORTANCE Human infection by the eukaryotic parasite Plasmodium falciparum causes malaria. Most well-studied eukaryotic cell cycles are driven by cyclins, which activate cyclin-dependent kinases (CDKs) to promote essential cell division processes. Remarkably, there are no identifiable cyclins that are predicted to control the cell cycle in the malaria parasite genome. Thus, our knowledge regarding the basic mechanisms of the malaria parasite cell cycle remains unsatisfactory. We demonstrate that P. falciparum Cyc1 (PfCyc1), a transcriptional cyclin homolog, complements a cell cycle cyclin-deficient yeast strain but not a transcriptional cyclin-deficient strain. We show that PfCyc1 forms a complex in the parasite with PfMRK and the P. falciparum MAT1 homolog. PfCyc1 is essential and nonredundant in blood-stage P. falciparum PfCyc1 knockdown causes a stage-specific arrest after nuclear division, demonstrating morphologically aberrant cytokinesis. This work demonstrates a conserved PfCyc1/PfMAT1/PfMRK complex in malaria and suggests that it functions as a schizont stage-specific regulator of the P. falciparum life cycle. Copyright © 2017 Robbins et al.

Penile fracture epidemiology, diagnosis and management in Iran: a narrative review

PubMed Central

Mirzazadeh, Majid; Fallahkarkan, Morteza

2017-01-01

Penile fracture (PF) is considered an emergency in urology. In the literature there are some case series reporting considerable incidence of PF in some parts of Iran. There are no accurate data about the incidence of PF all around Iran. Although it may be uncommon in other parts of the country and in the other countries, it can also be underreported. There are some challenges in diagnosis, management, and also reporting of these cases. In this review of Iranian medical literature, we searched for penile fracture and penile injury keywords in Medline, Scopus, SID, Google and Persian medical journals. We reviewed the status of epidemiology, etiology, diagnosis, management and complications of PF in different parts of Iran in the published literature. To collect more accurate data, we also performed a questionnaire-based study with sending questionnaires by emails to 700 urologists throughout the country with 14% response rate. Incidence of PF varies significantly in different parts of Iran. Western province of Kermanshah has a significantly higher rate of PF. Adding data from different regions of Iran, we calculated that incidence of PF in Iran can be estimated between 1.14 to 10.48 per 100,000 of male populations, most probably closer to lower end. Although the incidence of PF varies significantly in different geographical areas, urologists practicing in Iran on average may encounter a PF patient every 3.5 months. To diagnose PF, majority of reviewed studies relied on history and clinical examination and did not recommend imaging except in patients with possible urethral injuries. Immediate surgical intervention can make good functional results with low morbidity and short hospital stay. Delayed surgical intervention and observational management approaches need large population studies with long term follow up. PMID:28540222

Penile fracture epidemiology, diagnosis and management in Iran: a narrative review.

PubMed

Mirzazadeh, Majid; Fallahkarkan, Morteza; Hosseini, Jalil

2017-04-01

Penile fracture (PF) is considered an emergency in urology. In the literature there are some case series reporting considerable incidence of PF in some parts of Iran. There are no accurate data about the incidence of PF all around Iran. Although it may be uncommon in other parts of the country and in the other countries, it can also be underreported. There are some challenges in diagnosis, management, and also reporting of these cases. In this review of Iranian medical literature, we searched for penile fracture and penile injury keywords in Medline, Scopus, SID, Google and Persian medical journals. We reviewed the status of epidemiology, etiology, diagnosis, management and complications of PF in different parts of Iran in the published literature. To collect more accurate data, we also performed a questionnaire-based study with sending questionnaires by emails to 700 urologists throughout the country with 14% response rate. Incidence of PF varies significantly in different parts of Iran. Western province of Kermanshah has a significantly higher rate of PF. Adding data from different regions of Iran, we calculated that incidence of PF in Iran can be estimated between 1.14 to 10.48 per 100,000 of male populations, most probably closer to lower end. Although the incidence of PF varies significantly in different geographical areas, urologists practicing in Iran on average may encounter a PF patient every 3.5 months. To diagnose PF, majority of reviewed studies relied on history and clinical examination and did not recommend imaging except in patients with possible urethral injuries. Immediate surgical intervention can make good functional results with low morbidity and short hospital stay. Delayed surgical intervention and observational management approaches need large population studies with long term follow up.

Paeoniflorin inhibits cell growth and induces cell cycle arrest through inhibition of FoxM1 in colorectal cancer cells.

PubMed

Yue, Meng; Li, Shiquan; Yan, Guoqiang; Li, Chenyao; Kang, Zhenhua

2018-01-01

Paeoniflorin (PF) exhibits tumor suppressive functions in a variety of human cancers. However, the function of PF and molecular mechanism in colorectal cancer are elusive. In the present study, we investigated whether PF could exert its antiproliferative activity, anti-migration, and anti-invasive function in colorectal cancer cells. We found that PF inhibited cell growth and induced apoptosis and blocked cell cycle progression in the G0/G1 phase in colorectal cancer cells. Moreover, we found that PF suppressed cell migration and invasion in colorectal cancer cells. FoxM1 has been reported to play an important oncogenic role in human cancers. We also determine whether PF inhibited the expression of FoxM1, leading to its anti-cancer activity. We found that PF treatment in colorectal cancer cells resulted in down-regulation of FoxM1. The rescue experiments showed that overexpression of FoxM1 abrogated the tumor suppressive function induced by PF treatment. Notably, depletion of FoxM1 promoted the anti-tumor activity of PF in colorectal cancer cells. Therefore, inhibition of FoxM1 could participate in the anti-tumor activity of PF in colorectal cancer cells.

Physalis floridana Cell Number Regulator1 encodes a cell membrane-anchored modulator of cell cycle and negatively controls fruit size

PubMed Central

Li, Zhichao; He, Chaoying

2015-01-01

Physalis species show a significant variation in berry size; however, the underlying molecular basis is unknown. In this work, we showed that cell division difference in the ovaries might contribute to the ultimate berry size variation within Physalis species, and that mRNA abundance of Physalis floridana Cell Number Regulator1 (PfCNR1), the putative orthologue of the tomato fruit weight 2.2 (FW2.2), was negatively correlated with cell division in the ovaries. Moreover, heterochronic expression variation of the PfCNR1 genes in the ovaries concomitantly correlated with berry weight variation within Physalis species. In transgenic Physalis, multiple organ sizes could be negatively controlled by altering PfCNR1 levels, and cell division instead of cell expansion was primarily affected. PfCNR1 was shown to be anchored in the plasma membrane and to interact with PfAG2 (an AGAMOUS-like protein determining ovary identity). The expression of PfCYCD2;1, a putative orthologue of the mitosis-specific gene CyclinD2;1 in the cell cycle was negatively correlated with the PfCNR1 mRNA levels. PfAG2 was found to selectively bind to the CArG-box in the PfCYCD2;1 promoter and to repress PfCYCD2;1 expression, thus suggesting a PfAG2-mediated pathway for PfCNR1 to regulate cell division. The interaction of PfCNR1 with PfAG2 enhanced the repression of PfCYCD2;1 expression. The nuclear import of PfAG2 was essential in the proposed pathway. Our data provide new insights into the developmental pathways of a cell membrane-anchored protein that modulates cell division and governs organ size determination. This study also sheds light on the link between organ identity and organ growth in plants. PMID:25305759

Investigation of a Potential Protective Mechanism Against Heparin-Induced Thrombocytopenia in Patients on Chronic Intermittent Hemodialysis

PubMed Central

Tanhehco, Yvette C.; Cuker, Adam; Rudnick, Michael; Sachais, Bruce S.

2015-01-01

BACKGROUND Heparin-induced thrombocytopenia (HIT) develops as a result of platelet (PLT) activation by anti-platelet factor 4 (PF4)/heparin complex antibodies. Despite repeated exposure to heparin, patients undergoing chronic intermittent hemodialysis (HD) rarely develop HIT. We investigated the possibility that HD decreases/removes PF4 from PLT surfaces and/or plasma, thereby disfavoring immune complex formation as a mechanism of protection against HIT. MATERIALS AND METHODS We enrolled 20 patients undergoing chronic HD at the Penn Presbyterian Medical Center. Blood samples were drawn before, during and after treatment in the presence and absence of heparin. PF4, PF4/heparin antibody, heparin, and P-selectin levels were measured. RESULTS No patients demonstrated clinical symptoms of HIT. PLT surface PF4 levels decreased and plasma PF4 levels increased concurrently with increase in plasma heparin concentration. In the absence of heparin, PLT surface and plasma PF4 levels were unchanged. Anti-PF4/heparin antibodies, which were non-functional by the serotonin release assay, were detectable in 8 patients. PLT surface P-selectin levels did not change during treatment. CONCLUSIONS Removal of PLT surface and/or plasma PF4 as a mechanism of protection against HIT in patients undergoing HD is not supported by the results of our study, although the transient decrease in PLT surface PF4 in the presence of large amounts of heparin remains a candidate mechanism. The small sample size, single type of dialyzer membrane, and early sampling time points may have led to the inability to detect changes in PF4 levels. Future studies should explore other potential protective mechanisms. PMID:23305841

Human autoantibodies against a desmosomal core protein in pemphigus foliaceus

PubMed Central

1984-01-01

Pemphigus foliaceus (PF) is a human autoimmune disease in which antibodies are directed against the cell surface of epidermal cells with resultant blister formation. The histopathology of these blisters indicates that cells have detached from each other, and electron microscopy of early blisters shows diminished numbers, to complete loss, of desmosomes as well as abnormalities of the tonofilament- desmosome complex. In this study we demonstrate that autoantibodies from certain PF patients bind to a desmosomal core glycoprotein called desmoglein (DG) I. Proteins in extracts of normal human epidermis were separated by sodium dodecyl sulfate (SDS) polyacrylamide gel electrophoresis (PAGE), then transferred to nitrocellulose or 2- aminophenylthioether paper for immunoperoxidase staining. Results of these immunoblots indicated that sera from 6 of 13 PF patients specifically and intensely stained an approximately 160,000 mol wt polypeptide, "PF antigen". Such staining was not seen with normal human sera or sera from patients with pemphigus vulgaris or bullous pemphigoid, two autoimmune blistering skin diseases that are clinically, histologically, and immunochemically distinct from PF. However, rabbit antiserum directed against DGI, that was isolated from bovine muzzle desmosomes, stained a polypeptide band which co-migrated with PF antigen. Furthermore, when proteins from extracts of normal human epidermis were electrophoresed in two dimensions (isoelectric focusing, then SDS-PAGE) before transfer to nitrocellulose for immunoperoxidase staining, PF antibodies and antibodies to DGI stained identical spots. Finally, PF sera as well as PF IgG that was affinity purified with PF antigen from normal human epidermis, both selectively bound to DGI extracted from bovine muzzle desmosomes. These studies demonstrate that the human autoantibodies from certain patients with PF, a disease of epidermal cell adhesion, are directed against a desmosomal core protein. PMID:6491602

Studies on structural, thermal and AC conductivity scaling of PEO-LiPF6 polymer electrolyte with added ionic liquid [BMIMPF6

NASA Astrophysics Data System (ADS)

Chaurasia, S. K.; Saroj, A. L.; Shalu, Singh, V. K.; Tripathi, A. K.; Gupta, A. K.; Verma, Y. L.; Singh, R. K.

2015-07-01

Preparation and characterization of polymer electrolyte films of PEO+10wt.% LiPF6 + xwt.% BMIMPF6 (1-butyl-3-methylimidazolium hexafluorophosphate) containing dopant salt lithium hexafluorophosphate (LiPF6) and ionic liquid (BMIMPF6) having common anion PF6 - are reported. The ionic conductivity of the polymer electrolyte films has been found to increase with increasing concentration of BMIMPF6 in PEO+10 wt.% LiPF6 due to the plasticization effect of ionic liquid. DSC and XRD results show that the crystallinity of polymer electrolyte decreases with BMIMPF6 concentration which, in turn, is responsible for the increase in ionic conductivity. FTIR spectroscopic study shows the complexation of salt and/or ionic liquid cations with the polymer backbone. Ion dynamics behavior of PEO+LiPF6 as well as PEO+LiPF6 + BMIMPF6 polymer electrolytes was studied by frequency dependent conductivity, σ(f) measurements. The values σ(f) at various temperatures have been analyzed in terms of Jonscher power law (JPL) and scaled with respect to frequency which shows universal power law characteristics at all temperatures.

Study of the interrelation between the electrotechnical parameters of the plasma focus discharge circuit and the plasma compression dynamics on the PF-3 and PF-1000 facilities

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

Mitrofanov, K. N., E-mail: mitrkn@inbox.ru; Krauz, V. I., E-mail: krauz-vi@nrcki.ru, E-mail: vkrauz@yandex.ru; Grabovski, E. V.

The main stages of the plasma current sheath (PCS) dynamics on two plasma focus (PF) facilities with different geometries of the electrode system, PF-3 (Filippov type) and PF-1000 (Mather type), were studied by analyzing the results of the current and voltage measurements. Some dynamic characteristics, such as the PCS velocity in the acceleration phase in the Mather-type facility (PF-1000), the moment at which the PCS reaches the anode end, and the plasma velocity in the radial stage of plasma compression in the PF-3 Filippov-type facility, were determined from the time dependence of the inductance of the discharge circuit with amore » dynamic plasma load. The energy characteristics of the discharge circuit of the compressing PCS were studied for different working gases (deuterium, argon, and neon) at initial pressures of 1.5–3 Torr in discharges with energies of 0.3–0.6 MJ. In experiments with deuterium, correlation between the neutron yield and the electromagnetic energy deposited directly in the compressed PCS was investigated.« less

Induction of anti-PF4/heparin antibodies after arthroplasty for rheumatic diseases.

PubMed

Migita, Kiyoshi; Asano, Tomoyuki; Sato, Shuzo; Motokawa, Satoru

2018-04-17

Heparin-induced thrombocytopenia (HIT) is an immune complication of heparin therapy caused by antibodies to complexes of platelet factor 4 (PF4) and heparin. These pathogenic antibodies against PF4/heparin bind and activate cellular FcγRIIa on platelets to induce a hypercoagulable state culminating in thrombosis. Recent studies indicate several conditions, including joint surgery, induce spontaneous HIT, which can occur without exposure to heparin. To determine the real-world evidences concerning the incidences of venous thromboembolism (VTE) after total joint arthroplasty for rheumatic disease, we conducted a multicenter cohort study (J-PSVT) designed to document the VTE and seroconversion rates of anti-PF4/heparin antibody in 34 Japanese National hospital organization (NHO) hospitals. J-PSVT indicated that prophylaxis with fondaparinux, not enoxaparin, reduces the risk of deep vein thrombosis in patients undergoing arthroplasty. Multivariate analysis revealed that dynamic mechanical thromboprophylaxis (intermittent plantar device) was an independent risk factor for seroconversion of anti-PF4/heparin antibodies, which was also confirmed by propensity-score matching. Seroconversion rates of anti-PF4/heparin antibodies were significantly reduced in rheumatoid arthritis (RA) patients compared with osteoarthritis (OA) patients, which may link with the findings that IgG fractions isolated from RA patients not OA patients contained PF4. Our study indicated that a unique profile of anti-PF4/heparin antibodies is induced by arthroplasty for rheumatic diseases.

Physical function metric over measure: An illustration with the Patient-Reported Outcomes Measurement Information System (PROMIS) and the Functional Assessment of Cancer Therapy (FACT).

PubMed

Kaat, Aaron J; Schalet, Benjamin D; Rutsohn, Joshua; Jensen, Roxanne E; Cella, David

2018-01-01

Measuring patient-reported outcomes (PROs) is becoming an integral component of quality improvement initiatives, clinical care, and research studies in cancer, including comparative effectiveness research. However, the number of PROs limits comparability across studies. Herein, the authors attempted to link the Functional Assessment of Cancer Therapy-General Physical Well-Being (FACT-G PWB) subscale with the Patient-Reported Outcomes Measurement Information System (PROMIS) Physical Function (PF) calibrated item bank. The also sought to augment a subset of the conceptually most similar FACT-G PWB items with PROMIS PF items to improve the linking. Baseline data from 5506 participants in the Measuring Your Health (MY-Health) study were used to identify the optimal items for linking FACT-G PWB with PROMIS PF. A mixed methods approach identified the optimal items for creating the 5-item FACT/PROMIS-PF5 scale. Both the linked and augmented relationships were cross-validated using the follow-up MY-Health data. A 5-item FACT-G PWB item subset was found to be optimal for linking with PROMIS PF. In addition, a 2-item subset, including only items that were conceptually very similar to the PROMIS item bank content, were augmented with 3 PROMIS PF items. This new FACT/PROMIS-PF5 provided superior score recovery. The PROMIS PF metric allows for the evaluation of the extent to which similar questionnaires can be linked and therefore expressed on the same metric. These results allow for the aggregation of existing data and provide an optimal measure for future studies wishing to use the FACT yet also report on the PROMIS PF metric. Cancer 2018;124:153-60. © 2017 American Cancer Society. © 2017 American Cancer Society.

Plasmodium falciparum signal peptide peptidase cleaves malaria heat shock protein 101 (HSP101). Implications for gametocytogenesis

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

Baldwin, Michael; Russo, Crystal; Li, Xuerong

Highlights: • PfSPP is an ER resident protease. • PfSPP is expressed both as a monomer and dimer. • The signal peptide of HSP101 is the first known substrate of PfSPP. • Reduced PfSPP activity may significantly affect ER homeostasis. - Abstract: Previously we described the identification of a Plasmodium falciparum signal peptide peptidase (PfSPP) functioning at the blood stage of malaria infection. Our studies also demonstrated that mammalian SPP inhibitors prevent malaria parasite growth at the late-ring/early trophozoite stage of intra-erythrocytic development. Consistent with its role in development, we tested the hypothesis that PfSPP functions at the endoplasmic reticulummore » of P.falciparum where it cleaves membrane-bound signal peptides generated following the enzyme activity of signal peptidase. The localization of PfSPP to the endoplasmic reticulum was confirmed by immunofluorescence microscopy and immunogold electron microscopy. Biochemical analysis indicated the existence of monomer and dimer forms of PfSPP in the parasite lysate. A comprehensive bioinformatics screen identified several candidate PfSPP substrates in the parasite genome. Using an established transfection based in vivo luminescence assay, malaria heat shock protein 101 (HSP101) was identified as a substrate of PfSPP, and partial inhibition of PfSPP correlated with the emergence of gametocytes. This finding unveils the first known substrate of PfSPP, and provides new perspectives for the function of intra-membrane proteolysis at the erythrocyte stage of malaria parasite life cycle.« less

Physics First: Impact on SAT Math Scores

NASA Astrophysics Data System (ADS)

Bouma, Craig E.

Improving science, technology, engineering, and mathematics (STEM) education has become a national priority and the call to modernize secondary science has been heard. A Physics First (PF) program with the curriculum sequence of physics, chemistry, and biology (PCB) driven by inquiry- and project-based learning offers a viable alternative to the traditional curricular sequence (BCP) and methods of teaching, but requires more empirical evidence. This study determined impact of a PF program (PF-PCB) on math achievement (SAT math scores) after the first two cohorts of students completed the PF-PCB program at Matteo Ricci High School (MRHS) and provided more quantitative data to inform the PF debate and advance secondary science education. Statistical analysis (ANCOVA) determined the influence of covariates and revealed that PF-PCB program had a significant (p < .05) impact on SAT math scores in the second cohort at MRHS. Statistically adjusted, the SAT math means for PF students were 21.4 points higher than their non-PF counterparts when controlling for prior math achievement (HSTP math), socioeconomic status (SES), and ethnicity/race.

Limited variation in vaccine candidate Plasmodium falciparum Merozoite Surface Protein-6 over multiple transmission seasons.

PubMed

Neal, Aaron T; Jordan, Stephen J; Oliveira, Ana L; Hernandez, Jean N; Branch, Oralee H; Rayner, Julian C

2010-05-24

Plasmodium falciparum Merozoite Surface Protein-6 (PfMSP6) is a component of the complex proteinacious coat that surrounds P. falciparum merozoites. This location, and the presence of anti-PfMSP6 antibodies in P. falciparum-exposed individuals, makes PfMSP6 a potential blood stage vaccine target. However, genetic diversity has proven to be a major hurdle for vaccines targeting other blood stage P. falciparum antigens, and few endemic field studies assessing PfMSP6 gene diversity have been conducted. This study follows PfMSP6 diversity in the Peruvian Amazon from 2003 to 2006 and is the first longitudinal assessment of PfMSP6 sequence dynamics. Parasite DNA was extracted from 506 distinct P. falciparum infections spanning the transmission seasons from 2003 to 2006 as part of the Malaria Immunology and Genetics in the Amazon (MIGIA) cohort study near Iquitos, Peru. PfMSP6 was amplified from each sample using a nested PCR protocol, genotyped for allele class by agarose gel electrophoresis, and sequenced to detect diversity. Allele frequencies were analysed using JMP v.8.0.1.0 and correlated with clinical and epidemiological data collected as part of the MIGIA project. Both PfMSP6 allele classes, K1-like and 3D7-like, were detected at the study site, confirming that both are globally distributed. Allele frequencies varied significantly between transmission seasons, with 3D7-class alleles dominating and K1-class alleles nearly disappearing in 2005 and 2006. There was a significant association between allele class and village location (p-value = 0.0008), but no statistically significant association between allele class and age, sex, or symptom status. No intra-allele class sequence diversity was detected. Both PfMSP6 allele classes are globally distributed, and this study shows that allele frequencies can fluctuate significantly between communities separated by only a few kilometres, and over time in the same community. By contrast, PfMSP6 was highly stable at the sequence level, with no SNPs detected in the 506 samples analysed. This limited diversity supports further investigation of PfMSP6 as a blood stage vaccine candidate, with the clear caveat that any such vaccine must either contain both alleles or generate cross-protective responses that react against both allele classes. Detailed immunoepidemiology studies are needed to establish the viability of these approaches before PfMSP6 advances further down the vaccine development pipeline.

Solid state vibrational spectroscopy of anhydrous lithium hexafluorophosphate (LiPF6)

NASA Astrophysics Data System (ADS)

Kock, L. D.; Lekgoathi, M. D. S.; Crouse, P. L.; Vilakazi, B. M.

2012-10-01

Raman and infrared studies of solid anhydrous lithium hexafluorophosphate (LiPF6) have been carried out. The studies were complemented by X-ray powder diffraction (XRD) and Thermogravimetric (TG) analysis techniques. The results indicate that when solid LiPF6 is studied in a strictly anhydrous environment, more consistent thermal stability data can be obtained. TG analysis, using a scan rate of 10 °C min-1, indicate the onset of thermal decomposition of the anhydrous LiPF6 occurring at about 134.84 °C while the partially hydrolysed compound starts at 114.46 °C. The Raman spectra of anhydrous MPF6 (M = Li+, Na+ and K+) are best interpreted in terms of a cubic space group Fm3m(Ohs), (ZB = 1), giving rise to 21 vibrational modes (A1g(R)+Eg(R)+T1g+T2g(R)+3T1u(1R)+T2u) and as such, LiPF6 may be considered isostructural with NaPF6 and KPF6. Crystal symmetry distortions in the anhydrous LiPF6 give rise additional bands in the Raman spectrum due to T1u infrared active modes and the ν1 (A1g) Raman band appears in the infrared spectrum in violation of the mutual exclusion selection rule for centro-symmetric sites. When these observations are considered, the Raman spectrum of LiPF6 is similar to those of NaPF6 and KPF6, with observations of the expected shifts due to cation size and/or electronegativity effects.

Structure-property relation and relevance of beam theories for microtubules: a coupled molecular and continuum mechanics study.

PubMed

Li, Si; Wang, Chengyuan; Nithiarasu, Perumal

2018-04-01

Quasi-one-dimensional microtubules (MTs) in cells enjoy high axial rigidity but large transverse flexibility due to the inter-protofilament (PF) sliding. This study aims to explore the structure-property relation for MTs and examine the relevance of the beam theories to their unique features. A molecular structural mechanics (MSM) model was used to identify the origin of the inter-PF sliding and its role in bending and vibration of MTs. The beam models were then fitted to the MSM to reveal how they cope with the distinct mechanical responses induced by the inter-PF sliding. Clear evidence showed that the inter-PF sliding is due to the soft inter-PF bonds and leads to the length-dependent bending stiffness. The Euler beam theory is found to adequately describe MT deformation when the inter-PF sliding is largely prohibited. Nevertheless, neither shear deformation nor the nonlocal effect considered in the 'more accurate' beam theories can fully capture the effect of the inter-PF sliding. This reflects the distinct deformation mechanisms between an MT and its equivalent continuous body.

The COOH-terminal peptide of platelet factor-4 variant (CXCL4L1/PF-4var47-70) strongly inhibits angiogenesis and suppresses B16 melanoma growth in vivo.

PubMed

Vandercappellen, Jo; Liekens, Sandra; Bronckaers, Annelies; Noppen, Samuel; Ronsse, Isabelle; Dillen, Chris; Belleri, Mirella; Mitola, Stefania; Proost, Paul; Presta, Marco; Struyf, Sofie; Van Damme, Jo

2010-03-01

Chemokines influence tumor growth directly or indirectly via both angiogenesis and tumor-leukocyte interactions. Platelet factor-4 (CXCL4/PF-4), which is released from alpha-granules of activated platelets, is the first described angiostatic chemokine. Recently, it was found that the variant of CXCL4/PF-4 (CXCL4L1/PF-4var) could exert a more pronounced angiostatic and antitumoral effect than CXCL4/PF-4. However, the molecular mechanisms of the angiostatic activities of the PF-4 forms remain partially elusive. Here, we studied the biological properties of the chemically synthesized COOH-terminal peptides of CXCL4/PF-4 (CXCL4/PF-4(47-70)) and CXCL4L1/PF-4var (CXCL4L1/PF-4var(47-70)). Both PF-4 peptides lacked monocyte and lymphocyte chemotactic activity but equally well inhibited (25 nmol/L) endothelial cell motility and proliferation in the presence of a single stimulus (i.e., exogenous recombinant fibroblast growth factor-2). In contrast, when assayed in more complex angiogenesis test systems characterized by the presence of multiple mediators, including in vitro wound-healing (2.5 nmol/L versus 12.5 nmol/L), Matrigel (60 nmol/L versus 300 nmol/L), and chorioallantoic membrane assays, CXCL4L1/PF-4var(47-70) was found to be significantly (5-fold) more angiostatic than CXCL4/PF-4(47-70). In addition, low (7 microg total) doses of intratumoral CXCL4L1/PF-4var(47-70) inhibited B16 melanoma growth in mice more extensively than CXCL4/PF-4(47-70). This antitumoral activity was predominantly mediated through inhibition of angiogenesis (without affecting blood vessel stability) and induction of apoptosis, as evidenced by immunohistochemical and fluorescent staining of B16 tumor tissue. In conclusion, CXCL4L1/PF-4var(47-70) is a potent antitumoral and antiangiogenic peptide. These results may represent the basis for the design of CXCL4L1/PF-4var COOH-terminal-derived peptidomimetic anticancer drugs.

Assessment of the Plasmodium falciparum Preerythrocytic Antigen UIS3 as a Potential Candidate for a Malaria Vaccine.

PubMed

Longley, Rhea J; Halbroth, Benedict R; Salman, Ahmed M; Ewer, Katie J; Hodgson, Susanne H; Janse, Chris J; Khan, Shahid M; Hill, Adrian V S; Spencer, Alexandra J

2017-03-01

Efforts are under way to improve the efficacy of subunit malaria vaccines through assessments of new adjuvants, vaccination platforms, and antigens. In this study, we further assessed the Plasmodium falciparum antigen upregulated in infective sporozoites 3 (PfUIS3) as a vaccine candidate. PfUIS3 was expressed in the viral vectors chimpanzee adenovirus 63 (ChAd63) and modified vaccinia virus Ankara (MVA) and used to immunize mice in a prime-boost regimen. We previously demonstrated that this regimen could provide partial protection against challenge with chimeric P. berghei parasites expressing PfUIS3. We now show that ChAd63-MVA PfUIS3 can also provide partial cross-species protection against challenge with wild-type P. berghei parasites. We also show that PfUIS3-specific cellular memory responses could be recalled in human volunteers exposed to P. falciparum parasites in a controlled human malaria infection study. When ChAd63-MVA PfUIS3 was coadministered with the vaccine candidate P. falciparum thrombospondin-related adhesion protein (PfTRAP) expressed in the ChAd63-MVA system, there was no significant change in immunogenicity to either vaccine. However, when mice were challenged with double chimeric P. berghei - P. falciparum parasites expressing both PfUIS3 and PfTRAP, vaccine efficacy was improved to 100% sterile protection. This synergistic effect was evident only when the two vaccines were mixed and administered at the same site. We have therefore demonstrated that vaccination with PfUIS3 can induce a consistent delay in patent parasitemia across mouse strains and against chimeric parasites expressing PfUIS3 as well as wild-type P. berghei ; when this vaccine is combined with another partially protective regimen (ChAd63-MVA PfTRAP), complete protection is induced. Copyright © 2017 Longley et al.

Plasmodium falciparum chloroquine resistance transporter (PfCRT) isoforms PH1 and PH2 perturb vacuolar physiology.

PubMed

Callaghan, Paul S; Siriwardana, Amila; Hassett, Matthew R; Roepe, Paul D

2016-03-31

Recent work has perfected yeast-based methods for measuring drug transport by the Plasmodium falciparum chloroquine (CQ) resistance transporter (PfCRT). The approach relies on inducible heterologous expression of PfCRT in Saccharomyces cerevisiae yeast. In these experiments selecting drug concentrations are not toxic to the yeast, nor is expression of PfCRT alone toxic. Only when PfCRT is expressed in the presence of CQ is the growth of yeast impaired, due to inward transport of chloroquine (CQ) via the transporter. During analysis of all 53 known naturally occurring PfCRT isoforms, two isoforms (PH1 and PH2 PfCRT) were found to be intrinsically toxic to yeast, even in the absence of CQ. Additional analysis of six very recently identified PfCRT isoforms from Malaysia also showed some toxicity. In this paper the nature of this yeast toxicity is examined. Data also show that PH1 and PH2 isoforms of PfCRT transport CQ with an efficiency intermediate to that catalyzed by previously studied CQR conferring isoforms. Mutation of PfCRT at position 160 is found to perturb vacuolar physiology, suggesting a fitness cost to position 160 amino acid substitutions. These data further define the wide range of activities that exist for PfCRT isoforms found in P. falciparum isolates from around the globe.

Modification of the lipid moiety of the enterobacterial common antigen by the "Pseudomonas factor".

PubMed Central

Kuhn, H M; Neter, E; Mayer, H

1983-01-01

Pseudomonas aeruginosa produces a factor (PF) which affects the enterobacterial common antigen (ECA); resulting in failure of the antigen to modify erythrocytes for hemagglutination by ECA antibodies. In the present study the nature of PF was determined. Pronase treatment abolished its activity, indicating the protein nature of PF. PF-treated ECA no longer coated erythrocytes but still reacted with ECA antibodies in immunoelectrophoresis tests with monospecific antiserum to ECA, although differences were noted between the precipitation patterns of PF-treated and untreated ECA. Therefore, PF does not significantly affect the antigenic determinant of ECA but rather affects its lipid carrier, an L-glycerophosphatide. Accordingly, differences in the sugar chain could not be detected by high-voltage paper electrophoretic examinations of partial hydrolysates of PF-treated and untreated ECA. PF liberates all fatty acids from ECA, similarly to commercial lipases, as evidenced by the liberation of unsubstituted glycerol upon HF degradation at 0 degrees C of PF-treated ECA. The lipase activity of PF is indicated also by the observation that a strain of P. aeruginosa with reduced lipase production and an exolipase-negative strain affect ECA either less or not at all. We conclude that PF is a lipase acting on the lipid moiety of ECA, which is responsible for the coating of erythrocytes, but not significantly on the serological determinant, the amino sugar chain. Images PMID:6404831

Resting State and Elementary Steps of the Coupling of Aryl Halides with Thiols Catalyzed by Alkylbisphosphine Complexes of Palladium

PubMed Central

Alvaro, Elsa

2010-01-01

Detailed mechanistic studies on the coupling of aryl halides with thiols catalyzed by palladium complexes of the alkylbisphosphine ligand CyPF-tBu (1-dicyclohexylphosphino-2-di-tert-butylphosphinoethylferrocene) are reported. The elementary steps that constitute the catalytic cycle, i.e. oxidative addition, transmetalation and reductive elimination, have been studied, and their relative rates are reported. Each of the steps of the catalytic process occurs at temperatures that are much lower than those required for the reactions catalyzed by a combination of palladium precursors and CyPF-tBu. To explain these differences in rates between the catalytic and stoichiometric reactions, studies were conducted to identify the resting state of the catalyst of the reactions catalyzed by a combination of Pd(OAc)2 and CyPF-tBu, a combination of Pd(dba)2 and CyPF-tBu, or the likely intermediate Pd(CyPF-tBu)(Ar)(Br). These show that the major palladium complex in each case lies off of the catalytic cycle. The resting state of the reactions catalyzed by Pd(OAc)2 and CyPF-tBu was the palladium bis-thiolate complex [Pd(CyPF-tBu)(SR)2] (R = alkyl or aryl). The resting state in reactions catalyzed by Pd2(dba)3 and CyPF-tBu was the binuclear complex [Pd(CyPF-tBu)]2(μ2, η2-dba) (9). The resting state of reactions of both aromatic and aliphatic thiols catalyzed by [Pd(CyPF-tBu)(p-tolyl)(Br)] (3a) was the hydridopalladium thiolate complex [Pd(CyPF-tBu)(H)(SR)] (R= alkyl and aryl). All these palladium species have been prepared independently, and the mechanisms by which they enter the catalytic cycle have been examined in detail. These features of the reaction catalyzed by palladium and CyPF-tBu have been compared with those of reactions catalyzed by the alkylbisphosphine DiPPF and Pd(OAc)2 or Pd(dba)2. Our data indicate that the resting states of these reactions are similar to each other and that our mechanistic conclusions about reactions catalyzed by palladium and CyPF-tBu can be extrapolated to reactions catalyzed by complexes of other electron-rich bisphosphines. PMID:19453106

Immune complexes formed following the binding of anti–platelet factor 4 (CXCL4) antibodies to CXCL4 stimulate human neutrophil activation and cell adhesion

PubMed Central

Xiao, Zhihua; Visentin, Gian P.; Dayananda, Kannayakanahalli M.

2008-01-01

We tested the possibility that immune complexes formed following platelet factor 4 (PF4/CXCL4) binding to anti-PF4 antibody can stimulate neutrophil activation, similar to previous reports with platelets. Monoclonal Abs against PF4 and IgG from a heparin-induced thrombocytopenia (HIT) patient were applied. We observed that although PF4 or anti-PF4 antibody alone did not alter neutrophil function, costimulation with both reagents resulted in approximately 3-fold increase in cell surface Mac-1 expression, enhanced cell adhesion via L-selectin and CD18 integrins, and degranulation of secondary and tertiary granules. The level of Mac-1 up-regulation peaked at an intermediate PF4 dose, suggesting that functional response varies with antigen-antibody stoichiometry. PF4 binding to neutrophils was blocked by chondroitinase ABC. Cell activation was inhibited by both chondroitinase ABC and anti-CD32/FcγRII blocking mAb, IV.3. Confocal microscopy demonstrated that immune complexes colocalize with CD32a. Studies with HIT IgG demonstrated that neutrophils could be activated in the absence of exogenous heparin. These data, together, show that leukocyte surface chondroitin sulfates promote neutrophil activation by enhancing immune-complex binding to CD32a. Studies with recombinant PF4 suggest a role for arginine 49 in stabilizing PF4-chondroitin binding. Neutrophils activated via this mechanism may contribute to thrombosis and inflammation in patients mounting an immune response to PF4-heparin. PMID:18539895

Development of fisetin-loaded folate functionalized pluronic micelles for breast cancer targeting.

PubMed

Pawar, Atmaram; Singh, Srishti; Rajalakshmi, S; Shaikh, Karimunnisa; Bothiraja, C

2018-01-15

The natural flavonoid fisetin (FS) has shown anticancer properties but its in-vivo administration remains challenging due to its poor aqueous solubility. The aim of the study was to develop FS loaded pluronic127 (PF)-folic acid (FA) conjugated micelles (FS-PF-FA) by the way of increasing solubility, bioavailability and active targetability of FS shall increase its therapeutic efficacy. FA-conjugated PF was prepared by carbodiimide crosslinker chemistry. FS-PF-FA micelles were prepared by thin-film hydration method and evaluated in comparison with free FS and FS loaded PF micelles (FS-PF). The smooth surfaces with spherical in shape of FS-PF-PF micelles displayed smaller in size (103.2 ± 6.1 nm), good encapsulation efficiency (82.50 ± 1.78%), zeta potential (-26.7 ± 0.44 mV) and sustained FS release. Bioavailability of FS from FS-PF-PF micelles was increased by 6-fold with long circulation time, slower plasma elimination and no sign of tissue toxicity as compared to free FS. Further, the FS-PF-FA micelles demonstrated active targeting effect on folate overexpressed human breast cancer MCF-7 cells. The concentration of the drug needed for growth inhibition of 50% of cells in a designed time period (GI50) was 14.3 ± 1.2 µg/ml for FS while it was greatly decreased to 9.8 ± 0.78 µg/ml, i.e. a 31.46% decrease for the FS-PF. Furthermore, the GI50 value for FS-PF-FA was 4.9 ± 0.4 µg/ml, i.e. a 65.737% decrease compared to FS and 50% decrease compare to FS-PF. The results indicate that the FS-PF-FA micelles have the potential to be applied for targeting anticancer drug delivery.

Targeting colorectal cancer cells by a novel sphingosine kinase 1 inhibitor PF-543

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

Ju, TongFa; Gao, DaQuan; Fang, Zheng-yu, E-mail: fangzhengyu158@sina.com

In this study, we showed that PF-543, a novel sphingosine kinase 1 (SphK1) inhibitor, exerted potent anti-proliferative and cytotoxic effects against a panel of established (HCT-116, HT-29 and DLD-1) and primary human colorectal cancer (CRC) cells. Its sensitivity was negatively associated with SphK1 expression level in the CRC cells. Surprisingly, PF-543 mainly induced programmed necrosis, but not apoptosis, in the CRC cells. CRC cell necrotic death was detected by lactate dehydrogenase (LDH) release, mitochondrial membrane potential (MMP) collapse and mitochondrial P53-cyclophilin-D (Cyp-D) complexation. Correspondingly, the necrosis inhibitor necrostatin-1 largely attenuated PF-543-induced cytotoxicity against CRC cells. Meanwhile, the Cyp-D inhibitors (sanglifehrinmore » A and cyclosporin A), or shRNA-mediated knockdown of Cyp-D, remarkably alleviated PF-543-induced CRC cell necrotic death. Reversely, over-expression of wild-type Cyp-D in HCT-116 cells significantly increased PF-543's sensitivity. In vivo, PF-543 intravenous injection significantly suppressed HCT-116 xenograft growth in severe combined immunodeficient (SCID) mice, whiling remarkably improving the mice survival. The in vivo activity by PF-543 was largely attenuated when combined with the Cyp-D inhibitor cyclosporin A. Collectively, our results demonstrate that PF-543 exerts potent anti-CRC activity in vitro and in vivo. Mitochondrial programmed necrosis pathway is likely the key mechanism responsible for PF-543's actions in CRC cells. - Highlights: • PF-543 is anti-proliferative and cytotoxic to established and primary CRC cells. • PF-543 induces programmed necrosis, but not apoptosis, in CRC cells. • Modulation of mitochondrial protein cyclophilin-D alters PF-543's sensitivity. • PF-543 inhibits HCT-116 xenograft growth in SCID mice, improving mice survival. • Co-administration of cyclophilin-D inhibitor CsA inhibits PF-543's activity in vivo.« less

Pelvis width associated with bone mass distribution at the proximal femur in children 10–11 years old

PubMed Central

Cardadeiro, Graça; Baptista, Fátima; Janz, Kathleen F.; Rodrigues, Luís A.; Sardinha, Luís B.

2015-01-01

Differences in skeletal geometry may generate different patterns of mechanical loading to bone. Impact and muscle loading during physical activity have been shown to influence skeletal geometry. The purpose of this study was to compare geometric measures of the pelvis and proximal femur (PF) of young children and to analyze the contribution and potential interaction of these geometric measures with physical activity on PF bone mass distribution. Participants were 149 girls and 145 boys, aged 10–11 years. Total body and left hip DXA scans were used to derive pelvic and PF geometric measures and PF bone mineral density (BMD) at the femoral neck (FN), trochanter (TR), and intertrochanter (IT). These subregions were used to represent bone mass distribution via three BMD ratios: FN:PF, TR:PF, and IT:PF. Physical activity was objectively measured using accelerometry, and maturity was estimated as the years of distance from peak height velocity. When compared to boys, girls had a wider pelvic diameter and greater interacetabular distances (p < 0.001), lower BMD at FN, TR, and IT (p < 0.05), and higher TR:PF (p < 0.001). After controlling for maturity, body height, and lean body mass, the interacetabular distance in girls explained 21.1 % (β = 0.713, p < 0.001) in TR:PF and 2.9 % (β = −0.179, p = 0.031) in the IT:PF. Neck–shaft angle explained 5.6 % (β = −0.265, p = 0.001) of the IT:PF and 3.1 % (β = 0.194, p = 0.018) of the FN:PF. In boys, FN axis length explained 2.9 % (β = 0.195, p = 0.040) of TR:PF. There was no main effect of physical activity or interaction effect with pelvic geometry in explaining BMD differences among the subregions of the PF. Even before sexual dimorphism, girls have a wider pelvis than boys, which accounted for proportionally greater BMD of the TR than other subregions of the PF. PMID:23744478

Electric and Magnetic Dipole Strength at Low Energy.

PubMed

Sieja, K

2017-08-04

A low-energy enhancement of radiative strength functions was deduced from recent experiments in several mass regions of nuclei, which is believed to impact considerably the calculated neutron capture rates. In this Letter we investigate the behavior of the low-energy γ-ray strength of the ^{44}Sc isotope, for the first time taking into account both electric and magnetic dipole contributions obtained coherently in the same theoretical approach. The calculations are performed using the large-scale shell-model framework in a full 1ℏω  sd-pf-gds model space. Our results corroborate previous theoretical findings for the low-energy enhancement of the M1 strength but show quite different behavior for the E1 strength.

Clinical impact of culture-positive preservation fluid on solid organ transplantation: A systematic review and meta-analysis.

PubMed

Oriol, Isabel; Sabé, N; Tebé, C; Veroux, M; Boin, I F S F; Carratalà, J

2018-04-01

Contamination of the preservation fluid (PF) used for donated organs is a potential source of post-transplant infection. However, the information on this issue is scarce. We therefore conducted a systematic review and meta-analysis to assess the incidence of culture-positive PF and its impact on solid organ transplant (SOT) recipients. Seventeen studies were identified and included. The overall incidence of culture-positive PF was 37% (95% CI: 27% to 49%), and the incidence of PF-related infections among SOT recipients with PF cultures that grew pathogenic microorganisms was 10% (95% CI: 7% to 15%). There were differences in the rates of infections due to pathogenic microorganisms between SOT recipients who received pre-emptive treatment and those who did not, but without statistical significance. The mortality rate among SOT recipients with PF-related infection was 35% (95% CI: 21% to 53%). In conclusion, although contamination of the PF of donated organs is frequent, the incidence of PF-related infection is relatively low. A closely clinical and microbiologic monitoring of the SOT recipient in case of culture-positive PF, regardless of the type of microorganism isolated might be do in order to establish a prompt diagnosis of PF-related infection. Copyright © 2017 Elsevier Inc. All rights reserved.

Neural activation during imitation with or without performance feedback: An fMRI study.

PubMed

Zhang, Kaihua; Wang, Hui; Dong, Guangheng; Wang, Mengxing; Zhang, Jilei; Zhang, Hui; Meng, Weixia; Du, Xiaoxia

2016-08-26

In our daily lives, we often receive performance feedback (PF) during imitative learning, and we adjust our behaviors accordingly to improve performance. However, little is known regarding the neural mechanisms underlying this learning process. We hypothesized that appropriate PF would enhance neural activation or recruit additional brain areas during subsequent action imitation. Pictures of 20 different finger gestures without any social meaning were shown to participants from the first-person perspective. Imitation with or without PF was investigated by functional magnetic resonance imaging in 30 healthy subjects. The PF was given by a real person or by a computer. PF from a real person induced hyperactivation of the parietal lobe (precuneus and cuneus), cingulate cortex (posterior and anterior), temporal lobe (superior and transverse temporal gyri), and cerebellum (posterior and anterior lobes) during subsequent imitation. The positive PF and negative PF from a real person, induced the activation of more brain areas during the following imitation. The hyperactivation of the cerebellum, posterior cingulate cortex, precuneus, and cuneus suggests that the subjects exhibited enhanced motor control and visual attention during imitation after PF. Additionally, random PF from a computer had a small effect on the next imitation. We suggest that positive and accurate PF may be helpful for imitation learning. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Magnetic nanoparticles and thermally responsive polymer for targeted hyperthermia and sustained anti-cancer drug delivery.

PubMed

Wang, Sarah Y; Liu, Michelle C; Kang, Kyung A

2013-01-01

A novel cancer treatment method is being designed using a combination of iron oxide (Fe(3)O(4)) nanoparticles (IONPs) and Pluronic F-127 (PF127). IONPs have been used for heating tumors via an alternating electromagnetic (AEM) field. PF127 is a polymer possessing thermo-reversible and concentration-dependent gelation properties in aqueous solutions. PF127, as a gel, is an attractive drug delivery vehicle due to its zero-order drug release property. The combination of IONPs and PF127 would allow both short-term, tumor-specific, hyperthermic treatment, and long-term sustained drug delivery. As a preliminary study, the gelling and heating properties of IONPs/PF127 mixtures were investigated: 18% (w/w) PF127 was found to be ideal for our purpose because it gels at 28.0°C, i.e., it would be injectable at room temperature (20-25°C) and forms gel upon injection into the body (37°C). IONPs in PF127 showed little effect on gelation temperatures. The heating performance of IONPs in PF127 slightly, but linearly decreased with PF127. In the IONP concentration range of 0.01-0.05% (w/v) mixed with PF127 at 18% (w/w), the heating performance increased linearly with the increase in IONP concentration.

Hematological and biochemical features of postpartum fever in the heavy draft mare.

PubMed

Aoki, Takahiro; Kimura, Yuki; Oya, Anna; Chiba, Akiko; Ishii, Mitsuo; Nambo, Yasuo

2016-01-01

Heavy draft mares potentially have a higher risk of suffering from postpartum fever (PF) than light breed mares. The purpose of this study was to compare hematological and biochemical features between clinically healthy mares (n=40) and PF-affected mares (n=16). Mares were classified as having PF when their rectal temperature rose to >38.5°C within 96 hr of foaling. The numbers of leukocytes, lymphocytes, and neutrophils and the serum magnesium level were significantly lower in PF-affected mares. The serum SAA and NEFA levels were significantly higher in PF-affected mares. Strong inflammation responses, fat mobilization associated with negative energy balance and possibly endotoxin participate in hematological and biochemical features of PF in heavy draft mares.

Study of soft X-ray emission during wire array implosion under plasma focus conditions at the PF-3 facility

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

Dan’ko, S. A.; Mitrofanov, K. N., E-mail: mitrofan@triniti.ru; Krauz, V. I.

2015-11-15

Results of measurements of soft X-ray emission with photon energies of <1 keV under conditions of a plasma focus (PF) experiment are presented. The experiments were carried out at the world’s largest PF device—the PF-3 Filippov-type facility (I ⩽ 3 MA, T/4 ≈ 15–20 µs, W{sub 0} ⩽ 3 MJ). X-ray emission from both a discharge in pure neon and with a tungsten wire array placed on the axis of the discharge chamber was detected. The wire array imploded under the action of the electric current intercepted from the plasma current sheath of the PF discharge in neon. The measuredmore » soft X-ray powers from a conventional PF discharge in gas and a PF discharge in the presence of a wire array were compared for the first time.« less

Attenuated PfSPZ Vaccine induces strain-transcending T cells and durable protection against heterologous controlled human malaria infection.

PubMed

Lyke, Kirsten E; Ishizuka, Andrew S; Berry, Andrea A; Chakravarty, Sumana; DeZure, Adam; Enama, Mary E; James, Eric R; Billingsley, Peter F; Gunasekera, Anusha; Manoj, Anita; Li, Minglin; Ruben, Adam J; Li, Tao; Eappen, Abraham G; Stafford, Richard E; Kc, Natasha; Murshedkar, Tooba; Mendoza, Floreliz H; Gordon, Ingelise J; Zephir, Kathryn L; Holman, LaSonji A; Plummer, Sarah H; Hendel, Cynthia S; Novik, Laura; Costner, Pamela J M; Saunders, Jamie G; Berkowitz, Nina M; Flynn, Barbara J; Nason, Martha C; Garver, Lindsay S; Laurens, Matthew B; Plowe, Christopher V; Richie, Thomas L; Graham, Barney S; Roederer, Mario; Sim, B Kim Lee; Ledgerwood, Julie E; Hoffman, Stephen L; Seder, Robert A

2017-03-07

A live-attenuated malaria vaccine, Plasmodium falciparum sporozoite vaccine (PfSPZ Vaccine), confers sterile protection against controlled human malaria infection (CHMI) with Plasmodium falciparum (Pf) parasites homologous to the vaccine strain up to 14 mo after final vaccination. No injectable malaria vaccine has demonstrated long-term protection against CHMI using Pf parasites heterologous to the vaccine strain. Here, we conducted an open-label trial with PfSPZ Vaccine at a dose of 9.0 × 10 5 PfSPZ administered i.v. three times at 8-wk intervals to 15 malaria-naive adults. After CHMI with homologous Pf parasites 19 wk after final immunization, nine (64%) of 14 (95% CI, 35-87%) vaccinated volunteers remained without parasitemia compared with none of six nonvaccinated controls ( P = 0.012). Of the nine nonparasitemic subjects, six underwent repeat CHMI with heterologous Pf7G8 parasites 33 wk after final immunization. Five (83%) of six (95% CI, 36-99%) remained without parasitemia compared with none of six nonvaccinated controls. PfSPZ-specific T-cell and antibody responses were detected in all vaccine recipients. Cytokine production by T cells from vaccinated subjects after in vitro stimulation with homologous (NF54) or heterologous (7G8) PfSPZ were highly correlated. Interestingly, PfSPZ-specific T-cell responses in the blood peaked after the first immunization and were not enhanced by subsequent immunizations. Collectively, these data suggest durable protection against homologous and heterologous Pf parasites can be achieved with PfSPZ Vaccine. Ongoing studies will determine whether protective efficacy can be enhanced by additional alterations in the vaccine dose and number of immunizations.

Peritoneal fluid from endometriosis patients switches differentiation of monocytes from dendritic cells to macrophages.

PubMed

Na, Yong-Jin; Jin, Jun-O; Lee, Mi-Sook; Song, Min-Gyu; Lee, Kyu-Sup; Kwak, Jong-Young

2008-01-01

Immunological abnormalities of cell-mediated and humoral immunity might be associated with the pathogenesis of endometriosis. This study has examined the effects of peritoneal fluid obtained from patients with endometriosis (ePF) on the phenotypic characteristics of macrophages and dendritic cells (DCs) derived from monocytes. Monocytes were obtained from healthy young volunteers and cultured with ePF (n=12) or a control PF (cPF) (n=5) in the presence or absence of macrophage-colony stimulating factor (M-CSF) or IL-4 plus granulocyte macrophage-colony stimulating factor (GM-CSF). The ePF was demonstrated to increase expression levels of CD14 and CD64 on isolated monocytes in the presence or absence of M-CSF. Compared with cPF, addition of 10% ePF to GM-CSF plus IL-4-treated monocytes significantly down-regulated CD1a expression and up-regulated CD64 expression, but did not enhance expression levels of class II MHC. ePF had no effect, however, on tumor necrosis factor-alpha-induced maturation of DC. Levels of IL-6, IL-10 and M-CSF production were higher in ePF-treated than cPF-treated monocytes for both cell culture conditions with GM-CSF plus IL-4 and M-CSF. A neutralizing IL-6 antibody, but not an IL-10 antibody, abrogated the ePF-induced down-regulation of CD1a, up-regulation of CD64 and secretion of M-CSF. These results suggest that ePF favorably induces monocyte differentiation toward macrophages rather than DCs, and that this effect is mediated by IL-6. A reciprocal mode of cell differentiation between macrophages and DCs in response to ePF may be related to the pathogenesis of endometriosis.

The antigenic complex in HIT binds to B cells via complement and complement receptor 2 (CD21)

PubMed Central

Khandelwal, Sanjay; Lee, Grace M.; Hester, C. Garren; Poncz, Mortimer; McKenzie, Steven E.; Sachais, Bruce S.; Rauova, Lubica; Kelsoe, Garnett; Cines, Douglas B.; Frank, Michael

2016-01-01

Heparin-induced thrombocytopenia is a prothrombotic disorder caused by antibodies to platelet factor 4 (PF4)/heparin complexes. The mechanism that incites such prevalent anti-PF4/heparin antibody production in more than 50% of patients exposed to heparin in some clinical settings is poorly understood. To investigate early events associated with antigen exposure, we first examined the interaction of PF4/heparin complexes with cells circulating in whole blood. In healthy donors, PF4/heparin complexes bind preferentially to B cells (>90% of B cells bind to PF4/heparin in vitro) relative to neutrophils, monocytes, or T cells. Binding of PF4 to B cells is heparin dependent, and PF4/heparin complexes are found on circulating B cells from some, but not all, patients receiving heparin. Given the high proportion of B cells that bind PF4/heparin, we investigated complement as a mechanism for noncognate antigen recognition. Complement is activated by PF4/heparin complexes, co-localizes with antigen on B cells from healthy donors, and is present on antigen-positive B cells in patients receiving heparin. Binding of PF4/heparin complexes to B cells is mediated through the interaction between complement and complement receptor 2 (CR2 [CD21]). To the best of our knowledge, these are the first studies to demonstrate complement activation by PF4/heparin complexes, opsonization of PF4/heparin to B cells via CD21, and the presence of complement activation fragments on circulating B cells in some patients receiving heparin. Given the critical contribution of complement to humoral immunity, our observations provide new mechanistic insights into the immunogenicity of PF4/heparin complexes. PMID:27412887

Evaluation of the siRNA PF-04523655 versus ranibizumab for the treatment of neovascular age-related macular degeneration (MONET Study).

PubMed

Nguyen, Quan Dong; Schachar, Ronald A; Nduaka, Chudy I; Sperling, Marvin; Klamerus, Karen J; Chi-Burris, Katherine; Yan, Eric; Paggiarino, Dario A; Rosenblatt, Irit; Aitchison, Roger; Erlich, Shai S

2012-09-01

To evaluate the efficacy of different dosing paradigms of PF-04523655 (PF) versus ranibizumab (comparator) in subjects with neovascular age-related macular degeneration (AMD). Multicenter, open-label, prospective, randomized, comparator-controlled exploratory study. A total of 151 patients with subfoveal choroidal neovascularization (CNV) secondary to neovascular AMD who were naive to AMD therapy. In this phase 2 study, patients were randomized to 1 of 5 treatment groups with equal ratio. All groups received ranibizumab 0.5 mg at baseline and (a) PF 1 mg every 4 weeks (Q4W) from week 4 to week 12; (b) PF 3 mg Q4W from week 4 to week 12; (c) PF 3 mg every 2 weeks (Q2W) from week 4 to week 12; (d) PF 1 mg + ranibizumab (combination) Q4W from baseline to week 12; and (e) ranibizumab Q4W to week 12. All study treatments were given as intravitreal injections. The primary end point was the mean change in best-corrected visual acuity (BCVA) from baseline at week 16; secondary end points included the percentage of patients gaining ≥ 10 and ≥ 15 letters in BCVA and mean change in retinal central subfield thickness, lesion thickness, and CNV area. At week 16, the PF 1 mg + ranibizumab combination group achieved numerically greater improvement in mean BCVA from baseline (9.5 letters) than the ranibizumab group (6.8 letters). The difference was not statistically significant. The BCVA improvement in the PF monotherapy groups was less than in the ranibizumab group. Similar trends were observed in the percentage of patients who gained ≥ 10 and ≥ 15 letters. From baseline to week 16 (last observed carried forward), the combination and ranibizumab groups had similar mean reductions in central subfield retinal thickness and total CNV area, which were greater than in all PF monotherapy groups. There were no clinically meaningful differences in reduction of lesion thickness among treatment groups. In this early, underpowered study evaluating treatments for neovascular AMD, the combination of PF with ranibizumab led to an average gain in BCVA that was more than with ranibizumab monotherapy. No safety concerns were identified. Copyright © 2012 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

Centromedian-parafascicular deep brain stimulation induces differential functional inhibition of the motor, associative, and limbic circuits in large animals.

PubMed

Kim, Joo Pyung; Min, Hoon-Ki; Knight, Emily J; Duffy, Penelope S; Abulseoud, Osama A; Marsh, Michael P; Kelsey, Katherine; Blaha, Charles D; Bennet, Kevin E; Frye, Mark A; Lee, Kendall H

2013-12-15

Deep brain stimulation (DBS) of the centromedian-parafascicular (CM-Pf) thalamic nuclei has been considered an option for treating Tourette syndrome. Using a large animal DBS model, this study was designed to explore the network effects of CM-Pf DBS. The combination of DBS and functional magnetic resonance imaging is a powerful means of tracing brain circuitry and testing the modulatory effects of electrical stimulation on a neuronal network in vivo. With a within-subjects design, we tested the proportional effects of CM and Pf DBS by manipulating current spread and varying stimulation contacts in healthy pigs (n = 5). Our results suggests that CM-Pf DBS has an inhibitory modulating effect in areas that have been suggested as contributing to impaired sensory-motor and emotional processing. The results also help to define the differential neural circuitry effects of the CM and Pf with evidence of prominent sensorimotor/associative effects for CM DBS and prominent limbic/associative effects for Pf DBS. Our results support the notion that stimulation of deep brain structures, such as the CM-Pf, modulates multiple networks with cortical effects. The networks affected by CM-Pf stimulation in this study reinforce the conceptualization of Tourette syndrome as a condition with psychiatric and motor symptoms and of CM-Pf DBS as a potentially effective tool for treating both types of symptoms. Copyright © 2013 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Inhibition of protein synthesis and malaria parasite development by drug targeting of methionyl-tRNA synthetases.

PubMed

Hussain, Tahir; Yogavel, Manickam; Sharma, Amit

2015-04-01

Aminoacyl-tRNA synthetases (aaRSs) are housekeeping enzymes that couple cognate tRNAs with amino acids to transmit genomic information for protein translation. The Plasmodium falciparum nuclear genome encodes two P. falciparum methionyl-tRNA synthetases (PfMRS), termed PfMRS(cyt) and PfMRS(api). Phylogenetic analyses revealed that the two proteins are of primitive origin and are related to heterokonts (PfMRS(cyt)) or proteobacteria/primitive bacteria (PfMRS(api)). We show that PfMRS(cyt) localizes in parasite cytoplasm, while PfMRS(api) localizes to apicoplasts in asexual stages of malaria parasites. Two known bacterial MRS inhibitors, REP3123 and REP8839, hampered Plasmodium growth very effectively in the early and late stages of parasite development. Small-molecule drug-like libraries were screened against modeled PfMRS structures, and several "hit" compounds showed significant effects on parasite growth. We then tested the effects of the hit compounds on protein translation by labeling nascent proteins with (35)S-labeled cysteine and methionine. Three of the tested compounds reduced protein synthesis and also blocked parasite growth progression from the ring stage to the trophozoite stage. Drug docking studies suggested distinct modes of binding for the three compounds, compared with the enzyme product methionyl adenylate. Therefore, this study provides new targets (PfMRSs) and hit compounds that can be explored for development as antimalarial drugs. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

A 4-week study assessing the pharmacokinetics, pharmacodynamics, safety, and tolerability of the glucagon receptor antagonist PF-06291874 administered as monotherapy in subjects with type 2 diabetes mellitus.

PubMed

Bergman, Arthur; Tan, Beesan; Somayaji, Veena R; Calle, Roberto A; Kazierad, David J

2017-04-01

The glucagon receptor antagonist PF-06291874 has demonstrated robust glucose reductions in subjects with type 2 diabetes mellitus (T2DM) on background metformin. This study assessed the pharmacokinetics, pharmacodynamics, safety, and tolerability of PF-06291874 administered as monotherapy in subjects with T2DM. After a ≥4-week antidiabetic therapy washout period, 172 subjects were randomized to placebo or PF-06291874 15, 35, 75, or 150mg once daily for 28days. Mean daily glucose (MDG), fasting plasma glucose (FPG), and predefined safety endpoints were assessed at baseline and day 28. Dose-dependent reductions (placebo-adjusted) from baseline in MDG ranged from 40.3 to 68.8mg/dL and in FPG from 27.1 to 57.2mg/dL after 28days of dosing with PF-06291874. There were no significant changes in low-density lipoprotein cholesterol at doses ≤75mg relative to placebo. Small, dose-dependent increases in alanine aminotransferase and aspartate aminotransferase were observed; however, the incidence of these values >3×upper limit of normal was similar across doses. PF-06291874 exposures were consistent with previous studies and PF-06291874 was well tolerated, with minimal incidence of hypoglycemia. PF-06291874 as monotherapy was well tolerated and produced robust reductions in plasma glucose following 4weeks of dosing in subjects with T2DM. Copyright © 2017 Elsevier B.V. All rights reserved.

The tridimensional geometry of the proximal femur should determine the design of cementless femoral stem in total hip arthroplasty.

PubMed

Wegrzyn, Julien; Roux, Jean-Paul; Loriau, Charlotte; Bonin, Nicolas; Pibarot, Vincent

2018-02-22

Using a cementless femoral stem in total hip arthroplasty (THA), optimal filling of the proximal femoral metaphyseal volume (PFMV) and restoration of the extramedullary proximal femoral (PF) parameters (i.e., femoral offset (FO), neck length (FNL), and head height (FHH)) constitute key goals for optimal hip biomechanics, functional outcome, and THA survivorship. However, almost 30% of mismatch between the PF anatomy and implant geometry of the most widely implanted non-modular cementless femoral stem has been demonstrated in a computed tomography scan (CT scan) study. Therefore, this anatomic study aimed to evaluate the relationship between the intra- and extramedullary PF parameters using tridimensional CT scan reconstructions. One hundred fifty-one CT scans of adult healthy hips were obtained from 151 male Caucasian patients (mean age = 66 ± 11 years) undergoing lower limb CT scan arteriography. Tridimensional PF reconstructions and parameter measurements were performed using a corrected PF coronal plane-defined by the femoral neck and diaphyseal canal longitudinal axes-to avoid influence of PF helitorsion and femoral neck version on extramedullary PF parameters. Independently of the femoral neck-shaft angle, the PFMV was significantly and positively correlated with the FO, FNL, and FHH (r = 0.407 to 0.420; p < 0.0001). This study emphasized that the tridimensional PF geometry measurement in the corrected coronal plane of the femoral neck can be useful to determine and optimize the design of a non-modular cementless femoral stem. Particularly, continuous homothetic size progression of the intra- and extramedullary PF parameters should be achieved to assure stem fixation and restore anatomic hip biomechanics.

Restless legs syndrome status as a predictor for lower physical function

PubMed Central

Zhang, Chunbai; Li, Yanping; Malhotra, Atul; Ning, Yi

2014-01-01

Objective: To examine the potential long-term impact of restless legs syndrome (RLS) and other common sleep complaints on subsequent physical function (PF), we conducted a longitudinal analysis of 12,556 men in the Health Professionals Follow-up Study. Methods: We used a set of questions recommended by the International RLS Study Group to assess RLS in 2002. We asked questions regarding other sleep complaints—insomnia, sleep fragmentation, and excessive daytime sleepiness—in 2004. We used the Physical Function (PF-10) survey of the Short Form–36 Health Survey to characterize PF in 1996 and 2008. We examined the 2008 PF-10 scores across categories of baseline RLS (2002), adjusted for age, 1996 PF-10 score, and other potential confounders. Results: The participants with RLS at baseline had significantly lower PF-10 score 6 years later than those without RLS (mean difference = −2.32, p = 0.01), after adjusting for potential confounders. The magnitude of difference in PF-10 score for RLS symptoms ≥15 times/month vs no RLS was more than that of a 5-year increase of age or moderate amount of smoking. Having daily daytime sleepiness and sleep duration ≥9 hours/day were associated with lower mean PF value than not having these symptoms (p < 0.05 for both). Conclusions: RLS and other sleep complaints are associated with lower PF. Our findings need to be replicated by more longitudinal studies including women and populations of other social and cultural backgrounds. It is important to understand whether RLS is an independent risk factor or a marker for other unknown risk factors for disability. PMID:24598708

Comparing Universal Lynch Syndrome Tumor Screening Programs to Evaluate Associations Between Implementation Strategies and Patient Follow-through

PubMed Central

Cragun, Deborah; DeBate, Rita D.; Vadaparampil, Susan T.; Baldwin, Julie; Hampel, Heather; Pal, Tuya

2014-01-01

Purpose Universal tumor screening (UTS) for all colorectal cancer (CRC) patients can improve the identification of Lynch syndrome, the most common cause of hereditary CRC. This multiple-case study explored how variability in UTS procedures influence patient follow-through (PF) with germline testing after a screen-positive result. Methods Data were obtained through web-based surveys and telephone interviews with institutional informants. Institutions were categorized as Low-PF (≤10% underwent germline testing), Medium-PF (11–40%), or High-PF (>40%). To identify implementation procedures (i.e., conditions) unique High-PF institutions, qualitative comparative analysis was performed. Results Twenty-one informants from fifteen institutions completed surveys and/or interviews. Conditions present among all five High-PF institutions included: 1) disclosure of screen-positive results to patients by genetic counselors (GCs); and 2) GCs either facilitate physician referrals to genetics or eliminated the need for referrals. Although both of these High-PF conditions were present among two Medium-PF institutions, automatic reflex testing was lacking and difficulty contacting screen-positive patients was a barrier. The three remaining Medium-PF and five Low-PF institutions lacked High-PF conditions. Conclusion Methods for streamlining UTS procedures, incorporating a high level of involvement of GCs in results tracking and communication, and reducing barriers to patient contact are reviewed within a broader discussion on maximizing the effectiveness and public health impact of UTS. PMID:24651603

Plantarflexor weakness negatively impacts walking in persons with multiple sclerosis more than plantarflexor spasticity

PubMed Central

Wagner, Joanne M.; Kremer, Theodore R.; Van Dillen, Linda R.; Naismith, Robert T.

2014-01-01

Objective To determine if plantarflexor (PF) spasticity or ankle strength best predicts variance in walking capacity or self-perceived limitations in walking in persons with multiple sclerosis (pwMS), and if pwMS with PF spasticity are weaker and have greater walking dysfunction than pwMS without PF spasticity. Design Cross-sectional study. Setting University research laboratory. Participants Forty-two pwMS (age: 42.9 ± 10.1 years; Expanded Disability Status Scale (EDSS): median = 3.0, range = 0–6) and 14 adults without disability (WD) (age: 41.9 ± 10.1 years). Intervention Not applicable. Main Outcome Measures PF spasticity and dorsiflexion (DF) and PF maximum voluntary isometric torque (MVIT) were assessed using the Modified Ashworth Scale (MAS) and a computerized dynamometer, respectively. The Timed 25-Foot Walk Test (T25FWT) was the primary outcome measure of walking capacity. Secondary measures included the Six Minute Walk Test (6MWT) and 12-item Multiple Sclerosis Walking Scale (MSWS-12). Results PF strength was the most consistent predictor of the variance in walking capacity (T25FWT: R2 change = 0.23 to 0.29, p ≤ 0.001; 6MWT: R2 change = 0.12 to 0.29, p ≤ 0.012), and self-perceived limitations of walking (MSWS-12: R2 change = 0.04 to 0.14, p < 0.18). There were no significant differences (p > 0.05) between the pwMS with PF spasticity and pwMS without PF spasticity for any of the outcome measures. Conclusions Our study suggests a unique contribution of PF weakness to walking dysfunction in pwMS, and highlights the importance of evaluating PF strength in this clinical population. PMID:24582617

Determinant Factors of the Squat Jump in Sprinting and Jumping Athletes

PubMed Central

González-Badillo, Juan José; Jiménez-Reyes, Pedro; Ramírez-Lechuga, Jorge

2017-01-01

Abstract The aim of this study was to assess the relationship between strength variables and maximum velocity (Vmax) in the squat jump (SJ) in sprinting and jumping athletes. Thirty-two sprinting and jumping athletes of national level (25.4 ± 4.5 years; 79.4 ± 6.9 kg and 180.4 ± 6.0 cm) participated in the study. Vmax in the SJ showed significant relationships with peak force 1 (PF1) (r = 0.82, p ≤ 0.001), peak force 2 (PF2) (r = 0.68, p ≤ 0.001), PF2 by controlling for PF1 (r = 0.30, non-significant), the maximum rate of force development at peak force 1 (RFDmax1) (r = 0.62, p ≤ 0.001), mean RFD 1 (RFDmean1) (r = 0.48, p ≤ 0.01), mean RFD 2 (RFDmean2) (r = 0.70, p ≤ 0.001), force at RFDmax1 (r = 0.36, p ≤ 0.05), force at RFDmax2 (r = 0.83, p ≤ 0.001) and force at RFDmax2 by controlling for PF1 (r = 0.40, p ≤ 0.05). However, Vmax in the SJ was associated negatively with the ratio PF2/PF1 (r = -0.54, p ≤ 0.01), time at peak force 2 (Tp2) (r = -0.64, p ≤ 0.001) and maximum rate of force development at peak force 2 (RFDmax2) (r = -0.71, p ≤ 0.001). These findings indicate that the peak force achieved at the beginning of the movement (PF1) is the main predictor of performance in jumping, although the RFDmax values and the ratio PF2/PF1 are also variables to be taken into account when analyzing the determinant factors of vertical jumping. PMID:28828074

A retrospective study of antihypertensives in pemphigus: a still unchartered odyssey particularly between thiols, amides and phenols

PubMed Central

Gornowicz-Porowska, Justyna; Bowszyc-Dmochowska, Monika; Dmochowski, Marian

2015-01-01

Introduction Autoimmune pemphigus diseases comprise several entities with serious prognoses, including the pemphigus vulgaris (PV) group and pemphigus foliaceus (PF) group. Antihypertensives are suspected to be one of the factors triggering/sustaining pemphigus. Here, the data of pemphigus patients regarding arterial hypertension (AH) and taking potentially noxious drugs were statistically analyzed in a setting of a Polish university dermatology department. Material and methods Medical histories of pemphigus patients (40 admissions of 24 female patients – 13 PV, 11 PF; and 102 admissions of 38 male patients – 24 PV, 14 PF), diagnosed at both immunopathological and biochemical-molecular levels, were studied. Results Ten of 16 (62.50%) AH-positive PV patients received known PV triggers/sustainers 11 times (1–3 per patient). Fourteen of 15 (93.33%) AH-positive PF patients received known PF triggers/sustainers 21 times (1–3 per patient). No differences in numbers of patients taking potentially culprit drugs were shown between PV and PF (Fisher's exact test: p = 0.0829; Yates’ χ2 test: p = 0.1048). The most frequently used culprit drugs were ramipril in PV and enalapril in PF. On average, each PV/PF AH-positive patient received 3.161 different antihypertensives in his/her history of admissions (2.155 antihypertensives per admission). Conclusions Drug triggering should be suspected in every case of newly diagnosed or exacerbated pemphigus, as eliminating possible PV/PF triggers/sustainers may alleviate the clinical symptoms and enable the decrease of dose/range of immunosuppressants regardless of pemphigus form. Eliminating possible drug PV/PF triggers/sustainers may alleviate the clinical symptoms and enable the decrease of dose/range of immunosuppressants regardless of pemphigus form. PMID:26528346

An initial psychometric evaluation of the German PROMIS v1.2 Physical Function item bank in patients with a wide range of health conditions.

PubMed

Liegl, Gregor; Rose, Matthias; Correia, Helena; Fischer, H Felix; Kanlidere, Sibel; Mierke, Annett; Obbarius, Alexander; Nolte, Sandra

2018-01-01

To translate the PROMIS Physical Function (PF) item bank version 1.2 into German and to investigate psychometric properties of resulting full bank and seven derived short forms. Cross-sectional psychometric study. Inpatient and outpatient clinics of the Department of Psychosomatic Medicine at Charité-Universitätsmedizin Berlin, Germany. A total of 10 adult patients with various chronic diseases participated in cognitive debriefing interviews. The final item bank was administered to n = 266 adult patients with a broad range of medical conditions. Patient-reported outcome assessment as part of routine care. PROMIS v1.2 PF bank; MOS SF-36 PF scale (PF-10). Cross-cultural adaptation of the item bank followed established guidelines. For the final German translation, the corrected item-total correlations ranged from 0.44 to 0.84. Cronbach's alpha was high for each PROMIS PF short form ( α = 0.88-0.96). The full PROMIS PF bank and most short forms correlated highly with the SF-36 PF-10 ( r = 0.85-0.90), with the exception of PROMIS Upper Extremity ( r = 0.64). PROMIS Upper Extremity showed ceiling effects and lower agreement with the full bank than other short forms. Unidimensionality was supported for all PROMIS PF measures using traditional factor analysis and nonparametric item response theory. The German PROMIS PF bank was found to be conceptually equivalent to the English version and fulfilled the psychometric requirements for use of short forms in clinical practice. Future studies should pay particular attention to samples with upper extremity functional limitations to further investigate the dimensional structure of PF as conceptualized according to PROMIS.

Relationships between static foot alignment and dynamic plantar loads in runners with acute and chronic stages of plantar fasciitis: a cross-sectional study

PubMed Central

Ribeiro, Ana P.; Sacco, Isabel C. N.; Dinato, Roberto C.; João, Silvia M. A.

2016-01-01

BACKGROUND: The risk factors for the development of plantar fasciitis (PF) have been associated with the medial longitudinal arch (MLA), rearfoot alignment and calcaneal overload. However, the relationships between the biomechanical variables have yet to be determined. OBJECTIVE: The goal of this study was to investigate the relationships between the MLA, rearfoot alignment, and dynamic plantar loads in runners with unilateral PF in acute and chronic phases. METHOD: Cross-sectional study which thirty-five runners with unilateral PF were evaluated: 20 in the acute phase (with pain) and 15 with previous chronic PF (without pain). The MLA index and rearfoot alignment were calculated using digital images. The contact area, maximum force, peak pressure, and force-time integral over three plantar areas were acquired with Pedar X insoles while running at 12 km/h, and the loading rates were calculated from the vertical forces. RESULTS: The multiple regression analyses indicated that both the force-time integral (R 2=0.15 for acute phase PF; R 2=0.17 for chronic PF) and maximum force (R 2=0.35 for chronic PF) over the forefoot were predicted by an elevated MLA index. The rearfoot valgus alignment predicted the maximum force over the rearfoot in both PF groups: acute (R 2=0.18) and chronic (R 2=0.45). The rearfoot valgus alignment also predicted higher loading rates in the PF groups: acute (R 2=0.19) and chronic (R 2=0.40). CONCLUSION: The MLA index and the rearfoot alignment were good predictors of plantar loads over the forefoot and rearfoot areas in runners with PF. However, rearfoot valgus was demonstrated to be an important clinical measure, since it was able to predict the maximum force and both loading rates over the rearfoot. PMID:26786073

The characterization of obese polycystic ovary syndrome rat model suitable for exercise intervention.

PubMed

Wu, Chuyan; Lin, Feng; Qiu, Shuwei; Jiang, Zhongli

2014-01-01

To develop a new polycystic ovary syndrome (PCOS) rat model suitable for exercise intervention. Thirty six rats were randomly divided into three experimental groups: PCOS rats with high-fat diet (PF, n = 24), PCOS rats with ordinary diet (PO, n = 6), and control rats with ordinary diet (CO, n = 6). Two kinds of PCOS rat model were made by adjustment diet structure and testosterone injection for 28 days. After a successful animal model, PF model rats were randomly assigned to three groups: exercise with a continuation of high-fat diet (PF-EF, n = 6), sedentary with a continuation of high-fat diet (PF-SF, n = 6), exercise with an ordinary diet (PF-EO, n = 6). Fasting blood glucose (FBG) and insulin (FINS), estrogen (E2), progesterone (P), and testosterone (T) in serum were determined by RIA, and ovarian morphology was evaluated by Image-Pro plus 6.0. Body weight, Lee index, FINS increased significantly in PF rat model. Serum levels of E2 and T were significantly higher in PF and PO than in CO. Ovary organ index and ovarian areas were significant lower in PF than in CO. After intervention for 2 weeks, the levels of 1 h postprandial blood glucose (PBG1), 2 h postprandial blood glucose (PBG2), FINS and the serum levels of T decreased significantly in PF-EF rats and PF-EO rats. The ratio of FBG/FINS was significant higher in PF-EO rats than in PF-SF rats. Ovarian morphology showed that the numbers of preantral follicles and atretic follicles decreased significantly, and the numbers of antral follicles and corpora lutea increased significantly in the rats of PF-EF and PF-EO. By combination of high-fat diet and testosterone injection, the obese PCOS rat model is conformable with the lifestyle habits of fatty foods and insufficient exercise, and has metabolic and reproductive characteristics of human PCOS. This model can be applied to study exercise intervention.

Characterization and Structural Studies of the Plasmodium falciparum Ubiquitin and Nedd8 Hydrolase UCHL3

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

Artavanis-Tsakonas, Katerina; Weihofen, Wilhelm A.; Antos, John M.

Like their human hosts, Plasmodium falciparum parasites rely on the ubiquitin-proteasome system for survival. We previously identified PfUCHL3, a deubiquitinating enzyme, and here we characterize its activity and changes in active site architecture upon binding to ubiquitin. We find strong evidence that PfUCHL3 is essential to parasite survival. The crystal structures of both PfUCHL3 alone and in complex with the ubiquitin-based suicide substrate UbVME suggest a rather rigid active site crossover loop that likely plays a role in restricting the size of ubiquitin adduct substrates. Molecular dynamics simulations of the structures and a model of the PfUCHL3-PfNedd8 complex allowed themore » identification of shared key interactions of ubiquitin and PfNedd8 with PfUCHL3, explaining the dual specificity of this enzyme. Distinct differences observed in ubiquitin binding between PfUCHL3 and its human counterpart make it likely that the parasitic DUB can be selectively targeted while leaving the human enzyme unaffected.« less

A cross-species translational pharmacokinetic-pharmacodynamic evaluation of core body temperature reduction by the TRPM8 blocker PF-05105679.

PubMed

Gosset, James R; Beaumont, Kevin; Matsuura, Tomomi; Winchester, Wendy; Attkins, Neil; Glatt, Sophie; Lightbown, Ian; Ulrich, Kristina; Roberts, Sonia; Harris, Jolie; Mesic, Emir; van Steeg, Tamara; Hijdra, Diana; van der Graaf, Piet H

2017-11-15

PF-05105679 is a moderately potent TRPM8 blocker which has been evaluated for the treatment of cold pain sensitivity. The TRPM8 channel is responsible for the sensation of cold environmental temperatures and has been implicated in regulation of core body temperature. Consequently, blockade of TRPM8 has been suggested to result in lowering of core body temperature. As part of the progression to human studies, the effect of PF-05105679 on core body temperature has been investigated in animals. Safety pharmacology studies showed that PF-05105679 reduced core body temperature in a manner that was inversely related to body weight of the species tested (greater exposure to PF-05105679 was required to lower temperature by 1°C in higher species). Based on an allometric (body weight) relationship, it was hypothesized that PF-05105679 would not lower core body temperature in humans at exposures that could exhibit pharmacological effects on cold pain sensation. On administration to humans, PF-05105679 was indeed effective at reversing the cold pain sensation associated with the cold pressor test in the absence of effects on core body temperature. Copyright © 2017 Elsevier B.V. All rights reserved.

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

Park, Jeong Su; Yonsei Biomedical Research Institute, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu, Seoul 120-752; Kang, Dong Hoon

p70 ribosomal S6 kinase 1 (S6K1) is an important serine/threonine kinase and downstream target of the mechanistic target of rapamycin complex 1 (mTORC1) signaling pathway. PF-4708671 is a specific inhibitor of S6K1, and prevents S6K1-mediated phosphorylation of the S6 protein. PF-4708671 treatment often leads to apoptotic cell death. However, the protective mechanism against PF-4708671-induced cell death has not been elucidated. The nuclear factor erythroid 2-related factor 2 (Nrf2)-Kelch-like ECH-associated protein 1 (Keap1) pathway is essential for protecting cells against oxidative stress. p62, an adaptor protein in the autophagic process, enhances Nrf2 activation through the impairment of Keap1 activity. In thismore » study, we showed that PF-4708671 induces autophagic Keap1 degradation-mediated Nrf2 activation in p62-dependent manner. Furthermore, p62-dependent Nrf2 activation plays a crucial role in protecting cells from PF-4708671-mediated apoptosis. - Highlights: • PF-4708671, a S6K1-specific inhibitor, prevents S6K1-mediated S6 phosphorylation. • However, PF-4708671 treatment often leads to apoptotic cell death. • Protective mechanism against PF-4708671-induced cell death remains to be elucidated. • PF-4708671 induced p62-dependent, autophagic Keap1 degradation-mediated Nrf2 activation. • p62-dependent Nrf2 activation protects cells from PF-4708671-mediated apoptosis.« less

Elevated Peak Postoperative B-type Natriuretic Peptide Predicts Decreased Longer-Term Physical Function after Primary Coronary Artery Bypass Graft Surgery

PubMed Central

Fox, Amanda A.; Marcantonio, Edward R.; Collard, Charles D.; Thoma, Mathis; Perry, Tjorvi E.; Shernan, Stanton K.; Muehlschlegel, Jochen D.; Body, Simon C.

2011-01-01

Background Elevated peak postoperative B-type natriuretic peptide (BNP) is associated with increased major adverse cardiovascular events and all-cause mortality after coronary artery bypass graft (CABG) surgery. Whether elevated postoperative BNP predicts worse post-discharge physical function (PF) is unknown. We hypothesized that peak postoperative BNP associates with PF assessed up to 2 years after CABG surgery, even after adjusting for clinical risk factors including preoperative PF. Methods This two institution prospective cohort study included patients undergoing primary CABG surgery with cardiopulmonary bypass. Short Form-36 questionnaires were administered to subjects preoperatively and 6 months, 1 and 2 years postoperatively. Short Form-36 PF domain scores were calculated using the Short Form-36 norm based scoring algorithm. Plasma BNP concentrations measured preoperatively and on postoperative days 1–5 were log10 transformed before analysis. To determine whether peak postoperative BNP independently predicts PF scores 6 months through 2 years after CABG surgery, multivariable longitudinal regression analysis of the postoperative PF scores was performed, adjusting for important clinical risk factors. Results 845 subjects (mean age±SD: 65±10 years) were analyzed. Peak postoperative BNP was significantly associated with postoperative PF (effect estimate for log10 peak BNP = −7.66 PF score points; 95% CI = −9.68, −5.64; P=<0.0001). After multivariable adjustments, peak postoperative BNP remained independently associated with postoperative PF (effect estimate for log10 peak BNP =−3.06 PF score points; 95% CI = −5.15, −0.97; P=0.004). Conclusions Elevated peak postoperative BNP independently associates with worse longer-term physical function after primary CABG surgery. Future studies are needed to determine whether medical management targeted towards reducing elevated postoperative BNP can improve PF after CABG surgery. PMID:21427536

Modifications of Geometric Truncation of the Scattering Phase Function

NASA Astrophysics Data System (ADS)

Radkevich, A.

2017-12-01

Phase function (PF) of light scattering on large atmospheric particles has very strong peak in forward direction constituting a challenge for accurate numerical calculations of radiance. Such accurate (and fast) evaluations are important in the problems of remote sensing of the atmosphere. Scaling transformation replaces original PF with a sum of the delta function and a new regular smooth PF. A number of methods to construct such a PF were suggested. Delta-M and delta-fit methods require evaluation of the PF moments which imposes a numerical problem if strongly anisotropic PF is given as a function of angle. Geometric truncation keeps the original PF unchanged outside the forward peak cone replacing it with a constant within the cone. This approach is designed to preserve the asymmetry parameter. It has two disadvantages: 1) PF has discontinuity at the cone; 2) the choice of the cone is subjective, no recommendations were provided on the choice of the truncation angle. This choice affects both truncation fraction and the value of the phase function within the forward cone. Both issues are addressed in this study. A simple functional form of the replacement PF is suggested. This functional form allows for a number of modifications. This study consider 3 versions providing continuous PF. The considered modifications also bear either of three properties: preserve asymmetry parameter, provide continuity of the 1st derivative of the PF, and preserve mean scattering angle. The second problem mentioned above is addressed with a heuristic approach providing unambiguous criterion of selection of the truncation angle. The approach showed good performance on liquid water and ice clouds with different particle size distributions. Suggested modifications were tested on different cloud PFs using both discrete ordinates and Monte Carlo methods. It was showed that the modifications provide better accuracy of the radiance computation compare to the original geometric truncation.

The impact of newly produced protein and dietary fiber rich fractions of yellow pea (Pisum sativum L.) on the structure and mechanical properties of pasta-like sheets.

PubMed

Muneer, Faraz; Johansson, Eva; Hedenqvist, Mikael S; Plivelic, Tomás S; Markedal, Keld Ejdrup; Petersen, Iben Lykke; Sørensen, Jens Christian; Kuktaite, Ramune

2018-04-01

Two fractions from pea (Pisum sativum L.), protein isolate (PPI) and dietary fiber (PF), were newly produced by extraction-fractionation method and characterized in terms of particle size distribution and structural morphology using SEM. The newly produced PPI and PF fractions were processed into pasta-like sheets with varying protein to fiber ratios (100/0, 90/10, 80/20, 70/30 and 50/50, respectively) using high temperature compression molding. We studied protein polymerization, molecular structure and protein-fiber interactions, as well as mechanical performance and cooking characteristics of processed PPI-PF blends. Bi-modal particle size distribution and chemical composition of the PPI and PF fractions influenced significantly the physicochemical properties of the pasta-like sheets. Polymerization was most pronounced for the 100 PPI, 90/10 and 80/20 PPI-PF samples as studied by SE-HPLC, and polymerization decreased with addition of the PF fraction. The mechanical properties, as strength and extensibility, were likewise the highest for the 100 PPI and 90/10 PPI-PF blends, while the E-modulus was similar for all the studied blends (around 38 MPa). The extensibility decreased with the increasing amount of PF in the blend. The highest amounts of β-sheets were found in the pasta-like sheets with high amounts of PPI (100, 90 and 80%), by FT-IR. An increase in PF fraction in the blend, resulted into the high amounts of unordered structures as observed by FT-IR, as well as in an increase in the molecular scattering distances observed by SAXS. The water uptake increased and cooking loss decreased with increased proportions of the PF fraction, and the consistency of 10 min cooked pasta-like sheets were alike al dente texture. The new knowledge obtained in this study on the use of extraction-fractionation method to produce novel PPI and PF fractions for developing innovative high nutritious food can be of a great importance. The obtained knowledge on the pea protein and fiber processing behaviour could greatly contribute to a better control of functional properties of various temperature-processed products from yellow pea. Copyright © 2018 Elsevier Ltd. All rights reserved.

Advancing nutritional therapy: A novel polymeric formulation attenuates intestinal inflammation in a murine colitis model and suppresses pro-inflammatory cytokine production in ex-vivo cultured inflamed colonic biopsies.

PubMed

Alhagamhmad, Moftah H; Lemberg, Daniel A; Day, Andrew S; Tan, Li-Zsa; Ooi, Chee Y; Krishnan, Usha; Gupta, Nitin; Munday, John S; Leach, Steven T

2017-04-01

Nutritional therapy is a viable therapeutic option for the treatment of Crohn disease (CD). Therefore improving nutritional therapy would greatly benefit CD patients. The aim of this study was to define the anti-inflammatory properties of a novel nutritional polymeric formula (PF) in comparison to a currently available standard PF. Dextran sodium sulfate (DSS) was utilized to induce colitis in C57BL/6 mice with mice randomized to receive either standard PF or novel PF in addition to control groups. Changes in body weight were recorded and colonic damage was assessed histologically and biochemically. Additional experiments were also included where the cytokine response of colonic biopsies from pediatric CD patients was measured following exposure to standard PF or novel PF. DSS induced significant body weight loss, morphological changes in the colon, increased myeloperoxidase (MPO) activity and up-regulated colonic mRNA expression of tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-12 and monocyte chemoattractant protein (MCP)-1, as well as associated histological changes. Other than histological damage, these inflammatory changes were reversed by both novel and standard PF. However, the novel PF, but not standard PF, completely suppressed TNF-α, IL-6 and IL-8 levels from cultured biopsies. Newly developed nutritional formula reproducibly ameliorated DSS-induced colitis in a murine model, although this response was not measurably different to standard PF. However, the novel PF was significantly superior in suppressing inflammatory cytokine release from cultured colonic biopsies. Collectively, these findings support a possible role for novel PF in advancing nutritional therapy for CD patients. Crown Copyright © 2016. Published by Elsevier Ltd. All rights reserved.

Deep brain stimulation of the center median-parafascicular complex of the thalamus has efficient anti-parkinsonian action associated with widespread cellular responses in the basal ganglia network in a rat model of Parkinson's disease.

PubMed

Jouve, Loréline; Salin, Pascal; Melon, Christophe; Kerkerian-Le Goff, Lydia

2010-07-21

The thalamic centromedian-parafascicular (CM/Pf) complex, mainly represented by Pf in rodents, is proposed as an interesting target for the neurosurgical treatment of movement disorders, including Parkinson's disease. In this study, we examined the functional impact of subchronic high-frequency stimulation (HFS) of Pf in the 6-hydroxydopamine-lesioned hemiparkinsonian rat model. Pf-HFS had significant anti-akinetic action, evidenced by alleviation of limb use asymmetry (cylinder test). Whereas this anti-akinetic action was moderate, Pf-HFS totally reversed lateralized neglect (corridor task), suggesting potent action on sensorimotor integration. At the cellular level, Pf-HFS partially reversed the dopamine denervation-induced increase in striatal preproenkephalin A mRNA levels, a marker of the neurons of the indirect pathway, without interfering with the markers of the direct pathway (preprotachykinin and preprodynorphin). Pf-HFS totally reversed the lesion-induced changes in the gene expression of cytochrome oxidase subunit I in the subthalamic nucleus, the globus pallidus, and the substantia nigra pars reticulata, and partially in the entopeduncular nucleus. Unlike HFS of the subthalamic nucleus, Pf-HFS did not induce per se dyskinesias and directly, although partially, alleviated L-3,4-dihydroxyphenylalanine (L-DOPA)-induced forelimb dyskinesia. Conversely, L-DOPA treatment negatively interfered with the anti-parkinsonian effect of Pf-HFS. Altogether, these data show that Pf-DBS, by recruiting a large basal ganglia circuitry, provides moderate to strong anti-parkinsonian benefits that might, however, be affected by L-DOPA. The widespread behavioral and cellular outcomes of Pf-HFS evidenced here demonstrate that CM/Pf is an important node for modulating the pathophysiological functioning of basal ganglia and related disorders.

Long-term clinical and radiographic outcome of patello-femoral realignment procedures: a minimum of 15-year follow-up.

PubMed

Vivod, Gregor; Verdonk, Peter; Drobnič, Matej

2014-11-01

A retrospective single-centre study was focused on the long-term outcome after different patello-femoral (PF) realignment procedures. Thirty-nine patients treated for recurrent PF instability were examined after a mean post-operative time of 22.5 years. Their 78 knees were divided into: non-operated knees (NON-OPERATED)-N = 24, isolated proximal procedures (PROXIMAL)-N = 22, isolated distal procedures (DISTAL)-N = 10, and combined procedures (COMBINED)-N = 22. PF-related medical history together with clinical, subjective (KOOS and Kujala scores), and radiographic (Caton-Deschamps PF height index, Kellgren-Lawrence scale for tibio-femoral OA, and Iwano classification for PF OA) evaluation was conducted. PF re-dislocation rate was comparable between PROXIMAL (36%), DISTAL (20%), and COMBINED (32%). Isolated proximal procedures revealed less central patella positions (PROXIMAL 64%; DISTAL 90%; COMBINED 95%) and more frequent PF apprehension test (PROXIMAL 82%; DISTAL 40%, COMBINED 50%). KOOS and Kujala scores were similar in all three surgical subgroups, but significantly lower than in NON-OPERATED. Patellas were positioned lower after DISTAL, 0.8 (0.5-1.0) or COMBINED, 0.9 (0.4-1.3). Kellgren-Lawrence scores ≥2 were found in 42% NON-OPERATED, 37% PROXIMAL, 70% DISTAL, and 59% COMBINED, whereas Iwano classification ≥2 was confirmed in 46% NON-OPERATED, 64% PROXIMAL, 80% DISTAL, and 86% COMBINED. High PF re-dislocation rates together with a very high incidence of PF OA indicate that PF realignment strategies used traditionally had failed to reach their long-term expectations. The transfer of tibial tuberosity resulted in more constrained PF joints than isolated proximal procedures which allowed for more residual PF instability. Distal procedures additionally increased the likelihood for tibio-femoral OA. III.

Platelet factor 4/CXCL4 induces phagocytosis and the generation of reactive oxygen metabolites in mononuclear phagocytes independently of Gi protein activation or intracellular calcium transients.

PubMed

Pervushina, Olga; Scheuerer, Barbara; Reiling, Norbert; Behnke, Lars; Schröder, Jens-M; Kasper, Brigitte; Brandt, Ernst; Bulfone-Paus, Silvia; Petersen, Frank

2004-08-01

Platelet factor 4 (PF-4), a platelet-derived CXC chemokine, is known to prevent human monocytes from apoptosis and to promote differentiation of these cells into HLA-DR(-) macrophages. In this study, we investigated the role of PF-4 in the control of acute monocyte proinflammatory responses involved in the direct combat of microbial invaders. We show that PF-4 increases monocyte phagocytosis and provokes a strong formation of oxygen radicals but lacks a chemotactic activity in these cells. Compared with FMLP, PF-4-induced oxidative burst was later in its onset but was remarkably longer in its duration (lasting for up to 60 min). Furthermore, in PF-4-prestimulated cells, FMLP- as well as RANTES-induced burst responses became synergistically enhanced. As we could show, PF-4-mediated oxidative burst in monocytes does not involve Gi proteins, elevation of intracellular free calcium concentrations, or binding to CXCR3B, a novel PF-4 receptor recently discovered on endothelial cells. Moreover, we found that PF-4 acts on macrophages in a dual manner. On the one hand, very similar to GM-CSF or M-CSF, PF-4 treatment of monocytes generates macrophages with a high capacity for unspecific phagocytosis. On the other hand, short term priming of GM-CSF-induced human macrophages with PF-4 substantially increases their capability for particle ingestion and oxidative burst. A comparable effect was also observed in murine bone marrow-derived macrophages, indicating cross-reactivity of human PF-4 between both species. Taken together, PF-4 may play a crucial role in the induction and maintenance of an unspecific immune response.

Physical fitness and academic performance in youth: A systematic review.

PubMed

Santana, C C A; Azevedo, L B; Cattuzzo, M T; Hill, J O; Andrade, L P; Prado, W L

2017-06-01

Physical fitness (PF) is a construct of health- and skill-related attributes which have been associated with academic performance (AP) in youth. This study aimed to review the scientific evidence on the association among components of PF and AP in children and adolescents. A systematic review of articles using databases PubMed/Medline, ERIC, LILACS, SciELO, and Web of Science was undertaken. Cross-sectional and longitudinal studies examining the association between at least one component of PF and AP in children and adolescents, published between 1990 and June 2016, were included. Independent extraction of articles was carried out by the two authors using predefined data fields. From a total of 45 studies included, 25 report a positive association between components of PF with AP and 20 describe a single association between cardiorespiratory fitness (CRF) and AP. According to the Strengthening the Reporting of Observational Studies in Epidemiology guidelines: 12 were classified as low, 32 as medium risk, and 1 as high risk of bias. Thirty-one studies reported a positive association between AP and CRF, six studies with muscular strength, three studies with flexibility, and seven studies reported a positive association between clustered of PF components and AP. The magnitude of the associations is weak to moderate (β = 0.10-0.42 and odds = 1.01-4.14). There is strong evidence for a positive association between CRF and cluster of PF with AP in cross-sectional studies; and evidence from longitudinal studies for a positive association between cluster of PF and AP; the relationship between muscular strength and flexibility with AP remains uncertain. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

ULTRASONOGRAPHY, AN EFFECTIVE TOOL IN DIAGNOSING PLANTAR FASCIITIS: A SYSTEMATIC REVIEW OF DIAGNOSTIC TRIALS

PubMed Central

Wyland, Matthew; Applequist, Lee; Bolowsky, Erin; Klingensmith, Heather; Virag, Isaac

2016-01-01

Background Plantar fasciitis (PF) is the most common cause of heel pain that affects 10% of the general population, whether living an athletic or sedentary lifestyle. The most frequent mechanism of injury is an inflammatory response that is caused by repetitive micro trauma. Many techniques are available to diagnose PF, including the use of ultrasonography (US). Purpose The purpose of this study is to systematically review and appraise previously published articles published between the years 2000 and 2015 that evaluated the effectiveness of using US in the process of diagnosing PF, as compared to alternative diagnostic methods. Methods A total of eight databases were searched to systematically review scholarly (peer reviewed) diagnostic and intervention articles pertaining to the ability of US to diagnose PF. Results Using specific key words the preliminary search yielded 264 articles, 10 of which were deemed relevant for inclusion in the study. Two raters independently scored each article using the 15 point modified QUADAS scale. Discussion Six studies compared the diagnostic efficacy of US to another diagnostic technique to diagnose PF, and four studies focused on comparing baseline assessment of plantar fascia before subsequent intervention. The most notable US outcomes measured were plantar fascia thickness, enthesopathy, and hypoechogenicity. Conclusion US was found to be accurate and reliable compared to alternative reference standards like MRI in the diagnosis of PF. The general advantages of US (e.g. cost efficient, ease of administration, non-invasive, limited contraindications) make it a superior diagnostic modality in the diagnosis of PF. US should be considered in rehabilitation clinics to effectively diagnose PF and to accurately monitor improvement in the disease process following rehabilitation interventions. Level of Evidence 1A PMID:27757279

Evidence of C-F-P and aromatic π-F-P weak interactions in imidazolium ionic liquids and its consequences

NASA Astrophysics Data System (ADS)

Panja, Sumit Kumar; Srivastava, Nitin; Srivastava, Jyoti; Prasad, Namburi Eswara; Noothalapati, Hemanth; Shigeto, Shinsuke; Saha, Satyen

2018-04-01

A simple change from alkyl group to alkene in side chain of imidazolium cation with same anion resulted in a drastic impact on physical properties (e.g., melting point) from bmimPF6 IL to cmimPF6 IL. The underlying reasons have been elucidated by structural and interaction studies with the help of DSC, SCXRD, vibrational and multi-nuclear NMR spectroscopic techniques. Experiments reveal existence of new weak interactions involving the carbon and π cloud of the imidazolium aromatic ring with fluoride of PF6 anion (i.e., C2-F-P and π-F-P) in cmimPF6 but are absent in structurally similar prototype IL, bmimPF6. Though weak, these interactions helped to form ladder type supramolecular arrangement, resulting in quite high melting point for cmimPF6 IL compared to bmimPF6 IL. These findings emphasize that an IL system can behave uniquely because of the existence of uncommon weak interactions.

Beneficial influence of topical extra virgin olive oil application on an experimental model of penile fracture in rats.

PubMed

Gunes, Mustafa; Ozkol, Halil; Pirincci, Necip; Gecit, Ilhan; Bilici, Salim; Yildirim, Serkan

2015-08-01

Penile fracture (PF) is known as a traumatic rupture of the tunica albuginea of corpus cavernosum. In this study, we aimed to investigate the healing influence of topical extra virgin olive oil (EVOO) on PF through evaluating levels of some oxidative stress biomarkers for the first time. Histopathological evaluation was also realized. A total of 18 male Sprague-Dawley albino rats were divided into three groups of six rats each as control group, in PF (alone) group, and PF + EVOO group. Experimental PF was formed via incising from the proximal dorsal side of the penis in the rats of all groups except control. While in PF (alone) group, fracture was formed and the incision was primarily closed, in PF + EVOO group in addition to foregoing processes, EVOO was also administrated topically twice a day for 3 weeks. At the end of the experiment, all rats were killed and penectomy was carried out. While malondialdehyde, myeloperoxidase, lipid hyroperoxide, and total oxidant status significantly (p < 0.05) increased, reduced glutathione and total free sulfhydryl groups markedly (p < 0.05) decreased in PF (alone) group when compared with PF + EVOO group. Levels of these parameters were reversed to nearly normal values by topical EVOO application. Protection by EVOO is further substantiated via the improved histological findings in PF + EVOO group as against degenerative changes in the rats of PF (alone) group. Our data revealed that EVOO has protective effect in penile cavernosal tissue through probably its antioxidant, free radical defusing, anti-inflammatory, and antimicrobial effects. © The Author(s) 2013.

Experimental evidence for 56Ni-core breaking from the low-spin structure of the N=Z nucleus 5829Cu29

NASA Astrophysics Data System (ADS)

Lisetskiy, A. F.; Pietralla, N.; Honma, M.; Schmidt, A.; Schneider, I.; Gade, A.; von Brentano, P.; Otsuka, T.; Mizusaki, T.; Brown, B. A.

2003-09-01

Low-spin states in the odd-odd N=Z nucleus 58Cu were investigated with the 58Ni(p,nγ)58Cu fusion evaporation reaction at the FN-TANDEM accelerator in Cologne. γγ-coincidences, γγ-angular correlations, and signs of γ-ray polarizations were measured. Seventeen low-spin states below 3.6 MeV and 17 new transitions were observed. Ten multipole mixing ratios and 17 γ-branching ratios were determined for the first time. New detailed spectroscopic information on the 2+2 state, the isobaric analogue state (IAS) of the 2+1,T=1 state of 58Ni, makes 58Cu the heaviest odd-odd N=Z nucleus with known B(E2;2+,T=1→0+,T=1) value. The 4+ state at 2.751 MeV, observed here for the first time, is identified as the IAS of the 4+1,T=1 state in 58Ni. The new data are compared to full pf-shell-model calculations with the GXPF1 residual interaction and to calculations within a pf5/2 configurational space with a residual surface δ interaction. The role of the 56Ni core excitations for the low-spin structure in 58Cu is discussed.

The Armadillo Repeat Protein PF16 Is Essential for Flagellar Structure and Function in Plasmodium Male Gametes

PubMed Central

Ferguson, David J. P.; Bunting, Karen A.; Xu, Zhengyao; Bailes, Elizabeth; Sinden, Robert E.; Holder, Anthony A.; Smith, Elizabeth F.; Coates, Juliet C.; Rita Tewari

2010-01-01

Malaria, caused by the apicomplexan parasite Plasmodium, threatens 40% of the world's population. Transmission between vertebrate and insect hosts depends on the sexual stages of the life-cycle. The male gamete of Plasmodium parasite is the only developmental stage that possesses a flagellum. Very little is known about the identity or function of proteins in the parasite's flagellar biology. Here, we characterise a Plasmodium PF16 homologue using reverse genetics in the mouse malaria parasite Plasmodium berghei. PF16 is a conserved Armadillo-repeat protein that regulates flagellar structure and motility in organisms as diverse as green algae and mice. We show that P. berghei PF16 is expressed in the male gamete flagellum, where it plays a crucial role maintaining the correct microtubule structure in the central apparatus of the axoneme as studied by electron microscopy. Disruption of the PF16 gene results in abnormal flagellar movement and reduced fertility, but does not lead to complete sterility, unlike pf16 mutations in other organisms. Using homology modelling, bioinformatics analysis and complementation studies in Chlamydomonas, we show that some regions of the PF16 protein are highly conserved across all eukaryotes, whereas other regions may have species-specific functions. PF16 is the first ARM-repeat protein characterised in the malaria parasite genus Plasmodium and this study opens up a novel model for analysis of Plasmodium flagellar biology that may provide unique insights into an ancient organelle and suggest novel intervention strategies to control the malaria parasite. PMID:20886115

Plantar fascia anatomy and its relationship with Achilles tendon and paratenon

PubMed Central

Stecco, Carla; Corradin, Marco; Macchi, Veronica; Morra, Aldo; Porzionato, Andrea; Biz, Carlo; De Caro, Raffaele

2013-01-01

Although the plantar fascia (PF) has been studied quite well from a biomechanical viewpoint, its microscopic properties have been overlooked: nothing is known about its content of elastic fibers, the features of the extracellular matrix or the extent of innervation. From a functional and clinical standpoint, the PF is often correlated with the triceps surae muscle, but the anatomical grounds for this link are not clear. The aim of this work was to focus on the PF macroscopic and microscopic properties and study how Achilles tendon diseases might affect it. Twelve feet from unembalmed human cadavers were dissected to isolate the PF. Specimens from each PF were tested with various histological and immunohistochemical stains. In a second stage, 52 magnetic resonance images (MRI) obtained from patients complaining of aspecific ankle or foot pain were analyzed, dividing the cases into two groups based on the presence or absence of signs of degeneration and/or inflammation of the Achilles tendon. The thickness of PF and paratenon was assessed in the two groups and statistical analyses were conducted. The PF is a tissue firmly joined to plantar muscles and skin. Analyzing its possible connections to the sural structures showed that this fascia is more closely connected to the paratenon of Achilles tendon than to the Achilles tendon, through the periosteum of the heel. The PF extended medially and laterally, continuing into the deep fasciae enveloping the abductor hallucis and abductor digiti minimi muscles, respectively. The PF was rich in hyaluronan, probably produced by fibroblastic-like cells described as ‘fasciacytes’. Nerve endings and Pacini and Ruffini corpuscles were present, particularly in the medial and lateral portions, and on the surface of the muscles, suggesting a role for the PF in the proprioception of foot. In the radiological study, 27 of the 52 MRI showed signs of Achilles tendon inflammation and/or degeneration, and the PF was 3.43 ± 0.48 mm thick (99%CI and SD = 0.95), as opposed to 2.09 ± 0.24 mm (99%CI, SD = 0.47) in the patients in which the MRI revealed no Achilles tendon diseases; this difference in thickness of 1.29 ± 0.57 mm (99%CI) was statistically significant (P < 0.001). In the group of 27/52 patients with tendinopathies, the PF was more than 4.5 mm thick in 5, i.e. they exceeded the threshold for a diagnosis of plantar fasciitis. None of the other 25/52 paitents had a PF more than 4 mm thick. There was a statistically significant correlation between the thicknesses of the PF and the paratenon. These findings suggest that the plantar fascia has a role not only in supporting the longitudinal arch of the foot, but also in its proprioception and peripheral motor coordination. Its relationship with the paratenon of the Achilles tendon is consistent with the idea of triceps surae structures being involved in the PF pathology, so their rehabilitation can be considered appropriate. Finally, the high concentration of hyaluronan in the PF points to the feasibility of using hyaluronan injections in the fascia to treat plantar fasciitis. PMID:24028383

Dimensional stability of pineapple leaf fibre reinforced phenolic composites

NASA Astrophysics Data System (ADS)

Asim, M.; Jawaid, M.; Abdan, K.; Ishak, M. R.

2017-12-01

In this research, pineapple leaves fibre (PALF)/phenolic resin (PF) composites were fabricated by hand lay-up method. The aim of this work is to investigate the physical properties (water absorption and thickness swelling) of PALF reinforced phenolic resin composites. Long-term water absorption (WA) and thickness swelling (TS) behaviours of the PALF/PF composites were investigated at several water immersion times. The effects of different fibre loading on WA and TS of PALF/PF composites were also analyzed. Obtained results indicated that the WA and TS of PALF/PF composites vary with fibres content and water immersion time before reaching to equilibrium. WA and TS of PALF/PF composites were increased by increasing fibre loading. Results obtained in this study will be used for further study on hybridization of PALF and Kenaf fibre based phenolic composites.

During early to mid adolescence, moderate to vigorous physical activity is associated with restoring sleep, psychological functioning, mental toughness and male gender.

PubMed

Brand, Serge; Kalak, Nadeem; Gerber, Markus; Clough, Peter J; Lemola, Sakari; Sadeghi Bahmani, Dena; Pühse, Uwe; Holsboer-Trachsler, Edith

2017-03-01

Numerous studies showed that regular physical activity (PA) is associated with both favourable and restorative sleep and improved psychological functioning (PF). However, there is little research on the topic covering the early to mid-adolescence period. Moreover, curiosity and exploratory behaviour (CEB) and mental toughness (MT) as a result of PA remains thus far uninvestigated, as do possible gender differences. The aim of the present study was to explore the associations between PA, subjective sleep (sS), PF, CEB, and MT during early to mid-adolescence. A total of 1361 participants (mean age = 13.37 years; range: 11-16 years; 51.2% female) took part in the study. They completed questionnaires covering PA, sS, PF, CEB, and MT. Greater PA was related to improved PF, better sS, and increased CEB and MT. Compared to male participants, females reported less PA, poorer sS, and had lower PF and MT scores. The present pattern of results suggests that during early and mid-adolescence greater PA was associated with more favourable sS and better PF, including CEB and MT, and that female participants reported lower scores in PA, sS, and PF. Accordingly, if PA has a favourable impact on sleep and psychological functioning, then data suggest that sports participation should be more tailored to increase motivation among female adolescents.

Photoaffinity Labeling of the Plasmodium falciparum Chloroquine Resistance Transporter with a Novel Perfluorophenylazido Chloroquine†

PubMed Central

Lekostaj, Jacqueline K.; Natarajan, Jayakumar K.; Paguio, Michelle F.; Wolf, Christian; Roepe, Paul D.

2009-01-01

Several models describing how amino acid substitutions in the Plasmodium falciparum chloroquine resistance transporter (PfCRT) confer resistance to chloroquine (CQ) and other antimalarial drugs have been proposed. Further progress requires molecular analysis of interactions between purified reconstituted PfCRT protein and these drugs. We have thus designed and synthesized several perfluorophenyl azido (pfpa) CQ analogues for PfCRT photolabeling studies. One particularly useful probe (AzBCQ) places the pfpa group at the terminal aliphatic N of CQ via a flexible four-carbon ester linker and includes a convenient biotin tag. This probe photolabels PfCRT in situ with high specificity. Using reconstituted proteoliposomes harboring partially purified recombinant PfCRT, we analyze AzBCQ photolabeling versus competition with CQ and other drugs to probe the nature of the CQ binding site. We also inspect how pH, the chemoreversal agent verapamil (VPL), and various amino acid mutations in PfCRT that cause CQ resistance (CQR) affect the efficiency of AzBCQ photolabeling. Upon gel isolation of AzBCQ-labeled PfCRT followed by trypsin digestion and mass spectrometry analysis, we are able to define a single AzBCQ covalent attachment site lying within the digestive vacuolar-disposed loop between putative helices 9 and 10 of PfCRT. Taken together, the data provide important new insight into PfCRT function and, along with previous results, allow us to propose a model for a single CQ binding site in the PfCRT protein. PMID:18767816

Photoaffinity labeling of the Plasmodium falciparum chloroquine resistance transporter with a novel perfluorophenylazido chloroquine.

PubMed

Lekostaj, Jacqueline K; Natarajan, Jayakumar K; Paguio, Michelle F; Wolf, Christian; Roepe, Paul D

2008-09-30

Several models describing how amino acid substitutions in the Plasmodium falciparum chloroquine resistance transporter (PfCRT) confer resistance to chloroquine (CQ) and other antimalarial drugs have been proposed. Further progress requires molecular analysis of interactions between purified reconstituted PfCRT protein and these drugs. We have thus designed and synthesized several perfluorophenyl azido (pfpa) CQ analogues for PfCRT photolabeling studies. One particularly useful probe (AzBCQ) places the pfpa group at the terminal aliphatic N of CQ via a flexible four-carbon ester linker and includes a convenient biotin tag. This probe photolabels PfCRT in situ with high specificity. Using reconstituted proteoliposomes harboring partially purified recombinant PfCRT, we analyze AzBCQ photolabeling versus competition with CQ and other drugs to probe the nature of the CQ binding site. We also inspect how pH, the chemoreversal agent verapamil (VPL), and various amino acid mutations in PfCRT that cause CQ resistance (CQR) affect the efficiency of AzBCQ photolabeling. Upon gel isolation of AzBCQ-labeled PfCRT followed by trypsin digestion and mass spectrometry analysis, we are able to define a single AzBCQ covalent attachment site lying within the digestive vacuolar-disposed loop between putative helices 9 and 10 of PfCRT. Taken together, the data provide important new insight into PfCRT function and, along with previous results, allow us to propose a model for a single CQ binding site in the PfCRT protein.

Triazole-functionalized N-heterocyclic carbene complexes of palladium and platinum and efficient aqueous Suzuki-Miyaura coupling reaction.

PubMed

Gu, Shaojin; Xu, Hui; Zhang, Na; Chen, Wanzhi

2010-07-05

Imidazolium salts bearing triazole groups are synthesized via a copper catalyzed click reaction, and the silver, palladium, and platinum complexes of their N-heterocyclic carbenes are studied. [Ag(4)(L1)(4)](PF(6))(4), [Pd(L1)Cl](PF(6)), [Pt(L1)Cl](PF(6)) (L1=3-((1-benzyl-1H-1,2,3-triazol-4-yl)methyl)-1-(pyrimidin-2-yl)-1H-imidazolylidene), [Pd(2)(L2)(2)Cl(2)](PF(6))(2), and [Pd(L2)(2)](PF(6))(2) (L2=1-butyl-3-((1-(pyridin-2-yl)-1H-1,2,3-triazol-4-yl)methyl)imidazolylidene) have been synthesized and fully characterized by NMR, elemental analysis, and X-ray crystallography. The silver complex [Ag(4)(L1)(4)](PF(6))(4) consists of a Ag(4) zigzag chain. The complexes [Pd(L1)Cl](PF(6)) and [Pt(L1)Cl](PF(6)), containing a nonsymmetrical NCN' pincer ligand, are square planar with a chloride trans to the carbene donor. [Pd(2)(L2)(2)Cl(2)](PF(6))(2) consists of two palladium centers with CN(2)Cl coordination mode, whereas the palladium in [Pd(L2)(2)](PF(6))(2) is surrounded by two carbene and two triazole groups with two uncoordinated pyridines. The palladium compounds are highly active for Suzuki-Miyaura cross coupling reactions of aryl bromides and 1,1-dibromo-1-alkenes in neat water under an air atmosphere.

Molecular interaction of selected phytochemicals under the charged environment of Plasmodium falciparum chloroquine resistance transporter (PfCRT) model.

PubMed

Patel, Saumya K; Khedkar, Vijay M; Jha, Prakash C; Jasrai, Yogesh T; Pandya, Himanshu A; George, Linz-Buoy; Highland, Hyacinth N; Skelton, Adam A

2016-01-01

Phytochemicals of Catharanthus roseus Linn. and Tylophora indica have been known for their inhibition of malarial parasite, Plasmodium falciparum in cell culture. Resistance to chloroquine (CQ), a widely used antimalarial drug, is due to the CQ resistance transporter (CRT) system. The present study deals with computational modeling of Plasmodium falciparum chloroquine resistance transporter (PfCRT) protein and development of charged environment to mimic a condition of resistance. The model of PfCRT was developed using Protein homology/analogy engine (PHYRE ver 0.2) and was validated based on the results obtained using PSI-PRED. Subsequently, molecular interactions of selected phytochemicals extracted from C. roseus Linn. and T. indica were studied using multiple-iterated genetic algorithm-based docking protocol in order to investigate the translocation of these legends across the PfCRT protein. Further, molecular dynamics studies exhibiting interaction energy estimates of these compounds within the active site of the protein showed that compounds are more selective toward PfCRT. Clusters of conformations with the free energy of binding were estimated which clearly demonstrated the potential channel and by this means the translocation across the PfCRT is anticipated.

The Characterization of Obese Polycystic Ovary Syndrome Rat Model Suitable for Exercise Intervention

PubMed Central

Qiu, Shuwei; Jiang, Zhongli

2014-01-01

Objective To develop a new polycystic ovary syndrome (PCOS) rat model suitable for exercise intervention. Method Thirty six rats were randomly divided into three experimental groups: PCOS rats with high-fat diet (PF, n = 24), PCOS rats with ordinary diet (PO, n = 6), and control rats with ordinary diet (CO, n = 6). Two kinds of PCOS rat model were made by adjustment diet structure and testosterone injection for 28 days. After a successful animal model, PF model rats were randomly assigned to three groups: exercise with a continuation of high-fat diet (PF-EF, n = 6), sedentary with a continuation of high-fat diet (PF-SF, n = 6), exercise with an ordinary diet (PF-EO, n = 6). Fasting blood glucose (FBG) and insulin (FINS), estrogen (E2), progesterone (P), and testosterone (T) in serum were determined by RIA, and ovarian morphology was evaluated by Image-Pro plus 6.0. Results Body weight, Lee index, FINS increased significantly in PF rat model. Serum levels of E2 and T were significantly higher in PF and PO than in CO. Ovary organ index and ovarian areas were significant lower in PF than in CO. After intervention for 2 weeks, the levels of 1 h postprandial blood glucose (PBG1), 2 h postprandial blood glucose (PBG2), FINS and the serum levels of T decreased significantly in PF-EF rats and PF-EO rats. The ratio of FBG/FINS was significant higher in PF-EO rats than in PF-SF rats. Ovarian morphology showed that the numbers of preantral follicles and atretic follicles decreased significantly, and the numbers of antral follicles and corpora lutea increased significantly in the rats of PF-EF and PF-EO. Conclusion By combination of high-fat diet and testosterone injection, the obese PCOS rat model is conformable with the lifestyle habits of fatty foods and insufficient exercise, and has metabolic and reproductive characteristics of human PCOS. This model can be applied to study exercise intervention. PMID:24905232

Surfactant-assisted dispersion of carbon nanotubes: mechanism of stabilization and biocompatibility of the surfactant

NASA Astrophysics Data System (ADS)

Singh, Raman Preet; Jain, Sanyog; Ramarao, Poduri

2013-10-01

Nanoparticles (NPs) are thermodynamically unstable system and tend to aggregate to reduce free energy. The aggregation property of NPs results in inhomogeneous exposure of cells to NPs resulting in variable cellular responses. Several types of surfactants are used to stabilize NP dispersions and obtain homogenous dispersions. However, the effects of these surfactants, per se, on cellular responses are not completely known. The present study investigated the application of Pluronic F68 (PF68) for obtaining stable dispersion of NPs using carbon nanotubes as model NPs. PF68-stabilized NP suspensions are stable for long durations and do not show signs of aggregation or settling during storage or after autoclaving. The polyethylene oxide blocks in PF68 provide steric hindrance between adjacent NPs leading to stable NP dispersions. Further, PF68 is biocompatible in nature and does not affect integrity of mitochondria, lysosomes, DNA, and nuclei. Also, PF68 neither induce free radical or cytokine production nor does it interfere with cellular uptake mechanisms. The results of the present study suggest that PF68-assisted dispersion of NPs produced suspensions, which are stable after autoclaving. Further, PF68 does not interfere with normal physiological functions suggesting its application in nanomedicine and nanotoxicity evaluation.

Structure and Function of Plasmodium falciparum malate dehydrogenase: Role of Critical Amino Acids in C-substrate Binding Procket

USDA-ARS?s Scientific Manuscript database

Malaria parasite thrives on anaerobic fermentation of glucose for energy. Earlier studies from our lab have demonstrated that a cytosolic malate dehydrogenase (PfMDH) with striking similarity to lactate dehydrogenase (PfLDH) might complement PfLDH function in Plasmodium falciparum. The N-terminal g...

Protective effects of pseudoginsenoside-F11 on methamphetamine-induced neurotoxicity in mice.

PubMed

Wu, Chun Fu; Liu, Yan Li; Song, Ming; Liu, Wen; Wang, Jin Hui; Li, Xian; Yang, Jing Yu

2003-08-01

In the present study, pseudoginsenoside-F(11) (PF(11)), a saponin that existed in American ginseng, was studied on its protective effect on methamphetamine (MA)-induced behavioral and neurochemical toxicities in mice. MA was intraperitoneally administered at the dose of 10 mg/kg four times at 2-h intervals, and PF(11) was orally administered at the doses of 4 and 8 mg/kg two times at 4-h intervals, 60 min prior to MA administration. The results showed that PF(11) did not significantly influence, but greatly ameliorated, the anxiety-like behavior induced by MA in the light-dark box task. In the forced swimming task, PF(11) significantly shortened the prolonged immobility time induced by MA. In the appetitively motivated T-maze task, PF(11) greatly shortened MA-induced prolonged latency and decreased the error counts. Similar results were also observed in the Morris water maze task. PF(11) significantly shortened the escape latency prolonged by MA. There were significant decreases in the contents of dopamine (DA), 3,4-dihydroxyphenacetic acid (DOPAC), homovanillic acid (HVA), and 5-hydroxyindoacetic acid (5-HIAA) in the brain of MA-treated mice. PF(11) could partially, but significantly, antagonize MA-induced decreases of DA. The above results demonstrate that PF(11) is effective in protection of MA-induced neurotoxicity and also suggest that natural products, such as ginseng, might be potential candidates for the prevention and treatment of the neurological disorders induced by MA abuse.

Metabolic programming effects initiated in the suckling period predisposing for adult-onset obesity cannot be reversed by calorie restriction.

PubMed

Srinivasan, Malathi; Mahmood, Saleh; Patel, Mulchand S

2013-03-01

Neonatal rats reared on high-carbohydrate (HC) milk formula developed chronic hyperinsulinemia and adult-onset obesity due to programming of islets and the hypothalamic energy circuitry. In this study, calorie restriction by pair-feeding was imposed on HC male rats (HC/PF) to normalize food intake similar to that of mother-fed (MF) rats from weaning until postnatal day 140. A group of HC/PF rats was switched over to ad libitum feeding (HC/PF/AL) from days 90 to 140. Pair-feeding reduced body weight gains and serum insulin and leptin levels in HC/PF rats compared with HC rats, but these parameters were restored to HC levels in the HC/PF/AL rats after ad libitum feeding. Interestingly, the heightened insulin secretory response of isolated islets from adult HC/PF and HC/PF/ AL rats to glucose, acetylcholine, and oxymetazoline were not significantly different from the responses of islets from HC rats. Similarly, the expression of neuropeptide Y and proopiomelanocortin in the hypothalamus was not significantly different among HC, HC/PF, and HC/PF/AL rats. Expression of the leptin receptor in the hypothalami from the HC, HC/PF, and HC/PF/AL rats mirrored that of serum leptin, whereas suppressor of cytokine signaling 3 (Socs3) expression remained high in these three groups. The results indicate that, although calorie restriction resulted in reduction in body weight gain and normalized the serum hormonal pattern, the programed predisposition for the hypersecretory capacity of islets and the hypothalamic hyperphagic response in the HC rats could not be permanently overcome by the pair-feeding imposed on HC rats.

The effects of 18β-glycyrrhetinic acid and glycyrrhizin on intestinal absorption of paeoniflorin using the everted rat gut sac model.

PubMed

He, Rui; Xu, Yongsong; Peng, Jingjing; Ma, Tingting; Li, Jing; Gong, Muxin

2017-01-01

Paeoniflorin (PF), the main active component of Shaoyao-Gancao-tang, possesses significantly antinociceptive effects and many other pharmacological activities. However, its poor intestinal absorption results in low bioavailability. Therefore, enhancing PF absorption plays a vital role in exerting its therapeutic effect. Shaoyao combined with Gancao exhibited a synergistic effect. The enhancement of PF absorption through the interaction of its constituents in intestinal absorption would be greatly implicated. The present study aimed at investigating the effects of glycyrrhizin, the main constituent of Gancao, and its main metabolite, 18β-glycyrrhetinic acid (18β-GA), on the intestinal absorptive behavior of PF, and the role of P-glycoprotein (P-gp) in PF absorption using the in vitro everted rat gut sac model. The results demonstrated that 1 mM of 18β-GA significantly increased PF absorption in both the jejunum and the ileum, while 100 μM of 18β-GA only promoted the ileum absorption and had no obvious effect on the jejunum absorption. The effect of glycyrrhizin on intestinal PF absorption was related to concentrations. One mM of glycyrrhizin significantly increased PF absorption in the jejunum after 45 min and in the ileum after 90 min. But 100 μM of glycyrrhizin had an inhibitory effect in the jejunum and no effect in the ileum before 60 min. Moreover, verapamil, the well-known P-gp inhibitor, could significantly enhance the PF absorption. In conclusion, the influence of 18β-GA and glycyrrhizin on the PF absorption was related to concentrations and intestinal segments. This might be involved in the intervention of efflux transport of PF mediated by intestinal P-gp.

Multi-omics Based Identification of Specific Biochemical Changes Associated With PfKelch13-Mutant Artemisinin-Resistant Plasmodium falciparum.

PubMed

Siddiqui, Ghizal; Srivastava, Anubhav; Russell, Adrian S; Creek, Darren J

2017-05-01

The emergence of artemisinin resistance in the malaria parasite Plasmodium falciparum poses a major threat to the control and elimination of malaria. Certain point mutations in the propeller domain of PfKelch13 are associated with resistance, but PfKelch13 mutations do not always result in clinical resistance. The underlying mechanisms associated with artemisinin resistance are poorly understood, and the impact of PfKelch13 mutations on cellular biochemistry is not defined. This study aimed to identify global biochemical differences between PfKelch13-mutant artemisinin-resistant and -sensitive strains of P. falciparum by combining liquid chromatography-mass spectrometry (LC-MS)-based proteomics, peptidomics, and metabolomics. Proteomics analysis found both PfKelch13 mutations examined to be specifically associated with decreased abundance of PfKelch13 protein. Metabolomics analysis demonstrated accumulation of glutathione and its precursor, gamma-glutamylcysteine, and significant depletion of 1 other putative metabolite in resistant strains. Peptidomics analysis revealed lower abundance of several endogenous peptides derived from hemoglobin (HBα and HBβ) in the artemisinin-resistant strains. PfKelch13 mutations associated with artemisinin resistance lead to decreased abundance of PfKelch13 protein, decreased hemoglobin digestion, and enhanced glutathione production. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

Antibodies associated with heparin-induced thrombocytopenia (HIT) inhibit activated protein C generation: new insights into the prothrombotic nature of HIT.

PubMed

Kowalska, M Anna; Krishnaswamy, Sriram; Rauova, Lubica; Zhai, Li; Hayes, Vincent; Amirikian, Karine; Esko, Jeffrey D; Bougie, Daniel W; Aster, Richard H; Cines, Douglas B; Poncz, Mortimer

2011-09-08

Heparin-induced thrombocytopenia (HIT) is caused by antibodies that recognize complexes between platelet factor 4 (PF4) and heparin or glycosaminoglycan side chains. These antibodies can lead to a limb- and life-threatening prothrombotic state. We now show that HIT antibodies are able to inhibit generation of activated protein C (aPC) by thrombin/thrombomodulin (IIa/TM) in the presence of PF4. Tetrameric PF4 potentiates aPC generation by formation of complexes with chondroitin sulfate (CS) on TM. Formation of these complexes occurs at a specific molar ratio of PF4 to glycosaminoglycan. This observation and the finding that the effect of heparin on aPC generation depends on the concentration of PF4 suggest similarity between PF4/CS complexes and those that bind HIT antibodies. HIT antibodies reduced the ability of PF4 to augment aPC formation. Cationic protamine sulfate, which forms similar complexes with heparin, also enhanced aPC generation, but its activity was not blocked by HIT antibodies. Our studies provide evidence that complexes formed between PF4 and TM's CS may play a physiologic role in potentiating aPC generation. Recognition of these complexes by HIT antibodies reverses the PF4-dependent enhancement in aPC generation and may contribute to the prothrombotic nature of HIT.

Analysis of the interactome of the Ser/Thr Protein Phosphatase type 1 in Plasmodium falciparum.

PubMed

Hollin, Thomas; De Witte, Caroline; Lenne, Astrid; Pierrot, Christine; Khalife, Jamal

2016-03-17

Protein Phosphatase 1 (PP1) is an enzyme essential to cell viability in the malaria parasite Plasmodium falciparum (Pf). The activity of PP1 is regulated by the binding of regulatory subunits, of which there are up to 200 in humans, but only 3 have been so far reported for the parasite. To better understand the P. falciparum PP1 (PfPP1) regulatory network, we here report the use of three strategies to characterize the PfPP1 interactome: co-affinity purified proteins identified by mass spectrometry, yeast two-hybrid (Y2H) screening and in silico analysis of the P. falciparum predicted proteome. Co-affinity purification followed by MS analysis identified 6 PfPP1 interacting proteins (Pips) of which 3 contained the RVxF consensus binding, 2 with a Fxx[RK]x[RK] motif, also shown to be a PP1 binding motif and one with both binding motifs. The Y2H screens identified 134 proteins of which 30 present the RVxF binding motif and 20 have the Fxx[RK]x[RK] binding motif. The in silico screen of the Pf predicted proteome using a consensus RVxF motif as template revealed the presence of 55 potential Pips. As further demonstration, 35 candidate proteins were validated as PfPP1 interacting proteins in an ELISA-based assay. To the best of our knowledge, this is the first study on PfPP1 interactome. The data reports several conserved PP1 interacting proteins as well as a high number of specific interactors to PfPP1. Their analysis indicates a high diversity of biological functions for PP1 in Plasmodium. Based on the present data and on an earlier study of the Pf interactome, a potential implication of Pips in protein folding/proteolysis, transcription and pathogenicity networks is proposed. The present work provides a starting point for further studies on the structural basis of these interactions and their functions in P. falciparum.

Attenuation of ketamine-induced impairment in verbal learning and memory in healthy volunteers by the AMPA receptor potentiator PF-04958242.

PubMed

Ranganathan, M; DeMartinis, N; Huguenel, B; Gaudreault, F; Bednar, M M; Shaffer, C L; Gupta, S; Cahill, J; Sherif, M A; Mancuso, J; Zumpano, L; D'Souza, D C

2017-11-01

There is a need to develop treatments for cognitive impairment associated with schizophrenia (CIAS). The significant role played by N-methyl-d-aspartate receptors (NMDARs) in both the pathophysiology of schizophrenia and in neuronal plasticity suggests that facilitation of NMDAR function might ameliorate CIAS. One strategy to correct NMDAR hypofunction is to stimulate α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs) as AMPAR and NMDAR functioning are coupled and interdependent. In rats and nonhuman primates (NHP), AMPAR potentiators reduce spatial working memory deficits caused by the nonselective NMDAR antagonist ketamine. The current study assessed whether the AMPAR potentiator PF-04958242 would attenuate ketamine-induced deficits in verbal learning and memory in humans. Healthy male subjects (n=29) participated in two randomized treatment periods of daily placebo or PF-04958242 for 5 days separated by a washout period. On day 5 of each treatment period, subjects underwent a ketamine infusion for 75 min during which the effects of PF-04958242/placebo were assessed on ketamine-induced: (1) impairments in verbal learning and recall measured by the Hopkins Verbal Learning Test; (2) impairments in working memory on a CogState battery; and (3) psychotomimetic effects measured by the Positive and Negative Syndrome Scale and Clinician-Administered Dissociative Symptoms Scale. PF-04958242 significantly reduced ketamine-induced impairments in immediate recall and the 2-Back and spatial working memory tasks (CogState Battery), without significantly attenuating ketamine-induced psychotomimetic effects. There were no pharmacokinetic interactions between PF-04958242 and ketamine. Furthermore, PF-04958242 was well tolerated. 'High-impact' AMPAR potentiators like PF-04958242 may have a role in the treatment of the cognitive symptoms, but not the positive or negative symptoms, associated with schizophrenia. The excellent concordance between the preclinical (rat, NHP) and human studies with PF-04958242, and in silico modeling of AMPAR-NMDAR interactions in the hippocampus, highlights the translational value of this study.

Characterization of Plasmodium falciparum Calcium-dependent Protein Kinase 1 (PfCDPK1) and Its Role in Microneme Secretion during Erythrocyte Invasion*

PubMed Central

Bansal, Abhisheka; Singh, Shailja; More, Kunal R.; Hans, Dhiraj; Nangalia, Kuldeep; Yogavel, Manickam; Sharma, Amit; Chitnis, Chetan E.

2013-01-01

Calcium-dependent protein kinases (CDPKs) play important roles in the life cycle of Plasmodium falciparum and other apicomplexan parasites. CDPKs commonly have an N-terminal kinase domain (KD) and a C-terminal calmodulin-like domain (CamLD) with calcium-binding EF hands. The KD and CamLD are separated by a junction domain (JD). Previous studies on Plasmodium and Toxoplasma CDPKs suggest a role for the JD and CamLD in the regulation of kinase activity. Here, we provide direct evidence for the binding of the CamLD with the P3 region (Leu356 to Thr370) of the JD in the presence of calcium (Ca2+). Moreover, site-directed mutagenesis of conserved hydrophobic residues in the JD (F363A/I364A, L356A, and F350A) abrogates functional activity of PfCDPK1, demonstrating the importance of these residues in PfCDPK1 function. Modeling studies suggest that these residues play a role in interaction of the CamLD with the JD. The P3 peptide, which specifically inhibits the functional activity of PfCDPK1, blocks microneme discharge and erythrocyte invasion by P. falciparum merozoites. Purfalcamine, a previously identified specific inhibitor of PfCDPK1, also inhibits microneme discharge and erythrocyte invasion, confirming a role for PfCDPK1 in this process. These studies validate PfCDPK1 as a target for drug development and demonstrate that interfering with its mechanistic regulation may provide a novel approach to design-specific PfCDPK1 inhibitors that limit blood stage parasite growth and clear malaria parasite infections. PMID:23204525

Pleural Fluid Adenosine Deaminase (Pfada) in the Diagnosis of Tuberculous Effusions in a Low Incidence Population

PubMed Central

Arnold, David T.; Bhatnagar, Rahul; Fairbanks, Lynette D.; Zahan-Evans, Natalie; Clive, Amelia O.; Morley, Anna J.; Medford, Andrew R. L.; Maskell, Nicholas A.

2015-01-01

Introduction Previous studies have assessed the diagnostic ability of pleural fluid adenosine deaminase (pfADA) in detecting tuberculous pleural effusions, with good specificity and sensitivity reported. However, in North Western Europe pfADA is not routinely used in the investigation of a patient with an undiagnosed pleural effusion, mainly due to a lack of evidence as to its utility in populations with low mycobacterium tuberculosis (mTB) incidence. Methods Patients presenting with an undiagnosed pleural effusion to a tertiary pleural centre in South-West England over a 3 year period, were prospectively recruited to a pleural biomarker study. Pleural fluid from consecutive patients with robust 12-month follow up data and confirmed diagnosis were sent for pfADA analysis. Results Of 338 patients enrolled, 7 had confirmed tuberculous pleural effusion (2%). All mTB effusions were lymphocyte predominant with a median pfADA of 72.0 IU/L (range- 26.7 to 91.5) compared to a population median of 12.0 IU/L (range- 0.3 to 568.4). The optimal pfADA cut off was 35 IU/L, which had a negative predictive value (NPV) of 99.7% (95% CI; 98.2-99.9%) for the exclusion of mTB, and sensitivity of 85.7% (95% CI; 42.2-97.6%) with an area under the curve of 0.88 (95% CI; 0.732–1.000). Discussion This is the first study examining the diagnostic utility of pfADA in a low mTB incidence area. The chance of an effusion with a pfADA under 35 IU/L being of tuberculous aetiology was negligible. A pfADA of over 35 IU/L in lymphocyte-predominant pleural fluid gives a strong suspicion of mTB. PMID:25647479

Trophic response of the intestinal mucosa to inflammation in rats injected with turpentine: a study using pair-fed controls.

PubMed

Zarrabian, S; Fromont, G; Tran, T; Macry, J; Biou, D; Mendy, F; Roger, L; Cezard, J P

1999-10-01

The effects of restricted food intake and acute inflammation on the small bowel were studied, Wistar rats (250 g) were given subcutaneous injections of turpentine (TR) and compared to two control groups, at 18, 42 and 66 h. One was fed ad libitum (C), the other was pair fed (PF) with TR. The TR and PF rats showed hypoplasia of the jejunal mucosa with decreased protein and DNA contents at 42 h and 66 h. The hypoplasia resulted in a reduced villus height that was significantly different from the controls at 66 h (C: 468 +/- 17, TR[66] : 376 +/- 20, PF[66] : 258 +/- 2.9 microm, P<0.001). This decrease in villus height was significantly greater in the PF rats than in the TR rats at 66 h. The crypt height/villus height (C/V) ratio in the PF rats was greater than in the TR group at all times. However, the protein and DNA contents in the TR group were significantly higher than in the PF group at 42 h and 66 h (TR/PF[42] : 29.5 +/- 1.9 vs 20.5 +/- 2.0, P< 0.001, [66]: 25.8 +/- 2.0 vs 16.6 +/- 1.3 mg/10 cm, P,< 0.001). Disaccharidase activities (sucrase and glucoamylase) per 10 cm jejunum at 66 h were significantly lower in the PF group than in the control and TR groups (sucrase mU/10cm[66] C : 3090 +/- 144, TR 2683 +/- 479, PF 1969 +/- 144, P,< 0.001; glucoamylase mU/10 cm[66] 237 +/- 25, TR 169 +/- 40, PF 123 +/- 5, P< 0.01). The N-aminopeptidase patterns in the TR and PF groups were similar. These data suggest that dietary restriction during acute inflammation is the main factor causing hypoplasia of the jejunal mucosa. However, acute inflammation has a trophic effect on the morphological and function of the mucosa. This effect is probably due to inflammatory mediators, whose synthesis is stimulated by turpentine.

Plantar fascia anatomy and its relationship with Achilles tendon and paratenon.

PubMed

Stecco, Carla; Corradin, Marco; Macchi, Veronica; Morra, Aldo; Porzionato, Andrea; Biz, Carlo; De Caro, Raffaele

2013-12-01

Although the plantar fascia (PF) has been studied quite well from a biomechanical viewpoint, its microscopic properties have been overlooked: nothing is known about its content of elastic fibers, the features of the extracellular matrix or the extent of innervation. From a functional and clinical standpoint, the PF is often correlated with the triceps surae muscle, but the anatomical grounds for this link are not clear. The aim of this work was to focus on the PF macroscopic and microscopic properties and study how Achilles tendon diseases might affect it. Twelve feet from unembalmed human cadavers were dissected to isolate the PF. Specimens from each PF were tested with various histological and immunohistochemical stains. In a second stage, 52 magnetic resonance images (MRI) obtained from patients complaining of aspecific ankle or foot pain were analyzed, dividing the cases into two groups based on the presence or absence of signs of degeneration and/or inflammation of the Achilles tendon. The thickness of PF and paratenon was assessed in the two groups and statistical analyses were conducted. The PF is a tissue firmly joined to plantar muscles and skin. Analyzing its possible connections to the sural structures showed that this fascia is more closely connected to the paratenon of Achilles tendon than to the Achilles tendon, through the periosteum of the heel. The PF extended medially and laterally, continuing into the deep fasciae enveloping the abductor hallucis and abductor digiti minimi muscles, respectively. The PF was rich in hyaluronan, probably produced by fibroblastic-like cells described as 'fasciacytes'. Nerve endings and Pacini and Ruffini corpuscles were present, particularly in the medial and lateral portions, and on the surface of the muscles, suggesting a role for the PF in the proprioception of foot. In the radiological study, 27 of the 52 MRI showed signs of Achilles tendon inflammation and/or degeneration, and the PF was 3.43 ± 0.48 mm thick (99%CI and SD = 0.95), as opposed to 2.09 ± 0.24 mm (99%CI, SD = 0.47) in the patients in which the MRI revealed no Achilles tendon diseases; this difference in thickness of 1.29 ± 0.57 mm (99%CI) was statistically significant (P < 0.001). In the group of 27/52 patients with tendinopathies, the PF was more than 4.5 mm thick in 5, i.e. they exceeded the threshold for a diagnosis of plantar fasciitis. None of the other 25/52 paitents had a PF more than 4 mm thick. There was a statistically significant correlation between the thicknesses of the PF and the paratenon. These findings suggest that the plantar fascia has a role not only in supporting the longitudinal arch of the foot, but also in its proprioception and peripheral motor coordination. Its relationship with the paratenon of the Achilles tendon is consistent with the idea of triceps surae structures being involved in the PF pathology, so their rehabilitation can be considered appropriate. Finally, the high concentration of hyaluronan in the PF points to the feasibility of using hyaluronan injections in the fascia to treat plantar fasciitis. © 2013 Anatomical Society.

Recognition and Binding of the PF2 Lectin to α-Amylase From Zabrotes subfasciatus (Coleoptera:Bruchidae) Larval Midgut

PubMed Central

Lagarda-Diaz, I.; Geiser, D.; Guzman-Partida, A.M.; Winzerling, J.; Vazquez-Moreno, L.

2014-01-01

Abstract Amylases are an important family of enzymes involved in insect carbohydrate metabolism that are required for the survival of insect larvae. For this reason, enzymes from starch-dependent insects are targets for insecticidal control. PF2 ( Olneya tesota ) is a lectin that is toxic to Zabrotes subfasciatus (Coleoptera: Bruchidae) larvae. In this study, we evaluated recognition of the PF2 lectin to α-amylases from Z. subfasciatus midgut and the effect of PF2 on α-amylase activity. PF2 caused a decrease of total amylase activity in vitro. Subsequently, several α-amylase isoforms were isolated from insect midgut tissues using ion exchange chromatography. Three enzyme isoforms were verified by an in-gel assay for amylase activity; however, only one isoform was recognized by antiamylase serum and PF2. The identity of this Z. subfasciatus α-amylase was confirmed by liquid chromatography−tandem mass spectrometry. The findings strongly suggest that a glycosylated α-amylase isoform from larval Z. subfasciatus midgut interacts with PF2, which interferes with starch digestion. PMID:25528751

SAM domain-dependent activity of PfTKL3, an essential tyrosine kinase-like kinase of the human malaria parasite Plasmodium falciparum.

PubMed

Abdi, Abdirahman; Eschenlauer, Sylvain; Reininger, Luc; Doerig, Christian

2010-10-01

Over the last decade, several protein kinases inhibitors have reached the market for cancer chemotherapy. The kinomes of pathogens represent potentially attractive targets in infectious diseases. The functions of the majority of protein kinases of Plasmodium falciparum, the parasitic protist responsible for the most virulent form of human malaria, remain unknown. Here we present a thorough characterisation of PfTKL3 (PF13_0258), an enzyme that belongs to the tyrosine kinase-like kinase (TKL) group. We demonstrate by reverse genetics that PfTKL3 is essential for asexual parasite proliferation in human erythrocytes. PfTKL3 is expressed in both asexual and gametocytes stages, and in the latter the protein co-localises with cytoskeleton microtubules. Recombinant PfTKL3 displays in vitro autophosphorylation activity and is able to phosphorylate exogenous substrates, and both activities are dramatically dependent on the presence of an N-terminal "sterile alpha-motif" domain. This study identifies PfTKL3 as a validated drug target amenable to high-throughput screening.

Improving sound absorption property of polyurethane foams doped with natural fiber

NASA Astrophysics Data System (ADS)

Azahari, M. Shafiq M.; Rus, Anika Zafiah M.; Taufiq Zaliran, M.; Kormin, Shaharuddin

2017-08-01

This study investigates the acoustics behavior of wood fibre filler of Red Meranti - filled polyurethane foam as a sound absorbing material. Three different thicknesses have been selected which is 10 mm, 20 mm and 30 mm. By choosing percentage loading of Red Meranti (RM) wood fibre of 5%, 10%, 15% and 20% added with polymer foam is namely as polymer foam (PF) composites of PF5%, PF10%, PF15% and PF20%. The sound absorption coefficient (α) and pore structure of the foam samples have been examined by using Impedance Tube test and Scanning Electron Microscopy (SEM). The results revealed that the highest thickness of highest filler loading (PF20%) gives higher sound absorption coefficient (α). The absorption frequency level is observed at 0.9922 and 0.99889 which contributed from low and high frequency absorption level respectively. The smallest pores size structure was observed with highest filler loading of PF. The higher the thickness and the higher the percentage loading of wood filler gives smaller pore structure, consequently, increased the sound absorption coefficient level.

Dose-Related Target Occupancy and Effects on Circuitry, Behavior, and Neuroplasticity of the Glycine Transporter-1 Inhibitor PF-03463275 in Healthy and Schizophrenia Subjects.

PubMed

D'Souza, Deepak Cyril; Carson, Richard E; Driesen, Naomi; Johannesen, Jason; Ranganathan, Mohini; Krystal, John H

2018-01-31

Glycine transporter-1 (GlyT1) inhibitors may ameliorate cognitive impairments associated with schizophrenia. The dose-related occupancy and target engagement of the GlyT1 inhibitor PF-03463275 were studied to inform optimal dose selection for a clinical trial for cognitive impairments associated with schizophrenia. In substudy 1, the effects of PF-03463275 (10, 20, and 40 mg twice a day) on occupancy of GlyT1 were tested using positron emission tomography and 18 F-MK-6577, and visual long-term potentiation (LTP) in schizophrenia patients (SZs) and healthy control subjects. Furthermore, the capacity of PF-03463275 to attenuate ketamine-induced disruption of working memory-related activation of a "working memory" circuit was tested only in healthy control subjects using functional magnetic resonance imaging. Subsequently, the effects of PF-03463275 (60 mg twice a day) on occupancy of GlyT1 and long-term potentiation were examined only in SZs (substudy 2). PF-03463275 at 10, 20, 40, and 60 mg twice a day produced ∼44%, 61%, 76%, and 83% GlyT1 occupancy, respectively, in SZs with higher ligand binding to GlyT1 in subcortical versus cortical regions. PF-03463275 did not attenuate any ketamine-induced effects but did improve working memory accuracy in healthy control subjects. PF-03463275 increased long-term potentiation only in SZs with peak effects at 40 mg twice a day (∼75% GlyT1 occupancy) and with a profile suggestive of an inverted U dose response. PF-03463275 was well-tolerated. The dose-related GlyT1 occupancy of PF-03463275 is linear. While PF-03463275 did not show evidence of facilitating N-methyl-D-aspartate receptor function in the ketamine assay, it enhanced neuroplasticity in SZs. These findings provide support for a clinical trial to test the ability of PF-03463275 to enhance cognitive remediation toward addressing cognitive impairments associated with schizophrenia. Published by Elsevier Inc.

Cyto-, myelo- and chemoarchitecture of the prefrontal cortex of the Cebus monkey

PubMed Central

2011-01-01

Background According to several lines of evidence, the great expansion observed in the primate prefrontal cortex (PfC) was accompanied by the emergence of new cortical areas during phylogenetic development. As a consequence, the structural heterogeneity noted in this region of the primate frontal lobe has been associated with diverse behavioral and cognitive functions described in human and non-human primates. A substantial part of this evidence was obtained using Old World monkeys as experimental model; while the PfC of New World monkeys has been poorly studied. In this study, the architecture of the PfC in five capuchin monkeys (Cebus apella) was analyzed based on four different architectonic tools, Nissl and myelin staining, histochemistry using the lectin Wisteria floribunda agglutinin and immunohistochemistry using SMI-32 antibody. Results Twenty-two architectonic areas in the Cebus PfC were distinguished: areas 8v, 8d, 9d, 12l, 45, 46v, 46d, 46vr and 46dr in the lateral PfC; areas 11l, 11m, 12o, 13l, 13m, 13i, 14r and 14c in the orbitofrontal cortex, with areas 14r and 14c occupying the ventromedial corner; areas 32r, 32c, 25 and 9m in the medial PfC, and area 10 in the frontal pole. This number is significantly higher than the four cytoarchitectonic areas previously recognized in the same species. However, the number and distribution of these areas in Cebus were to a large extent similar to those described in Old World monkeys PfC in more recent studies. Conclusions The present parcellation of the Cebus PfC considerably modifies the scheme initially proposed for this species but is in line with previous studies on Old World monkeys. Thus, it was observed that the remarkable anatomical similarity between the brains of genera Macaca and Cebus may extend to architectonic aspects. Since monkeys of both genera evolved independently over a long period of time facing different environmental pressures, the similarities in the architectonic maps of PfC in both genera are issues of interest. However, additional data about the connectivity and function of the Cebus PfC are necessary to evaluate the possibility of potential homologies or parallelisms. PMID:21232115

The impact of combined pulmonary fibrosis and chronic obstructive pulmonary disease on long-term survival after lung cancer surgery.

PubMed

Sekine, Yasuo; Sakairi, Yuichi; Yoshino, Mitsuru; Koh, Eitetsu; Hata, Atsushi; Suzuki, Hidemi; Yoshino, Ichiro

2014-06-01

The purpose of this study was to determine the impact of pulmonary fibrosis (PF) on postoperative complications and on long-term survival after surgical resection in lung cancer patients with chronic obstructive pulmonary disease (COPD). A retrospective chart review was conducted of 380 patients with COPD who had undergone pulmonary resection for lung cancer at the University Hospital between 1990 and 2005. The definition of COPD was a preoperative forced expiratory volume in 1 second/forced vital capacity (FEV1/FVC) ratio of less than 70%; PF was defined as obvious bilateral fibrous change in the lower lung fields, confirmed by computed tomography. PF was present in 41 patients (10.8%) with COPD; the remaining 339 patients (89.2%) did not have PF. The preoperative FVC/FEV1 was significantly lower in the group of patients with PF than in the group without (p < 0.05). Acute lung injury and home oxygen therapy were significantly more common in the PF group; however, the 30-day mortality was similar between the groups. The cumulative survival at 3 and 5 years was 53.6 and 36.9%, respectively, in the PF group and 71.4 and 66.1%, respectively, in the non-PF group (p = 0.0009). Increased age, decreased body mass index, advanced pathologic stage, and the existence of PF were identified as independent risk factors for decreased survival. PF is a risk factor for decreased survival after surgical treatment in lung cancer patients with COPD. Georg Thieme Verlag KG Stuttgart · New York.

Plantar fasciitis

PubMed Central

Tahririan, Mohammad Ali; Motififard, Mehdi; Tahmasebi, Mohammad Naghi; Siavashi, Babak

2012-01-01

Heel pain, mostly caused by plantar fasciitis (PF), is a common complaint of many patients who requiring professional orthopedic care and are mostly suffering from chronic pain beneath their heels. The present article reviews studies done by preeminent practitioners related to the anatomy of plantar fasciitis and their histo-pathological features, factors associated with PF, clinical features, imaging studies, differential diagnoses, and diverse treatment modalities for treatment of PF, with special emphasis on non-surgical treatment. Anti-inflammatory agents, plantar stretching, and orthosis proved to have highest priority; corticosteroid injection, night splints and extracorporeal shock wave therapy were of next priority, in patients with PF. In patients resistant to the mentioned treatments surgical intervention should be considered. PMID:23798950

A 2-amino quinoline, 5-(3-(2-(7-chloroquinolin-2-yl)ethenyl)phenyl)-8-dimethylcarbamyl-4,6-dithiaoctanoic acid, interacts with PfMDR1 and inhibits its drug transport in Plasmodium falciparum.

PubMed

Edaye, Sonia; Reiling, Sarah J; Leimanis, Mara L; Wunderlich, Juliane; Rohrbach, Petra; Georges, Elias

2014-06-01

Malaria is a major disease in the tropics where chemotherapy remains the main mode of treatment and as such the rise and spread of drug-resistant malaria can lead to human tragedy. Two membrane transport proteins, PfMDR1 (Plasmodium falciparum multidrug resistance protein 1) and PfCRT (P. falciparum chloroquine resistance transporter), have been shown to cause resistance to several antimalarials. Both PfMDR1 and PfCRT are localized to the digestive vacuolar membrane and appear to regulate the transport of drugs and physiological metabolites. In this study we have used MK571, a 2-amino quinoline, to explore its interaction with PfMDR1 and PfCRT in chloroquine-sensitive and -resistant strains of P. falciparum. Our results show that chloroquine-resistant strains (e.g., K1, Dd2, and 7G8) are consistently more sensitive to MK571 than chloroquine-sensitive strains (e.g., 3D7, 106/1 and D10). This association, however, was not maintained with the chloroquine-resistant strain FCB which IC50 value was similar to chloroquine-sensitive strains. Moreover, the susceptibility of chloroquine-sensitive and -resistant strains to MK571 does not correlate with mutated PfCRT, nor is it reversible with verapamil; but correlates with mutations in PfMDR1. Furthermore, MK571 appears to target the parasite's digestive vacuole (DV), as demonstrated by the ability of MK571 to: (1) block the accumulation of the fluorescent dye Fluo-4 AM, a PfMDR1 substrate, into the digestive vacuole; (2) reduce the transvacuolar pH gradient; and (3) inhibit the formation of β-hematin in vitro. Moreover, the presence of non-toxic concentrations of MK571 sensitized both chloroquine-sensitive and -resistant parasites to mefloquine and halofantrine, likely by competing against PfMDR1-mediated sequestering of the drugs into the DV compartment and away from the drugs' cytosolic targets. Our data, nevertheless, found only a minimal decrease in MK571 IC50 value in FCB parasite which second pfmdr1 copy was inactivated via gene disruption. Taken together, the findings of this study suggest that MK571 interacts with native and mutant PfMDR1 and modulates the import of drugs or solutes into the parasite's DV and, as such, MK571 may be a useful tool in the characterization of PfMDR1 drug interactions and substrate specificity. Copyright © 2014 Elsevier B.V. All rights reserved.

Controlled human malaria infection by intramuscular and direct venous inoculation of cryopreserved Plasmodium falciparum sporozoites in malaria-naïve volunteers: effect of injection volume and dose on infectivity rates.

PubMed

Gómez-Pérez, Gloria P; Legarda, Almudena; Muñoz, Jose; Sim, B Kim Lee; Ballester, María Rosa; Dobaño, Carlota; Moncunill, Gemma; Campo, Joseph J; Cisteró, Pau; Jimenez, Alfons; Barrios, Diana; Mordmüller, Benjamin; Pardos, Josefina; Navarro, Mireia; Zita, Cecilia Justino; Nhamuave, Carlos Arlindo; García-Basteiro, Alberto L; Sanz, Ariadna; Aldea, Marta; Manoj, Anita; Gunasekera, Anusha; Billingsley, Peter F; Aponte, John J; James, Eric R; Guinovart, Caterina; Antonijoan, Rosa M; Kremsner, Peter G; Hoffman, Stephen L; Alonso, Pedro L

2015-08-07

Controlled human malaria infection (CHMI) by mosquito bite is a powerful tool for evaluation of vaccines and drugs against Plasmodium falciparum malaria. However, only a small number of research centres have the facilities required to perform such studies. CHMI by needle and syringe could help to accelerate the development of anti-malaria interventions by enabling centres worldwide to employ CHMI. An open-label CHMI study was performed with aseptic, purified, cryopreserved P. falciparum sporozoites (PfSPZ Challenge) in 36 malaria naïve volunteers. In part A, the effect of the inoculation volume was assessed: 18 participants were injected intramuscularly (IM) with a dose of 2,500 PfSPZ divided into two injections of 10 µL (n = 6), 50 µL (n = 6) or 250 µL (n = 6), respectively. In part B, the injection volume that resulted in highest infectivity rates in part A (10 µL) was used to formulate IM doses of 25,000 PfSPZ (n = 6) and 75,000 PfSPZ (n = 6) divided into two 10-µL injections. Results from a parallel trial led to the decision to add a positive control group (n = 6), each volunteer receiving 3,200 PfSPZ in a single 500-µL injection by direct venous inoculation (DVI). Four/six participants in the 10-µL group, 1/6 in the 50-µL group and 2/6 in the 250-µL group developed parasitaemia. Geometric mean (GM) pre-patent periods were 13.9, 14.0 and 15.0 days, respectively. Six/six (100%) participants developed parasitaemia in the 25,000 and 75,000 PfSPZ IM and 3,200 PfSPZ DVI groups. GM pre-patent periods were 12.2, 11.4 and 11.4 days, respectively. Injection of PfSPZ Challenge was well tolerated and safe in all groups. IM injection of 75,000 PfSPZ and DVI injection of 3,200 PfSPZ resulted in infection rates and pre-patent periods comparable to the bite of five PfSPZ-infected mosquitoes. Remarkably, it required 23.4-fold more PfSPZ administered IM than DVI to achieve the same parasite kinetics. These results allow for translation of CHMI from research to routine use, and inoculation of PfSPZ by IM and DVI regimens. ClinicalTrials.gov NCT01771848.

Physical fitness and plasma leptin in women with recent gestational diabetes.

PubMed

Gar, C; Rottenkolber, M; Grallert, H; Banning, F; Freibothe, I; Sacco, V; Wichmann, C; Reif, S; Potzel, A; Dauber, V; Schendell, C; Sommer, N N; Wolfarth, B; Seissler, J; Lechner, A; Ferrari, U

2017-01-01

Low physical fitness (PF) is a risk factor for type 2 diabetes mellitus (T2D). Women with a history of gestational diabetes (GDM) are at risk for T2D at a young age, but the role of PF in this population is not clear. PF has also been found to correlate inversely with plasma leptin in previous studies. Here, we examine whether women who had GDM have lower PF than women after a normoglycemic pregnancy and, second, whether PF is associated with plasma leptin, independently of body fat mass. Cross-sectional analysis of 236 participants in the PPSDiab Study (cohort study of women 3-16 months after delivery, 152 after gestational diabetes (pGDM), 84 after normoglycemic pregnancy (control subjects); consecutively recruited 2011-16); medical history, physical examination with bioelectrical impedance analysis (BIA), whole body magnetic resonance imaging (MRI) (n = 154), 5-point oral glucose tolerance test, cardiopulmonary exercise testing, clinical chemistry including fasting plasma leptin; statistical analysis with Mann-Whitney U and t -test, Spearman correlation coefficient, multiple linear regression. Women pGDM had lower maximally achieved oxygen uptake (VO2peak/kg: 25.7(21.3-29.9) vs. 30.0(26.6-34.1)ml/min/kg; total VO2peak: 1733(1552-2005) vs. 1970(1767-2238)ml/min; p<0.0001 for both), and maximum workload (122.5(105.5-136.5) vs. 141.0(128.5-159.5)W; p<0.0001). Fasting plasma leptin correlated inversely with PF (VO2peak/kg ρ = -0.72 p<0.0001; VO2peak ρ = -0.16 p = 0.015; max. load ρ = -0.35 p<0.0001). These associations remained significant with adjustment for body mass index, or for body fat mass (BIA and MRI). Women with a recent history of GDM were less fit than control subjects. Low PF may therefore contribute to the risk for T2D after GDM. This should be tested in intervention studies. Low PF also associated with increased leptin levels-independently of body fat. PF may therefore influence leptin levels and signaling. This hypothesis requires further investigation.

Focus is key: Panic-focused interpretations are associated with symptomatic improvement in panic-focused psychodynamic psychotherapy.

PubMed

Keefe, John R; Solomonov, Nili; Derubeis, Robert J; Phillips, Alexander C; Busch, Fredric N; Barber, Jacques P; Chambless, Dianne L; Milrod, Barbara L

2018-04-18

This study examines whether, in panic-focused psychodynamic psychotherapy (PFPP), interpretations of conflicts that underlie anxiety (panic-focused or PF-interpretations) are specifically associated with subsequent panic disorder (PD) symptom improvement, over and above the provision of non-symptom-focused interpretations. Technique use in Sessions 2 and 10 of a 24-session PFPP protocol was assessed for the 65 patients with complete outcome data randomized to PFPP in a two-site trial of psychotherapies for PD. Sessions were rated in 15-min segments for therapists' use of PF-interpretations, non-PF-interpretations, and PF-clarifications. Robust regressions were conducted to examine the relationship between these interventions and symptom change subsequent to the sampled session. Interpersonal problems were examined as a moderator of the relationship of PF-interpretations to symptom change. At Session 10, but not at Session 2, patients who received a higher degree of PF-interpretations experienced greater subsequent improvement in panic symptoms. Non-PF-interpretations were not predictive. Patients with more interpersonal distress benefitted particularly from the use of PF-interpretations at Session 10. By the middle phase of PFPP, panic-focused interpretations may drive subsequent improvements in panic symptoms, especially among patients with higher interpersonal distress. Interpretations of conflict absent a panic focus may not be especially helpful.

Elucidation of Transport Mechanism of Paeoniflorin and the Influence of Ligustilide, Senkyunolide I and Senkyunolide A on Paeoniflorin Transport through Mdck-Mdr1 Cells as Blood-Brain Barrier in Vitro Model.

PubMed

Hu, Peng-Yi; Liu, Dan; Zheng, Qin; Wu, Qing; Tang, Yu; Yang, Ming

2016-03-02

The objectives of the present investigation were to: (1) elucidate the transport mechanism of paeoniflorin (PF) across MDCK-MDR1 monolayers; and (2) evaluate the effect of ligustilide (LIG), senkyunolide I (SENI) and senkyunolide A (SENA) on the transport of PF through blood-brain barrier so as to explore the enhancement mechanism. Transport studies of PF were performed in both directions, from apical to basolateral side (A→B) and from basolateral to apical sides (B→A). Drug concentrations were analyzed by LC-MS/MS. PF showed relatively poor absorption in MDCK-MDR1 cells, apparent permeability coefficients (Papp) ranging from 0.587 × 10(-6) to 0.705 × 10(-6) cm/s. In vitro experiments showed that the transport of PF in both directions was concentration dependent and not saturable. The B→A/A→B permeability ER of PF was more than 2 in the MDCK-MDR1 cells, which indicated that the transport mechanism of PF might be passive diffusion as the dominating process with the active transportation mediated mechanism involved. The increased Papp of PF in A→B direction by EDTA-Na₂ suggested that PF was absorbed via the paracellular route. The P-gp inhibitor verapamil could significantly increase the transport of PF in A→B direction, and ER decreased from 2.210 to 0.690, which indicated that PF was P-gp substance. The transport of PF in A→B direction significantly increased when co-administrated with increasing concentrations of LIG, SENI and SENA. An increased cellular accumulation of Rho 123 and Western blot analysis indicated that LIG, SENI and SENA had increased the transport of PF in the BBB models attribute to down-regulate P-gp expression. A decrease in transepithelial electrical resistance (TEER) during the permeation experiment can be explained by the modulation and opening of the tight junctions caused by the permeation enhancer LIG, SENI and SENA.

Osthole Alleviates Bleomycin-Induced Pulmonary Fibrosis via Modulating Angiotensin-Converting Enzyme 2/Angiotensin-(1-7) Axis and Decreasing Inflammation Responses in Rats.

PubMed

Hao, Yuewen; Liu, Yan

2016-01-01

Studies have shown that angiotensin-converting enzyme 2 (ACE2) plays modulating roles in lung pathophysiology, including pulmonary fibrosis (PF) and acute lung injury. Pulmonary fibrosis is a common complication in these interstitial lung diseases, and PF always has a poor prognosis and short survival. To date, there are few promising methods for treating PF, and they are invariably accompanied by severe side effects. Recent studies have showed that the traditional Chinese herbal extract, osthole, had beneficial effects on lipopolysaccharide (LPS) induced acute lung injury (ALI) via an ACE2 pathway. Here we further investigated the protective effects of osthole on bleomycin induced pulmonary fibrosis and attempted to determine the underlying mechanism. PF mode rats were induced by bleomycin (BLM) and then subsequently administered osthole. Histopathological analyses were employed to identify PF changes. The results showed that BLM resulted in severe PF and diffuse lung inflammation, together with significant elevation of inflammatory factors and a marked increase in expression of angiotensin II (ANG II) and transforming growth factor-beta 1 (TGF-β1). ACE2 and angiotensin-(1-7) [ANG-(1-7)] were both greatly reduced after BLM administration. Meanwhile, osthole treatment attenuated BLM induced PF and inflammation, decreased the expression of these inflammatory mediators, ANG II, and TGF-β1, and reversed ACE2 and ANG-(1-7) production in rat lungs. We conclude that osthole may exert beneficial effects on BLM induced PF in rats, perhaps via modulating the ACE2/ANG-(1-7) axis and inhibiting lung inflammation pathways.

Validation of predicted patellofemoral mechanics in a finite element model of the healthy and cruciate-deficient knee.

PubMed

Ali, Azhar A; Shalhoub, Sami S; Cyr, Adam J; Fitzpatrick, Clare K; Maletsky, Lorin P; Rullkoetter, Paul J; Shelburne, Kevin B

2016-01-25

Healthy patellofemoral (PF) joint mechanics are critical to optimal function of the knee joint. Patellar maltracking may lead to large joint reaction loads and high stresses on the articular cartilage, increasing the risk of cartilage wear and the onset of osteoarthritis. While the mechanical sources of PF joint dysfunction are not well understood, links have been established between PF tracking and abnormal kinematics of the tibiofemoral (TF) joint, specifically following cruciate ligament injury and repair. The objective of this study was to create a validated finite element (FE) representation of the PF joint in order to predict PF kinematics and quadriceps force across healthy and pathological specimens. Measurements from a series of dynamic in-vitro cadaveric experiments were used to develop finite element models of the knee for three specimens. Specimens were loaded under intact, ACL-resected and both ACL and PCL-resected conditions. Finite element models of each specimen were constructed and calibrated to the outputs of the intact knee condition, and subsequently used to predict PF kinematics, contact mechanics, quadriceps force, patellar tendon moment arm and patellar tendon angle of the cruciate resected conditions. Model results for the intact and cruciate resected trials successfully matched experimental kinematics (avg. RMSE 4.0°, 3.1mm) and peak quadriceps forces (avg. difference 5.6%). Cruciate resections demonstrated either increased patellar tendon loads or increased joint reaction forces. The current study advances the standard for evaluation of PF mechanics through direct validation of cruciate-resected conditions including specimen-specific representations of PF anatomy. Copyright © 2015 Elsevier Ltd. All rights reserved.

Biopharmaceutical profile of pranoprofen-loaded PLGA nanoparticles containing hydrogels for ocular administration.

PubMed

Abrego, Guadalupe; Alvarado, Helen; Souto, Eliana B; Guevara, Bessy; Bellowa, Lyda Halbaut; Parra, Alexander; Calpena, Ana; Garcia, María Luisa

2015-09-01

Two optimized pranoprofen-loaded poly-l-lactic-co glycolic acid (PLGA) nanoparticles (PF-F1NPs; PF-F2NPs) have been developed and further dispersed into hydrogels for the production of semi-solid formulations intended for ocular administration. The optimized PF-NP suspensions were dispersed in freshly prepared carbomer hydrogels (HG_PF-F1NPs and HG_PF-F2NPs) or in hydrogels containing 1% azone (HG_PF-F1NPs-Azone and HG_PF-F2NPs-Azone) in order to improve the ocular biopharmaceutical profile of the selected non-steroidal anti-inflammatory drug (NSAID), by prolonging the contact of the pranoprofen with the eye, increasing the drug retention in the organ and enhancing its anti-inflammatory and analgesic efficiency. Carbomer 934 has been selected as gel-forming polymer. The hydrogel formulations with or without azone showed a non-Newtonian behavior and adequate physicochemical properties for ocular instillation. The release study of pranoprofen from the semi-solid formulations exhibited a sustained release behavior. The results obtained from ex vivo corneal permeation and in vivo anti-inflammatory efficacy studies suggest that the ocular application of the hydrogels containing azone was more effective over the azone-free formulations in the treatment of edema on the ocular surface. No signs of ocular irritancy have been detected for the produced hydrogels. Copyright © 2015 Elsevier B.V. All rights reserved.

The Colletotrichum boninense species complex

PubMed Central

Damm, U.; Cannon, P.F.; Woudenberg, J.H.C.; Johnston, P.R.; Weir, B.S.; Tan, Y.P.; Shivas, R.G.; Crous, P.W.

2012-01-01

Although only recently described, Colletotrichum boninense is well established in literature as an anthracnose pathogen or endophyte of a diverse range of host plants worldwide. It is especially prominent on members of Amaryllidaceae, Orchidaceae, Proteaceae and Solanaceae. Reports from literature and preliminary studies using ITS sequence data indicated that C. boninense represents a species complex. A multilocus molecular phylogenetic analysis (ITS, ACT, TUB2, CHS-1, GAPDH, HIS3, CAL) of 86 strains previously identified as C. boninense and other related strains revealed 18 clades. These clades are recognised here as separate species, including C. boninense s. str., C. hippeastri, C. karstii and 12 previously undescribed species, C. annellatum, C. beeveri, C. brassicicola, C. brasiliense, C. colombiense, C. constrictum, C. cymbidiicola, C. dacrycarpi, C. novae-zelandiae, C. oncidii, C. parsonsiae and C. torulosum. Seven of the new species are only known from New Zealand, perhaps reflecting a sampling bias. The new combination C. phyllanthi was made, and C. dracaenae Petch was epitypified and the name replaced with C. petchii. Typical for species of the C. boninense species complex are the conidiogenous cells with rather prominent periclinal thickening that also sometimes extend to form a new conidiogenous locus or annellations as well as conidia that have a prominent basal scar. Many species in the C. boninense complex form teleomorphs in culture. Taxonomic novelties: New combination - Colletotrichum phyllanthi (H. Surendranath Pai) Damm, P.F. Cannon & Crous. Name replacement - C. petchii Damm, P.F. Cannon & Crous. New species - C. annellatum Damm, P.F. Cannon & Crous, C. beeveri Damm, P.F. Cannon, Crous, P.R. Johnst. & B. Weir, C. brassicicola Damm, P.F. Cannon & Crous, C. brasiliense Damm, P.F. Cannon, Crous & Massola, C. colombiense Damm, P.F. Cannon, Crous, C. constrictum Damm, P.F. Cannon, Crous, P.R. Johnst. & B. Weir, C. cymbidiicola Damm, P.F. Cannon, Crous, P.R. Johnst. & B. Weir, C. dacrycarpi Damm, P.F. Cannon, Crous, P.R. Johnst. & B. Weir, C. novae-zelandiae Damm, P.F. Cannon, Crous, P.R. Johnst. & B. Weir, C. oncidii Damm, P.F. Cannon & Crous, C. parsonsiae Damm, P.F. Cannon, Crous, P.R. Johnst. & B. Weir, C. torulosum Damm, P.F. Cannon, Crous, P.R. Johnst. & B. Weir. Typifications: Epitypifications - C. dracaenae Petch. PMID:23136457

Thermal stability of LiPF 6 salt and Li-ion battery electrolytes containing LiPF 6

NASA Astrophysics Data System (ADS)

Yang, Hui; Zhuang, Guorong V.; Ross, Philip N.

The thermal stability of the neat lithium hexafluorophosphate (LiPF 6) salt and of 1 molal (m) solutions of LiPF 6 in prototypical Li-ion battery solvents was studied with thermogravimetric analysis (TGA) and on-line Fourier transform infrared (FTIR). Pure LiPF 6 salt is thermally stable up to 107 °C in a dry inert atmosphere, and its decomposition path is a simple dissociation producing lithium fluoride (LiF) as solid and PF 5 as gaseous products. In the presence of water (300 ppm) in the carrier gas, its decomposition onset temperature is lowered as a result of direct thermal reaction between LiPF 6 and water vapor to form phosphorous oxyfluoride (POF 3) and hydrofluoric acid (HF). No new products were observed in 1 m solutions of LiPF 6 in ethylene carbonate (EC), dimethyl carbonate (DMC) and ethyl methyl carbonate (EMC) by on-line TGA-FTIR analysis. The storage of the same solutions in sealed containers at 85 °C for 300-420 h did not produce any significant quantity of new products as well. In particular, no alkylflurophosphates were found in the solutions after storage at elevated temperature. In the absence of either an impurity like alcohol or cathode active material that may (or may not) act as a catalyst, there is no evidence of thermally induced reaction between LiPF 6 and the prototypical Li-ion battery solvents EC, PC, DMC or EMC.

MeRIP-PF: An Easy-to-use Pipeline for High-resolution Peak-finding in MeRIP-Seq Data

PubMed Central

Li, Yuli; Song, Shuhui; Li, Cuiping; Yu, Jun

2013-01-01

RNA modifications, especially methylation of the N6 position of adenosine (A)—m6A, represent an emerging research frontier in RNA biology. With the rapid development of high-throughput sequencing technology, in-depth study of m6A distribution and function relevance becomes feasible. However, a robust method to effectively identify m6A-modified regions has not been available yet. Here, we present a novel high-efficiency and user-friendly analysis pipeline called MeRIP-PF for the signal identification of MeRIP-Seq data in reference to controls. MeRIP-PF provides a statistical P-value for each identified m6A region based on the difference of read distribution when compared to the controls and also calculates false discovery rate (FDR) as a cut off to differentiate reliable m6A regions from the background. Furthermore, MeRIP-PF also achieves gene annotation of m6A signals or peaks and produce outputs in both XLS and graphical format, which are useful for further study. MeRIP-PF is implemented in Perl and is freely available at http://software.big.ac.cn/MeRIP-PF.html. PMID:23434047

Nutritional aspects of phytoene and phytofluene, carotenoid precursors to lycopene.

PubMed

Engelmann, Nancy J; Clinton, Steven K; Erdman, John W

2011-01-01

Epidemiological studies suggest an inverse relationship between tomato consumption and serum and tissue lycopene (LYC) levels with risk of some chronic diseases, including several cancers and cardiovascular disease. LYC, the red carotenoid found in tomatoes, is often considered to be the primary bioactive carotenoid in tomatoes that mediates health benefits, but other colorless precursor carotenoids, phytoene (PE) and phytofluene (PF), are also present in substantial quantities. PE and PF are readily absorbed from tomato foods and tomato extracts by humans. Animal models of carotenoid absorption suggest preferential accumulation of PE and PF in some tissues. The reasonably high concentrations of PE and PF detected in serum and tissues relative to the concentrations in foods suggest that absorption or metabolism of these compounds may be different from that of LYC. Experimental studies, both in vitro and in vivo, suggest that PE and PF exhibit bioactivity but little is known about their impact in humans. Methods for producing isotopically labeled PE, PF, and LYC tracers from tomato plant cell culture offer a unique tool for further understanding the differential bioavailability and metabolism of these 3 prominent tomato carotenoids and how they may affect health.

Pulmonary function in pubertal synchronized swimmers: 1-year follow-up results and its relation to competitive achievement.

PubMed

Gabrilo, Goran; Peric, Mia; Stipic, Marija

2011-03-01

Pulmonary function (PF) is particularly important in synchronized swimming, considering the characteristics of this sport. However, the sanitizing agents (chlorine) used in pools can have a possible negative influence on the PF parameters. In this study, we observed 24 swimmers (all women, 14 to 16 years of age) and measured their PF and competitive achievement. PF was measured before and after a 1-year period and included standard spirometric variables. Competitive achievement was evidenced during the National Championship. The t-test showed significant increases in body height and weight of the participants and a resulting increase in most of the absolute respiratory flows and pulmonary capacities. Forced vital capacity (FVC) and forced expiratory volume (both in proportion to norm for body height, gender, and age) increased significantly within the study period. FVC significantly predicted the competitive achievement of young swimmers, most probably because artists have to achieve exceptional breath control when upside down underwater. In conclusion, we found no evidence for the eventual negative influence of chlorine and its compounds on the PF of swimmers, and results showed that regular synchronized swim training could improve the PF of young artists.

Bipyrimidine ruthenium(II) arene complexes: structure, reactivity and cytotoxicity.

PubMed

Betanzos-Lara, Soledad; Novakova, Olga; Deeth, Robert J; Pizarro, Ana M; Clarkson, Guy J; Liskova, Barbora; Brabec, Viktor; Sadler, Peter J; Habtemariam, Abraha

2012-10-01

The synthesis and characterization of complexes [(η(6)-arene)Ru(N,N')X][PF(6)], where arene is para-cymene (p-cym), biphenyl (bip), ethyl benzoate (etb), hexamethylbenzene (hmb), indane (ind) or 1,2,3,4-tetrahydronaphthalene (thn), N,N' is 2,2'-bipyrimidine (bpm) and X is Cl, Br or I, are reported, including the X-ray crystal structures of [(η(6)-p-cym)Ru(bpm)I][PF(6)], [(η(6)-bip)Ru(bpm)Cl][PF(6)], [(η(6)-bip)Ru(bpm)I][PF(6)] and [(η(6)-etb)Ru(bpm)Cl][PF(6)]. Complexes in which N,N' is 1,10-phenanthroline (phen), 1,10-phenanthroline-5,6-dione or 4,7-diphenyl-1,10-phenanthroline (bathophen) were studied for comparison. The Ru(II) arene complexes undergo ligand-exchange reactions in aqueous solution at 310 K; their half-lives for hydrolysis range from 14 to 715 min. Density functional theory calculations on [(η(6)-p-cym)Ru(bpm)Cl][PF(6)], [(η(6)-p-cym)Ru(bpm)Br][PF(6)], [(η(6)-p-cym)Ru(bpm)I][PF(6)], [(η(6)-bip)Ru(bpm)Cl][PF(6)], [(η(6)-bip)Ru(bpm)Br][PF(6)] and [(η(6)-bip)Ru(bpm)I][PF(6)] suggest that aquation occurs via an associative pathway and that the reaction is thermodynamically favourable when the leaving ligand is I > Br ≈ Cl. pK (a)* values for the aqua adducts of the complexes range from 6.9 to 7.32. A binding preference for 9-ethylguanine (9-EtG) compared with 9-ethyladenine (9-EtA) was observed for [(η(6)-p-cym)Ru(bpm)Cl][PF(6)], [(η(6)-hmb)Ru(bpm)Cl](+), [(η(6)-ind)Ru(bpm)Cl](+), [(η(6)-thn)Ru(bpm)Cl](+), [(η(6)-p-cym)Ru(phen)Cl](+) and [(η(6)-p-cym)Ru(bathophen)Cl](+) in aqueous solution at 310 K. The X-ray crystal structure of the guanine complex [(η(6)-p-cym)Ru(bpm)(9-EtG-N7)][PF(6)](2) shows multiple hydrogen bonding. Density functional theory calculations show that the 9-EtG adducts of all complexes are thermodynamically preferred compared with those of 9-EtA. However, the bmp complexes are inactive towards A2780 human ovarian cancer cells. Calf thymus DNA interactions for [(η(6)-p-cym)Ru(bpm)Cl][PF(6)] and [(η(6)-p-cym)Ru(phen)Cl][PF(6)] consist of weak coordinative, intercalative and monofunctional coordination. Binding to biomolecules such as glutathione may play a role in deactivating the bpm complexes.

[Application study on PHI and 16PF and SCL-90 for freshman's psychology inspection].

PubMed

Niu, Peng

2009-07-01

To explore the effect of application of the measurement table of PHI and 16PF and SCL-90 for freshmen psychology inspection. The measurement tables of PHI and 16PF for psychology inspection of freshmen of 2004-2007 years were used to sift crisis intervention objects. Continuous four years test showed certain stability, in addition to excited factors,the scores of Freshmen's PHI factors were more lower than normal. The incidence rates of mental problems screened by PHI table were very low and 3-5 serious-mental-problem students weren't detected. The problem can be resolved by the application of PHI combined with 16PF through remesuring the suspected cases by SCL-90. The combinative application of PHI, 16PF and SCL-90 would be better.

Study of new mononuclear platinum group metal complexes containing η 5 and η 6 - Carbocyclic ligands and nitrogen based derivatives and formation of helices due to N sbnd H⋯Cl interactions

NASA Astrophysics Data System (ADS)

Gupta, Gajendra; Gloria, Sairem; Das, Babulal; Rao, Kollipara Mohan

2010-08-01

A quite general approach for the preparation of η 5- and η 6-cyclichydrocarbon platinum group metal complexes is reported. The dinuclear arene ruthenium complexes [(η 6-arene)Ru(μ-Cl)Cl] 2 (arene = C 6H 6, C 10H 14 and C 6Me 6) and η 5-pentamethylcyclopentadienyl rhodium and iridium complexes [(η 5-C 5Me 5)M(μ-Cl)Cl] 2 (M = Rh and Ir) reacts with two equivalents of the ligands 2-chloro-3-(pyrazolyl)quinoxaline ( L 1) and di-(2-pyridyl)amine ( L 2) in presence of NH 4PF 6 to afford the corresponding mononuclear complexes of the type [(η 6-arene)Ru(L 1)Cl]PF 6 {arene = C 6H 6 ( 1), C 10H 14 ( 2) and C 6Me 6 ( 3)}, [(η 6-arene)Ru(L 2)Cl]PF 6 {arene = C 6H 6 ( 4), C 10H 14 ( 5) and C 6Me 6 ( 6)}, and [(η 5-C 5Me 5)M(L 1)Cl]PF 6 {M = Rh ( 7), Ir ( 8)} and [(η 5-C 5Me 5)M(L 2)Cl]PF 6 {M = Rh ( 9), Ir ( 10)}. However the mononuclear η 5-cyclopentadienyl analogues such as [(η 5-C 5H 5)Ru(PPh 3) 2Cl], [(η 5-C 5H 5)Os(PPh 3) 2Br], [(η 5-C 5Me 5)Ru(PPh 3) 2Cl] and [(η 5-C 9H 7)Ru(PPh 3) 2Cl] complexes react in presence of one equivalent of ligands 2-chloro-3-(pyrazolyl)quinoxaline ( L 1) and di-(2-pyridyl)amine ( L 2) and one equivalent of NH 4PF 6 in methanol yielded mononuclear complexes [(η 5-C 5H 5)Ru(PPh 3)(L 1)]PF 6 ( 11), [(η 5-C 5H 5)Os(PPh 3)(L 1)]PF 6 ( 12), [(η 5-C 5Me 5)Ru(PPh 3)(L 1)]PF 6 ( 13) and [(η 5-C 9H 7)Ru(PPh 3)(L 1)]PF 6 ( 14) and [(η 5-C 5H 5)Ru(PPh 3)(L 2)]PF 6 ( 15), [(η 5-C 5H 5)Os(PPh 3)(L 2)]PF 6 ( 16), [(η 5-C 5Me 5)Ru(PPh 3)(L 2)]PF 6 ( 17) and [(η 5-C 9H 7)Ru(PPh 3)(L 2)]PF 6 ( 18) respectively. These compounds have been systematically characterized by IR, NMR and mass spectrometry. The molecular structures of 2, 4 and 15 have been established by single crystal X-ray diffraction study and some of the representative complexes have also been studied by UV-visible spectroscopy. The crystal packing diagram of complex 4 reveals that the cation [(η 6-C 6H 6)Ru(L 2)Cl] + is engaged in non-covalent interaction. This compound gives rise to a 1D helical architecture along the ' a' axis via intermolecular N sbnd H⋯Cl hydrogen bonds.

A molecular mechanism of artemisinin resistance in Plasmodium falciparum malaria

PubMed Central

Mbengue, Alassane; Bhattacharjee, Souvik; Pandharkar, Trupti; Liu, Haining; Estiu, Guillermina; Stahelin, Robert V.; Rizk, Shahir; Njimoh, Dieudonne L.; Ryan, Yana; Chotivanich, Kesinee; Nguon, Chea; Ghorbal, Mehdi; Lopez-Rubio, Jose-Juan; Pfrender, Michael; Emrich, Scott; Mohandas, Narla; Dondorp, Arjen M.; Wiest, Olaf; Haldar, Kasturi

2015-01-01

Artemisinins are the corner stone of anti-malarial drugs1. Emergence and spread of resistance to them2–4 raises risk of wiping out recent gains achieved in reducing world-wide malaria burden and threatens future malaria control and elimination on a global level. Genome wide association studies (GWAS) have revealed parasite genetic loci associated with artemisinin resistance5–10. However, there is no consensus on biochemical targets of artemisinin. Whether and how these targets interact with genes identified by GWAS, remains unknown. Here we provide biochemical and cellular evidence that artemisinins are potent inhibitors of Plasmodium falciparum phosphatidylinositol-3-kinase (PfPI3K), revealing an unexpected mechanism of action. In resistant clinical strains, increased PfPI3K was associated with the C580Y mutation in P. falciparum Kelch13 (PfKelch13), a primary marker of artemisinin resistance. Polyubiquitination of PfPI3K and its binding to PfKelch13 were reduced by PfKelch13 mutation, which limited proteolysis of PfPI3K and thus increased levels of the kinase as well as its lipid product phosphatidylinositol 3-phosphate (PI3P). We find PI3P levels to be predictive of artemisinin resistance in both clinical and engineered laboratory parasites as well as across non-isogenic strains. Elevated PI3P induced artemisinin resistance in absence of PfKelch13 mutations, but remained responsive to regulation by PfKelch13. Evidence is presented for PI3P-dependent signaling, where transgenic expression of an additional kinase confers resistance. Together these data present PI3P as the key mediator of artemisinin resistance and the sole PfPI3K as an important target for malaria elimination. PMID:25874676

A molecular mechanism of artemisinin resistance in Plasmodium falciparum malaria.

PubMed

Mbengue, Alassane; Bhattacharjee, Souvik; Pandharkar, Trupti; Liu, Haining; Estiu, Guillermina; Stahelin, Robert V; Rizk, Shahir S; Njimoh, Dieudonne L; Ryan, Yana; Chotivanich, Kesinee; Nguon, Chea; Ghorbal, Mehdi; Lopez-Rubio, Jose-Juan; Pfrender, Michael; Emrich, Scott; Mohandas, Narla; Dondorp, Arjen M; Wiest, Olaf; Haldar, Kasturi

2015-04-30

Artemisinins are the cornerstone of anti-malarial drugs. Emergence and spread of resistance to them raises risk of wiping out recent gains achieved in reducing worldwide malaria burden and threatens future malaria control and elimination on a global level. Genome-wide association studies (GWAS) have revealed parasite genetic loci associated with artemisinin resistance. However, there is no consensus on biochemical targets of artemisinin. Whether and how these targets interact with genes identified by GWAS, remains unknown. Here we provide biochemical and cellular evidence that artemisinins are potent inhibitors of Plasmodium falciparum phosphatidylinositol-3-kinase (PfPI3K), revealing an unexpected mechanism of action. In resistant clinical strains, increased PfPI3K was associated with the C580Y mutation in P. falciparum Kelch13 (PfKelch13), a primary marker of artemisinin resistance. Polyubiquitination of PfPI3K and its binding to PfKelch13 were reduced by the PfKelch13 mutation, which limited proteolysis of PfPI3K and thus increased levels of the kinase, as well as its lipid product phosphatidylinositol-3-phosphate (PI3P). We find PI3P levels to be predictive of artemisinin resistance in both clinical and engineered laboratory parasites as well as across non-isogenic strains. Elevated PI3P induced artemisinin resistance in absence of PfKelch13 mutations, but remained responsive to regulation by PfKelch13. Evidence is presented for PI3P-dependent signalling in which transgenic expression of an additional kinase confers resistance. Together these data present PI3P as the key mediator of artemisinin resistance and the sole PfPI3K as an important target for malaria elimination.

Plantar fascia segmentation and thickness estimation in ultrasound images.

PubMed

Boussouar, Abdelhafid; Meziane, Farid; Crofts, Gillian

2017-03-01

Ultrasound (US) imaging offers significant potential in diagnosis of plantar fascia (PF) injury and monitoring treatment. In particular US imaging has been shown to be reliable in foot and ankle assessment and offers a real-time effective imaging technique that is able to reliably confirm structural changes, such as thickening, and identify changes in the internal echo structure associated with diseased or damaged tissue. Despite the advantages of US imaging, images are difficult to interpret during medical assessment. This is partly due to the size and position of the PF in relation to the adjacent tissues. It is therefore a requirement to devise a system that allows better and easier interpretation of PF ultrasound images during diagnosis. This study proposes an automatic segmentation approach which for the first time extracts ultrasound data to estimate size across three sections of the PF (rearfoot, midfoot and forefoot). This segmentation method uses artificial neural network module (ANN) in order to classify small overlapping patches as belonging or not-belonging to the region of interest (ROI) of the PF tissue. Features ranking and selection techniques were performed as a post-processing step for features extraction to reduce the dimension and number of the extracted features. The trained ANN classifies the image overlapping patches into PF and non-PF tissue, and then it is used to segment the desired PF region. The PF thickness was calculated using two different methods: distance transformation and area-length calculation algorithms. This new approach is capable of accurately segmenting the PF region, differentiating it from surrounding tissues and estimating its thickness. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Epitope mapping of PfCP-2.9, an asexual blood-stage vaccine candidate of Plasmodium falciparum.

PubMed

Li, Changling; Wang, Rui; Wu, Yuan; Zhang, Dongmei; He, Zhicheng; Pan, Weiqing

2010-04-12

Apical membrane antigen 1 (AMA-1) and merozoite surface protein 1 (MSP1) of Plasmodium falciparum are two leading blood-stage malaria vaccine candidates. A P. falciparum chimeric protein 2.9 (PfCP-2.9) has been constructed as a vaccine candidate, by fusing AMA-1 domain III (AMA-1 (III)) with a C-terminal 19 kDa fragment of MSP1 (MSP1-19) via a 28-mer peptide hinge. PfCP-2.9 was highly immunogenic in animal studies, and antibodies elicited by the PfCP-2.9 highly inhibited parasite growth in vitro. This study focused on locating the distribution of epitopes on PfCP-2.9. A panel of anti-PfCP-2.9 monoclonal antibodies (mAbs) were produced and their properties were examined by Western blot as well as in vitro growth inhibition assay (GIA). In addition, a series of PfCP-2.9 mutants containing single amino acid substitution were produced in Pichia pastoris. Interaction of the mAbs with the PfCP-2.9 mutants was measured by both Western blot and enzyme-linked immunosorbent assay (ELISA). Twelve mAbs recognizing PfCP-2.9 chimeric protein were produced. Of them, eight mAbs recognized conformational epitopes and six mAbs showed various levels of inhibitory activities on parasite growth in vitro. In addition, seventeen PfCP-2.9 mutants with single amino acid substitution were produced in Pichia pastoris for interaction with mAbs. Reduced binding of an inhibitory mAb (mAb7G), was observed in three mutants including M62 (Phe491-->Ala), M82 (Glu511-->Gln) and M84 (Arg513-->Lys), suggesting that these amino acid substitutions are critical to the epitope corresponding to mAb7G. The binding of two non-inhibitory mAbs (mAbG11.12 and mAbW9.10) was also reduced in the mutants of either M62 or M82. The substitution of Leu31 to Arg resulted in completely abolishing the binding of mAb1E1 (a blocking antibody) to M176 mutant, suggesting that the Leu residue at this position plays a crucial role in the formation of the epitope. In addition, the Asn15 residue may also play an important role in the global folding of PfCP-2.9, as its substitution by Arg lead to reduced binding of most mAbs and abolishing the binding of mAb6G and mAbP5-W12. This study provided valuable information on epitopes of PfCP-2.9 vaccine candidate through generation of a panel of mAbs and a series of PfCP-2.9 mutants. The information may prove to be useful for designing more effective malaria vaccines against blood-stage parasites.

Discovery of a highly selective glycogen synthase kinase-3 inhibitor (PF-04802367) that modulates tau phosphorylation in brain: Translation for PET neuroimaging

PubMed Central

Liang, Steven H.; Chen, Jinshan Michael; Normandin, Marc D.; Chang, Jeanne S.; Chang, George C.; Taylor, Christine K.; Trapa, Patrick; Plummer, Mark S.; Para, Kimberly S.; Conn, Edward L.; Lopresti-Morrow, Lori; Lanyon, Lorraine F.; Cook, James M.; Richter, Karl E. G.; Nolan, Charlie E.; Schachter, Joel B.; Janat, Fouad; Che, Ye; Shanmugasundaram, Veerabahu; Lefker, Bruce A.; Enerson, Bradley E.; Livni, Elijahu; Wang, Lu; Guehl, Nicolas; Patnaik, Debasis; Wagner, Florence F.; Perlis, Roy; Holson, Edward B.; Haggarty, Stephen J.; Fakhri, Georges El

2016-01-01

Glycogen synthase kinase-3 (GSK-3) regulates multiple cellular processes in diabetes, oncology and neurology. We have identified N-(3-(1H-1,2,4-triazol-1-yl)propyl)-5-(3-chloro-4-methoxyphenyl)oxazole-4-carboxamide (PF-04802367 or PF-367) as a highly potent inhibitor, which is among the most selective antagonists of GSK-3 to date. We demonstrated its efficacy in modulation of tau phosphorylation in vitro and in vivo. Whereas the kinetics of PF-367 binding in brain tissues are too fast for an effective therapeutic agent, the pharmacokinetic profile of PF-367 is ideal for discovery of radiopharmaceuticals for GSK-3 in the central nervous system. A 11C-isotopologue of PF-367 was synthesized and preliminary PET imaging studies in non-human primates confirmed that we have overcome the two major obstacles for imaging GSK-3, namely, reasonable brain permeability and displaceable binding. PMID:27355874

Preparation and in vitro characterization of pluronic-attached polyamidoamine dendrimers for drug delivery.

PubMed

Gu, Zhuojun; Wang, Meng; Fang, Qiongyan; Zheng, Huaiyu; Wu, Feiyue; Lin, Dai; Xu, Ying; Jin, Yi

2015-05-01

Polyamidoamine (PAMAM) dendrimers have attracted lots of interest as drug carriers. And little study about whether pluronic-attached PAMAM dendrimers could be potential drug delivery systems has been carried on. Pluronic F127 (PF127) attached PAMAM dendrimers were designed as novel drug carriers. Two conjugation ratios of PF127-attached PAMAM dendrimers were synthesized. (1)H nuclear magnetic resonance ((1)H-NMR), Fourier transform infrared spectrum (FTIR), element analysis and ninhydrin assay were used to characterize the conjugates. Size, zeta potential and critical micelle concentrations (CMC) were also detected. And DOX was incorporated into the hydrophobic interior of the conjugates. Studies on their drug loading and drug release were carried on. Furthermore, hemolysis and cytotoxicity assay were used to evaluate the toxicity of the conjugates. PF127 was successfully conjugated to the fifth generation PAMAM dendrimer at two molar ratios of 19% and 57% (PF127 to surface amine per PAMAM dendrimer molecular). The conjugates showed an increased size and a reduced zeta potential. And higher CMC values were obtained than pure PF127. Compared with unconjugated PAMAM dendrimer, PF127 conjugation significantly reduced the hemolytic toxicity and cytotoxicity of PAMAM dendrimer in vitro. The encapsulation results showed that the ability to encapsulate DOX by the conjugate of 19% conjugation ratio was better than that of 57% conjugation ratio. And the maximum is ∼12.87 DOX molecules per conjugate molecule. Moreover, the complexes showed a sustained release behavior compared to pure DOX. Findings from the in vitro study show that the PF127-attached PAMAM dendrimers may be potential carriers for drug delivery.

Improvement of stability of polidocanol foam for nonsurgical permanent contraception.

PubMed

Guo, Jian Xin; Lucchesi, Lisa; Gregory, Kenton W

2015-08-01

Polidocanol foam (PF), used clinically as a venous sclerosant, has recently been studied as a safe and inexpensive means for permanent contraception. Delivering the sclerosant to the fallopian tubes as a foam rather than a liquid increases the surface areas and thus enhances the desired epithelial disrupting activity of the agent. However, the foam is inherently unstable and degrades with time. Therefore, increasing foam stability and thus duration of the agent exposure time could increase epithelial effect while allowing reduction in agent concentration and potential toxicity. We studied methods to improve foam properties that might improve safety and efficacy of PF for intrauterine application. Several types of microporous filters adapted to a syringe-based foaming device were used to study the effect of pore structures on the formation of PF. The foam drainage time and bubble size were characterized. The addition of benzalkonium chloride (BZK) to polidocanol was also investigated for its effects on foam characteristics. A syringe-based foaming device adapted with an inline filter produced smaller bubble PF with a longer foam drainage time. PF generated with a circular pore filter lasts longer than with a noncircular pore filter. The addition of 0.01% of BZK also improved the stability of PF. The stability of PF is affected by the pore characteristics of the filter used for foam generation and enhanced by the presence of a small amount of BZK. The improved foam, if shown to be efficacious in animal models of contraception, could lead to a safe, simple and inexpensive method alternative to surgical contraception. Copyright © 2015 Elsevier Inc. All rights reserved.

Targeting the Fatty Acid Biosynthesis Enzyme, β-Ketoacyl–Acyl Carrier Protein Synthase III (PfKASIII), in the Identification of Novel Antimalarial Agents

PubMed Central

Lee, Patricia J.; Bhonsle, Jayendra B.; Gaona, Heather W.; Huddler, Donald P.; Heady, Tiffany N.; Kreishman-Deitrick, Mara; Bhattacharjee, Apurba; McCalmont, William F.; Gerena, Lucia; Lopez-Sanchez, Miriam; Roncal, Norma E.; Hudson, Thomas H.; Johnson, Jacob D.; Prigge, Sean T.; Waters, Norman C.

2009-01-01

The importance of fatty acids to the human malaria parasite, Plasmodium falciparum, and differences due to a type I fatty acid synthesis (FAS) pathway in the parasite, make it an attractive drug target. In the present study, we developed and a utilized a pharmacophore to select compounds for testing against PfKASIII, the initiating enzyme of FAS. This effort identified several PfKASIII inhibitors that grouped into various chemical classes of sulfides, sulfonamides, and sulfonyls. Approximately 60% of the submicromolar inhibitors of PfKASIII inhibited in vitro growth of the malaria parasite. These compounds inhibited both drug sensitive and resistant parasites and testing against a mammalian cell line revealed an encouraging in vitro therapeutic index for the most active compounds. Docking studies into the active site of PfKASIII suggest a potential binding mode that exploits amino acid residues at the mouth of the substrate tunnel. PMID:19191586

Inhibition of human megakaryocytopoiesis in vitro by platelet factor 4 (PF4) and a synthetic COOH-terminal PF4 peptide.

PubMed Central

Gewirtz, A M; Calabretta, B; Rucinski, B; Niewiarowski, S; Xu, W Y

1989-01-01

We report that highly purified human platelet factor 4 (PF4) inhibits human megakaryocytopoiesis in vitro. At greater than or equal to 25 micrograms/ml, PF4 inhibited megakaryocyte colony formation approximately 80% in unstimulated cultures, and approximately 58% in cultures containing recombinant human IL 3 and granulocyte-macrophage colony-stimulating factor. Because PF4 (25 micrograms/ml) had no effect on either myeloid or erythroid colony formation lineage specificity of this effect was suggested. A synthetic COOH-terminal PF4 peptide of 24, but not 13 residues, also inhibited megakaryocyte colony formation, whereas a synthetic 18-residue beta-thromboglobulin (beta-TG) peptide and native beta-TG had no such effect when assayed at similar concentrations. The mechanism of PF4-mediated inhibition was investigated. First, we enumerated total cell number, and examined cell maturation in control colonies (n = 200) and colonies (n = 100) that arose in PF4-containing cultures. Total cells per colony did not differ dramatically in the two groups (6.1 +/- 3.0 vs. 4.2 +/- 1.6, respectively), but the numbers of mature large cells per colony was significantly decreased in the presence of PF4 when compared with controls (1.6 +/- 1.5 vs. 3.9 +/- 2.3; P less than 0.001). Second, by using the human leukemia cell line HEL as a model for primitive megakaryocytic cells, we studied the effect of PF4 on cell doubling time, on the expression of both growth-regulated (H3, p53, c-myc,and c-myb), and non-growth-regulated (beta 2-microglobulin) genes. At high concentrations of native PF4 (50 micrograms/ml), no effect on cell doubling time, or H3 or p53 expression was discerned. In contrast, c-myc and c-myb were both upregulated. These results suggested the PF4 inhibited colony formation by impeding cell maturation, as opposed to cell proliferation, perhaps by inducing expression of c-myc and c-myb. The ability of PF4 to inhibit a normal cell maturation function was then tested. Megakaryocytes were incubated in synthetic PF4, or beta-TG peptides for 18 h and effect on Factor V steady-state mRNA levels was determined in 600 individual cells by in situ hybridization. beta-TG peptide had no effect on FV mRNA levels, whereas a approximately 60% decrease in expression of Factor V mRNA was found in megakaryocytes exposed to greater than or equal 100 ng/ml synthetic COOH-terminal PF4 peptide. Accordingly, PF4 modulates megakaryocyte maturation in vitro, and may function as a negative autocrine regulator of human megakaryocytopoiesis. Images PMID:2523411

A Positive Correlation between Atypical Memory B Cells and Plasmodium falciparum Transmission Intensity in Cross-Sectional Studies in Peru and Mali

PubMed Central

Weiss, Greta E.; Clark, Eva H.; Li, Shanping; Traore, Boubacar; Kayentao, Kassoum; Ongoiba, Aissata; Hernandez, Jean N.; Doumbo, Ogobara K.; Pierce, Susan K.; Branch, OraLee H.; Crompton, Peter D.

2011-01-01

Background Antibodies that protect against Plasmodium falciparum (Pf) malaria are only acquired after years of repeated infections. The B cell biology that underlies this observation is poorly understood. We previously reported that “atypical” memory B cells are increased in children and adults exposed to intense Pf transmission in Mali, similar to what has been observed in individuals infected with HIV. In this study we examined B cell subsets of Pf -infected adults in Peru and Mali to determine if Pf transmission intensity correlates with atypical memory B cell expansion. Methodology/Principal Findings In this cross-sectional study venous blood was collected from adults in areas of zero (U.S., n = 10), low (Peru, n = 18) and high (Mali, n = 12) Pf transmission. Adults in Peru and Mali were infected with Pf at the time of blood collection. Thawed lymphocytes were analyzed by flow cytometry to quantify B cell subsets, including atypical memory B cells, defined by the cell surface markers CD19+ CD20+ CD21− CD27− CD10−. In Peru, the mean level of atypical memory B cells, as a percent of total B cells, was higher than U.S. adults (Peru mean: 5.4% [95% CI: 3.61–7.28]; U.S. mean: 1.4% [95% CI: 0.92–1.81]; p<0.0001) but lower than Malian adults (Mali mean 13.1% [95% CI: 10.68–15.57]; p = 0.0001). In Peru, individuals self-reporting ≥1 prior malaria episodes had a higher percentage of atypical memory B cells compared to those reporting no prior episodes (≥1 prior episodes mean: 6.6% [95% CI: 4.09–9.11]; no prior episodes mean: 3.1% [95% CI: 1.52–4.73]; p = 0.028). Conclusions/Significance Compared to Pf-naive controls, atypical memory B cells were increased in Peruvian adults exposed to low Pf transmission, and further increased in Malian adults exposed to intense Pf transmission. Understanding the origin, function and antigen specificity of atypical memory B cells in the context of Pf infection could contribute to our understanding of naturally-acquired malaria immunity. PMID:21264245

Recognition and binding of the PF2 lectin to α-amylase from Zabrotes subfasciatus (Coleoptera:Bruchidae) larval midgut.

PubMed

Lagarda-Diaz, I; Geiser, D; Guzman-Partida, A M; Winzerling, J; Vazquez-Moreno, L

2014-01-01

Amylases are an important family of enzymes involved in insect carbohydrate metabolism that are required for the survival of insect larvae. For this reason, enzymes from starch-dependent insects are targets for insecticidal control. PF2 (Olneya tesota) is a lectin that is toxic to Zabrotes subfasciatus (Coleoptera: Bruchidae) larvae. In this study, we evaluated recognition of the PF2 lectin to α-amylases from Z. subfasciatus midgut and the effect of PF2 on α-amylase activity. PF2 caused a decrease of total amylase activity in vitro. Subsequently, several α-amylase isoforms were isolated from insect midgut tissues using ion exchange chromatography. Three enzyme isoforms were verified by an in-gel assay for amylase activity; however, only one isoform was recognized by antiamylase serum and PF2. The identity of this Z. subfasciatus α-amylase was confirmed by liquid chromatography-tandem mass spectrometry. The findings strongly suggest that a glycosylated α-amylase isoform from larval Z. subfasciatus midgut interacts with PF2, which interferes with starch digestion. © The Author 2014. Published by Oxford University Press on behalf of the Entomological Society of America.

Effect of Opalescence(®) bleaching gels on the elution of bulk-fill composite components.

PubMed

Schuster, Lena; Reichl, Franz-Xaver; Rothmund, Lena; He, Xiuli; Yang, Yang; Van Landuyt, Kirsten L; Kehe, Kai; Polydorou, Olga; Hickel, Reinhard; Högg, Christof

2016-02-01

Bleaching treatments can affect release of components from conventional composites. In this continuing study the influence of two different bleaching gels on the elution of bulk-fill composite components was investigated. The composites Tetric EvoCeram(®) Bulk Fill, QuiXFil™ and X-tra fil were treated with the bleaching gels Opalescence PF 15% (PF 15%) for 5 h and PF 35% (PF 35%) for 30 min and then stored in methanol and water for 24 h and 7 d. The eluates were analyzed by gas chromatography/mass spectrometry (GC/MS). Unbleached specimens were used as control group. A total of 7 different elutable substances have been identified from the investigated composites after bleaching-treatment. Three of them were methacrylates: 2-hydroxyethyl methacrylate (HEMA), triethylene glycol dimethacrylate (TEGDMA) and trimethylolpropane trimethacrylate (TMPTMA). Compared to the unbleached controls an increase in elution after PF 15%-treatment of following compounds was found: HEMA (Tetric EvoCeram(®) Bulk Fill), TEGDMA (QuiXFil™, X-tra fil) and 4-N,N-dimethylaminobenzoic acid butyl ethoxy ester (DMABEE) (Tetric EvoCeram(®) Bulk Fill, QuiXFil™, X-tra fil). Following compounds showed a reduction in elution after PF 35%-treatment compared to controls: TEGDMA (QuiXFil™) and DMABEE (Tetric EvoCeram(®) Bulk Fill). The highest concentration of HEMA was 0.22 mmol/l (Tetric EvoCeram(®) Bulk Fill, methanol, 7 d, PF 15%), the highest concentration of TEGDMA was 0.3 mmol/l (X-tra fil, water, 7 d, PF 15%) and the highest concentration of DMABEE was 0.05 mmol/l (QuiXFil™, water, 7 d, PF 35%). PF 15% and PF 35% can lead to reduced and/or increased elution of some bulk-fill components, compared to unbleached bulk-fill composites. Copyright © 2015 Academy of Dental Materials. Published by Elsevier Ltd. All rights reserved.

An infrared and Raman study of the reorientational motions and phase transition in and structure of CsPF6

NASA Astrophysics Data System (ADS)

Heyns, Anton M.; de Waal, Danita

1992-12-01

CsPF6I is face-centered cubic and the PF6- ions are randomly distributed among the six equivalent orientations in the crystal. The ions librate in equilibrium positions for an average time τ, and also jump from one orientation to another in a time which is much shorter than τ. The six different orientations in CsPF6I are of much lower symmetry than the full molecular one. The full vibrational spectra of CsPF6 are reported over the temperature range of 300-4 K and can be analyzed in Phase I in terms of (Oh,C¯4v) where C¯4v denotes the symmetry of the ion and Oh that of the site symmetry S. The polarized Raman spectra of single crystals of CsPF6I are interpreted in terms of all the different orientations of the PF6- ions and excellent agreement is obtained between predicted and experimental results. At 90 K CsPF6 undergoes a phase transition and a crystal structure of P4/nmm-D4h7 is assigned to Phase II. This transition is of the second order and shows behavior which corresponds to those of critical phenomena. An order parameter ξ is defined and a critical constant β is calculated to be equal to 0.3. In CsPF6II two orientations of the PF6- ions exist, both conforming to 4mm-C4v symmetry and the disorder persisting in this phase causes the splitting of the vibrational bands to be fully resolved below 60 K only. An activation energy of ˜3.0 kJ/mol is calculated for the motions of the PF6- ions between 90 and 60 K from the variation of the linewidths and intensities of vibrational bands.

Physical fitness as a mediator between objectively measured physical activity and clustered metabolic syndrome in children and adolescents: The UP&DOWN study.

PubMed

Segura-Jiménez, V; Parrilla-Moreno, F; Fernández-Santos, J R; Esteban-Cornejo, I; Gómez-Martínez, S; Martinez-Gomez, D; Marcos, A; Castro-Piñero, J

2016-11-01

The extent to which physical fitness (PF) attenuates or modifies the association between physical activity (PA) and clustered metabolic syndrome risk factors (CMetSRF) is controversial. We aimed: i) To examine the independent and combined association of objectively measured PA and PF with CMetSRF in children and adolescents; ii) To test the mediating effect of PF in the association of PA with CMetSRF. A total of 226 children and 256 adolescents participated. Levels of PA (light, moderate, vigorous and moderate-to-vigorous [MVPA]) and PF were measured by accelerometry and ALPHA battery, respectively. Cardiorespiratory and muscular fitness values were combined in a global PF variable. A CMetSRF was computed by assessing the following variables: waist circumference, systolic blood pressure, high-density lipoprotein cholesterol, triglycerides and glucose. In children, the highest vigorous PA (β = -0.193; P = 0.003) and MVPA (β = -0.149; P = 0.025) were individually associated with lower CMetSRF, but these associations were not independent of global PF. In adolescents, the association of moderate (β = -0.123; P = 0.046) and MVPA (β = -0.147; P = 0.024) with CMetSRF was independent of PF. Among unfit adolescents, the higher time they spent in MVPA the lower CMetSRF levels were found (P = 0.032). The results are suggestive of a full mediation of global PF in the association of MVPA and vigorous PA with CMetSRF in children. In adolescents, the association of higher moderate and MVPA with lower CMetSRF was independent of levels of PF, and mediation analyses suggest only a partial mediation of global PF in the association of MVPA with CMetSRF. Copyright © 2016 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.

Comparison between Frailty Index of Deficit Accumulation and Phenotypic Model to Predict Risk of Falls: Data from the Global Longitudinal Study of Osteoporosis in Women (GLOW) Hamilton Cohort

PubMed Central

Thabane, Lehana; Ioannidis, George; Kennedy, Courtney; Papaioannou, Alexandra

2015-01-01

Objectives To compare the predictive accuracy of the frailty index (FI) of deficit accumulation and the phenotypic frailty (PF) model in predicting risks of future falls, fractures and death in women aged ≥55 years. Methods Based on the data from the Global Longitudinal Study of Osteoporosis in Women (GLOW) 3-year Hamilton cohort (n = 3,985), we compared the predictive accuracy of the FI and PF in risks of falls, fractures and death using three strategies: (1) investigated the relationship with adverse health outcomes by increasing per one-fifth (i.e., 20%) of the FI and PF; (2) trichotomized the FI based on the overlap in the density distribution of the FI by the three groups (robust, pre-frail and frail) which were defined by the PF; (3) categorized the women according to a predicted probability function of falls during the third year of follow-up predicted by the FI. Logistic regression models were used for falls and death, while survival analyses were conducted for fractures. Results The FI and PF agreed with each other at a good level of consensus (correlation coefficients ≥ 0.56) in all the three strategies. Both the FI and PF approaches predicted adverse health outcomes significantly. The FI quantified the risks of future falls, fractures and death more precisely than the PF. Both the FI and PF discriminated risks of adverse outcomes in multivariable models with acceptable and comparable area under the curve (AUCs) for falls (AUCs ≥ 0.68) and death (AUCs ≥ 0.79), and c-indices for fractures (c-indices ≥ 0.69) respectively. Conclusions The FI is comparable with the PF in predicting risks of adverse health outcomes. These findings may indicate the flexibility in the choice of frailty model for the elderly in the population-based settings. PMID:25764521

Efficacy and Safety of the Glucagon Receptor Antagonist PF-06291874: A 12-Week, Randomized, Dose-Response Study in Patients With Type 2 Diabetes Mellitus on Background Metformin Therapy.

PubMed

Kazierad, David J; Chidsey, Kristin; Somayaji, Veena R; Bergman, Arthur J; Calle, Roberto A

2018-06-19

To conduct a dose-response assessment of the efficacy and safety of the glucagon receptor antagonist PF-06291874 in adults with type 2 diabetes (T2DM) receiving stable doses of metformin. This randomized, double-blind, statin-stratified, placebo-controlled, 4-arm, parallel-group study was conducted in patients with T2DM receiving background metformin. After an 8-week, non-metformin oral antidiabetic agent washout period, 206 patients were randomized to placebo or PF-06291874 (30, 60, or 100 mg once daily) for 12 weeks. Glycosylated hemoglobin (HbA1c), fasting plasma glucose (FPG), and safety endpoints were assessed at baseline and postbaseline. Dose-dependent mean reductions from baseline in HbA1c for PF-06291874 ranged from -0.67% (-7.29 mmol/mol) to -0.93% (-10.13 mmol/mol); and in FPG from -16.6 to -33.3 mg/dL after 12 weeks of dosing. The incidence of hypoglycemia was low and similar between groups receiving PF-06291874. Small, non-dose-dependent increases in LDL cholesterol (<10%) and blood pressure (BP; systolic BP>2 mmHg, diastolic BP>1 mmHg) were observed with PF-06291874. Modest non-dose-dependent median increases were observed across PF-06291874 groups at 12 weeks for alanine aminotransferase (range, 37.6-48.7 U/L versus placebo) and aspartate aminotransferase (range, 33.3-36.6 U/L versus placebo) that were not associated with bilirubin changes. Small increases were observed for body weight (<0.5 kg) in each PF-06291874 group versus placebo. In patients with T2DM, PF-06291874 significantly lowered HbA1c and glucose, was well tolerated, and had low risk of hypoglycemia. Small, non-dose-related increases in BP, lipids, and hepatic transaminases were observed. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Assessment and Implication of Prognostic Imbalance in Randomized Controlled Trials with a Binary Outcome – A Simulation Study

PubMed Central

Chu, Rong; Walter, Stephen D.; Guyatt, Gordon; Devereaux, P. J.; Walsh, Michael; Thorlund, Kristian; Thabane, Lehana

2012-01-01

Background Chance imbalance in baseline prognosis of a randomized controlled trial can lead to over or underestimation of treatment effects, particularly in trials with small sample sizes. Our study aimed to (1) evaluate the probability of imbalance in a binary prognostic factor (PF) between two treatment arms, (2) investigate the impact of prognostic imbalance on the estimation of a treatment effect, and (3) examine the effect of sample size (n) in relation to the first two objectives. Methods We simulated data from parallel-group trials evaluating a binary outcome by varying the risk of the outcome, effect of the treatment, power and prevalence of the PF, and n. Logistic regression models with and without adjustment for the PF were compared in terms of bias, standard error, coverage of confidence interval and statistical power. Results For a PF with a prevalence of 0.5, the probability of a difference in the frequency of the PF≥5% reaches 0.42 with 125/arm. Ignoring a strong PF (relative risk = 5) leads to underestimating the strength of a moderate treatment effect, and the underestimate is independent of n when n is >50/arm. Adjusting for such PF increases statistical power. If the PF is weak (RR = 2), adjustment makes little difference in statistical inference. Conditional on a 5% imbalance of a powerful PF, adjustment reduces the likelihood of large bias. If an absolute measure of imbalance ≥5% is deemed important, including 1000 patients/arm provides sufficient protection against such an imbalance. Two thousand patients/arm may provide an adequate control against large random deviations in treatment effect estimation in the presence of a powerful PF. Conclusions The probability of prognostic imbalance in small trials can be substantial. Covariate adjustment improves estimation accuracy and statistical power, and hence should be performed when strong PFs are observed. PMID:22629322

Comparison between frailty index of deficit accumulation and phenotypic model to predict risk of falls: data from the global longitudinal study of osteoporosis in women (GLOW) Hamilton cohort.

PubMed

Li, Guowei; Thabane, Lehana; Ioannidis, George; Kennedy, Courtney; Papaioannou, Alexandra; Adachi, Jonathan D

2015-01-01

To compare the predictive accuracy of the frailty index (FI) of deficit accumulation and the phenotypic frailty (PF) model in predicting risks of future falls, fractures and death in women aged ≥55 years. Based on the data from the Global Longitudinal Study of Osteoporosis in Women (GLOW) 3-year Hamilton cohort (n = 3,985), we compared the predictive accuracy of the FI and PF in risks of falls, fractures and death using three strategies: (1) investigated the relationship with adverse health outcomes by increasing per one-fifth (i.e., 20%) of the FI and PF; (2) trichotomized the FI based on the overlap in the density distribution of the FI by the three groups (robust, pre-frail and frail) which were defined by the PF; (3) categorized the women according to a predicted probability function of falls during the third year of follow-up predicted by the FI. Logistic regression models were used for falls and death, while survival analyses were conducted for fractures. The FI and PF agreed with each other at a good level of consensus (correlation coefficients ≥ 0.56) in all the three strategies. Both the FI and PF approaches predicted adverse health outcomes significantly. The FI quantified the risks of future falls, fractures and death more precisely than the PF. Both the FI and PF discriminated risks of adverse outcomes in multivariable models with acceptable and comparable area under the curve (AUCs) for falls (AUCs ≥ 0.68) and death (AUCs ≥ 0.79), and c-indices for fractures (c-indices ≥ 0.69) respectively. The FI is comparable with the PF in predicting risks of adverse health outcomes. These findings may indicate the flexibility in the choice of frailty model for the elderly in the population-based settings.

Production, Quality Control, Stability and Pharmacotoxicity of a Malaria Vaccine Comprising Three Highly Similar PfAMA1 Protein Molecules to Overcome Antigenic Variation

PubMed Central

Houard, Sophie; Havelange, Nicolas; Drossard, Jürgen; Mertens, Hubert; Croon, Alexander; Kastilan, Robin; Byrne, Richard; van der Werff, Nicole; van der Eijk, Marjolein; Thomas, Alan W.; Kocken, Clemens H. M.; Remarque, Edmond J.

2016-01-01

Plasmodium falciparum apical membrane antigen 1 (PfAMA1) is a leading asexual blood stage vaccine candidate for malaria. In preparation for clinical trials, three Diversity Covering (DiCo) PfAMA1 ectodomain proteins, designed to overcome the intrinsic polymorphism that is present in PfAMA1, were produced under Good Manufacturing Practice (GMP) in Pichia pastoris. Using identical methodology, the 3 strains were cultivated in 70-L scale fed-batch fermentations and PfAMA1-DiCos were purified by two chromatography steps, an ultrafiltration/diafiltration procedure and size exclusion chromatography, resulting in highly pure (>95%) PfAMA1-DiCo1, PfAMA1 DiCo2 and PfAMA1 DiCo3, with final yields of 1.8, 1.9 and 1.3 gram, respectively. N-terminal determinations showed that approximately 50% of each of the proteins lost 12 residues from their N-terminus, in accordance with SDS-PAGE (2 main bands) and MS-data. Under reducing conditions a site of limited proteolytic cleavage within a disulphide bonded region became evident. The three proteins quantitatively bound to the mAb 4G2 that recognizes a conformational epitope, suggesting proper folding of the proteins. The lyophilized Drug Product (1:1:1 mixture of PfAMA1-DiCo1, DiCo2, DiCo3) fulfilled all pre-set release criteria (appearance, dissolution rate, identity, purity, protein content, moisture content, sub-visible particles, immuno-potency (after reconstitution with adjuvant), abnormal toxicity, sterility and endotoxin), was stable in accelerated and real-time stability studies at -20°C for over 24 months. When formulated with adjuvants selected for clinical phase I evaluation, the Drug Product did not show adverse effect in a repeated-dose toxicity study in rabbits. The Drug Product has entered a phase Ia/Ib clinical trial. PMID:27695087

Influence of central metalloligand geometry on electronic communication between metals: syntheses, crystal structures, MMCT properties of isomeric cyanido-bridged Fe2Ru complexes, and TDDFT calculations.

PubMed

Ma, Xiao; Lin, Chen-Sheng; Hu, Sheng-Min; Tan, Chun-Hong; Wen, Yue-Hong; Sheng, Tian-Lu; Wu, Xin-Tao

2014-06-02

To investigate how the central metalloligand geometry influences distant or vicinal metal-to-metal charge-transfer (MMCT) properties of polynuclear complexes, cis- and trans-isomeric heterotrimetallic complexes, and their one- and two-electron oxidation products, cis/trans-[Cp(dppe)Fe(II)NCRu(II)(phen)2CN-Fe(II)(dppe)Cp][PF6]2 (cis/trans-1[PF6]2), cis/trans-[Cp(dppe)Fe(II)NCRu(II)(phen)2CNFe(III)-(dppe)Cp][PF6]3 (cis/trans-1[PF6]3) and cis/trans-[Cp(dppe)Fe(III)NCRu(II)(phen)2CN-Fe(III)(dppe)Cp][PF6]4 (cis/trans-1[PF6]4) have been synthesized and characterized. Electrochemical measurements show the presence of electronic interactions between the two external Fe(II) atoms of the cis- and trans-isomeric complexes cis/trans-1[PF6]2. The electronic properties of all these complexes were studied and compared by spectroscopic techniques and TDDFT//DFT calculations. As expected, both mixed valence complexes cis/trans-1[PF6]3 exhibited different strong absorption signals in the NIR region, which should mainly be attributed to a transition from an MO that is delocalized over the Ru(II)-CN-Fe(II) subunit to a Fe(III) d orbital with some contributions from the co-ligands. Moreover, the NIR transition energy in trans-1[PF6]3 is lower than that in cis-1[PF6]3, which is related to the symmetry of their molecular orbitals on the basis of the molecular orbital analysis. Also, the electronic spectra of the two-electron oxidized complexes show that trans-1[PF6]4 possesses lower vicinal Ru(II) → Fe(III) MMCT transition energy than cis-1[PF6]4. Moreover, the assignment of MMCT transition of the oxidized products and the differences of the electronic properties between the cis and trans complexes can be well rationalized using TDDFT//DFT calculations. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

A review of model applications for structured soils: b) Pesticide transport.

PubMed

Köhne, John Maximilian; Köhne, Sigrid; Simůnek, Jirka

2009-02-16

The past decade has seen considerable progress in the development of models simulating pesticide transport in structured soils subject to preferential flow (PF). Most PF pesticide transport models are based on the two-region concept and usually assume one (vertical) dimensional flow and transport. Stochastic parameter sets are sometimes used to account for the effects of spatial variability at the field scale. In the past decade, PF pesticide models were also coupled with Geographical Information Systems (GIS) and groundwater flow models for application at the catchment and larger regional scales. A review of PF pesticide model applications reveals that the principal difficulty of their application is still the appropriate parameterization of PF and pesticide processes. Experimental solution strategies involve improving measurement techniques and experimental designs. Model strategies aim at enhancing process descriptions, studying parameter sensitivity, uncertainty, inverse parameter identification, model calibration, and effects of spatial variability, as well as generating model emulators and databases. Model comparison studies demonstrated that, after calibration, PF pesticide models clearly outperform chromatographic models for structured soils. Considering nonlinear and kinetic sorption reactions further enhanced the pesticide transport description. However, inverse techniques combined with typically available experimental data are often limited in their ability to simultaneously identify parameters for describing PF, sorption, degradation and other processes. On the other hand, the predictive capacity of uncalibrated PF pesticide models currently allows at best an approximate (order-of-magnitude) estimation of concentrations. Moreover, models should target the entire soil-plant-atmosphere system, including often neglected above-ground processes such as pesticide volatilization, interception, sorption to plant residues, root uptake, and losses by runoff. The conclusions compile progress, problems, and future research choices for modelling pesticide displacement in structured soils.

Dynamic Patterns of Forces and Loading Rate in Runners with Unilateral Plantar Fasciitis: A Cross-Sectional Study

PubMed Central

Ribeiro, Ana Paula; João, Silvia Maria Amado; Dinato, Roberto Casanova; Tessutti, Vitor Daniel; Sacco, Isabel Camargo Neves

2015-01-01

Aim/Hypothesis The etiology of plantar fasciitis (PF) has been related to several risk factors, but the magnitude of the plantar load is the most commonly described factor. Although PF is the third most-common injury in runners, only two studies have investigated this factor in runners, and their results are still inconclusive regarding the injury stage. Objective Analyze and compare the plantar loads and vertical loading rate during running of runners in the acute stage of PF to those in the chronic stage of the injury in relation to healthy runners. Methods Forty-five runners with unilateral PF (30 acute and 15 chronic) and 30 healthy control runners were evaluated while running at 12 km/h for 40 meters wearing standardized running shoes and Pedar-X insoles. The contact area and time, maximum force, and force-time integral over the rearfoot, midfoot, and forefoot were recorded and the loading rate (20–80% of the first vertical peak) was calculated. Groups were compared by ANOVAs (p<0.05). Results Maximum force and force-time integral over the rearfoot and the loading rate was higher in runners with PF (acute and chronic) compared with controls (p<0.01). Runners with PF in the acute stage showed lower loading rate and maximum force over the rearfoot compared to runners in the chronic stage (p<0.01). Conclusion Runners with PF showed different dynamic patterns of plantar loads during running over the rearfoot area depending on the injury stage (acute or chronic). In the acute stage of PF, runners presented lower loading rate and forces over the rearfoot, possibly due to dynamic mechanisms related to pain protection of the calcaneal area. PMID:26375815

Verification of predicted specimen-specific natural and implanted patellofemoral kinematics during simulated deep knee bend.

PubMed

Baldwin, Mark A; Clary, Chadd; Maletsky, Lorin P; Rullkoetter, Paul J

2009-10-16

Verified computational models represent an efficient method for studying the relationship between articular geometry, soft-tissue constraint, and patellofemoral (PF) mechanics. The current study was performed to evaluate an explicit finite element (FE) modeling approach for predicting PF kinematics in the natural and implanted knee. Experimental three-dimensional kinematic data were collected on four healthy cadaver specimens in their natural state and after total knee replacement in the Kansas knee simulator during a simulated deep knee bend activity. Specimen-specific FE models were created from medical images and CAD implant geometry, and included soft-tissue structures representing medial-lateral PF ligaments and the quadriceps tendon. Measured quadriceps loads and prescribed tibiofemoral kinematics were used to predict dynamic kinematics of an isolated PF joint between 10 degrees and 110 degrees femoral flexion. Model sensitivity analyses were performed to determine the effect of rigid or deformable patellar representations and perturbed PF ligament mechanical properties (pre-tension and stiffness) on model predictions and computational efficiency. Predicted PF kinematics from the deformable analyses showed average root mean square (RMS) differences for the natural and implanted states of less than 3.1 degrees and 1.7 mm for all rotations and translations. Kinematic predictions with rigid bodies increased average RMS values slightly to 3.7 degrees and 1.9 mm with a five-fold decrease in computational time. Two-fold increases and decreases in PF ligament initial strain and linear stiffness were found to most adversely affect kinematic predictions for flexion, internal-external tilt and inferior-superior translation in both natural and implanted states. The verified models could be used to further investigate the effects of component alignment or soft-tissue variability on natural and implant PF mechanics.

Peritoneal fluid of women with endometriosis reduces SOD1 in bovine oocytes in vitro maturation.

PubMed

Malvezzi, Helena; Da Broi, Michele Gomes; Meola, Juliana; Rosa-E-Silva, Júlio César; Ferriani, Rui Alberto; Navarro, Paula Andrea

2018-06-01

Studies have demonstrated oxidative stress in peritoneal fluid (PF) from women with endometriosis and the importance of enzymatic antioxidant machinery to avoid oocyte oxidative damage. Considering that PF constantly surrounds the ovaries and has direct contact with the oocyte at ovulation, we wonder if PF from women with endometriosis may affect antioxidant enzyme gene expression. Thus, the present study aims to evaluate the PF impact from infertile women with minimal and mild endometriosis and from fertile control women without endometriosis on SOD1, CAT, GSR gene's expression in experimental bovine oocytes matured in vitro. Samples of PF were obtained from women who underwent videolaparoscopy-7 infertile with EI/II and 7 fertile without endometriosis. Immature bovine oocytes underwent in vitro maturation in the absence of PF and in the presence of three concentrations (1, 5 and 10%) of PF from fertile and from infertile women with EI/II. After 22 to 24 h of IVM, oocytes were denuded and stored for analysis of SOD1, CAT and GSR by real-time polymerase chain reaction. Oocyte SOD1 expression was significantly lower in the 10% endometriosis group (0.67 ± 0.32) when compared with no-peritoneal fluid (1.05 ± 0.24, p < 0.008) and 10% control groups (1.06 ± 0.22, p < 0.006). These findings raise the possibility of a deleterious influence of PF from women with EI/II on the oocyte, not only after ovulation but also during the maturation process, which could contribute to worsening oocyte quality, being one of the mechanisms related to infertility in patients with endometriosis.

The correlation between malaria RDT (Paracheck pf.®) faint test bands and microscopy in the diagnosis of malaria in Malawi.

PubMed

Makuuchi, Ryoko; Jere, Sandy; Hasejima, Nobuchika; Chigeda, Thoms; Gausi, January

2017-05-02

Faint test bands of Paracheck Pf.® are interpreted as malaria positive according to world health organization (WHO) guideline. However if there are conspicuous number of faint test bands, a performance of Paracheck Pf.® could be influenced depending on whether interpreting faint test bands as malaria positive or negative. Finding out the frequency and accurate interpretation of faint test bands are important to prevent the overdiagnosis and drug resistance. A cross-sectional, descriptive study was conducted to find out the frequency of faint test bands and evaluate the performance of Paracheck Pf.® by sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy of diagnosis of Paracheck Pf.® using microscopy as the gold standard. 388 suspected patients with malaria in Malawi were recruited in this study. Malaria rapid diagnostic tests (RDTs) and microscopy were used and patients' information which includes age, sex, body temperature and signs or symptoms of malaria were recorded. Among all patients involved in the study, 29.1% (113/388) were found malaria positive by RDT. Overall 5.4% (21/388) of all Paracheck Pf.® tests resulted in a "faint test band" and 85.7% (18/21) corresponded with malaria negative by microscopy. Faint test bands which corresponded with malaria positive by microscopy were lower parasite density and there are no patients who showed definitive symptom of malaria, such as fever. When Paracheck Pf.® "faint test bands" were classified as positive, accuracy of diagnosis was 76.5% (95% CI 72%-80.7%) as compared to 80.4% (95% CI 76.1%-84.2%) when Paracheck Pf.® "faint test bands" were classified as negative. This study shows that frequency of faint test bands is 5.4% in all malaria RDTs. The accuracy of diagnosis was improved when faint test bands were interpreted as malaria negative. However information and data obtained in this study may not be enough and more intensive research including a frequency and property of faint test bands is needed for significant interpretation of faint test bands.

Electrostatic Estimation of Intercalant Jump-Diffusion Barriers Using Finite-Size Ion Models.

PubMed

Zimmermann, Nils E R; Hannah, Daniel C; Rong, Ziqin; Liu, Miao; Ceder, Gerbrand; Haranczyk, Maciej; Persson, Kristin A

2018-02-01

We report on a scheme for estimating intercalant jump-diffusion barriers that are typically obtained from demanding density functional theory-nudged elastic band calculations. The key idea is to relax a chain of states in the field of the electrostatic potential that is averaged over a spherical volume using different finite-size ion models. For magnesium migrating in typical intercalation materials such as transition-metal oxides, we find that the optimal model is a relatively large shell. This data-driven result parallels typical assumptions made in models based on Onsager's reaction field theory to quantitatively estimate electrostatic solvent effects. Because of its efficiency, our potential of electrostatics-finite ion size (PfEFIS) barrier estimation scheme will enable rapid identification of materials with good ionic mobility.

Paeoniflorin ameliorates AGEs-induced mesangial cell injury through inhibiting RAGE/mTOR/autophagy pathway.

PubMed

Chen, Juan; Zhao, Di; Zhu, Maomao; Zhang, Minghua; Hou, Xuefeng; Ding, Wenbo; Sun, Shuai; Bu, Weiquan; Feng, Liang; Ma, Shiping; Jia, Xiaobin

2017-05-01

Glomerular mesangial cell plays a vital role in diabetic nephropathy (DN). Recent research has demonstrated that autophagy involved in the development of DN. Paeoniflorin (PF), a monoterpene glucoside, has been proved to attenuate advanced glycation end products (AGEs)-induced mesangial cell injury. However, the regulatory mechanism of PF on autophagy in mesangial cell remains unclear. The aim of this study was to explore the effect of PF on autophagy in AGEs-induced mesangial cell dysfunction. In this study, the leakage of the lactic dehydrogenase (LDH) into the extracellular medium was measured by LDH kit. Transmission electron microscopy (TEM) and mRFP-GFP-microtubule-associated protein light chain 3 (LC3) transfection were performed to observe the formation of autophagy in AGEs-induced mesangial cell. The RAGE/mTOR/autophagy pathway was analyzed by western blotting and small-interfering RNA transfection. Our results showed that the expression of LC3II, p62 were changed in a time-dependent manner in AGEs-stimulated mesangial cell. While PF could decrease the expression of LC3II/LC3I and reduce the number of autophagosomes. Knockdown of Atg5 promoted the protective effect of PF on AGEs-induced HBZY-1 injury. Furthermore, we found PF inhibited autophagy at least partly through inhibiting RAGE and upregulating the level of p-mTOR to against AGEs-induced mesangial cell dysfunction. Thus, PF could be a potential agent for the treatment of DN. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Nitrogen uptake by phytoplankton in surface waters of the Indian sector of Southern Ocean during austral summer

NASA Astrophysics Data System (ADS)

Tripathy, S. C.; Patra, Sivaji; Vishnu Vardhan, K.; Sarkar, A.; Mishra, R. K.; Anilkumar, N.

2018-03-01

This study reports the nitrogen uptake rate (using 15N tracer) of phytoplankton in surface waters of different frontal zones in the Indian sector of the Southern Ocean (SO) during austral summer of 2013. The investigated area encompasses four major frontal systems, i.e., the subtropical front (STF), subantarctic front (SAF), polar front-1 (PF1) and polar front-2 (PF2). Southward decrease of surface water temperature was observed, whereas surface salinity did not show any significant trend. Nutrient (NO3 - and SiO4 4-) concentrations increased southward from STF to PF; while ammonium (NH4 +), nitrite (NO2 -) and phosphate (PO4 3-) remained comparatively stable. Analysis of nutrient ratios indicated potential N-limited conditions at the STF and SAF but no such scenario was observed for PF. In terms of phytoplankton biomass, PF1 was found to be the most productive followed by SAF, whereas PF2 was the least productive region. Nitrate uptake rate increased with increasing latitude, as no systematic spatial variation was discerned for NH4 + and urea (CO(NH2)2). Linear relationship between nitrate and total N-uptake reveals that the studied area is capable of exporting up to 60% of the total production to the deep ocean if the environmental settings are favorable. Like N-uptake rates the f-ratio also increased towards PF region indicating comparatively higher new production in the PF than in the subtropics. The moderately high average f-ratio (0.53) indicates potentially near equal contributions by new production and regenerated production to the total productivity in the study area. Elevation in N-uptake rates with declining temperature suggests that the SO with its vast quantity of cool water could play an important role in drawing down the atmospheric CO2 through the "solubility pump".

Temporal and Spatial Patterns of Preferential Flow Occurrence in the Shale Hills Catchment: From the Hillslope to the Catchment Scales

NASA Astrophysics Data System (ADS)

Liu, H.; Lin, H.

2013-12-01

Understanding temporal and spatial patterns of preferential flow (PF) occurrence is important in revealing hillslope and catchment hydrologic and biogeochemical processes. Quantitative assessment of the frequency and control of PF occurrence in the field, however, has been limited, especially at the landscape scale of hillslope and catchment. By using 5.5-years' (2007-2012) real-time soil moisture at 10 sites response to 323 precipitation events, we tested the temporal consistency of PF occurrence at the hillslope scale in the forested Shale Hills Catchment; and by using 25 additional sites with at least 1-year data (2011-2012), we evaluated the spatial patterns of PF occurrence across the catchment. To explore the potential effects of PF occurrence on catchment hydrology, wavelet analysis was performed on the recorded time series of hydrological signals (i.e., precipitation, soil moisture, catchment discharge). Considerable temporal consistence was observed in both the frequency and the main controls of PF occurrence at the hillslope scale, which was attributed largely to the statistical stability of precipitation pattern over the monitoring period and the relatively stable subsurface preferential pathways. Preferential flow tended to occur more often in response to intense rainfall events, and favored the conditions at dry hilltop or wet valley floor sites. When upscaling to the entire catchment, topographic control on the PF occurrence was amplified remarkably, leading to the identification of a subsurface PF network in the catchment. Higher frequency of PF occurrence was observed at the valley floor (average 48%), hilltop (average 46%), and swales/hillslopes near the stream (average 40%), while the hillslopes in the eastern part of the catchment were least likely to experience PF (0-20%). No clear relationship, however, was observed between terrain attributes and PF occurrence, because the initiation and persistency of PF in this catchment was controlled jointly by complex interactions among landform units, soil types, initial soil moisture, precipitation features, and season. Through the wavelet method (coherence spectrum and phase differences), dual-pore filtering effects of soil system were proven, rendering it possible to further infer characteristic properties of the underlying hydrological processes in the subsurface. We found that preferential flow dominates the catchment discharge response at short-time periods (< 3 days), while the matrix flow may dominate the discharge response at the time scales of around 10-12 days. The temporal and spatial patterns of PF occurrence revealed in this study can help advance the modeling and prediction of complex PF dynamics in this and other similar landscapes.

Seeking and sharing: why the pulmonary fibrosis community engages the web 2.0 environment.

PubMed

Albright, Karen; Walker, Tarik; Baird, Susan; Eres, Linda; Farnsworth, Tara; Fier, Kaitlin; Kervitsky, Dolly; Korn, Marjorie; Lederer, David J; McCormick, Mark; Steiner, John F; Vierzba, Thomas; Wamboldt, Frederick S; Swigris, Jeffrey J

2016-01-12

Pulmonary fibrosis (PF) is a rare, progressive disease that affects patients and their loved ones on many levels. We sought to better understand the needs and interests of PF patients and their loved ones (collectively "reader-participants") by systematically analyzing their engagement with the World Wide Web (the current version referred to as Web 2.0). Data were collected from three PF-focused, interactive websites hosted by physician-investigators with expertise in PF. All data generated by reader-participants for approximately 10 months were downloaded and then analyzed using qualitative content analysis methods. PF experts posted 38 blog entries and reader-participants posted 40 forum entries. Blogs received 363 responses, and forum entries received 108 responses from reader-participants. Reader-participants primarily used the three websites to seek information from or offer a contribution to the PF community. Information was sought about PF symptoms, diagnosis, prognosis, treatments, research, pathophysiology, and disease origin; reader-participants also made requests for new posts and pleas for research and sought clarification on existing content. Contributions included personal narratives about experiences with PF, descriptions of activities or behaviors found to be helpful with PF symptoms, resources or information about PF, and supportive comments to other PF sufferers. PF patients and their loved ones engage the Web 2.0 environment at these PF-focused sites to satisfy their needs to better understand PF and its impacts and to support others facing similar challenges. Clinicians may find it beneficial to encourage PF patients' involvement in internet forums that foster dynamic, bi-directional information sharing.

Long-term topical application of preservative-free prostaglandin analogues evokes macrophage infiltration in the ocular adnexa.

PubMed

Trzeciecka, Anna; Paterno, J Jussi; Toropainen, Elisa; Koskela, Ali; Podracka, Lucia; Korhonen, Eveliina; Kauppinen, Anu; Kaarniranta, Kai; Smedowski, Adrian

2016-10-05

Success of the long-term glaucoma therapy and preservation of the visual function strongly depend on patients' compliance which may be affected by the inconvenience of treatment and its side effects. Recently, introduction of preservative-free anti-glaucoma agents has become an important step towards improved glaucoma care by eliminating the negative effects of preservatives on the eye surface. Although, newly developed eye drop formulations do not contain standard preservatives, they still can be harmful to ocular surface due to other excipients. In this study, we compared tolerability of commercial preservative-free (pf) prostaglandin analogues (pf tafluprost, pf latanoprost and pf bimatoprost) in long-term topical application in rabbits in vivo. We found that after eight weeks treatment, pf latanoprost was the worst tolerated among the tested drops. It expressed increased conjunctival redness and blinking frequency. Furthermore, it caused increased LDH release in the aqueous humour, infiltration of macrophages in the eyelids and visible defects in conjunctival goblet cells. However, we did not detect increased levels of inflammatory markers in the tear fluid or in the aqueous humour. Based on our study, we suspect that these negative effects are related to excipients included in pf latanoprost formulation. Copyright © 2016 Elsevier B.V. All rights reserved.

MeRIP-PF: an easy-to-use pipeline for high-resolution peak-finding in MeRIP-Seq data.

PubMed

Li, Yuli; Song, Shuhui; Li, Cuiping; Yu, Jun

2013-02-01

RNA modifications, especially methylation of the N(6) position of adenosine (A)-m(6)A, represent an emerging research frontier in RNA biology. With the rapid development of high-throughput sequencing technology, in-depth study of m(6)A distribution and function relevance becomes feasible. However, a robust method to effectively identify m(6)A-modified regions has not been available yet. Here, we present a novel high-efficiency and user-friendly analysis pipeline called MeRIP-PF for the signal identification of MeRIP-Seq data in reference to controls. MeRIP-PF provides a statistical P-value for each identified m(6)A region based on the difference of read distribution when compared to the controls and also calculates false discovery rate (FDR) as a cut off to differentiate reliable m(6)A regions from the background. Furthermore, MeRIP-PF also achieves gene annotation of m(6)A signals or peaks and produce outputs in both XLS and graphical format, which are useful for further study. MeRIP-PF is implemented in Perl and is freely available at http://software.big.ac.cn/MeRIP-PF.html. Copyright © 2013. Production and hosting by Elsevier Ltd.

Description of two new plasmids isolated from Francisella philomiragia strains and construction of shuttle vectors for the study of Francisella tularensis.

PubMed

Le Pihive, E; Blaha, D; Chenavas, S; Thibault, F; Vidal, D; Valade, E

2009-11-01

Francisella tularensis is the causative agent of tularemia, a zoonotic disease often transmitted to humans by infected animals. The lack of useful specific genetic tools has long hampered the study of F. tularensis subspecies. We identified and characterized two new plasmids, pF242 and pF243, isolated from Francisella philomiragia strains ATCC 25016 and ATCC 25017, respectively. Sequence analysis revealed that pF242 and pF243 are closely related to pC194 and pFNL10 plasmids, respectively. Two generations of pF242- and pF243-based shuttle vectors, harboring several antibiotic resistance markers, were developed. We used the first generation to compare transformation efficiencies in two virulent F. tularensis subspecies. We found that electroporation was more efficient than cryotransformation: almost all vectors tested were successfully introduced by electroporation into Francisella strains with a high level of efficiency. The second generation of shuttle vectors, containing a multiple cloning site and/or gfp gene downstream of Francisella groES promotor, was used for GFP production in F. tularensis. The development of new shuttle vectors offers new perspectives in the genetic manipulation of F. tularensis, helping to elucidate the mechanisms underlying its virulence.

Effects of cryogenic temperature on the mechanical and failure characteristics of melamine-urea-formaldehyde adhesive plywood

NASA Astrophysics Data System (ADS)

Kim, Jeong-Hyeon; Choi, Sung-Woong; Park, Doo-Hwan; Park, Seong-Bo; Kim, Seul-Kee; Park, Kwang-Jun; Lee, Jae-Myung

2018-04-01

The present study investigates the applicability of melamine-urea-formaldehyde (MUF) resin plywood in cryogenic applications, including liquefied natural gas (LNG) carrier insulation systems. Phenolic-formaldehyde (PF) resin plywood has been extensively used as a structural material in industrial applications. However, many shortcomings of PF resin plywood have been reported, and replacement of PF resin plywood with a new material is necessary to resolve these problems. MUF resin plywood has the advantages of short fabrication time, low veneer cost, and economic feasibility compared to PF resin plywood. However, the mechanical and failure characteristics of MUF resin plywood have not yet been investigated at low temperature ranges. For this reason, adapting MUF resin plywood for cryogenic applications has been difficult, despite the many strong points of the material in engineering aspects. In this study, the effects of cryogenic temperature and thermal treatment on the mechanical characteristics of MUF resin plywood are investigated. The performance of MUF resin plywood is compared with that of PF resin plywood to verify the applicability of the material for use as a structural material in LNG insulation systems. The results demonstrate that MUF resin plywood has mechanical properties comparable with those of PF resin plywood, even at cryogenic conditions.

Correlation between the outcome of extracorporeal shockwave therapy and pretreatment MRI findings for chronic plantar fasciitis.

PubMed

Maki, Masahiro; Ikoma, Kazuya; Imai, Kan; Kido, Masamitsu; Hara, Yusuke; Arai, Yuji; Fujiwara, Hiroyoshi; Kubo, Toshikazu

2015-05-01

The purpose of this study was to investigate the relationship between magnetic resonance imaging (MRI) findings before extracorporeal shockwave therapy (ESWT) and the treatment outcome of ESWT. This study examined 50 feet with chronic plantar fasciitis. The scores before ESWT and after a six-month follow-up were investigated using the Japanese Society for Surgery of the Foot (JSSF) Ankle-Hindfoot Scale and the Visual Analog Scale (VAS). MRI before ESWT was used for image evaluation. MRI revealed thickening of the plantar fascia (PF), and an investigation was conducted regarding the findings of a high-signal-intensity area (HSIA) inside the PF, edema near the PF, and bone marrow edema (BME) of the calcaneus. The average JSSF score and VAS score improved significantly at follow-up. In total, 44 feet were noted in the improved group. MRI revealed that the average amounts of PF thickening did not significantly differ between the improved group and the non-improved group. HSIA, edema near the PF, and BME were observed in 36, 41, and 11 feet in the improved group, respectively; and 2, 4, and 2 feet in the non-improved group, respectively. An HSIA in the PF predicted symptom improvement more easily than other MRI findings. IV.

Abundance and Genetic Diversity of Microbial Polygalacturonase and Pectate Lyase in the Sheep Rumen Ecosystem

PubMed Central

Wang, Yaru; Luo, Huiying; Huang, Huoqing; Shi, Pengjun; Bai, Yingguo; Yang, Peilong; Yao, Bin

2012-01-01

Background Efficient degradation of pectin in the rumen is necessary for plant-based feed utilization. The objective of this study was to characterize the diversity, abundance, and functions of pectinases from microorganisms in the sheep rumen. Methodology/Principal Findings A total of 103 unique fragments of polygalacturonase (PF00295) and pectate lyase (PF00544 and PF09492) genes were retrieved from microbial DNA in the rumen of a Small Tail Han sheep, and 66% of the sequences of these fragments had low identities (<65%) with known sequences. Phylogenetic tree building separated the PF00295, PF00544, and PF09492 sequences into five, three, and three clades, respectively. Cellulolytic and noncellulolytic Butyrivibrio, Prevotella, and Fibrobacter species were the major sources of the pectinases. The two most abundant pectate lyase genes were cloned, and their protein products, expressed in Escherichia coli, were characterized. Both enzymes probably act extracellularly as their nucleotide sequences contained signal sequences, and they had optimal activities at the ruminal physiological temperature and complementary pH-dependent activity profiles. Conclusion/Significance This study reveals the specificity, diversity, and abundance of pectinases in the rumen ecosystem and provides two additional ruminal pectinases for potential industrial use under physiological conditions. PMID:22815874

Democratization as a United States Strategy for Middle East Security

DTIC Science & Technology

2005-03-18

the Middle East presents a wide variety of governments across the region. Republics exists in Algeria, Egypt, Lebanon , Syria, Tunisia, and Yemen...PF 4 5 PF 4 5 PF 4 5 PF 4 5 PF Lebanon 6 5 NF 6 5 NF 6 5 NF 6 5 NF 6 5 NF Libya 7 7 NF 7 7 NF 7 7 NF 7 7 NF 7 7 NF Morocco 5 4 PF 5 5 PF 5 5 PF 5 5...more open discussion of previously taboo topics.17 Syria’s firm control continues to be the greatest impediment to freedom in Lebanon . The Lebanese

Cellular immune responses to platelet factor 4 and heparin complexes in patients with heparin-induced thrombocytopenia.

PubMed

Nazy, Ishac; Clare, Rumi; Staibano, Phillip; Warkentin, Theodore E; Larche, Mark; Moore, Jane C; Smith, James W; Whitlock, Richard P; Kelton, John G; Arnold, Donald M

2018-05-03

Heparin-induced thrombocytopenia (HIT) is an adverse reaction to heparin characterized by thrombocytopenia and thrombotic complications. HIT is caused by pathogenic antibodies that bind to complexes of platelet factor 4 and heparin (PF4/heparin) leading to platelet activation and inducing a hypercoagulable state. Previous studies have shown immunity to PF4/heparin occurs early in life even before heparin exposure; however, the immunogenesis of HIT is not well characterized. The aim of this study was to investigate cellular proliferation in response to PF4/heparin complexes in patients with HIT. Peripheral blood mononuclear cells (PBMCs) from healthy controls (n = 30), postoperative cardiac surgery patients who underwent cardiopulmonary bypass (CPB, n = 17), and patients with confirmed HIT (n = 41) were cultured with PF4 and PF4/heparin. Cellular proliferation was assessed by 3 H-thymidine uptake and 5-ethynyl-2'-deoxyuridine (EdU) detection. PBMCs proliferated in the presence of PF4 and was enhanced by the addition of heparin in all study groups. CPB and HIT patients exhibited significantly higher proliferative responses compared to healthy controls. PBMC proliferation was antigen-specific, depended on the presence of platelets, and only CD14 + cells were identified as proliferating cells. Culture supernatants were tested for the levels of regulatory cytokines and both CPB and HIT patients produced significantly lower levels of IL-10 and TGF-β1 compared to healthy controls. These findings further demonstrate that cellular immune sensitization to PF4/heparin occurs before heparin exposure and suggests that immune dysregulation can contribute to the immunogenesis of HIT. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Adaptations of phytoplankton in the Indian Ocean sector of the Southern Ocean during austral summer of 1998—2014

NASA Astrophysics Data System (ADS)

Mishra, R. K.; Naik, R. K.; Anil Kumar, N.

2015-12-01

This study investigates the effects of light and temperature on the surface water diatoms and chlorophytes, phytoplankton in the Indian Ocean sector of the Southern Ocean (SO) during the austral summer of 1998‒2014. Significant longitudinal variations in hydrographic and biological parameters were observed at the Sub tropical front (STF), Sub Antarctic front (SAF) and Polar front (PF) along 56°E‒58°E. The concentrations of total surface chlorophyll a ( Chl a), diatoms, and chlorophytes measured by the National Aeronautics Space Agency (NASA) estimated by the Sea-Viewing Wide Field-of-View Sensors (SeaWiFS), the Moderate Resolution Imaging Spectro Radiometer (MODIS), and the NASA Ocean Biological Model (NOBM) were used in the study. Variations in the concentration of total Chl a was remarkable amongst the fronts during the study period. The contribution of diatoms to the total concentration of surface Chl a increased towards south from the STF to the PF while it decreased in the case of chlorophytes. The maximum photosynthetically active radiation (PAR) was observed at the STF and it progressively decreased to the PF through the SAF. At the PF region the contribution of diatoms to the total Chl a biomass was ≥80%. On the other hand, the chlorophytes showed a contrary distribution pattern with ≥70% of the total Chl a biomass recorded at the STF which gradually decreased towards the PF, mainly attributed to the temperate adaptation. This clearly reveals that the trend of diatoms increased at the STF and decreased at the SAF and the PF. Further, the trend of chlorophytes was increased at the STF, SAF and PF with a shift in the community in the frontal system of the Indian Ocean sector of the SO.

A dipole-bound dianion

NASA Astrophysics Data System (ADS)

Skurski, Piotr; Simons, Jack

2000-04-01

The possibility of binding two electrons by the dipole potential of a molecule was examined earlier by us using model potentials. That study suggested that large dipole moments μ=qR and large charge separation distances R (or equivalently large charges q) would be required to achieve binding two electrons. For example, even with a charge q=1.5 a.u. which might be achieved using di- or tri-valent cations, a dipole moment exceeding 15.922 D is needed. The presence of inner-shell electrons even further increases the value of μ that is required because the dipole-bound electrons' orbital must be orthogonal to and excluded from such inner shells. In the present work, we discuss our efforts to find a real molecule that can actually bind two electrons to a single dipole site. Numerical results are presented for the mono- and dianions of a double 5-member carbon ring system substituted with a Ca atom and three superhalogen -PF5 groups. The dianion of this molecule is found to be geometrically stable and to have a vertical electron detachment energy of ca. 0.8 eV. Its two excess electrons occupy the same fully symmetric a1 molecular orbital localized at the electropositive Ca end of the neutral system as is routinely observed in dipole-bound monoanions. Although our final candidate is chemically unusual, it is hoped that our predictions about it will encourage others to search for more synthetically tractable alternatives.

Engineering Pseudomonas protegens Pf-5 for nitrogen fixation and its application to improve plant growth under nitrogen-deficient conditions.

PubMed

Setten, Lorena; Soto, Gabriela; Mozzicafreddo, Matteo; Fox, Ana Romina; Lisi, Christian; Cuccioloni, Massimiliano; Angeletti, Mauro; Pagano, Elba; Díaz-Paleo, Antonio; Ayub, Nicolás Daniel

2013-01-01

Nitrogen is the second most critical factor for crop production after water. In this study, the beneficial rhizobacterium Pseudomonas protegens Pf-5 was genetically modified to fix nitrogen using the genes encoding the nitrogenase of Pseudomonas stutzeri A1501 via the X940 cosmid. Pf-5 X940 was able to grow in L medium without nitrogen, displayed high nitrogenase activity and released significant quantities of ammonium to the medium. Pf-5 X940 also showed constitutive expression and enzymatic activity of nitrogenase in ammonium medium or in nitrogen-free medium, suggesting a constitutive nitrogen fixation. Similar to Pseudomonas protegens Pf-5, Pseudomonas putida, Pseudomonas veronii and Pseudomonas taetrolens but not Pseudomonas balearica and Pseudomonas stutzeri transformed with cosmid X940 showed constitutive nitrogenase activity and high ammonium production, suggesting that this phenotype depends on the genome context and that this technology to obtain nitrogen-fixing bacteria is not restricted to Pf-5. Interestingly, inoculation of Arabidopsis, alfalfa, tall fescue and maize with Pf-5 X940 increased the ammonium concentration in soil and plant productivity under nitrogen-deficient conditions. In conclusion, these results open the way to the production of effective recombinant inoculants for nitrogen fixation on a wide range of crops.

Engineering Pseudomonas protegens Pf-5 for Nitrogen Fixation and its Application to Improve Plant Growth under Nitrogen-Deficient Conditions

PubMed Central

Setten, Lorena; Soto, Gabriela; Mozzicafreddo, Matteo; Fox, Ana Romina; Lisi, Christian; Cuccioloni, Massimiliano; Angeletti, Mauro; Pagano, Elba; Díaz-Paleo, Antonio; Ayub, Nicolás Daniel

2013-01-01

Nitrogen is the second most critical factor for crop production after water. In this study, the beneficial rhizobacterium Pseudomonas protegens Pf-5 was genetically modified to fix nitrogen using the genes encoding the nitrogenase of Pseudomonas stutzeri A1501 via the X940 cosmid. Pf-5 X940 was able to grow in L medium without nitrogen, displayed high nitrogenase activity and released significant quantities of ammonium to the medium. Pf-5 X940 also showed constitutive expression and enzymatic activity of nitrogenase in ammonium medium or in nitrogen-free medium, suggesting a constitutive nitrogen fixation. Similar to Pseudomonas protegens Pf-5, Pseudomonas putida, Pseudomonas veronii and Pseudomonas taetrolens but not Pseudomonas balearica and Pseudomonas stutzeri transformed with cosmid X940 showed constitutive nitrogenase activity and high ammonium production, suggesting that this phenotype depends on the genome context and that this technology to obtain nitrogen-fixing bacteria is not restricted to Pf-5. Interestingly, inoculation of Arabidopsis, alfalfa, tall fescue and maize with Pf-5 X940 increased the ammonium concentration in soil and plant productivity under nitrogen-deficient conditions. In conclusion, these results open the way to the production of effective recombinant inoculants for nitrogen fixation on a wide range of crops. PMID:23675499

Folic acid modified Pluronic F127 coating Ag2S quantum dot for photoacoustic imaging of tumor cell-targeting

NASA Astrophysics Data System (ADS)

Zhang, Ruo-Yun; Wang, Zhao-Yang; Yang, Xiao-Quan; Xuan, Yang; Cheng, Kai; Li, Cheng; Song, Xian-Lin; An, Jie; Hou, Xiao-Lin; Zhao, Yuan-Di

2018-02-01

In this study, an oil-soluble Ag2S quantum dot (QD) was synthesized through thermal decomposition using the single-source precursor method, and Pluronic F127 (PF127), a triblock copolymer functionalized with folic acid (FA), was deposited on the surface of the QD, then a water-soluble PF127-FA@Ag2S nanoprobe with targeting ability was fabricated. The as-prepared PF127-FA@Ag2S exhibited spheroidal morphology and high dispersibility, with average diameters of 115 ± 20.7 nm (as observed by transmission electron microscopy). No obvious toxicity of the PF127-FA@Ag2S nanoprobe was found in standard 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide assay and colony-formation assay, indicating good biocompatibility and safety. The resulting PF127-FA@Ag2S exhibited excellent stability between 4 °C-40 °C. Additionally, the capacity of the tumor cell-targeting high contrast enhanced photoacoustic imaging of PF127-FA@Ag2S was verified in comparison with A547 and HeLa cells. In other words, the excellent properties of PF127-FA@Ag2S show great potential in further research for targeting and photoacoustic imaging.

A Comparison of ACQ, AIE and AEE-Based Polymers Loaded on Polyurethane Foams as Sensors for Explosives Detection.

PubMed

Chu, Zhiwei; Fan, Zhuxin; Zhang, Xiang; Tan, Xiaofeng; Li, Dongxu; Chen, Guohua; Zhao, Qinghua

2018-05-15

An aggregation-caused quenching (ACQ)-active polymer (PF), an aggregation-induced emission (AIE)-active polymer (PFTPE) and an aggregation-enhanced emission (AEE)-active polymer (PTTPE) were synthesized by tetraphenylethane (TPE), fluorene and thiophene moieties. Polyurethane (PU) foams modified by PF, PFTPE and PTTPE, namely PU-PF, PU-PFTPE and PU-PTTPE, using ultrasonication-assisted method have been prepared. A comparative study of PU-PF, PU-PFTPE and PU-PTTPE for detection explosives had been performed, and significant fluorescence quenching was observed with the introduction of PA solutions. The as-prepared PU-PF, PU-PFTPE and PU-PTTPE sensors exhibited a superior sensitivity for PA solutions with different concentrations. Remarkably, PU-PF gave a quenching efficiency of 96.2%, higher than 93.5% for PU-PFTPE and 86.7% for PU-PTTPE at a PA concentration of 180 µg·mL -1 in methanol, which was attributed to the effective energy transfer from the fluorophore (PF) to the nitro explosive (PA). This suggested that some ACQ polymers, applied to detect explosives, could afford better performances than AIE or AEE polymers through modification of structures and selection of adequate carriers. At the same time, these chemical sensors can be recycled many times.

A Comparison of ACQ, AIE and AEE-Based Polymers Loaded on Polyurethane Foams as Sensors for Explosives Detection

PubMed Central

Chu, Zhiwei; Fan, Zhuxin; Zhang, Xiang; Tan, Xiaofeng; Chen, Guohua; Zhao, Qinghua

2018-01-01

An aggregation-caused quenching (ACQ)-active polymer (PF), an aggregation-induced emission (AIE)-active polymer (PFTPE) and an aggregation-enhanced emission (AEE)-active polymer (PTTPE) were synthesized by tetraphenylethane (TPE), fluorene and thiophene moieties. Polyurethane (PU) foams modified by PF, PFTPE and PTTPE, namely PU-PF, PU-PFTPE and PU-PTTPE, using ultrasonication-assisted method have been prepared. A comparative study of PU-PF, PU-PFTPE and PU-PTTPE for detection explosives had been performed, and significant fluorescence quenching was observed with the introduction of PA solutions. The as-prepared PU-PF, PU-PFTPE and PU-PTTPE sensors exhibited a superior sensitivity for PA solutions with different concentrations. Remarkably, PU-PF gave a quenching efficiency of 96.2%, higher than 93.5% for PU-PFTPE and 86.7% for PU-PTTPE at a PA concentration of 180 µg·mL−1 in methanol, which was attributed to the effective energy transfer from the fluorophore (PF) to the nitro explosive (PA). This suggested that some ACQ polymers, applied to detect explosives, could afford better performances than AIE or AEE polymers through modification of structures and selection of adequate carriers. At the same time, these chemical sensors can be recycled many times. PMID:29762497

A subunit of the dynein regulatory complex in Chlamydomonas is a homologue of a growth arrest–specific gene product

PubMed Central

Rupp, Gerald; Porter, Mary E.

2003-01-01

The dynein regulatory complex (DRC) is an important intermediate in the pathway that regulates flagellar motility. To identify subunits of the DRC, we characterized a Chlamydomonas motility mutant obtained by insertional mutagenesis. The pf2-4 mutant displays an altered waveform that results in slow swimming cells. EM analysis reveals defects in DRC structure that can be rescued by reintroduction of the wild-type PF2 gene. Immunolocalization studies show that the PF2 protein is distributed along the length of the axoneme, where it is part of a discrete complex of polypeptides. PF2 is a coiled-coil protein that shares significant homology with a mammalian growth arrest–specific gene product (Gas11/Gas8) and a trypanosome protein known as trypanin. PF2 and its homologues appear to be universal components of motile axonemes that are required for DRC assembly and the regulation of flagellar motility. The expression of Gas8/Gas11 transcripts in a wide range of tissues may also indicate a potential role for PF2-related proteins in other microtubule-based structures. PMID:12847082

Potassium ferrate addition as an alternative pre-treatment to enhance short-chain fatty acids production from waste activated sludge.

PubMed

He, Zhang-Wei; Liu, Wen-Zong; Gao, Qin; Tang, Cong-Cong; Wang, Ling; Guo, Ze-Chong; Zhou, Ai-Juan; Wang, Ai-Jie

2018-01-01

A potentially practical technology based on ferrate (VI), i.e. potassium ferrate (PF), pretreatment integrated into waste activated sludge (WAS) anaerobic fermentation has been presented to greatly enhance short-chain fatty acids (SCFAs) production with a shortened fermentation time. The maximum production of SCFAs, 343mg chemical oxygen demand/g volatile suspended solid with acetic acid proportion of 48.2%, was obtained with PF dosage of 56mg Fe(VI)/g total suspended solid within 5days, which was increased to 5.72times compared to that of control. The mechanism study showed that PF accelerated the release rate of both intracellular and extracellular constituents. And the activities of key hydrolytic enzymes were much improved with PF addition. Moreover, PF positively enriched the abundance of microorganisms responsible for WAS hydrolysis and SCFAs production, especially acetic acid-forming characteristic genera such as Petrimonas, Fusibacter and Acetoanaerobium. Besides, the incubation time of acidogenesis and methanogenesis were separated by PF. Copyright © 2017 Elsevier Ltd. All rights reserved.

Using transparent polyurethane film and hydrocolloid dressings to prevent pressure ulcers.

PubMed

Dutra, R A A; Salomé, G M; Alves, J R; Pereira, V O S; Miranda, F D; Vallim, V B; de Brito, M J A; Ferreira, L M

2015-06-01

To compare the performance and effectiveness of a hydrocolloid dressing (HD) and a transparent polyurethane film (PF) in preventing pressure ulcer (PU) development. The study was conducted in the intensive care unit, coronary care unit and medical clinic of the Holy House of Mercy of Passos, Brazil. Data were collected 48 hours after admission and during hospitalisation. The Braden scale was used for PU risk assessment. Consecutive eligible patients without PUs were randomly assigned by lottery to the two groups, either the HD or PF group. Of the 160 eligible patients, significant between-group differences were found in the mean total number of dressing changes (HD, 6.09±1.655 changes; PF, 5.59±2.036 changes; p=0.010), and mean number of dressing changes in the sacral region (HD, 2.50±0.871; PF, 2.05±0.825; p=0.001), with the PF group requiring significantly fewer changes than the HD group. The most common reasons for changing dressings in both groups were moisture (PF 51.1%; HD 47.9%) and shear (HD 43%; PF 38.9%), with a significant difference in shear between groups. The incidence of PUs was significantly lower (p=0.038) in the PF group (8.7%) compared with that in the HD group (15%). The results suggest that the transparent polyurethane film had a better performance and was more effective than the hydrocolloid dressing in preventing PU development.

2-O, 3-O desulfated heparin mitigates murine chemotherapy- and radiation-induced thrombocytopenia

PubMed Central

Tkaczynski, Elizabeth; Arulselvan, Abinaya; Tkaczynski, John; Avery, Stephen; Xiao, Liqing; Torok-Storb, Beverly; Abrams, Kraig; Rao, Narayanam V.; Johnson, Gregory; Poncz, Mortimer

2018-01-01

Thrombocytopenia is a significant complication of chemotherapy and radiation therapy. Platelet factor 4 (PF4; CXCL4) is a negative paracrine of megakaryopoiesis. We have shown that PF4 levels are inversely related to steady-state platelet counts, and to the duration and severity of chemotherapy- and radiation-induced thrombocytopenia (CIT and RIT, respectively). Murine studies suggest that blocking the effect of PF4 improves megakaryopoiesis, raising nadir platelet counts and shortening the time to platelet count recovery. We examined the ability of 2-O, 3-O desulfated heparin (ODSH), a heparin variant with little anticoagulant effects, to neutralize PF4’s effects on megakaryopoiesis. Using megakaryocyte colony assays and liquid cultures, we show that ODSH restored megakaryocyte proliferation in PF4-treated Cxcl4−/− murine and human CD34+-derived megakaryocyte cultures (17.4% megakaryocyte colonies, P < .01 compared with PF4). In murine CIT and RIT models, ODSH, started 24 hours after injury, was examined for the effect on hematopoietic recovery demonstrating higher platelet count nadirs (9% ± 5% treated vs 4% ± 4% control) and significantly improved survival in treated animals (73% treated vs 36% control survival). Treatment with ODSH was able to reduce intramedullary free PF4 concentrations by immunohistochemical analysis. In summary, ODSH mitigated CIT and RIT in mice by neutralizing the intramedullary negative paracrine PF4. ODSH, already in clinical trials in humans as an adjuvant to chemotherapy, may be an important, clinically relevant therapeutic for CIT and RIT. PMID:29599195

Autoantibodies in the Autoimmune Disease Pemphigus Foliaceus Induce Blistering via p38 Mitogen-Activated Protein Kinase-Dependent Signaling in the Skin

PubMed Central

Berkowitz, Paula; Chua, Michael; Liu, Zhi; Diaz, Luis A.; Rubenstein, David S.

2008-01-01

Pemphigus foliaceus (PF) is a human autoimmune blistering disease in which a humoral immune response targeting the skin results in a loss of keratinocyte cell-cell adhesion in the superficial layers of the epidermal epithelium. In PF, desmoglein-1-specific autoantibodies induce blistering. Evidence is beginning to accumulate that activation of signaling may have an important role in the ability of pathogenic pemphigus IgGs to induce blistering and that both p38 mitogen-activated protein kinase (MAPK) and heat shock protein (HSP) 27 are part of this signaling pathway. This study was undertaken to investigate the ability of PF IgGs to activate signaling as well as the contribution of this signaling pathway to blister induction in an in vivo model of PF. Phosphorylation of both p38 MAPK and HSP25, the murine HSP27 homolog, was observed in the skin of PF IgG-treated mice. Furthermore, inhibition of p38 MAPK blocked the ability of PF IgGs to induce blistering in vivo. These results indicate that PF IgG-induced blistering is dependent on activation of p38 MAPK in the target keratinocyte. Rather than influencing the immune system, limiting the autoantibody-induced intracellular signaling response that leads to target end-organ damage may be a more viable therapeutic strategy for the treatment of autoimmune diseases. Inhibition of p38 MAPK may be an effective strategy for the treatment of PF. PMID:18988808

Neuroprotection by Paeoniflorin in the MPTP mouse model of Parkinson's disease.

PubMed

Zheng, Meizhu; Liu, Chunming; Fan, Yajun; Yan, Pan; Shi, Dongfang; Zhang, Yuchi

2017-04-01

Paeoniflorin (PF) is a major bioactive ingredient in Radix Paeonia alba roots that has low toxicity and has been shown to have neuroprotective effects. Our in vitro experiments suggested that PF affords a significant neuroprotective effect against MPP + -induced damage and apoptosis in PC12 cells through Bcl-2/Bax/caspase-3 pathway. The objectives of the present study were to explore the potential neuroprotective effect of PF in 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP)-treated mouse model of Parkinson's disease (PD). Our results demonstrated that PF treatment ameliorated the behavioral deficits of "in spontaneous motor activity and latency to fall of the rotarod test", and reduced dopaminergic cell loss that were induced by MPTP in a dose-dependent manner in an in vivo model of PD. In addition, we found that treatment of PF protected dopaminergic neurons by preventing MPTP-induced decreases in striatal and substantia nigra dopaminergic transporter (DAT) and tyrosine hydroxylase (TH) protein levels, and by changing dopamine catabolism and inhibiting dopamine turnover. Furthermore, it was also associated with up-regulation of the Bcl-2/BAD ratio, and inhibition of the activation of caspase-9 and caspase-3. These results showed that PF promoted dopamine neuron survival in vivo due to the MAO-B inhibition, and the PI3K/Akt signaling pathway may have mediated the protection of PF against MPTP, suggesting that PF treatment might represent a neuroprotective treatment for PD. Copyright © 2017 Elsevier Ltd. All rights reserved.

Analgesic effect of paeoniflorin in rats with neonatal maternal separation-induced visceral hyperalgesia is mediated through adenosine A(1) receptor by inhibiting the extracellular signal-regulated protein kinase (ERK) pathway.

PubMed

Zhang, Xiao-Jun; Chen, Hong-Li; Li, Zhi; Zhang, Hong-Qi; Xu, Hong-Xi; Sung, Joseph J Y; Bian, Zhao-Xiang

2009-11-01

Paeoniflorin (PF), a chief active ingredient in the root of Paeonia lactiflora Pall (family Ranunculaceae), is effective in relieving colorectal distention (CRD)-induced visceral pain in rats with visceral hyperalgesia induced by neonatal maternal separation (NMS). This study aimed at exploring the underlying mechanisms of PF's analgesic effect on CRD-evoked nociceptive signaling in the central nervous system (CNS) and investigating whether the adenosine A(1) receptor is involved in PF's anti-nociception. CRD-induced visceral pain as well as phosphorylated-extracellular signal-regulated protein kinase (p-ERK) and phospho-cAMP response element-binding protein (p-CREB) expression in the CNS structures of NMS rats were suppressed by NMDA receptor antagonist dizocilpine (MK-801) and ERK phosphorylation inhibitor U0126. PF could similarly inhibit CRD-evoked p-ERK and c-Fos expression in laminae I-II of the lumbosacral dorsal horn and anterior cingulate cortex (ACC). PF could also reverse the CRD-evoked increased glutamate concentration by CRD as shown by dynamic microdialysis monitoring in ACC, whereas, DPCPX, an antagonist of adenosine A(1) receptor, significantly blocked the analgesic effect of PF and PF's inhibition on CRD-induced p-ERK and p-CREB expression. These results suggest that PF's analgesic effect is possibly mediated by adenosine A(1) receptor by inhibiting CRD-evoked glutamate release and the NMDA receptor dependent ERK signaling.

Structure-Activity Relationships of the Human Immunodeficiency Virus Type 1 Maturation Inhibitor PF-46396.

PubMed

Murgatroyd, Christopher; Pirrie, Lisa; Tran, Fanny; Smith, Terry K; Westwood, Nicholas J; Adamson, Catherine S

2016-09-15

HIV-1 maturation inhibitors are a novel class of antiretroviral compounds that consist of two structurally distinct chemical classes: betulinic acid derivatives and the pyridone-based compound PF-46396. It is currently believed that both classes act by similar modes of action to generate aberrant noninfectious particles via inhibition of CA-SP1 cleavage during Gag proteolytic processing. In this study, we utilized a series of novel analogues with decreasing similarity to PF-46396 to determine the chemical groups within PF-46396 that contribute to antiviral activity, Gag binding, and the relationship between these essential properties. A spectrum of antiviral activity (active, intermediate, and inactive) was observed across the analogue series with respect to CA-SP1 cleavage and HIV-1 (NL4-3) replication kinetics in Jurkat T cells. We demonstrate that selected inactive analogues are incorporated into wild-type (WT) immature particles and that one inactive analogue is capable of interfering with PF-46396 inhibition of CA-SP1 cleavage. Mutations that confer PF-46396 resistance can impose a defective phenotype on HIV-1 that can be rescued in a compound-dependent manner. Some inactive analogues retained the capacity to rescue PF-46396-dependent mutants (SP1-A3V, SP1-A3T, and CA-P157S), implying that they can also interact with mutant Gag. The structure-activity relationships observed in this study demonstrate that (i) the tert-butyl group is essential for antiviral activity but is not an absolute requirement for Gag binding, (ii) the trifluoromethyl group is optimal but not essential for antiviral activity, and (iii) the 2-aminoindan group is important for antiviral activity and Gag binding but is not essential, as its replacement is tolerated. Combinations of antiretroviral drugs successfully treat HIV/AIDS patients; however, drug resistance problems make the development of new mechanistic drug classes an ongoing priority. HIV-1 maturation inhibitors are novel as they target the Gag protein, specifically by inhibiting CA-SP1 proteolytic cleavage. The lack of high-resolution structural information of the CA-SP1 target in Gag has hindered our understanding of the inhibitor-binding pocket and maturation inhibitor mode of action. Therefore, we utilized analogues of the maturation inhibitor PF-46396 as chemical tools to determine the chemical components of PF-46396 that contribute to antiviral activity and Gag binding and the relationship between these essential properties. This is the first study to report structure-activity relationships of the maturation inhibitor PF-46396. PF-46396 is chemically distinct from betulinic acid-derived maturation inhibitors; therefore, our data provide a foundation of knowledge that will aid our understanding of how structurally distinct maturation inhibitors act by similar modes of action. Copyright © 2016 Murgatroyd et al.

An Interspecies Signaling System Mediated by Fusaric Acid Has Parallel Effects on Antifungal Metabolite Production by Pseudomonas protegens Strain Pf-5 and Antibiosis of Fusarium spp.

PubMed

Quecine, Maria Carolina; Kidarsa, Teresa A; Goebel, Neal C; Shaffer, Brenda T; Henkels, Marcella D; Zabriskie, T Mark; Loper, Joyce E

2015-12-11

Pseudomonas protegens strain Pf-5 is a rhizosphere bacterium that suppresses soilborne plant diseases and produces at least seven different secondary metabolites with antifungal properties. We derived mutants of Pf-5 with single and multiple mutations in biosynthesis genes for seven antifungal metabolites: 2,4-diacetylphoroglucinol (DAPG), pyrrolnitrin, pyoluteorin, hydrogen cyanide, rhizoxin, orfamide A, and toxoflavin. These mutants were tested for inhibition of the pathogens Fusarium verticillioides and Fusarium oxysporum f. sp. pisi. Rhizoxin, pyrrolnitrin, and DAPG were found to be primarily responsible for fungal antagonism by Pf-5. Previously, other workers showed that the mycotoxin fusaric acid, which is produced by many Fusarium species, including F. verticillioides, inhibited the production of DAPG by Pseudomonas spp. In this study, amendment of culture media with fusaric acid decreased DAPG production, increased pyoluteorin production, and had no consistent influence on pyrrolnitrin or orfamide A production by Pf-5. Fusaric acid also altered the transcription of biosynthetic genes, indicating that the mycotoxin influenced antibiotic production by Pf-5 at the transcriptional level. Addition of fusaric acid to the culture medium reduced antibiosis of F. verticillioides by Pf-5 and derivative strains that produce DAPG but had no effect on antibiosis by Pf-5 derivatives that suppressed F. verticillioides due to pyrrolnitrin or rhizoxin production. Our results demonstrated the importance of three compounds, rhizoxin, pyrrolnitrin, and DAPG, in suppression of Fusarium spp. by Pf-5 and confirmed that an interspecies signaling system mediated by fusaric acid had parallel effects on antifungal metabolite production and antibiosis by the bacterial biological control organism. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

An Interspecies Signaling System Mediated by Fusaric Acid Has Parallel Effects on Antifungal Metabolite Production by Pseudomonas protegens Strain Pf-5 and Antibiosis of Fusarium spp.

PubMed Central

Quecine, Maria Carolina; Kidarsa, Teresa A.; Goebel, Neal C.; Shaffer, Brenda T.; Henkels, Marcella D.; Zabriskie, T. Mark

2015-01-01

Pseudomonas protegens strain Pf-5 is a rhizosphere bacterium that suppresses soilborne plant diseases and produces at least seven different secondary metabolites with antifungal properties. We derived mutants of Pf-5 with single and multiple mutations in biosynthesis genes for seven antifungal metabolites: 2,4-diacetylphoroglucinol (DAPG), pyrrolnitrin, pyoluteorin, hydrogen cyanide, rhizoxin, orfamide A, and toxoflavin. These mutants were tested for inhibition of the pathogens Fusarium verticillioides and Fusarium oxysporum f. sp. pisi. Rhizoxin, pyrrolnitrin, and DAPG were found to be primarily responsible for fungal antagonism by Pf-5. Previously, other workers showed that the mycotoxin fusaric acid, which is produced by many Fusarium species, including F. verticillioides, inhibited the production of DAPG by Pseudomonas spp. In this study, amendment of culture media with fusaric acid decreased DAPG production, increased pyoluteorin production, and had no consistent influence on pyrrolnitrin or orfamide A production by Pf-5. Fusaric acid also altered the transcription of biosynthetic genes, indicating that the mycotoxin influenced antibiotic production by Pf-5 at the transcriptional level. Addition of fusaric acid to the culture medium reduced antibiosis of F. verticillioides by Pf-5 and derivative strains that produce DAPG but had no effect on antibiosis by Pf-5 derivatives that suppressed F. verticillioides due to pyrrolnitrin or rhizoxin production. Our results demonstrated the importance of three compounds, rhizoxin, pyrrolnitrin, and DAPG, in suppression of Fusarium spp. by Pf-5 and confirmed that an interspecies signaling system mediated by fusaric acid had parallel effects on antifungal metabolite production and antibiosis by the bacterial biological control organism. PMID:26655755

The median preoptic nucleus reciprocally modulates activity of arousal-related and sleep-related neurons in the perifornical lateral hypothalamus.

PubMed

Suntsova, Natalia; Guzman-Marin, Ruben; Kumar, Sunil; Alam, Md Noor; Szymusiak, Ronald; McGinty, Dennis

2007-02-14

The perifornical-lateral hypothalamic area (PF/LH) contains neuronal groups playing an important role in control of waking and sleep. Among the brain regions that regulate behavioral states, one of the strongest sources of projections to the PF/LH is the median preoptic nucleus (MnPN) containing a sleep-active neuronal population. To evaluate the role of MnPN afferents in the control of PF/LH neuronal activity, we studied the responses of PF/LH cells to electrical stimulation or local chemical manipulation of the MnPN in freely moving rats. Single-pulse electrical stimulation evoked responses in 79% of recorded PF/LH neurons. No cells were activated antidromically. Direct and indirect transsynaptic effects depended on sleep-wake discharge pattern of PF/LH cells. The majority of arousal-related neurons, that is, cells discharging at maximal rates during active waking (AW) or during AW and rapid eye movement (REM) sleep, exhibited exclusively or initially inhibitory responses to stimulation. Sleep-related neurons, the cells with elevated discharge during non-REM and REM sleep or selectively active in REM sleep, exhibited exclusively or initially excitatory responses. Activation of the MnPN via microdialytic application of L-glutamate or bicuculline resulted in reduced discharge of arousal-related and in excitation of sleep-related PF/LH neurons. Deactivation of the MnPN with muscimol caused opposite effects. The results indicate that the MnPN contains subset(s) of neurons, which exert inhibitory control over arousal-related and excitatory control over sleep-related PF/LH neurons. We hypothesize that MnPN sleep-active neuronal group has both inhibitory and excitatory outputs that participate in the inhibitory control of arousal-promoting PF/LH mechanisms.

Affective states and adaptation to parabolic flights

NASA Astrophysics Data System (ADS)

Collado, Aurélie; Langlet, Cécile; Tzanova, Tzvetomira; Hainaut, Jean-Philippe; Monfort, Vincent; Bolmont, Benoît

2017-05-01

This exploratory study investigates (i) inter-individual variations of affective states before a parabolic flight (i.e., PF) on the basis of quality of adaptation to physical demands, and (ii) intra-individual variations of affective states during a PF. Mood-states, state-anxiety and salivary cortisol were assessed in two groups with a different quality of adaptation (an Adaptive Group, i.e., AG, and a Maladaptive Group, i.e., MG) before and during a PF. Before PF, MG scored higher on mood states (Anger-Hostility, Fatigue-Inertia) than AG. During the flight, while AG seemed to present "normal" affective responses to the demanding environment (e.g., increase in salivary cortisol), MG presented increases in mood states such as Confusion-Bewilderment or Tension-Anxiety. The findings suggest that the psychological states of MG could have disturbed their ability to integrate sensory information from an unusual environment, which led to difficulties in coping with the physical demands of PF.

The hypolipidemic effect and antithrombotic activity of Mucuna pruriens protein hydrolysates.

PubMed

Herrera Chalé, Francisco; Ruiz Ruiz, Jorge Carlos; Betancur Ancona, David; Acevedo Fernández, Juan José; Segura Campos, Maira Rubi

2016-01-01

Hydrolysates and peptide fractions (PF) obtained from M. pruriens protein concentrates with commercial and digestive enzymatic systems were studied for their hypolipidemic and antithrombotic activities. Hydrolysates obtained with Pepsin-Pancreatin (PP) and their peptide fractions inhibited cholesterol micellar solubility with a maximum value of 1.83% in PP. Wistar rats were used to evaluate the hypolipidemic effect of hydrolysates and PF. The higher reductions of cholesterol and triglyceride levels were exhibited by PP and both peptide fractions <1 kDa obtained from PP and Alcalase®-Flavourzyme® hydrolysate (AF) at a dose of 15 mg kg(-1) of animal weight. PF > 10 kDa from both hydrolysates showed the maximum antithrombotic activity with values of 33.33% for PF > 10 kDa from AF and 31.72% for PF > 10 kDa from PP. The results suggest that M. pruriens bioactive peptides with the hypolipidemic effect and antithrombotic activity might be utilized as nutraceuticals.

Application of ultrasound in the assessment of plantar fascia in patients with plantar fasciitis: a systematic review.

PubMed

Mohseni-Bandpei, Mohammad Ali; Nakhaee, Masoomeh; Mousavi, Mohammad Ebrahim; Shakourirad, Ali; Safari, Mohammad Reza; Vahab Kashani, Reza

2014-08-01

Plantar fasciitis (PFS) is one of the most common causes of heel pain, estimated to affect 10% of the general population during their lifetime. Ultrasound (US) imaging technique is increasingly being used to assess plantar fascia (PF) thickness, monitor the effect of different interventions and guide therapeutic interventions in patients with PFS. The purpose of the present study was to systematically review previously published studies concerning the application of US in the assessment of PF in patients with PFS. A literature search was performed for the period 2000-2012 using the Science Direct, Scopus, PubMed, CINAHL, Medline, Embase and Springer databases. The key words used were: ultrasound, sonography, imaging techniques, ultrasonography, interventional ultrasonography, plantar fascia and plantar fasciitis. The literature search yielded 34 relevant studies. Sixteen studies evaluated the effect of different interventions on PF thickness in patients with PFS using US; 12 studies compared PF thickness between patients with and without PFS using US; 6 studies investigated the application of US as a guide for therapeutic intervention in patients with PFS. There were variations among studies in terms of methodology used. The results indicated that US can be considered a reliable imaging technique for assessing PF thickness, monitoring the effect of different interventions and guiding therapeutic interventions in patients with PFS. Copyright © 2014 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

[11C]PF-3274167 as a PET radiotracer of oxytocin receptors: Radiosynthesis and evaluation in rat brain.

PubMed

Vidal, Benjamin; Karpenko, Iuliia A; Liger, François; Fieux, Sylvain; Bouillot, Caroline; Billard, Thierry; Hibert, Marcel; Zimmer, Luc

2017-12-01

Oxytocin plays a major role in the regulation of social interactions in mammals by interacting with the oxytocin receptor (OTR) expressed in the brain. Furthermore, the oxytocin system appears as a possible therapeutic target in autism spectrum disorders and other psychiatric troubles, justifying current pharmacological researches. Since no specific PET radioligand is currently available to image OTR in the brain, the aim of this study was to radiolabel the specific OTR antagonist PF-3274167 and to evaluate [ 11 C]PF-3274167 as a potential PET tracer for OTR in rat brains. [ 11 C]PF-3274167 was prepared via the O-methylation of its desmethyl precursor with [ 11 C]methyl iodide. The lipophilicity of the radioactive compound was evaluated by measuring the n-octanol-buffer partition coefficient (logD). Autoradiography experiments were performed on rat brain tissue to evaluate the in vitro distribution of the [ 11 C]PF-3274167. MicroPET experiments were conducted with and without pre-injection of ciclosporin in order to evaluate the influence of the P-glycoprotein (P-gp) on the brain uptake. [ 11 C]PF-3274167 was synthesized with high radiochemical and chemical purities (>95%) and good specific activity. The measured logD was 1.93. In vitro, [ 11 C]PF-3274167 did not show any evidence of specific binding to OTR. PET imaging showed that [ 11 C]PF-3274167 uptake in rat brain was very low in basal conditions but increased significantly after the administration of ciclosporin, suggesting that it is a substrate of the P-gp. In the ciclosporin-pre-injected rat, however, [ 11 C]PF-3274167 distribution did not match with the known distribution of OTR in rats. [ 11 C]PF-3274167 is not a suitable tracer for imaging of OTR in rat brain, probably because of a too low affinity for this receptor in addition to a poor brain penetration. Copyright © 2017 Elsevier Inc. All rights reserved.

B-Cell Responses to Pregnancy-Restricted and -Unrestricted Plasmodium falciparum Erythrocyte Membrane Protein 1 Antigens in Ghanaian Women Naturally Exposed to Malaria Parasites

PubMed Central

Ampomah, Paulina; Stevenson, Liz; Ofori, Michael F.; Barfod, Lea

2014-01-01

Protective immunity to Plasmodium falciparum malaria acquired after natural exposure is largely antibody mediated. IgG-specific P. falciparum EMP1 (PfEMP1) proteins on the infected erythrocyte surface are particularly important. The transient antibody responses and the slowly acquired protective immunity probably reflect the clonal antigenic variation and allelic polymorphism of PfEMP1. However, it is likely that other immune-evasive mechanisms are also involved, such as interference with formation and maintenance of immunological memory. We measured PfEMP1-specific antibody levels by enzyme-linked immunosorbent assay (ELISA) and memory B-cell frequencies by enzyme-linked immunosorbent spot (ELISPOT) assay in a cohort of P. falciparum-exposed nonpregnant Ghanaian women. The antigens used were a VAR2CSA-type PfEMP1 (IT4VAR04) with expression restricted to parasites infecting the placenta, as well as two commonly recognized PfEMP1 proteins (HB3VAR06 and IT4VAR60) implicated in rosetting and not pregnancy restricted. This enabled, for the first time, a direct comparison in the same individuals of immune responses specific for a clinically important parasite antigen expressed only during well-defined periods (pregnancy) to responses specific for comparable antigens expressed independent of pregnancy. Our data indicate that PfEMP1-specific B-cell memory is adequately acquired even when antigen exposure is infrequent (e.g., VAR2CSA-type PfEMP1). Furthermore, immunological memory specific for VAR2CSA-type PfEMP1 can be maintained for many years without antigen reexposure and after circulating antigen-specific IgG has disappeared. The study provides evidence that natural exposure to P. falciparum leads to formation of durable B-cell immunity to clinically important PfEMP1 antigens. This has encouraging implications for current efforts to develop PfEMP1-based vaccines. PMID:24566620

Mapping the receptivity of malaria risk to plan the future of control in Somalia

PubMed Central

Alegana, Victor Adagi; Patil, Anand Prabhakar; Moloney, Grainne; Borle, Mohammed; Yusuf, Fahmi; Amran, Jamal; Snow, Robert William

2012-01-01

Objectives To measure the receptive risks of malaria in Somalia and compare decisions on intervention scale-up based on this map and the more widely used contemporary risk maps. Design Cross-sectional community Plasmodium falciparum parasite rate (PfPR) data for the period 2007–2010 corrected to a standard age range of 2 to <10 years (PfPR2–10) and used within a Bayesian space–time geostatistical framework to predict the contemporary (2010) mean PfPR2–10 and the maximum annual mean PfPR2–10 (receptive) from the highest predicted PfPR2–10 value over the study period as an estimate of receptivity. Setting Randomly sampled communities in Somalia. Participants Randomly sampled individuals of all ages. Main outcome measure Cartographic descriptions of malaria receptivity and contemporary risks in Somalia at the district level. Results The contemporary annual PfPR2–10 map estimated that all districts (n=74) and population (n=8.4 million) in Somalia were under hypoendemic transmission (≤10% PfPR2–10). Of these, 23% of the districts, home to 13% of the population, were under transmission of <1% PfPR2–10. About 58% of the districts and 55% of the population were in the risk class of 1% to <5% PfPR2–10. In contrast, the receptivity map estimated 65% of the districts and 69% of the population were under mesoendemic transmission (>10%–50% PfPR2–10) and the rest as hypoendemic. Conclusion Compared with maps of receptive risks, contemporary maps of transmission mask disparities of malaria risk necessary to prioritise and sustain future control. As malaria risk declines across Africa, efforts must be invested in measuring receptivity for efficient control planning. PMID:22855625

CYP-dependent metabolism of PF9601N, a new monoamine oxidase-B inhibitor, by C57BL/6 mouse and human liver microsomes.

PubMed

Dragoni, Stefania; Materozzi, Giada; Pessina, Federica; Frosini, Maria; Marco, José Luis; Unzeta, Mercedes; Sgaragli, Giampietro; Valoti, Massimo

2007-01-01

The selective monoamine oxidase-B (MAO-B) inhibitor, l-deprenyl, is still used for treating Parkinson's patients, however, a disadvantage of its use lies in the formation of l-amphetamine and l-methamphetamine. Subsequently, this has promoted the design of a novel, more potent, MAO-B inhibitor PF9601N, which also has neuroprotective and antioxidant properties. The aim of this work was to investigate the effect of treatment with PF9601N on its own phase I hepatic metabolism. Kinetic parameters of PF9601N CYP-dependent N-dealkylation reaction was also studied and compared with those of l-deprenyl. C57BL/6 mice were treated with PF9601N for 4 days. After CYP content and related monooxygenase activities were assayed in liver microsomes of control and treated animals. CYP activities, cytochrome b5 content, NADPH-cytochrome P450 reductase and various monooxygenase activities were unaffected by in vivo PF9601N treatment. With microsomes from both control and treated mice, the PF9601N-dealkylation product, FA72, was the only detected metabolite with its formation rate following an hyperbolic, Michaelis-Menten curve. Among various inhibitors, only ketoconazole inhibited the FA72 formation rate, indicating a major involvement for CYP3A. Apparent Km and Vmax values generated by human liver microsomes were similar to those found with mouse microsomes. Ketoconazole inhibition indicates that CYP3A is one of the major enzymes involved in PF9601N metabolism also by human liver microsomes. In mouse liver microsomes, the intrinsic clearance of PF9601N was significantly lower than that of l-deprenyl suggestive of an improved bioavailability for the former. The observed favourable metabolic profile may suggest suitability of PF9601N for clinical use.

Clinical Characteristics and Outcomes Are Similar in ARDS Diagnosed by Oxygen Saturation/Fio2 Ratio Compared With Pao2/Fio2 Ratio

PubMed Central

Janz, David R.; Shaver, Ciara M.; Bernard, Gordon R.; Bastarache, Julie A.; Ware, Lorraine B.

2015-01-01

BACKGROUND: Oxygen saturation as measured by pulse oximetry/Fio2 (SF) ratio is highly correlated with the Pao2/Fio2 (PF) ratio in patients with ARDS. However, it remains uncertain whether SF ratio can be substituted for PF ratio for diagnosis of ARDS and whether SF ratio might identify patients who are systemically different from patients diagnosed by PF ratio. METHODS: We conducted a secondary analysis of a large observational prospective cohort study. Patients were eligible if they were admitted to the medical ICU and fulfilled the Berlin definition of ARDS with hypoxemia criteria using either the standard PF threshold (PF ratio ≤ 300) or a previously published SF threshold (SF ratio ≤ 315). RESULTS: Of 362 patients with ARDS, 238 (66%) received a diagnosis by PF ratio and 124 (34%) by SF ratio. In a small group of patients who received diagnoses of ARDS by SF ratio who had arterial blood gas measurements on the same day (n = 10), the PF ratio did not meet ARDS criteria. There were no major differences in clinical characteristics or comorbidities between groups with the exception of APACHE (Acute Physiology and Chronic Health Evaluation) II scores, which were higher in the group diagnosed by PF ratio. However, this difference was no longer apparent when arterial blood gas-dependent variables (pH, Pao2) were removed from the APACHE II score. There were also no differences in clinical outcomes including duration of mechanical ventilation (mean, 7 days in both groups; P = .25), duration of ICU stay (mean, 10 days vs 9 days in PF ratio vs SF ratio; P = .26), or hospital mortality (36% in both groups, P = .9). CONCLUSIONS: Patients with ARDS diagnosed by SF ratio have very similar clinical characteristics and outcomes compared with patients diagnosed by PF ratio. These findings suggest that SF ratio could be considered as a diagnostic tool for early enrollment into clinical trials. PMID:26271028

Preliminary Studies of Ions Emission in a Small Plasma Focus Device of Hundreds of Joules

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

Moreno, Jose; Pavez, Cristian; Soto, Leopoldo

2009-01-21

Ion beam emission in plasma focus (PF) discharges was originally investigated to explain the strong forward anisotropy observed in the neutron. Several properties of PF emitted deuteron beams have been measured, including their angular distributions and energy spectra in devices operating with energies from 1 kJ to 1 MJ. At present there is a growing interest in the development of very small PF devices operating under 1 kJ. As part of the characterization program of the very low energy PF devices (<1 kJ) developed at the Chilean Nuclear Energy Commission, the charges particle emission in hydrogen (H{sub 2}) and mixturemore » (H{sub 2}+%Ar) are being studied. In order to obtain an estimation of the ions energy spectrum and ionization grade, by using time of flight method, a graphite collector system operating in the bias ion collector mode was constructed and it is being used. Preliminary results of the ion beams measurements in different experimental conditions, at a plasma focus device of 400 joules (PF-400 J) are presented.« less

High mobility group box (HMGB) proteins of Plasmodium falciparum: DNA binding proteins with pro-inflammatory activity.

PubMed

Kumar, Krishan; Singal, Ankita; Rizvi, M Moshahid A; Chauhan, Virander S

2008-06-01

High mobility group box chromosomal protein 1 (HMGB1), known as an abundant, non-histone architectural chromosomal protein, is highly conserved across different species. Homologues of HMGB1 were identified and cloned from malaria parasite, Plasmodium falciparum. Sequence analyses showed that the P. falciparum HMGB1 (PfHMGB1) exhibits 45, 23 and 18%, while PfHMGB2 shares 42, 21 and 17% homology with Saccharomyces cerevisiae, human and mouse HMG box proteins respectively. Parasite PfHMGB1and PfHMGB2 proteins contain one HMG Box domain similar to B-Box of mammalian HMGB1. Electrophoretic Mobility Shift Assay (EMSA) showed that recombinant PfHMGB1 and PfHMGB2 bind to DNA. Immunofluorescence Assay using specific antibodies revealed that these proteins are expressed abundantly in the ring stage nuclei. Significant levels of PfHMGB1 and PfHMGB2 were also present in the parasite cytosol at trophozoite and schizont stages. Both, PfHMGB1 and PfHMGB2 were found to be potent inducers of pro-inflammatory cytokines such as TNFalpha from mouse peritoneal macrophages as analyzed by both reverse transcription PCR and by ELISA. These results suggest that secreted PfHMGB1 and PfHMGB2 may be responsible for eliciting/ triggering host inflammatory immune responses associated with malaria infection.

The Plasmodium falciparum exported protein PF3D7_0402000 binds to erythrocyte ankyrin and band 4.1

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

Shakya, Bikash; Penn, Wesley D.; Nakayasu, Ernesto S.

Plasmodium falciparum extensively modifies the infected red blood cell (RBC), resulting in changes in deformability, shape and surface properties. These alterations suggest that the RBC cytoskeleton is a major target for modification during infection. However, the molecular mechanisms leading to these changes are largely unknown. To begin to address this question, we screened for exported P. falciparum proteins that bound to the erythrocyte cytoskeleton proteins ankyrin 1 (ANK1) and band 4.1 (4.1R), which form critical interactions with other cytoskeletal proteins that contribute to the deformability and stability of RBCs. Yeast two-hybrid screens with ANK1 and 4.1R identified eight interactions withmore » P. falciparum exported proteins, including an interaction between 4.1R and PF3D7_0402000 (PFD0090c). This interaction was first identified in a large-scale screen (Vignali et al., Malaria J, 7:211, 2008), which also reported an interaction between PF3D7_0402000 and ANK1. We confirmed the interactions of PF3D7_0402000 with 4.1R and ANK1 in pair-wise yeast two-hybrid and co-precipitation assays. In both cases, an intact PHIST domain in PF3D7_0402000 was required for binding. Complex purification followed by mass spectrometry analysis provided additional support for the interaction of PF3D7_0402000 with ANK1 and 4.1R. RBC ghost cells loaded with maltose-binding protein (MBP)-PF3D7_0402000 passed through a metal microsphere column less efficiently than mock- or MBP-loaded controls, consistent with an effect of PF3D7_0402000 on RBC rigidity or membrane stability. This study confirmed the interaction of PF3D7_0402000 with 4.1R in multiple independent assays, provided the first evidence that PF3D7_0402000 also binds to ANK1, and suggested that PF3D7_0402000 affects deformability or membrane stability of uninfected RBC ghosts.« less

Sterile protection against human malaria by chemoattenuated PfSPZ vaccine.

PubMed

Mordmüller, Benjamin; Surat, Güzin; Lagler, Heimo; Chakravarty, Sumana; Ishizuka, Andrew S; Lalremruata, Albert; Gmeiner, Markus; Campo, Joseph J; Esen, Meral; Ruben, Adam J; Held, Jana; Calle, Carlos Lamsfus; Mengue, Juliana B; Gebru, Tamirat; Ibáñez, Javier; Sulyok, Mihály; James, Eric R; Billingsley, Peter F; Natasha, K C; Manoj, Anita; Murshedkar, Tooba; Gunasekera, Anusha; Eappen, Abraham G; Li, Tao; Stafford, Richard E; Li, Minglin; Felgner, Phil L; Seder, Robert A; Richie, Thomas L; Sim, B Kim Lee; Hoffman, Stephen L; Kremsner, Peter G

2017-02-23

A highly protective malaria vaccine would greatly facilitate the prevention and elimination of malaria and containment of drug-resistant parasites. A high level (more than 90%) of protection against malaria in humans has previously been achieved only by immunization with radiation-attenuated Plasmodium falciparum (Pf) sporozoites (PfSPZ) inoculated by mosquitoes; by intravenous injection of aseptic, purified, radiation-attenuated, cryopreserved PfSPZ ('PfSPZ Vaccine'); or by infectious PfSPZ inoculated by mosquitoes to volunteers taking chloroquine or mefloquine (chemoprophylaxis with sporozoites). We assessed immunization by direct venous inoculation of aseptic, purified, cryopreserved, non-irradiated PfSPZ ('PfSPZ Challenge') to malaria-naive, healthy adult volunteers taking chloroquine for antimalarial chemoprophylaxis (vaccine approach denoted as PfSPZ-CVac). Three doses of 5.12 × 10 4 PfSPZ of PfSPZ Challenge at 28-day intervals were well tolerated and safe, and prevented infection in 9 out of 9 (100%) volunteers who underwent controlled human malaria infection ten weeks after the last dose (group III). Protective efficacy was dependent on dose and regimen. Immunization with 3.2 × 10 3 (group I) or 1.28 × 10 4 (group II) PfSPZ protected 3 out of 9 (33%) or 6 out of 9 (67%) volunteers, respectively. Three doses of 5.12 × 10 4 PfSPZ at five-day intervals protected 5 out of 8 (63%) volunteers. The frequency of Pf-specific polyfunctional CD4 memory T cells was associated with protection. On a 7,455 peptide Pf proteome array, immune sera from at least 5 out of 9 group III vaccinees recognized each of 22 proteins. PfSPZ-CVac is a highly efficacious vaccine candidate; when we are able to optimize the immunization regimen (dose, interval between doses, and drug partner), this vaccine could be used for combination mass drug administration and a mass vaccination program approach to eliminate malaria from geographically defined areas.

Effects of 17β-estradiol on the release of monocyte chemotactic protein-1 and MAPK activity in monocytes stimulated with peritoneal fluid from endometriosis patients.

PubMed

Lee, Dong-Hyung; Kim, Seung-Chul; Joo, Jong-Kil; Kim, Hwi-Gon; Na, Young-Jin; Kwak, Jong-Young; Lee, Kyu-Sup

2012-03-01

Hormones and inflammation have been implicated in the pathological process of endometriosis; therefore, we investigated the combined effects of 17β-estradiol (E2) and peritoneal fluid obtained from patients with endometriosis (ePF) or a control peritoneal fluid (cPF) obtained from patients without endometriosis on the release of monocyte chemotactic protein-1 (MCP-1) by monocytes and the role of signaling pathways. Monocytes were cultured with ePF and cPF in the presence of E2; the MCP-1 levels in the supernatants were then measured by ELISA. In addition, mitogen activated protein kinase (MAPK) activation was measured by Western blotting of phosphorylated proteins. E2 down-regulated MCP-1 release by lipopolysaccharide- or cPF-treated monocytes, but failed to suppress its release by ePF-treated monocytes. The release of MCP-1 by ePF- and cPF-treated monocytes was efficiently abrogated by p38 mitogen activated protein kinase (MAPK) inhibitors; however, the MCP-1 release by cPF-treated monocytes, but not by ePF-treated monocytes, was blocked by a MAPK kinase inhibitor. In addition, ePF and cPF induced the phosphorylation of extracellular stress regulated kinase (ERK)1/2, p38 MAPK and c-Jun N-terminal kinase (JNK). E2 decreased the phosphorylation of p38 MAPK, but not ERK1/2 in ePF-treated monocytes; however, E2 decreased the phosphorylation of p38 MAPK, ERK1/2 and JNK in cPF-treated monocytes. The ability of E2 to modulate MCP-1 production is impaired in ePF-treated monocytes, which may be related to regulation of MAPK activity. These findings suggest that the failure of E2 to suppress ePF-treated production of MCP-1 may be involved in the pathogenesis of endometriosis. © 2012 The Authors. Journal of Obstetrics and Gynaecology Research © 2012 Japan Society of Obstetrics and Gynecology.

The Pavlovian power of palatable food: lessons for weight-loss adherence from a new rodent model of cue-induced overeating

PubMed Central

Boggiano, M M; Dorsey, J R; Thomas, J M; Murdaugh, D L

2009-01-01

Objective Relapsing to overeating is a stubborn problem in obesity treatment. We tested the hypothesis that context cues surrounding palatable food (PF) intake have the power to disrupt caloric regulation even of less PF. Context cues are non-food cues that are in the environment where PF is habitually eaten. Design Rats were conditioned to associate intake of Oreo cookies as the PF to cages with distinct context cues that differed from cues in cages were they were only given chow. PF naturally stimulated greater caloric intake. The rats were then tested in the PF cage with only chow available to determine if the PF-paired cues, alone, could elicit overeating of plain chow. Subjects Non food-deprived female Sprague-Dawley rats. Measurements Intake of plain chow under PF-paired cues vs. chow-paired cues was compared. This was also measured in tests that included a morsel of PF as a priming stimulus. We also controlled for any effect of binge-prone vs. binge–resistant status to predict cued-overeating. Results Rats consumed significantly more chow when exposed to context cues previously paired with PF than with chow (p<0.01). This effect occurred using various cues (e.g., different types of bedding or wallpaper). The effect was strengthened by priming with a morsel of PF (p<0.001) and was unaffected by baseline differences in propensity to binge on PF. Conclusion Context-cues associated with PF intake can drive overeating even of a less PF and abolish the ability of rats to compensate for the calories of a PF primer. Just as drug-associated context cues can reinstate drug-addiction relapse, PF-paired cues may trigger overeating relapses linked to weight regain and obesity. This model should help identify the reflex-like biology that sabotages attempts to adhere to healthy reduced calorie regimens and call greater attention to the cue-factor in the treatment of binge-eating and obesity. PMID:19350040

Pharmacokinetics and C-Reactive Protein Modelling of Anti-IL-6 Antibody (PF-04236921) in Healthy Volunteers and Patients with Autoimmune Disease.

PubMed

Li, Cheryl; Shoji, Satoshi; Beebe, Jean

2018-05-18

The purpose of this study was to characterize pharmacokinetics (PK) of PF-04236921, a novel anti-IL-6 monoclonal antibody, and its pharmacokinetics/pharmacodynamics (PK/PD) relationship on serum C-Reactive Protein (CRP) in healthy volunteers and patients with rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and Crohn's disease (CD) METHODS: Population modelling analyses were conducted using nonlinear mixed effects modelling. Data from 2 phase 1 healthy volunteer studies, a phase 1 RA study, a Phase 2 CD study, and a Phase 2 SLE study were included. A 2-compartment model with first order absorption and linear elimination and a mechanism-based indirect response model adequately described the PK and PK/PD relationships, respectively. Central compartment volume of distribution (Vc) positively correlated with body weight. Clearance (CL) negatively correlated with baseline albumin concentration and positively correlated with baseline CRP and creatinine clearance, and was slightly lower in females. After correcting for covariates, CL in CD subjects was approximately 60% higher than other populations. Maximum inhibition of PF-04236921 on CRP production (I max ) negatively correlated with baseline albumin. I max positively correlated with baseline CRP and the relationship was captured as a covariance structure in the PK/PD model. Integrated population PK and PK/PD models of PF-04236921 have been developed using pooled data from healthy subjects and autoimmune patients. The current model enables simulation of PF-04236921 PK and PD profiles under various dosing regimens and patient populations and should facilitate future clinical study of PF-04236921 and other anti-IL6 monoclonal antibodies. This article is protected by copyright. All rights reserved.

Precise orbit determination using the batch filter based on particle filtering with genetic resampling approach

NASA Astrophysics Data System (ADS)

Kim, Young-Rok; Park, Eunseo; Choi, Eun-Jung; Park, Sang-Young; Park, Chandeok; Lim, Hyung-Chul

2014-09-01

In this study, genetic resampling (GRS) approach is utilized for precise orbit determination (POD) using the batch filter based on particle filtering (PF). Two genetic operations, which are arithmetic crossover and residual mutation, are used for GRS of the batch filter based on PF (PF batch filter). For POD, Laser-ranging Precise Orbit Determination System (LPODS) and satellite laser ranging (SLR) observations of the CHAMP satellite are used. Monte Carlo trials for POD are performed by one hundred times. The characteristics of the POD results by PF batch filter with GRS are compared with those of a PF batch filter with minimum residual resampling (MRRS). The post-fit residual, 3D error by external orbit comparison, and POD repeatability are analyzed for orbit quality assessments. The POD results are externally checked by NASA JPL’s orbits using totally different software, measurements, and techniques. For post-fit residuals and 3D errors, both MRRS and GRS give accurate estimation results whose mean root mean square (RMS) values are at a level of 5 cm and 10-13 cm, respectively. The mean radial orbit errors of both methods are at a level of 5 cm. For POD repeatability represented as the standard deviations of post-fit residuals and 3D errors by repetitive PODs, however, GRS yields 25% and 13% more robust estimation results than MRRS for post-fit residual and 3D error, respectively. This study shows that PF batch filter with GRS approach using genetic operations is superior to PF batch filter with MRRS in terms of robustness in POD with SLR observations.

Motor Imagery Practice for Enhancing Elevé Performance Among Professional Dancers: A Pilot Study.

PubMed

Abraham, Amit; Dunsky, Ayelet; Dickstein, Ruth

2016-09-01

Elevé is a core dance movement requiring the greatest ankle plantarflexion (PF) range of motion (ROM). One possible way to enhance elevé performance is by using motor imagery practice (MIP). The aims of this pilot study were to investigate: 1) functional ankle PF maximal angles and ROM while performing elevé among professional dancers, 2) the effect of MIP on enhancing elevé performance, and 3) participants' views on the MIP intervention and its feasibility in a professional dance company setting. Five professional dancers, mean age 31 yrs (SD 1.87), participated in a 2-week MIP intervention. Data on ankle PF maximal angles and ROM were collected pre- and post-intervention using 3-dimensional motion capture while performing repeat (10 repetitions) and static (10 sec) elevé. At baseline, ankle PF maximal angles were 169.20° (SD 2.81°) and 168.36° (2.23°) and ankle PF ROM were 40.21° (3.35°) and 35.94° (3.95°) for the repeat and static tasks, respectively. After the MIP intervention, ankle PF maximal angles were 170.28° (4.26°) and 170.74° (3.77°) and ankle PF ROM were 41.53° (2.33°) and 39.30° (2.30°) for the repeat and static tasks, respectively. Feasibility of MIP was established with 100% compliance and positive views were expressed by participants. The results suggest MIP holds potential as an adjunct training method for enhancing elevé performance among professional dancers.

Forward and Backward Aortic Components and Reflection Indexes in Children and Adolescents: Determinants and Role in High Pressure States.

PubMed

Zocalo, Yanina; Castro, Juan M; Garcia-Espinosa, Victoria; Curcio, Santiago; Chiesa, Pedro; Giachetto, Gustavo; Cabrera-Fischer, Edmundo I; Bia, Daniel

2018-04-12

High blood pressure states (HBP) would differ in wave components and reflections indexes, which could associate clinical and prognostic implications. 1) to characterize the association of aortic wave components and reflection parameters (backward [Pb], forward [Pf], Pb/Pf ratio and augmentation index [AIx]) with demographic, anthropometric, hemodynamic and arterial parameters in healthy children and adolescents; 2) to generate multivariate prediction models for the associations, to contribute to understand main determinants of Pf, Pb, Pb/Pf and AIx; 3) to identify if differences in wave reflection indexes observed in HBP could be explained by differences in the analyzed parameters. Healthy children and adolescents (n=816, females: 386; Age: 3-20 years) were studied. central aortic pressure and wave components (Pb, Pf, Pb/Pf and AIx determination with SphygmoCor [SCOR] and Mobil-o-Graph [MOG]); anthropometric assessment; regional arterial stiffness (carotid-femoral, carotid-radial pulse wave velocity [PWV] and PWV ratio); carotid intima-media thickness; carotid and femoral distensbility; cardiac output; systemic vascular resistances (SVR). Simple and multiple regression models were constructed to determine aortic wave parameters main explanatory variables. Normotensive and HBP groups were compared. Differences in wave reflection indexes were analyzed before and after controlling for explanatory variables. Equivalences between SphygmoCor and Mobil-O-Graph data were assessed (correlation and Bland-Altman analyses). There were systematic and proportional differences between data obtained with SphygmoCor and Mobil-O-Graph devices. Heart rate (HR), peripheral pulse pressure, height and weight were the variables that isolated (simple associations) or combined (multiple associations) showed the major capability to explain interindividual differences in Pf, Pb, Pb/Pf and AIx. Arterial stiffness also showed explanatory capacity, being the carotid the artery with major contribution. HBP associated higher Pf, Pb, AIx and lower Pb/Pf ratio. Those findings were observed together with higher weight, arterial stiffness and HR. After adjusting for anthropometric characteristics, HR, cardiac output and SVR, the HBP group showed greater Pf and Pb. Then, Pf and Pb characteristics associated with HBP would not be explained by anthropometric or hemodynamic factors. To evaluate wave components and reflection parameters could contribute to improve comprehension and management of HBP states. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Plasmodium falciparum ookinete expression of plasmepsin VII and plasmepsin X.

PubMed

Li, Fengwu; Bounkeua, Viengngeun; Pettersen, Kenneth; Vinetz, Joseph M

2016-02-24

Plasmodium invasion of the mosquito midgut is a population bottleneck in the parasite lifecycle. Interference with molecular mechanisms by which the ookinete invades the mosquito midgut is one potential approach to developing malaria transmission-blocking strategies. Plasmodium aspartic proteases are one such class of potential targets: plasmepsin IV (known to be present in the asexual stage food vacuole) was previously shown to be involved in Plasmodium gallinaceum infection of the mosquito midgut, and plasmepsins VII and plasmepsin X (not known to be present in the asexual stage food vacuole) are upregulated in Plasmodium falciparum mosquito stages. These (and other) parasite-derived enzymes that play essential roles during ookinete midgut invasion are prime candidates for transmission-blocking vaccines. Reverse transcriptase PCR (RT-PCR) was used to determine timing of P. falciparum plasmepsin VII (PfPM VII) and plasmepsin X (PfPM X) mRNA transcripts in parasite mosquito midgut stages. Protein expression was confirmed by western immunoblot and immunofluorescence assays (IFA) using anti-peptide monoclonal antibodies (mAbs) against immunogenic regions of PfPM VII and PfPM X. These antibodies were also used in standard membrane feeding assays (SMFA) to determine whether inhibition of these proteases would affect parasite transmission to mosquitoes. The Mann-Whitney U test was used to analyse mosquito transmission assay results. RT-PCR, western immunoblot and immunofluorescence assay confirmed expression of PfPM VII and PfPM X in mosquito stages. Whereas PfPM VII was expressed in zygotes and ookinetes, PfPM X was expressed in gametes, zygotes, and ookinetes. Antibodies against PfPM VII and PfPM X decreased P. falciparum invasion of the mosquito midgut when used at high concentrations, indicating that these proteases play a role in Plasmodium mosquito midgut invasion. Failure to generate genetic knockouts of these genes limited determination of the precise role of these proteases in parasite transmission but suggests that they are essential during the intraerythrocytic life cycle. PfPM VII and PfPM X are present in the mosquito-infective stages of P. falciparum. Standard membrane feeding assays demonstrate that antibodies against these proteins reduce the infectivity of P. falciparum for mosquitoes, suggesting their viability as transmission-blocking vaccine candidates. Further study of the role of these plasmepsins in P. falciparum biology is warranted.

Multiple Drugs Compete for Transport via the Plasmodium falciparum Chloroquine Resistance Transporter at Distinct but Interdependent Sites*

PubMed Central

Bellanca, Sebastiano; Summers, Robert L.; Meyrath, Max; Dave, Anurag; Nash, Megan N.; Dittmer, Martin; Sanchez, Cecilia P.; Stein, Wilfred D.; Martin, Rowena E.; Lanzer, Michael

2014-01-01

Mutations in the “chloroquine resistance transporter” (PfCRT) are a major determinant of drug resistance in the malaria parasite Plasmodium falciparum. We have previously shown that mutant PfCRT transports the antimalarial drug chloroquine away from its target, whereas the wild-type form of PfCRT does not. However, little is understood about the transport of other drugs via PfCRT or the mechanism by which PfCRT recognizes different substrates. Here we show that mutant PfCRT also transports quinine, quinidine, and verapamil, indicating that the protein behaves as a multidrug resistance carrier. Detailed kinetic analyses revealed that chloroquine and quinine compete for transport via PfCRT in a manner that is consistent with mixed-type inhibition. Moreover, our analyses suggest that PfCRT accepts chloroquine and quinine at distinct but antagonistically interacting sites. We also found verapamil to be a partial mixed-type inhibitor of chloroquine transport via PfCRT, further supporting the idea that PfCRT possesses multiple substrate-binding sites. Our findings provide new mechanistic insights into the workings of PfCRT, which could be exploited to design potent inhibitors of this key mediator of drug resistance. PMID:25378409

Evaluation of a Plasmodium-Specific Carrier Protein To Enhance Production of Recombinant Pfs25, a Leading Transmission-Blocking Vaccine Candidate.

PubMed

Parzych, Elizabeth M; Miura, Kazutoyo; Ramanathan, Aarti; Long, Carole A; Burns, James M

2018-01-01

Challenges with the production and suboptimal immunogenicity of malaria vaccine candidates have slowed the development of a Plasmodium falciparum multiantigen vaccine. Attempting to resolve these issues, we focused on the use of highly immunogenic merozoite surface protein 8 (MSP8) as a vaccine carrier protein. Previously, we showed that a genetic fusion of the C-terminal 19-kDa fragment of merozoite surface protein 1 (MSP1 19 ) to P. falciparum MSP8 ( Pf MSP8) facilitated antigen production and folding and the induction of neutralizing antibodies to conformational B cell epitopes of MSP1 19 Here, using the Pf MSP1/8 construct, we further optimized the recombinant Pf MSP8 (r Pf MSP8) carrier by the introduction of two cysteine-to-serine substitutions (CΔS) to improve the yield of the monomeric product. We then sought to test the broad applicability of this approach using the transmission-blocking vaccine candidate Pf s25. The production of r Pf s25-based vaccines has presented challenges. Antibodies directed against the four highly constrained epidermal growth factor (EGF)-like domains of Pf s25 block sexual-stage development in mosquitoes. The sequence encoding mature Pf s25 was codon harmonized for expression in Escherichia coli We produced a r Pf s25- Pf MSP8 fusion protein [r Pf s25/8(CΔS)] as well as unfused, mature r Pf s25. r Pf s25 was purified with a modest yield but required the incorporation of refolding protocols to obtain a proper conformation. In comparison, chimeric r Pf s25/8(CΔS) was expressed and easily purified, with the Pf s25 domain bearing the proper conformation without renaturation. Both antigens were immunogenic in rabbits, inducing IgG that bound native Pf s25 and exhibited potent transmission-reducing activity. These data further demonstrate the utility of Pf MSP8 as a parasite-specific carrier protein to enhance the production of complex malaria vaccine targets. Copyright © 2017 American Society for Microbiology.

A comparative study on the effects of amphiphilic and hydrophilic polymers on the release profiles of a poorly water-soluble drug.

PubMed

Irwan, Anastasia W; Berania, Jacqueline E; Liu, Xueming

2016-03-01

This paper reports the use of two crystalline polymers, an amphiphilic Pluronic® F-127 (PF-127) and a hydrophilic poly(ethylene glycol) (PEG6000) as drug delivery carriers for improving the drug release of a poorly water-soluble drug, fenofibrate (FEN), via micelle formation and formation of a solid dispersion (SD). In 10% PF-127 (aq.), FEN showed an equilibrium solubility of ca. 0.6 mg/mL, due to micelle formation. In contrast, in 10% PEG6000 (aq.), FEN only exhibited an equilibrium solubility of 0.0037 mg/mL. FEN-loaded micelles in PF-127 were prepared by direct dissolution and membrane dialysis. Both methods only yielded a highest drug loading (DL) of 0.5%. SDs of FEN in PF-127 and PEG6000, at DLs of 5-80%, were prepared by solvent evaporation. In-vitro dissolution testing showed that both micelles and SDs significantly improved FEN's release rate. The SDs of FEN in PF-127 showed significantly faster release than crystalline FEN, when the DL was as high as 50%, whereas SDs of PEG6000 showed similar enhancement in the release rate when the DL was not more than 20%. The DSC thermograms of SDs of PF-127 exhibited a single phase transition peak at ca. 55-57 °C when the DL was not more than 50%, whereas those in PEG6000 exhibited a similar peak at ca. 61-63 °C when the DL was not more than 35%. When the DL exceeded 50% for SDs of PF-127 and 35% for SDs of PEG6000, DSC thermograms showed two melting peaks for the carrier polymer and FEN, respectively. FT-IR studies revealed that PF-127 has a stronger hydrophobic-hydrophobic interaction with FEN than PEG6000. It is likely that both dispersion and micelle formation contributed to the stronger effect of PF-127 on enhancing the release rate of FEN in its SDs.

Plasmodium falciparum Calcium-Dependent Protein Kinase 2 Is Critical for Male Gametocyte Exflagellation but Not Essential for Asexual Proliferation.

PubMed

Bansal, Abhisheka; Molina-Cruz, Alvaro; Brzostowski, Joseph; Mu, Jianbing; Miller, Louis H

2017-10-17

Drug development efforts have focused mostly on the asexual blood stages of the malaria parasite Plasmodium falciparum Except for primaquine, which has its own limitations, there are no available drugs that target the transmission of the parasite to mosquitoes. Therefore, there is a need to validate new parasite proteins that can be targeted for blocking transmission. P. falciparum calcium-dependent protein kinases ( Pf CDPKs) play critical roles at various stages of the parasite life cycle and, importantly, are absent in the human host. These features mark them as attractive drug targets. In this study, using CRISPR/Cas9 we successfully knocked out Pf CDPK2 from blood-stage parasites, which was previously thought to be an indispensable protein. The growth rate of the Pf CDPK2 knockout (KO) parasites was similar to that of wild-type parasites, confirming that Pf CDPK2 function is not essential for the asexual proliferation of the parasite in vitro The mature male and female gametocytes of Pf CDPK2 KO parasites become round after induction. However, they fail to infect female Anopheles stephensi mosquitoes due to a defect(s) in male gametocyte exflagellation and possibly in female gametes. IMPORTANCE Despite reductions in the number of deaths it causes, malaria continues to be a leading infectious disease of the developing world. For effective control and elimination of malaria, multiple stages of the parasite need to be targeted. One such stage includes the transmission of the parasite to mosquitoes. Here, we demonstrate the successful knockout of Pf CDPK2, which was previously thought to be indispensable for parasite growth in red blood cells. The Pf CDPK2 KO parasites are incapable of establishing an infection in mosquitoes. Therefore, our study suggests that targeting Pf CDPK2 may be a good strategy to control malaria transmission in countries with high transmission. Moreover, molecular understanding of the signaling pathway of Pf CDPK2 may provide additional targets for malaria control. Copyright © 2017 Bansal et al.

Use of PROMIS for Patients Undergoing Primary Total Shoulder Arthroplasty

PubMed Central

Dowdle, S. Blake; Glass, Natalie; Anthony, Chris A.; Hettrich, Carolyn M.

2017-01-01

Background: The Patient-Reported Outcomes Measurement Information System (PROMIS) consists of question banks for health domains through computer adaptive testing (CAT). Hypothesis: For patients with glenohumeral arthritis, (1) there would be high correlation between traditional patient-reported outcome (PRO) measures and the PROMIS upper extremity item bank (PROMIS UE) and PROMIS physical function CAT (PROMIS PF CAT), and (2) PROMIS PF CAT would not demonstrate ceiling effects. Study Design: Cohort study (diagnosis); Level of evidence, 3. Methods: Sixty-one patients with glenohumeral osteoarthritis were included. Each patient completed the American Shoulder and Elbow Surgeons (ASES) assessment form, Marx Shoulder Activity Scale, Short Form–36 physical function scale (SF-36 PF), EuroQol 5 Dimensions (EQ-5D) questionnaire, Western Ontario Osteoarthritis Shoulder (WOOS) index, PROMIS PF CAT, and the PROMIS UE. Correlation was defined as high (>0.7), moderate (0.4-0.6), or weak (0.2-0.3). Significant floor and ceiling effects were present if more than 15% of individuals scored the lowest or highest possible total score on any PRO. Results: The PROMIS PF demonstrated excellent correlation with the SF-36 PF (r = 0.81, P < .0001) and good correlation with the ASES (r = 0.62, P < .0001), EQ-5D (r = 0.64, P < .001), and WOOS index (r = 0.51, P < .01). The PROMIS PF demonstrated low correlation with the Marx scale (r = 0.29, P = .02). The PROMIS UE demonstrated good correlation with the ASES (r = 0.55, P < .0001), SF-36 (r = 0.53, P < .01), EQ-5D (r = 0.48, P < .01), and WOOS (r = 0.34, P <.01), and poor correlation with the Marx scale (r = 0.06, P = .62). There were no ceiling or floor effects observed. The mean number of items administered by the PROMIS PRO was 4. Conclusion: These data suggest that for a patient population with operative shoulder osteoarthritis, PROMIS UE and PROMIS PF CAT may be valid alternative PROs. Additionally, PROMIS PF CAT offers a decreased question burden with no ceiling effects. PMID:28944248

A critical period for functional vestibular development in zebrafish

NASA Technical Reports Server (NTRS)

Moorman, Stephen J.; Cordova, Rodolfo; Davies, Sarah A.

2002-01-01

We have determined a critical period for vestibular development in zebrafish by using a bioreactor designed by NASA to simulate microgravity for cells in culture. A critical period is defined as the briefest period of time during development when stimulus deprivation results in long lasting or permanent sensory deficits. Zebrafish eggs were collected within 3 hours of being laid and fertilized. In experiment 1, eggs were placed in the bioreactor at 3, 24, 30, 36, 48, or 72 hours postfertilization (hPF) and maintained in the bioreactor until 96 hPF. In experiment 2, eggs were placed in the bioreactor immediately after they were collected and maintained in the bioreactor until 24, 36, 48, 60, 66, 72, or 96 hPF. Beginning at 96 hPF, all larvae had their vestibulo-ocular reflexes (VOR) evaluated once each day for 5 days. Only larvae that hatched from eggs that were placed in the bioreactor before 30 hPF in experiment 1 or removed from the bioreactor later than 66 hPF in experiment 2 had VOR deficits that persisted for at least 5 days. These data suggest a critical period for vestibular development in the zebrafish that begins before 30 hPF and ends after 66 hPF. To confirm this, zebrafish eggs were placed in the bioreactor at 24 hPF and removed at 72 hPF. VORs were evaluated in these larvae once each day for 5 days beginning at 96 hPF. These larvae had VOR deficits that persisted for at least 5 days. In addition, larvae that had been maintained in the bioreactor from 24 to 66 hPF or from 30 to 72 hPF, had only temporary VOR deficits. In a final experiment, zebrafish eggs were placed in the bioreactor at 3 hPF and removed at 96 hPF but the bioreactor was turned off from 24 hPF to 72 hPF. These larvae had normal VORs when they were removed from the bioreactor at 96 hPF. Taken as a whole, these data support the idea that there is a critical period for functional maturation of the zebrafish vestibular system. The developmental period identified includes the timeframe during which the vestibular primary afferent neurons are born, innervate their central and peripheral targets, and remodel their central projections. Copyright 2002 Wiley-Liss, Inc.

Effects of peritoneal fluid from endometriosis patients on the release of monocyte-specific chemokines by leukocytes.

PubMed

Na, Yong-Jin; Lee, Dong-Hyung; Kim, Seung-Chul; Joo, Jong-Kil; Wang, Ji-Won; Jin, Jun-O; Kwak, Jong-Young; Lee, Kyu-Sup

2011-06-01

Chemokines have been implicated in the pathological process of endometriosis. We compared the effects of peritoneal fluid obtained from patients with endometriosis (ePF) and controls without endometriosis (cPF) on the release of monocyte-specific CC chemokines such as monocyte chemotactic protein-1 (MCP-1), regulated upon activation normal T cell expressed and secreted (RANTES), and macrophage inflammatory protein-1α (MIP-1α) by neutrophils, monocytes, and T cells. Moreover, we evaluated the correlation between the levels of chemokines in ePF and their release by these cells. Cells were obtained from healthy young volunteers and cultured with ePF (n = 12) or cPF (n = 8). The chemokine levels in the ePF and the supernatants of cultured cells with ePF were then measured by ELISA. There was a positive correlation between the levels of MCP-1 and MIP-1α in ePF. The addition of ePF to the cell cultures failed to increase the release of MCP-1, RANTES, and MIP-1α when compared to cPF, but the levels of RANTES in ePF were positively correlated with the release of RANTES by ePF-treated monocytes and T cells. Moreover, there was a positive correlation between the levels of RANTES and MIP-1α released by neutrophils and between the levels of MCP-1 and MIP-1α released by T cells. Finally, the levels of RANTES released by monocyte-derived macrophages and monocytes cultured with ePF were positively correlated. These findings suggest that monocytes, neutrophils, and T cells release differential levels of MCP-1, RANTES, and MIP-1α in response to stimulation with ePF.

Implications of Parasites Lacking Plasmodium falciparum Histidine-Rich Protein 2 on Malaria Morbidity and Control When Rapid Diagnostic Tests Are Used for Diagnosis.

PubMed

Gatton, Michelle L; Dunn, Jessica; Chaudhry, Alisha; Ciketic, Sadmir; Cunningham, Jane; Cheng, Qin

2017-04-01

Rapid diagnostic tests (RDTs) are an important tool for malaria diagnosis, with most using antibodies against Plasmodium falciparum histidine-rich protein 2 (PfHRP2). Reports of P. falciparum lacking this protein are increasing, creating a problem for diagnosis of falciparum malaria in locations without quality-assured microscopy. An agent-based stochastic simulation model of P. falciparum transmission was used to investigate the selective pressure exerted on parasite populations by use of RDTs for diagnosis of symptomatic cases. The model considered parasites with normal, reduced, or no PfHRP2, and diagnosis using PfHRP2-only or combination RDTs. Use of PfHRP2-only RDTs in communities where a PfHRP2-negative parasite was introduced during the simulation resulted in transmission of the parasite in >80% of cases, compared with <30% for normal or PfHRP2-reduced parasites. Using PfHRP2-only RDTs in the presence of PfHRP2-negative parasites caused an increase in prevalence, reduced RDT positivity within symptomatic patients but no change in the number of antimalarial treatments due to false-negative RDT results. Diagnosis with PfHRP2/Pf-Plasmodium lactate dehydrogenase combination RDTs did not select for PfHRP2-negative parasites. The use of PfHRP2-only RDTs is sufficient to select P. falciparum parasites lacking this protein, thus posing a significant public health problem, which could be moderated by using PfHRP2/Pf-Plasmodium lactate dehydrogenase combination RDTs. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

[Evidence of pudendal neuropathy in Proctalgia Fugax: perineal neurophysiological assessment in 55 patients].

PubMed

Damphousse, M; Jousse, M; Verollet, D; Guinet, A; Le Breton, F; Lacroix, P; Sheik Ismael, S; Amarenco, G

2012-04-01

Proctalgia fugax (PF) is a very common condition especially in women. Causes and pathophysiological mechanisms of PF are unknown. Recently, a pudendal neuropathy was clinically suspected in women with PF. The goal of our study was to demonstrate, or not, such abnormalities by means electrophysiological testing. Fifty-five patients with PF (45 female and 10 male, mean age 50.2 years) were evaluated. EMG testing with motor unit potential analysis of pelvic floor muscles (bulbocavernosus muscle and striated external anal sphincter), study of bulbocavernosus reflex and pudendal nerve terminal motor latencies (PNTML) were performed. EMG testing was altered in two males out of 10 (20%) and 29/45 females (64%). In women, denervation was found bilateral in 25/29 (86%). Sacral latency was delayed in eight out of 29 (bilateral in five cases, unilateral in three cases) and PNTML altered in 17 cases (13 bilateral alteration, four unilateral). A significant difference (P<0.002 Chi(2) test) was demonstrated between male and female concerning pelvic floor muscles denervation. Pelvic floor muscles denervation was a common feature in women suffering from PF, due to a stretch bilateral pudendal neuropathy. Distal lesions of the pudendal nerves, principally due to a stretch perineal neuropathy, can be imagined as a factor or co-factor of PF. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

The effects of residual pump blood on patient plasma free haemoglobin levels post cardiac surgery.

PubMed

Schotola, H; Wetz, A J; Popov, A F; Bergmann, I; Danner, B C; Schöndube, F A; Bauer, M; Bräuer, A

2016-09-01

At the end of cardiopulmonary bypass, there are invariably several hundred millilitres of residual pump blood in the reservoir, which can either be re-transfused or discarded. The objective of this prospective observational study was to investigate the quality of the residual pump blood, focusing on plasma free haemoglobin (pfHb) and blood cell counts. Fifty-one consecutive patients were included in the study. Forty-nine units of residual pump blood and 58 units of transfused red blood cell (RBC) concentrates were analysed. The mean preoperative pfHb of the patients was 0.057 ± 0.062 g/l, which increased gradually to 0.55 ± 0.36 g/l on arrival in the intensive care unit postoperatively. On the first postoperative day, the mean pfHb had returned to within the normal range. Our data showed that haemoglobin, haematocrit, and erythrocyte counts of residual pump blood were approximately 40% of the values in standardised RBC concentrates. Plasma free haemoglobin was significantly higher in residual pump blood compared to RBC concentrates, and nearly twice as high as the pfHb in patient blood samples taken contemporaneously. Our findings indicate that residual pump blood pfHb levels are markedly higher compared to patients' blood and RBC concentrates, but that its administration does not significantly increase patients' pfHb levels.

A multilevel analysis of health-related physical fitness. The Portuguese sibling study on growth, fitness, lifestyle and health

PubMed Central

Pereira, Sara; Todd Katzmarzyk, Peter; Gomes, Thayse Natacha; Souza, Michele; Chaves, Raquel Nichele; dos Santos, Fernanda Karina; Santos, Daniel; Hedeker, Donald; Maia, José

2017-01-01

This study investigates biological, behavioural and sociodemographic correlates of intra-pair similarities, and estimates sibling resemblance in health-related physical fitness (PF). The sample comprises 1101 biological siblings (525 females) aged 9–20 years. PF components and markers were: morphological [waist circumference (WC) and %body fat (%BF)], muscular [handgrip strength (GS) and standing long jump (SLJ)], motor [50-yard dash (50YD) and shuttle run (SR)], and cardiorespiratory (1-mile run). Biological maturation was assessed; physical activity (PA), TV viewing and socioeconomic status (SES) information was obtained. On average, older and more mature subjects are better performers in all PF components; PA was negatively associated with SR, while SES was negatively associated with SLJ and SR. A pattern was observed in the intraclass correlations (ρ) wherein same sex siblings demonstrate greater resemblance for most PF components (sister-sister: 0.35≤ ρ≤0.55; brother-brother: (0.25≤ρ≤0.60) than brother-sister pairs (BS) (0≤ρ≤0.15), except for %BF (ρBB>ρSS>ρBS), and the 1-mile run (ρSS>ρBS>ρBB). In conclusion, behavioural and sociodemographic correlates play different roles in siblings PF expression. Further, a significant familial PF resemblance was observed with different trends in different sibling types, probably due to variations in shared genetic factors and sociodemographic conditions. PMID:28187195

Differences in ability to perform activities of daily living among women with fibromyalgia: A cross-sectional study.

PubMed

von Bülow, Cecilie; Amris, Kirstine; la Cour, Karen; Danneskiold-Samsøe, Bente; Ejlersen, Eva Wæhrens

2015-11-01

To investigate whether the Assessment of Motor and Process Skills (AMPS), the physical function subscales of the Fibromyalgia Impact Questionnaire (FIQ PF) and the 36-item Short Form (SF-36 PF) can identify subgroups of women with fibromyalgia with clinically relevant differences in ability to perform activities of daily living. Cross-sectional study. A total of 257 women with fibromyalgia. Participants were evaluated with the AMPS (measuring activities of daily living motor and activities of daily living process ability), FIQ and SF-36. AMPS independence cut-offs were used to divide the participants into 4 subgroups. Clinically relevant differences between subgroups were investigated based on the AMPS, FIQ PF and SF-36 PF. Participants in the 4 AMPS-derived subgroups demon-strated clinically relevant differences in observed activities of daily living motor and process ability. Neither the FIQ PF nor the SF-36 PF could differentiate between subgroups with clinically relevant differences in AMPS activities of daily living process ability. Activities of daily living process skills reflect underlying organizational and adaptive capacities of the individual and are relevant targets for interventions aiming at improving activities of daily living ability. Since self-report instruments do not capture differences in activities of daily living process ability, clinicians should include observations-based assessment of activities of daily living ability in order to individualize interventions offered.

The role of the CXC chemokines platelet factor-4 (CXCL4/PF-4) and its variant (CXCL4L1/PF-4var) in inflammation, angiogenesis and cancer.

PubMed

Vandercappellen, Jo; Van Damme, Jo; Struyf, Sofie

2011-02-01

Chemokines are chemotactic cytokines which recruit leukocytes to inflammatory sites. They also affect tumor development and metastasis by acting as growth factor, by attracting pro- or anti-tumoral leukocytes or by influencing angiogenesis. Platelet factor-4 (CXCL4/PF-4) was the first chemokine shown to inhibit angiogenesis. CXCL4L1/PF-4var, recently isolated from thrombin-stimulated platelets, differing from authentic CXCL4/PF-4 in three carboxy-terminally located amino acids, was found to be more potent than CXCL4/PF-4 in inhibiting angiogenesis and tumor growth. Both glycosaminoglycans (GAG) and CXCR3 are implicated in the activities of the PF-4 variants. This report reviews the current knowledge on the role of CXCL4/PF-4 and CXCL4L1/PF-4var in physiological and pathological processes. In particular, the role of CXCL4/PF-4 in cancer, heparin-induced thrombocytopenia and atherosclerosis is described. Copyright © 2010 Elsevier Ltd. All rights reserved.

Controlled Human Malaria Infection of Tanzanians by Intradermal Injection of Aseptic, Purified, Cryopreserved Plasmodium falciparum Sporozoites

PubMed Central

Shekalaghe, Seif; Rutaihwa, Mastidia; Billingsley, Peter F.; Chemba, Mwajuma; Daubenberger, Claudia A.; James, Eric R.; Mpina, Maximillian; Ali Juma, Omar; Schindler, Tobias; Huber, Eric; Gunasekera, Anusha; Manoj, Anita; Simon, Beatus; Saverino, Elizabeth; Church, L. W. Preston; Hermsen, Cornelus C.; Sauerwein, Robert W.; Plowe, Christopher; Venkatesan, Meera; Sasi, Philip; Lweno, Omar; Mutani, Paul; Hamad, Ali; Mohammed, Ali; Urassa, Alwisa; Mzee, Tutu; Padilla, Debbie; Ruben, Adam; Lee Sim, B. Kim; Tanner, Marcel; Abdulla, Salim; Hoffman, Stephen L.

2014-01-01

Controlled human malaria infection (CHMI) by mosquito bite has been used to assess anti-malaria interventions in > 1,500 volunteers since development of methods for infecting mosquitoes by feeding on Plasmodium falciparum (Pf) gametocyte cultures. Such CHMIs have never been used in Africa. Aseptic, purified, cryopreserved Pf sporozoites, PfSPZ Challenge, were used to infect Dutch volunteers by intradermal injection. We conducted a double-blind, placebo-controlled trial to assess safety and infectivity of PfSPZ Challenge in adult male Tanzanians. Volunteers were injected intradermally with 10,000 (N = 12) or 25,000 (N = 12) PfSPZ or normal saline (N = 6). PfSPZ Challenge was well tolerated and safe. Eleven of 12 and 10 of 11 subjects, who received 10,000 and 25,000 PfSPZ respectively, developed parasitemia. In 10,000 versus 25,000 PfSPZ groups geometric mean days from injection to Pf positivity by thick blood film was 15.4 versus 13.5 (P = 0.023). Alpha-thalassemia heterozygosity had no apparent effect on infectivity. PfSPZ Challenge was safe, well tolerated, and infectious. PMID:25070995

PROMIS PF CAT Outperforms the ODI and SF-36 Physical Function Domain in Spine Patients.

PubMed

Brodke, Darrel S; Goz, Vadim; Voss, Maren W; Lawrence, Brandon D; Spiker, William Ryan; Hung, Man

2017-06-15

The Oswestry Disability Index v2.0 (ODI), SF36 Physical Function Domain (SF-36 PFD), and PROMIS Physical Function CAT v1.2 (PF CAT) questionnaires were prospectively collected from 1607 patients complaining of back or leg pain, visiting a university-based spine clinic. All questionnaires were collected electronically, using a tablet computer. The aim of this study was to compare the psychometric properties of the PROMIS PF CAT with the ODI and SF36 Physical Function Domain in the same patient population. Evidence-based decision-making is improved by using high-quality patient-reported outcomes measures. Prior studies have revealed the shortcomings of the ODI and SF36, commonly used in spine patients. The PROMIS Network has developed measures with excellent psychometric properties. The Physical Function domain, delivered by Computerized Adaptive Testing (PF CAT), performs well in the spine patient population, though to-date direct comparisons with common measures have not been performed. Standard Rasch analysis was performed to directly compare the psychometrics of the PF CAT, ODI, and SF36 PFD. Spearman correlations were computed to examine the correlations of the three instruments. Time required for administration was also recorded. One thousand six hundred seven patients were administered all assessments. The time required to answer all items in the PF CAT, ODI, and SF-36 PFD was 44, 169, and 99 seconds. The ceiling and floor effects were excellent for the PF CAT (0.81%, 3.86%), while the ceiling effects were marginal and floor effects quite poor for the ODI (6.91% and 44.24%) and SF-36 PFD (5.97% and 23.65%). All instruments significantly correlated with each other. The PROMIS PF CAT outperforms the ODI and SF-36 PFD in the spine patient population and is highly correlated. It has better coverage, while taking less time to administer with fewer questions to answer. 2.

Convalescent Plasmodium falciparum-specific seroreactivity does not correlate with paediatric malaria severity or Plasmodium antigen exposure.

PubMed

Kessler, Anne; Campo, Joseph J; Harawa, Visopo; Mandala, Wilson L; Rogerson, Stephen J; Mowrey, Wenzhu B; Seydel, Karl B; Kim, Kami

2018-04-25

Antibody immunity is thought to be essential to prevent severe Plasmodium falciparum infection, but the exact correlates of protection are unknown. Over time, children in endemic areas acquire non-sterile immunity to malaria that correlates with development of antibodies to merozoite invasion proteins and parasite proteins expressed on the surface of infected erythrocytes. A 1000 feature P. falciparum 3D7 protein microarray was used to compare P. falciparum-specific seroreactivity during acute infection and 30 days after infection in 23 children with uncomplicated malaria (UM) and 25 children with retinopathy-positive cerebral malaria (CM). All children had broad P. falciparum antibody reactivity during acute disease. IgM reactivity decreased and IgG reactivity increased in convalescence. Antibody reactivity to CIDR domains of "virulent" PfEMP1 proteins was low with robust reactivity to the highly conserved, intracellular ATS domain of PfEMP1 in both groups. Although children with UM and CM differed markedly in parasite burden and PfEMP1 exposure during acute disease, neither acute nor convalescent PfEMP1 seroreactivity differed between groups. Greater seroprevalence to a conserved Group A-associated ICAM binding extracellular domain was observed relative to linked extracellular CIDRα1 domains in both case groups. Pooled immune IgG from Malawian adults revealed greater reactivity to PfEMP1 than observed in children. Children with uncomplicated and cerebral malaria have similar breadth and magnitude of P. falciparum antibody reactivity. The utility of protein microarrays to measure serological recognition of polymorphic PfEMP1 antigens needs to be studied further, but the study findings support the hypothesis that conserved domains of PfEMP1 are more prominent targets of cross reactive antibodies than variable domains in children with symptomatic malaria. Protein microarrays represent an additional tool to identify cross-reactive Plasmodium antigens including PfEMP1 domains that can be investigated as strain-transcendent vaccine candidates.

Diagnostic Accuracy of Natriuretic Peptides for Heart Failure in Patients with Pleural Effusion: A Systematic Review and Updated Meta-Analysis

PubMed Central

Cheng, Juan-Juan; Zhao, Shi-Di; Gao, Ming-Zhu; Huang, Hong-Yu; Gu, Bing; Ma, Ping; Chen, Yan; Wang, Jun-Hong; Yang, Cheng-Jian; Yan, Zi-He

2015-01-01

Background Previous studies have reported that natriuretic peptides in the blood and pleural fluid (PF) are effective diagnostic markers for heart failure (HF). These natriuretic peptides include N-terminal pro-brain natriuretic peptide (NT-proBNP), brain natriuretic peptide (BNP), and midregion pro-atrial natriuretic peptide (MR-proANP). This systematic review and meta-analysis evaluates the diagnostic accuracy of blood and PF natriuretic peptides for HF in patients with pleural effusion. Methods PubMed and EMBASE databases were searched to identify articles published in English that investigated the diagnostic accuracy of BNP, NT-proBNP, and MR-proANP for HF. The last search was performed on 9 October 2014. The quality of the eligible studies was assessed using the revised Quality Assessment of Diagnostic Accuracy Studies tool. The diagnostic performance characteristics (sensitivity, specificity, and other measures of accuracy) were pooled and examined using a bivariate model. Results In total, 14 studies were included in the meta-analysis, including 12 studies reporting the diagnostic accuracy of PF NT-proBNP and 4 studies evaluating blood NT-proBNP. The summary estimates of PF NT-proBNP for HF had a diagnostic sensitivity of 0.94 (95% confidence interval [CI]: 0.90–0.96), specificity of 0.91 (95% CI: 0.86–0.95), positive likelihood ratio of 10.9 (95% CI: 6.4–18.6), negative likelihood ratio of 0.07 (95% CI: 0.04–0.12), and diagnostic odds ratio of 157 (95% CI: 57–430). The overall sensitivity of blood NT-proBNP for diagnosis of HF was 0.92 (95% CI: 0.86–0.95), with a specificity of 0.88 (95% CI: 0.77–0.94), positive likelihood ratio of 7.8 (95% CI: 3.7–16.3), negative likelihood ratio of 0.10 (95% CI: 0.06–0.16), and diagnostic odds ratio of 81 (95% CI: 27–241). The diagnostic accuracy of PF MR-proANP and blood and PF BNP was not analyzed due to the small number of related studies. Conclusions BNP, NT-proBNP, and MR-proANP, either in blood or PF, are effective tools for diagnosis of HF. Additional studies are needed to rigorously evaluate the diagnostic accuracy of PF and blood MR-proANP and BNP for the diagnosis of HF. PMID:26244664

Lack of an Association between Antibodies to Plasmodium falciparum Glycosylphosphatidylinositols and Malaria-Associated Placental Changes in Cameroonian Women with Preterm and Full-Term Deliveries

PubMed Central

Suguitan, Amorsolo L.; Gowda, D. Channe; Fouda, Genevieve; Thuita, Lucy; Zhou, Ainong; Djokam, Rosine; Metenou, Simon; Leke, Rose G. F.; Taylor, Diane Wallace

2004-01-01

Sequestration of Plasmodium falciparum parasites within the placenta often leads to an accumulation of macrophages within the intervillous space and increased production of tumor necrosis factor alpha (TNF-α), a cytokine associated with placental pathology and poor pregnancy outcomes. P. falciparum glycosylphosphatidylinositol (GPI) anchors have been shown to be the major parasite component that induces TNF-α production by monocytes and macrophages. Antibodies against P. falciparum GPI (anti-PfGPI), however, can inhibit the induction of TNF-α and inflammation. Thus, the study was undertaken to determine whether anti-PfGPI antibodies down-regulate inflammatory-type changes in the placentas of women with malaria. Anti-PfGPI immunoglobulin M (IgM) and IgG levels were measured in 380 pregnant women with or without placental malaria, including those who delivered prematurely and at term. Results showed that anti-PfGPI antibody levels increased with gravidity and age and that malaria infection boosted anti-PfGPI antibodies in pregnant women. However, no association was found between anti-PfGPI antibodies and placental TNF-α levels or the presence of acute or chronic placental malaria. Furthermore, anti-PfGPI antibody levels were similar in women with preterm and full-term deliveries and were not associated with an increase in infant birth weight. Thus, these results fail to support a strong role for anti-PfGPI antibodies in the prevention of chronic placental malaria infections and malaria-associated poor birth outcomes. PMID:15322022

Notch Inhibitor PF-03084014 Inhibits Hepatocellular Carcinoma Growth and Metastasis via Suppression of Cancer Stemness due to Reduced Activation of Notch1-Stat3.

PubMed

Wu, Chuan Xing; Xu, Aimin; Zhang, Cathy C; Olson, Peter; Chen, Lin; Lee, Terence K; Cheung, Tan To; Lo, Chung Mau; Wang, Xiao Qi

2017-08-01

Aberrant activation of the Notch signaling pathway is implicated in many solid tumors, including hepatocellular carcinoma, indicating a potential use of Notch inhibitors for treatment. In this study, we investigated the antitumor and antimetastasis efficacy of the novel Notch inhibitor (γ-secretase inhibitor) PF-03084014 in hepatocellular carcinoma. Hepatocellular carcinoma spherical cells (stem-like cancer cells), a sphere-derived orthotopic tumor model and one patient-derived xenograft (PDX) model were used in our experiment. We demonstrated that PF-03084014 inhibited the self-renewal and proliferation of cancer stem cells. PF-03084014 reduced the hepatocellular carcinoma sphere-derived orthotopic tumor and blocked the hepatocellular carcinoma tumor liver to lung metastasis. We further tested the PF-03084014 in PDX models and confirmed the inhibition tumor growth effect. In addition, a low dose of PF-03084014 induced hepatocellular carcinoma sphere differentiation, resulting in chemosensitization. Antitumor activity was associated with PF-03084014-induced suppression of Notch1 activity, decreased Stat3 activation and phosphorylation of the Akt signaling pathway, and reduced epithelial-mesenchymal transition. These are the key contributors to the maintenance of cancer stemness and the promotion of cancer metastasis. Moreover, the Notch-Stat3 association was implicated in the clinical hepatocellular carcinoma prognosis. Collectively, PF-03084014 revealed antitumor and antimetastatic effects in hepatocellular carcinoma, providing evidence for the potential use of gamma-secretase inhibitors as a therapeutic option for the treatment of hepatocellular carcinoma. Mol Cancer Ther; 16(8); 1531-43. ©2017 AACR . ©2017 American Association for Cancer Research.

Effect of dietary protein quality and feeding level on milk secretion and mammary protein synthesis in the rat

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

Sampson, D.A.; Jansen, G.R.

1985-04-01

Protein synthesis was studied in mammary tissue of rats fed diets deficient in protein quality and/or restricted in food intake throughout gestation and lactation. Diets containing 25% wheat gluten (WG), wheat gluten plus lysine and threonine (WGLT), or casein (C) were pair-fed from conception until day 15 of lactation at 100% or 85% of WG ad libitum consumption (PF100 and PF85, respectively). A seventh group was fed C ad libitum. Rates of protein synthesis were measured in vivo at day 15 of lactation from incorporation of (3-/sup 3/H)phenylalanine. At both PF100 and PF85, fractional and absolute rates of mammary glandmore » protein synthesis were two- to three-fold higher in rats fed C than in those fed WG. Pup weights showed similar treatment effects. Both mammary protein synthesis rates and pup weights were significantly higher in rats fed C at PF85 than rats fed WG ad libitum. Food restriction from PF100 to PF85 depressed pup weights and mammary protein synthesis rates in rats fed WGLT, but had no effect in rats fed WG. These results demonstrate that when food intake is restricted, improvement of protein quality of the maternal diet increases milk output in the rat in association with increased rates of mammary protein synthesis.« less

Atomic features of an autoantigen in heparin-induced thrombocytopenia (HIT).

PubMed

Cai, Zheng; Zhu, Zhiqiang; Greene, Mark I; Cines, Douglas B

2016-07-01

Autoantigen development is poorly understood at the atomic level. Heparin-induced thrombocytopenia (HIT) is an autoimmune thrombotic disorder caused by antibodies to an antigen composed of platelet factor 4 (PF4) and heparin or cellular glycosaminoglycans (GAGs). In solution, PF4 exists as an equilibrium among monomers, dimers and tetramers. Structural studies of these interacting components helped delineate a multi-step process involved in the pathogenesis of HIT. First, heparin binds to the 'closed' end of the PF4 tetramer and stabilizes its conformation; exposing the 'open' end. Second, PF4 arrays along heparin/GAG chains, which approximate tetramers, form large antigenic complexes that enhance antibody avidity. Third, pathogenic HIT antibodies bind to the 'open' end of stabilized PF4 tetramers to form an IgG/PF4/heparin ternary immune complex and also to propagate the formation of 'ultralarge immune complexes' (ULCs) that contain multiple IgG antibodies. Fourth, ULCs signal through FcγRIIA receptors, activating platelets and monocytes directly and generating thrombin, which transactivates hematopoietic and endothelial cells. A non-pathogenic anti-PF4 antibody prevents tetramer formation, binding of pathogenic antibody, platelet activation and thrombosis, providing a new approach to manage HIT. An improved understanding of the pathogenesis of HIT may lead to novel diagnostics and therapeutics for this autoimmune disease. Copyright © 2016 Elsevier B.V. All rights reserved.

Language experience and consonantal context effects on perceptual assimilation of French vowels by American-English learners of French1

PubMed Central

Levy, Erika S.

2009-01-01

Recent research has called for an examination of perceptual assimilation patterns in second-language speech learning. This study examined the effects of language learning and consonantal context on perceptual assimilation of Parisian French (PF) front rounded vowels ∕y∕ and ∕œ∕ by American English (AE) learners of French. AE listeners differing in their French language experience (no experience, formal instruction, formal-plus-immersion experience) performed an assimilation task involving PF ∕y, œ, u, o, i, ε, a∕ in bilabial ∕rabVp∕ and alveolar ∕radVt∕ contexts, presented in phrases. PF front rounded vowels were assimilated overwhelmingly to back AE vowels. For PF ∕œ∕, assimilation patterns differed as a function of language experience and consonantal context. However, PF ∕y∕ revealed no experience effect in alveolar context. In bilabial context, listeners with extensive experience assimilated PF ∕y∕ to ∕ju∕ less often than listeners with no or only formal experience, a pattern predicting the poorest ∕u-y∕ discrimination for the most experienced group. An “internal consistency” analysis indicated that responses were most consistent with extensive language experience and in bilabial context. Acoustical analysis revealed that acoustical similarities among PF vowels alone cannot explain context-specific assimilation patterns. Instead it is suggested that native-language allophonic variation influences context-specific perceptual patterns in second-language learning. PMID:19206888

Is goniometry suitable for measuring ankle range of motion in female ballet dancers? An initial comparison with radiographic measurement.

PubMed

Russell, Jeffrey A; Shave, Ruth M; Kruse, David W; Nevill, Alan M; Koutedakis, Yiannis; Wyon, Matthew A

2011-06-01

Female ballet dancers require extreme ankle motion to attain the demi-plié (weight-bearing full dorsiflexion [DF]) and en pointe (weight-bearing full plantar flexion [PF]) positions of ballet. However, techniques for assessing this amount of motion have not yet received sufficient scientific scrutiny. Therefore, the purpose of this study was to examine possible differences between weight-bearing goniometric and radiographic ankle range of motion measurements in female ballet dancers. Ankle range of motion in 8 experienced female ballet dancers was assessed by goniometry and 2 radiographic measurement methods. The latter were performed on 3 mediolateral x-rays, in demi-plié, neutral, and en pointe positions; one of them used the same landmarks as goniometry. DF values were not significantly different among the methods, but PF values were (P < .05). Not only was PF of the talocrural joint significantly less than the other 2 measurements (P < .001), PF from the goniometric method applied to the x-rays was significantly less than PF obtained from clinical goniometry (P < .05). These data provide insight into the extreme ankle and foot motion, particularly PF, required in female ballet dancers and suggest that goniometry may not be ideal for assessing ankle range of motion in these individuals. Therefore, further research is needed to standardize how DF and PF are measured in ballet dancers. Diagnostic, Level I.

Phase II evaluation of anti-MAdCAM antibody PF-00547659 in the treatment of Crohn's disease: report of the OPERA study.

PubMed

Sandborn, William J; Lee, Scott D; Tarabar, Dino; Louis, Edouard; Klopocka, Maria; Klaus, Jochen; Reinisch, Walter; Hébuterne, Xavier; Park, Dong-Il; Schreiber, Stefan; Nayak, Satyaprakash; Ahmad, Alaa; Banerjee, Anindita; Brown, Lisa S; Cataldi, Fabio; Gorelick, Kenneth J; Cheng, John B; Hassan-Zahraee, Mina; Clare, Robert; D'Haens, Geert R

2017-10-05

This phase II, randomised, double-blind, placebo-controlled clinical trial was designed to evaluate the efficacy and safety of PF-00547659, a fully human monoclonal antibody that binds to human mucosal addressin cell adhesion molecule (MAdCAM) to selectively reduce lymphocyte homing to the intestinal tract, in patients with moderate-to-severe Crohn's disease (CD). Eligible adults were aged 18-75 years, with active moderate-to-severe CD (Crohn's Disease Activity Index (CDAI) 220-450), a history of failure or intolerance to antitumour necrosis factor and/or immunosuppressive agents, high-sensitivity C reactive protein >3.0 mg/L and ulcers on colonoscopy. Patients were randomised to PF-00547659 22.5 mg, 75 mg or 225 mg or placebo. The primary endpoint was CDAI 70-point decrease from baseline (CDAI-70) at week 8 or 12. In all, 265 patients were eligible for study entry. Although CDAI-70 response was not significantly different with placebo versus PF-00547659 treatment at weeks 8 or 12, remission rate was greater in patients with higher baseline C reactive protein (>5 mg/L vs >18.8 mg/L, respectively). Soluble MAdCAM decreased significantly from baseline to week 2 in a dose-related manner and remained low during the study in PF-00547659-treated patients. Circulating β 7 + CD4+ central memory T-lymphocytes increased at weeks 8 and 12 with PF-00547659 treatment. No safety signal was seen. Clinical endpoint differences between PF-00547659 and placebo did not reach statistical significance in patients with moderate-to-severe CD. PF-00547659 was pharmacologically active, as shown by a sustained dose-related decrease in soluble MAdCAM and a dose-related increase in circulating β 7 + central memory T cells. NCT01276509; Results. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Clinical characteristics of fulminant type 1 diabetes associated with pregnancy in China.

PubMed

Liu, Lan; Mao, Jiping; Lu, Zeyuan; Yan, Xiaojie; Bai, Xiaosu; Ye, Yiyi; Zou, Gang

2011-12-01

To report 12 cases of pregnancy-associated fulminant type 1 diabetes mellitus (PF) found in China from 2003 to 2010. The clinical and biochemical characteristics of these cases with PF were compared with a group of cases of child-bearing age with fulminant type 1 diabetes that was not associated with pregnancy (NPF). The clinical and biochemical characteristics of 12 PF cases were analyzed retrospectively and then compared with those characteristics of 20 NPF cases in China. The difference between Chinese and Japanese PF cases was investigated. The mean values of the characteristics from PF and NPF cases in China, including postprandial serum C-peptide concentration, plasma glucose concentration, and serum chloride were different. Compared to the 22 PF cases in Japan, the mean age of these 12 PF cases was much younger. The mean fasting and postprandial serum C-peptide concentration level were lower, and the mean HbA1c levels was higher in 12 PF cases in China. Eight of 12 PF cases in China developed the disease during pregnancy. Other four PF case developed the disease within 2 weeks after delivery. 12 PF cases in China showed more severe beta-cell destruction, the prognosis of their fetuses was extremely poor.

Differential response of oyster shell powder on enzyme profile and nutritional value of oyster mushroom Pleurotus florida PF05.

PubMed

Naraian, Ram; Narayan, Om Prakash; Srivastava, Jatin

2014-01-01

Oyster mushroom Pleurotus florida was cultivated on different combinations of wheat straw (WS) as basal substrate and oyster shell powder (OSP) supplement. The OSP supplementation considerably responded to different cultivation phases. The mycelium grew fast and showed rapid growth rate (8.91 mmd(-1)) in WS + OSP (97 + 3) combination while WS + OSP (92 + 8) showed maximum laccase (3.133 U/g) and Mn peroxidase (MnP) activities (0.091 U/g). The climax level of laccase (5.433 U/g) and MnP (0.097 U/g) was recorded during fruit body initiation in WS + OSP (97 + 3) and WS + OSP (98 + 2) combinations, respectively. The WS + OSP (97 + 3) combination represented the best condition for mushroom cultivation and produced the highest biological efficiency (147%). In addition, protein and lipid contents in fruit bodies were slightly improved in response to OSP. The carbohydrate was significantly increased by raising concentration of OSP. The highest values of protein, carbohydrate, and lipid noted were 31.3 μg/g, 0.0639 (g/g), and 0.373 (g/g) correspondingly. Conclusively it was evident that lower concentrations of OSP acted positively and relatively to higher concentrations and improved nutritional content which may suitably be used to enhance both yield and nutritional values of mushroom.

Experimental Guidance of ISB Corrections via Direct Nuclear Reactions

NASA Astrophysics Data System (ADS)

Leach, K. G.; Garrett, P. E.; Ball, G. C.; Bangay, J. C.; Bianco, L.; Demand, G. A.; Faestermann, T.; Finlay, P.; Green, K. L.; Hertenberger, R.; Kriicken, R.; Phillips, A. A.; Rand, E. T.; Sumithrarachchi, C. S.; Svensson, C. E.; Towner, I. S.; Triambak, S.; Wirth, H.-F.; Wong, J.

2011-09-01

The most recent isospin-symmetry-breaking corrections, δc, of Towner and Hardy for superallowed Fermi β-decay transitions, have included the opening of specific core orbitals. This change has resulted in significant deviations in some of the δc factors from their previous calculations, and an improved agreement of the individual corrected Script Ft values with the overall world average of the 13 most precise cases. While this is consistent with the conserved-vector-current (CVC) hypothesis of the Standard Model, these new calculations must be thoroughly tested, and guidance must be given for the improvement of calculations for the upper-pf shell nuclei. Using the (d,t) reaction mechanism to probe the single neutron wavefunction overlap, information regarding the relevant shell-model configurations needed in the calculation can be determined. An experiment was therefore performed with a 22 MeV polarized deuterium beam from the MP tandem Van de Graaff accelerator in Munich, Germany. Using the Q3D magnetic spectrograph, and a cathode-strip focal-plane detector, outgoing tritons were analyzed at 9 angles between 10° and 60°, up to an excitation energy of 4.8 MeV. This proceeding reports the motivational and experimental details for the 64Zn(d,t)63Zn transfer work presented.

Augmenting the antibiofilm efficacy of advanced noninvasive light activated disinfection with emulsified oxidizer and oxygen carrier.

PubMed

George, Saji; Kishen, Anil

2008-09-01

In this study, we tested the hypothesis that the inclusion of an oxidizer and oxygen carrier in the photosensitization formulation would facilitate comprehensive disinfection of matured endodontic biofilm by light-activated disinfection (LAD). Photosensitizing formulations containing methylene blue (MB) and an oxygen carrier alone (perfluorodecahydronaphthalene) (PF1) or in combination with oxidizer (H(2)O(2)) (PF2) or their emulsions formed with triton-X100 (Bio-Rad Laboratories, Hercules, CA) in different proportions (PF3 and PF4) were tested for photochemical properties and damage to the biofilm structure using confocal laser scanning microscopy. Conventional chemomechanical preparation, LAD using MB in water, and LAD using MB in emulsion (PF4) were also conducted on 10-week-old Enterococcus faecalis biofilm within root canals. MB in emulsion (PF4) was overall the most effective photosensitizer formulation for photooxidation, generation of singlet oxygen (p = 0.001), and in disinfecting biofilm bacteria. Advanced noninvasive LAD using a photosensitizer formulation containing oxidizer and oxygen carrier disrupted the biofilm matrix and facilitated comprehensive inactivation of biofilm bacteria. This modified photosensitizer formulation will have potential advantages in endodontic disinfection.

Atomic description of the immune complex involved in heparin-induced thrombocytopenia

DOE PAGES

Cai, Zheng; Yarovoi, Serge V.; Zhu, Zhiqiang; ...

2015-09-22

Heparin-induced thrombocytopenia (HIT) is an autoimmune thrombotic disorder caused by immune complexes containing platelet factor 4 (PF4), antibodies to PF4 and heparin or cellular glycosaminoglycans (GAGs). Here we solve the crystal structures of the: (1) PF4 tetramer/fondaparinux complex, (2) PF4 tetramer/KKO-Fab complex (a murine monoclonal HIT-like antibody) and (3) PF4 monomer/RTO-Fab complex (a non-HIT anti-PF4 monoclonal antibody). Fondaparinux binds to the ‘closed’ end of the PF4 tetramer and stabilizes its conformation. This interaction in turn stabilizes the epitope for KKO on the ‘open’ end of the tetramer. Fondaparinux and KKO thereby collaborate to ‘stabilize’ the ternary pathogenic immune complex. Bindingmore » of RTO to PF4 monomers prevents PF4 tetramerization and inhibits KKO and human HIT IgG-induced platelet activation and platelet aggregation in vitro, and thrombus progression in vivo. Lastly, the atomic structures provide a basis to develop new diagnostics and non-anticoagulant therapeutics for HIT.« less

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

Cai, Zheng; Yarovoi, Serge V.; Zhu, Zhiqiang

Heparin-induced thrombocytopenia (HIT) is an autoimmune thrombotic disorder caused by immune complexes containing platelet factor 4 (PF4), antibodies to PF4 and heparin or cellular glycosaminoglycans (GAGs). Here we solve the crystal structures of the: (1) PF4 tetramer/fondaparinux complex, (2) PF4 tetramer/KKO-Fab complex (a murine monoclonal HIT-like antibody) and (3) PF4 monomer/RTO-Fab complex (a non-HIT anti-PF4 monoclonal antibody). Fondaparinux binds to the ‘closed’ end of the PF4 tetramer and stabilizes its conformation. This interaction in turn stabilizes the epitope for KKO on the ‘open’ end of the tetramer. Fondaparinux and KKO thereby collaborate to ‘stabilize’ the ternary pathogenic immune complex. Bindingmore » of RTO to PF4 monomers prevents PF4 tetramerization and inhibits KKO and human HIT IgG-induced platelet activation and platelet aggregation in vitro, and thrombus progression in vivo. Lastly, the atomic structures provide a basis to develop new diagnostics and non-anticoagulant therapeutics for HIT.« less

Safety and efficacy of polymer-free biolimus-eluting stents in all-comer patients: the RUDI-FREE study.

PubMed

Sardella, Gennaro; Stefanini, Giulio G; Briguori, Carlo; Tamburino, Corrado; Fabbiocchi, Franco; Rotolo, Francesco; Tomai, Fabrizio; Paggi, Anita; Lombardi, Mario; Gioffrè, Gaetano; Sclafani, Rocco; Rolandi, Andrea; Sciahbasi, Alessandro; Scardaci, Francesco; Signore, Nicola; Calcagno, Simone; Mancone, Massimo; Chiarito, Mauro; Giordano, Arturo

2018-05-21

Polymer-free biolimus-eluting stents (PF-BES) have been shown superior to bare metal stents in high bleeding risk (HBR) patients treated with 1-month dual antiplatelet therapy (DAPT). However, limited evidence is available on PF-BES in non-HBR patients. We aim to evaluate the safety and efficacy of PF-BES in all-comer patients undergoing percutaneous coronary interventions (PCI). Patients with stable coronary artery disease or acute coronary syndromes (ACS) undergoing PCI with PF-BES in routine clinical practice were included in a multicenter, prospective registry. DAPT duration was left at the discretion of the operator. The primary endpoint was the composite of cardiovascular death, myocardial infarction (MI), and definite/probable stent thrombosis (ST) at 1 year. Overall, 1,104 consecutive patients treated with PF-BES were included at 16 Italian centers. Mean age was 68.7±11.2 years, 77.2% of patients were men, 30% had diabetes, 15.1% had chronic kidney disease, and 40.5% had ACS at baseline. Mean CRUSADE score was 24.1±13.1, and 83.7% of patients did not have high bleeding risk features. At 1-year, the primary endpoint occurred in 4.1% of patients, cardiovascular death in 2.4%, MI in 1.8%, and definite/probable ST in 1.1%. With respect to efficacy, target-lesion revascularization occurred in 1.2% of patients. This is the first study providing clinical evidence on the use of PF-BES in all-comer patients irrespective of HBR status. Our findings suggest that PF-BES has a favorable safety and efficacy profile in a real world clinical setting. Further investigation in randomised clinical trials against new-generation DES is warranted.

Limited artemisinin resistance-associated polymorphisms in Plasmodium falciparum K13-propeller and PfATPase6 gene isolated from Bioko Island, Equatorial Guinea

PubMed Central

Li, Jian; Chen, Jiangtao; Xie, Dongde; Eyi, Urbano Monsuy; Matesa, Rocio Apicante; Ondo Obono, Maximo Miko; Ehapo, Carlos Sala; Yang, Liye; Yang, Huitian; Lin, Min

2016-01-01

Objective With emergence and geographically expanding of antimalarial resistance worldwide, molecular markers are essential tool for surveillance of resistant Plasmodium parasites. Recently, single-nucleotide polymorphisms (SNPs) in the PF3D7_1343700 kelch propeller (K13-propeller) domain are shown to be associated with artemisinin (ART) resistance in vivo and in vitro. This study aims to investigate the ART resistance-associated polymorphisms of K13-propeller and PfATPase6 genes in Plasmodium falciparum isolates from Bioko Island, Equatorial Guinea (EG). Methods A total of 172 samples were collected from falciparum malaria patients on Bioko Island between 2013 and 2014. The polymorphisms of K13-propeller and PfATPase6 genes were analyzed by Nest-PCR and sequencing. Results Sequences of K13-propeller and PfATPase6 were obtained from 90.74% (98/108) and 91.45% (139/152) samples, respectively. The 2.04% (2/98) cases had non-synonymous K13-propeller A578S mutation but no found the mutations associated with ART resistance in Southeast Asia. For PfATPase6, the mutations were found at positions N569K and A630S with the mutation prevalence of 7.91% (11/139) and 1.44% (2/139), respectively. In addition, a sample with the mixed type at position I723V was discovered (0.72%, 1/139). Conclusions This study initially offers an insight of K13-propeller and PfATPase6 polymorphisms on Bioko Island, EG. It suggests no widespread ART resistance or tolerance in the region, and might be helpful for developing and updating guidance for the use of ART-based combination therapies (ACTs). PMID:27054064

Limited artemisinin resistance-associated polymorphisms in Plasmodium falciparum K13-propeller and PfATPase6 gene isolated from Bioko Island, Equatorial Guinea.

PubMed

Li, Jian; Chen, Jiangtao; Xie, Dongde; Eyi, Urbano Monsuy; Matesa, Rocio Apicante; Ondo Obono, Maximo Miko; Ehapo, Carlos Sala; Yang, Liye; Yang, Huitian; Lin, Min

2016-04-01

With emergence and geographically expanding of antimalarial resistance worldwide, molecular markers are essential tool for surveillance of resistant Plasmodium parasites. Recently, single-nucleotide polymorphisms (SNPs) in the PF3D7_1343700 kelch propeller (K13-propeller) domain are shown to be associated with artemisinin (ART) resistance in vivo and in vitro. This study aims to investigate the ART resistance-associated polymorphisms of K13-propeller and PfATPase6 genes in Plasmodium falciparum isolates from Bioko Island, Equatorial Guinea (EG). A total of 172 samples were collected from falciparum malaria patients on Bioko Island between 2013 and 2014. The polymorphisms of K13-propeller and PfATPase6 genes were analyzed by Nest-PCR and sequencing. Sequences of K13-propeller and PfATPase6 were obtained from 90.74% (98/108) and 91.45% (139/152) samples, respectively. The 2.04% (2/98) cases had non-synonymous K13-propeller A578S mutation but no found the mutations associated with ART resistance in Southeast Asia. For PfATPase6, the mutations were found at positions N569K and A630S with the mutation prevalence of 7.91% (11/139) and 1.44% (2/139), respectively. In addition, a sample with the mixed type at position I723V was discovered (0.72%, 1/139). This study initially offers an insight of K13-propeller and PfATPase6 polymorphisms on Bioko Island, EG. It suggests no widespread ART resistance or tolerance in the region, and might be helpful for developing and updating guidance for the use of ART-based combination therapies (ACTs).

The Performance and Association Between Patient-reported and Performance-based Measures of Physical Functioning in Research on Individuals with Arthritis.

PubMed

Pinheiro, Laura C; Callahan, Leigh F; Cleveland, Rebecca J; Edwards, Lloyd J; Reeve, Bryce B

2016-01-01

To evaluate the association between patient-reported outcome (PRO) and performance-based (PB) measures of physical functioning (PF) among individuals with self-identified arthritis to inform decisions of which to use when evaluating the effectiveness of a physical activity intervention. Secondary data analysis of a nonrandomized 2-arm pre-post community trial of 462 individuals who self-identified as having arthritis and participated in the Walk with Ease (WWE) intervention. Two PRO and 8 PB assessments were collected at baseline (preintervention) and at 6-week followup. We calculated correlations between PB and PRO measures, assessed how measures identified changes in PF from baseline to followup, and compared PRO and PB measures to arthritis symptoms of pain, stiffness, and fatigue. Strength of correlations between PB and PRO measures varied depending on the PB measure, ranging from 0.21 to 0.54. PRO and PB measures identified PF improvements from baseline to followup, but none showed significant differences between the 2 WWE modalities (instructor-led or self-directed groups). Correlations with arthritis symptoms were stronger for PRO (0.30-0.46) than PB measures (0.03-0.31). PRO measures may provide us with insights into aspects of PF that are not identified by PB measures alone. Use of PRO measures allows patients to communicate their perceptions of PF, which may provide a more accurate representation of overall PF. Our study does not suggest abandoning the use of PB measures to characterize PF in patients with self-identified arthritis, but recommends that PRO measures may serve as complementary or surrogate endpoints for some studies.

Ratio of progesterone-to-number of follicles as a prognostic tool for in vitro fertilization cycles.

PubMed

Roque, Matheus; Valle, Marcello; Sampaio, Marcos; Geber, Selmo; Checa, Miguel Angel

2015-06-01

To establish a ratio of the P level to the number of follicles (P/F ratio) on the day of human chorionic gonadotropin (hCG) administration and to evaluate whether this ratio is associated with in vitro fertilization (IVF) outcome. This study was conducted between January 2012 and June 2013. A total of 337 patients with cleavage-stage day-3 fresh embryo transfer with P levels ≤1.5 ng/mL on the day of hCG administration were included in the study. The main outcome was ongoing pregnancy rate. The P/F ratio was calculated according to the equation (P[ng/mL]/number of follicles) on the day of final oocyte maturation. Using ROC, we established a cut-off level of 0.075 for the P/F ratio. The area under the curve (AUC) (0.756; 95 % confidence interval [CI]: 0.704-0.807) indicated that it was a good prognostic test. In group 1 (patients under 36 years old), the ongoing pregnancy rates were 57 and 30 % for patients with P/F ratios ≤ .075 and > .075, respectively, (p = 0.003). In group 2 (patients between 36 and 39 years old), the ongoing pregnancy rates were 58 % and 17 % (p = 0.001) for patients with P/F ratios ≤ .075 and > .075, respectively. In group 3 (patients ≥ 40 years old), the ongoing pregnancy rates were 41.7 and 10.9 % (p = 0.001) for patients with P/F ratios ≤ .075 and > .075, respectively. The P/F ratio is a good prognostic test for predicting IVF outcome that can correlate the P level with ovarian response.

Cerebrospinal fluid Plasmodium falciparum histidine-rich protein-2 in pediatric cerebral malaria.

PubMed

Thakur, Kiran T; Vareta, Jimmy; Carson, Kathryn A; Kampondeni, Samuel; Potchen, Michael J; Birbeck, Gretchen L; MacCormick, Ian; Taylor, Terrie; Sullivan, David J; Seydel, Karl B

2018-03-23

Cerebral malaria (CM) causes a rapidly developing coma, and remains a major contributor to morbidity and mortality in malaria-endemic regions. This study sought to determine the relationship between cerebrospinal fluid (CSF) Plasmodium falciparum histidine rich protein-2 (PfHRP-2) and clinical, laboratory and radiographic features in a cohort of children with retinopathy-positive CM. Patients included in the study were admitted (2009-2013) to the Pediatric Research Ward (Queen Elizabeth Central Hospital, Blantyre, Malawi) meeting World Health Organization criteria for CM with findings of malarial retinopathy. Enzyme-linked immunosorbent assay was used to determine plasma and CSF PfHRP-2 levels. Wilcoxon rank-sum tests and multivariable logistic regression analysis assessed the association of clinical and radiographic characteristics with the primary outcome of death during hospitalization. In this cohort of 94 patients, median age was 44 (interquartile range 29-62) months, 53 (56.4%) patients were male, 6 (7%) were HIV-infected, and 10 (11%) died during hospitalization. Elevated concentrations of plasma lactate (p = 0.005) and CSF PfHRP-2 (p = 0.04) were significantly associated with death. On multivariable analysis, higher PfHRP-2 in the CSF was associated with death (odds ratio 9.00, 95% confidence interval 1.44-56.42) while plasma PfHRP-2 was not (odds ratio 2.05, 95% confidence interval 0.45-9.35). Elevation of CSF, but not plasma PfHRP-2, is associated with death in this paediatric CM cohort. PfHRP-2 egress into the CSF may represent alteration of blood brain barrier permeability related to the sequestration of parasitized erythrocytes in the cerebral microvasculature.

Relationship between ankle range of motion and Biodex Balance System in females and males.

PubMed

Sung, Eun-Sook; Kim, Jung-Hyun

2018-02-01

This study examined whether there are differences between range of motion (ROM) and balance in lower extremities according to gender. A total of 31 male and 28 female students measured plantar flexion (PF), dorsiflexion, inversion (IV), eversion (EV), hip flexion (HF), hip internal rotation (HIR), and hip external rotation (HER) and tested on the Biodex Balance System. ROM of PF and HF were significantly high the female group and ROMs of IV, EV, HIR, and HER were significantly higher the male group than in the female group. Low ROM of PF may be more negative related to overall balance, especially, back balance in males; therefore, it is necessary to assess and plan the training program for PF ROM in male students.

Molecular identification of lipase LipA from Pseudomonas protegens Pf-5 and characterization of two whole-cell biocatalysts Pf-5 and Top10lipA.

PubMed

Zha, Daiming; Xu, Li; Zhang, Houjin; Yan, Yunjun

2014-05-01

To identify lipase LipA (PFL_0617) from Pseudomonas protegens Pf-5, a lipA deletion mutant (Pf0617) and a complementary strain (Pf0617lipA) were constructed, and their effects on the lipase production were examined. Pf0617 remarkably decreased its whole-cell lipase activity, whereas Pf0617lipA made its whole-cell lipase activity not only restore to wild-type level but also get a further increment. However, the deletion and overexpression of lipA did not affect the extracellular lipase activity. In addition, the unbroken whole cells of these strains were able to catalyze the hydrolysis of membrane-permeable p-nitrophenyl esters, but could not hydrolyze the membrane-impermeable olive oil. These results confirmed that LipA was an intracellular lipase and Pf-5 could also be used as a natural whole-cell biocatalyst. To evaluate the potential of Pf-5 as a whole-cell biocatalyst and separately characterize the whole-cell LipA, the properties of the whole-cell lipases from Pf-5 and Top10lipA were characterized. The results demonstrated that both Pf-5 and Top10lipA exhibited high tolerance to alkaline condition, high temperature, heavy metal ions, surfactants, and organic solvents. Taken together, lipA can realize functional expression in E. coli Top10, and Pf-5 and Top10lipA as whole-cell biocatalysts may have enormous potential in applications.

Developmental regulation of vascular endothelial growth/permeability factor messenger ribonucleic acid levels in and vascularization of the villous placenta during baboon pregnancy.

PubMed

Hildebrandt, V A; Babischkin, J S; Koos, R D; Pepe, G J; Albrecht, E D

2001-05-01

Vascular endothelial growth/permeability factor (VEG/PF) has an important role in angiogenesis; however, very little is known about the developmental regulation of VEG/PF and the vascular system within the placenta during human pregnancy. In the present study, therefore, a developmental approach was used in the baboon to determine the placental source of VEG/PF and its fms-like tyrosine kinase (flt-1) and kinase-insert domain containing (KDR/flk-1) receptors, and whether the rise in estrogen with advancing pregnancy was associated with a corresponding increase in placental VEG/PF expression and vascularization. VEG/PF messenger RNA (mRNA) levels were determined by competitive RT-PCR in villous cell fractions isolated by Percoll gradient centrifugation from placentas obtained on days 45 and 54 (very early), 60 (early), 100 (mid), and 165-170 (late) of baboon pregnancy (term = 184 days). Maternal peripheral serum estradiol increased from very low concentrations early in gestation (0.15-0.20 ng/ml) to an early surge of over 2.5 ng/ml on days 60-85, and peak levels of 4-6 ng/ml late in baboon pregnancy. VEG/PF mRNA was expressed in low level in the syncytiotrophoblast (<2,000 attomol/microgram total RNA), and values in this fraction did not change significantly with advancing gestation. VEG/PF mRNA expression was slightly greater in the inner villous core cell fraction; however, levels decreased (P < 0.05) between early and late gestation. Cytotrophoblasts were a major source of VEG/PF mRNA and levels increased (P < 0.01) from 3,631 +/- 844 attomol/microgram total RNA on day 45 to 25,807 +/- 5,873 attomol/microgram total RNA on day 170. VEG/PF protein expression determined by immunocytochemistry was abundant in cytotrophoblasts and lower in the syncytiotrophoblast and inner villous core cells. The flt-1 and KDR/flk-1 receptors were expressed in the vascular endothelial cells of the baboon villous placenta. The percentage of villous placenta occupied by blood vessels and the number of vessels/mm(2) villous tissue, determined by image analysis, progressively increased (P < 0.001; r = 0.97) from 3.4 +/- 0.2% and 447 +/- 29, respectively, on day 54 to 15.9 +/- 0.9% and 1,375 +/- 71, respectively, on day 170. In summary, the present study shows that villous cytotrophoblasts were a major source of VEG/PF mRNA and protein in the baboon villous placenta, and that cytotrophoblast VEG/PF mRNA levels and vascularization of the villous placenta closely paralleled the increase in estradiol concentrations of advancing pregnancy. These results are consistent with the concept that estrogen has an important role in establishing the new vascular system within the developing placenta during primate pregnancy and that VEG/PF mediates this process.

Cross-cultural Adaptation and Validation of the Victorian Institute of Sport Assessment-Patella Questionnaire for French-Speaking Patients With Patellar Tendinopathy.

PubMed

Kaux, Jean-François; Delvaux, François; Oppong-Kyei, Julian; Beaudart, Charlotte; Buckinx, Fanny; Croisier, Jean-Louis; Forthomme, Bénédicte; Crielaard, Jean-Michel; Bruyère, Olivier

2016-05-01

Study Design Clinical measurement study. Background The Victorian Institute of Sport Assessment-Patella (VISA-P), originally developed in English, assesses the severity of patellar tendinopathy symptoms. To date, no French version of the questionnaire exists. Objectives The aim of our study was to translate the VISA-P into French and verify its psychometric properties. Methods The translation and cultural adaptation were performed according to international recommendations in 6 steps: initial translation, translation merging, back translation to the original language, use of an expert committee to reach a prefinal version, test of the prefinal version, and expert committee appraisal of a final version. Afterward, the psychometric properties of the final French version (VISA-PF) were assessed in 92 subjects, divided into 3 groups: pathological subjects (n = 28), asymptomatic subjects (n = 22), and sports-risk subjects (n = 42). Results All members of the expert committee agreed with the final version. On a scale ranging from 0 to 100, with 100 representing an asymptomatic subject, the average ± SD scores on the VISA-PF were 53 ± 17 for the pathological group, 99 ± 2 for the healthy group, and 86 ± 14 for the sports-risk group. The test-retest reliability of the VISA-PF was excellent, with good internal consistency. Correlations between the VISA-PF and divergent validity of the Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36) were low, and the correlation coefficient values measured between the VISA-PF scores and converged items of the SF-36 were higher. Conclusion The VISA-PF is understandable, valid, and suitable for French-speaking patients with patellar tendinopathy. J Orthop Sports Phys Ther 2016;46(5):384-390. Epub 21 Mar 2016. doi:10.2519/jospt.2016.5937.

Demonstration of an anti-hyperalgesic effect of a novel pan-Trk inhibitor PF-06273340 in a battery of human evoked pain models.

PubMed

Loudon, Peter; Siebenga, Pieter; Gorman, Donal; Gore, Katrina; Dua, Pinky; van Amerongen, Guido; Hay, Justin L; Groeneveld, Geert Jan; Butt, Richard P

2018-02-01

Inhibitors of nerve growth factor (NGF) reduce pain in several chronic pain indications. NGF signals through tyrosine kinase receptors of the tropomyosin-related kinase (Trk) family and the unrelated p75 receptor. PF-06273340 is a small molecule inhibitor of Trks A, B and C that reduces pain in nonclinical models, and the present study aimed to investigate the pharmacodynamics of this first-in-class molecule in humans. A randomized, double-blind, single-dose, placebo- and active-controlled five-period crossover study was conducted in healthy human subjects (NCT02260947). Subjects received five treatments: PF-06273340 50 mg, PF-06273340 400 mg, pregabalin 300 mg, ibuprofen 600 mg and placebo. The five primary endpoints were the pain detection threshold for the thermal pain tests and the pain tolerance threshold for the cold pressor, electrical stair and pressure pain tests. The trial had predefined decision rules based on 95% confidence that the PF-06273340 effect was better than that of placebo. Twenty subjects entered the study, with 18 completing all five periods. The high dose of PF-06273340 met the decision rules on the ultraviolet (UV) B skin thermal pain endpoint [least squares (LS) mean vs. placebo: 1.13, 95% confidence interval: 0.64-1.61], but not on the other four primary endpoints. The low dose did not meet the decision criteria for any of the five primary endpoints. Pregabalin (cold pressor and electrical stair tests) and ibuprofen (UVB thermal pain) showed significant analgesic effects on expected endpoints. The study demonstrated, for the first time, the translation of nonclinical effects into man in an inflammatory pain analgesic pharmacodynamic endpoint using a pan-Trk inhibitor. © 2017 The British Pharmacological Society.

Two-cation competition in ionic-liquid-modified electrolytes for lithium ion batteries.

PubMed

Lee, Sang-Young; Yong, Hyun Hang; Lee, Young Joo; Kim, Seok Koo; Ahn, Soonho

2005-07-21

It is a common observation that when ionic liquids are added to electrolytes the performances of lithium ion cells become poor, while the thermal safeties of the electrolytes might be improved. In this study, this behavior is investigated based on the kinetics of ionic diffusion. As a model ionic liquid, we chose butyldimethylimidazolium hexafluorophosphate (BDMIPF(6)). The common solvent was propylene carbonate (PC), and lithium hexafluorophosphate (LiPF(6)) was selected as the lithium conducting salt. Ionic diffusion coefficients are estimated by using a pulsed field gradient NMR technique. From a basic study on the model electrolytes (BDMIPF(6) in PC, LiPF(6) in PC, and BDMIPF(6) + LiPF(6) in PC), it was found that the BDMI(+) from BDMIPF(6) shows larger diffusion coefficients than the Li(+) from LiPF(6). However, the anionic (PF(6)(-)) diffusion coefficients present little difference between the model electrolytes. The higher diffusion coefficient of BDMI(+) than that of Li(+) suggests that the poor C-rate performance of lithium ion cells containing ionic liquids as an electrolyte component can be attributed to the two-cation competition between Li(+) and BDMI(+).

Electrochemical Characterization of O2 Plasma Functionalized Multi-Walled Carbon Nanotube Electrode for Legionella pneumophila DNA Sensor

NASA Astrophysics Data System (ADS)

Park, Eun Jin; Lee, Jun-Yong; Hyup Kim, Jun; Kug Kim, Sun; Lee, Cheol Jin; Min, Nam Ki

2010-08-01

An electrochemical DNA sensor for Legionella pneumophila detection was constructed using O2 plasma functionalized multi-walled carbon nanotube (MWCNT) film as a working electrode (WE). The cyclic voltammetry (CV) results revealed that the electrocatalytic activity of plasma functionalized MWCNT (pf-MWCNT) significantly changed depending on O2 plasma treatment time due to some oxygen containing functional groups on the pf-MWCNT surface. Scanning electron microscope (SEM) images and X-ray photoelectron spectroscopy (XPS) spectra were also presented the changes of their surface morphologies and oxygen composition before and after plasma treatment. From a comparison study, it was found that the pf-MWCNT WEs had higher electrocatalytic activity and more capability of probe DNA immobilization: therefore, electrochemical signal changes by probe DNA immobilization and hybridization on pf-MWCNT WEs were larger than on Au WEs. The pf-MWCNT based DNA sensor was able to detect a concentration range of 10 pM-100 nM of target DNA to detect L. pneumophila.

Rubbing skin with nylon towels as a major cause of pseudomonas folliculitis in a Japanese population.

PubMed

Teraki, Yuichi; Nakamura, Kaori

2015-01-01

Pseudomonas folliculitis (PF) is a community-acquired skin infection, which develops after exposure to contaminated water such as whirlpools, swimming pools, water slides and hot tubs. In Japan, this condition has been sporadically reported, often in association with bathing; however, the exact cause of PF in the Japanese population remains unclear. In this study, we retrospectively reviewed 10 patients with PF diagnosed at our dermatology clinic (two males and eight females). Four patients had recurrences over 1-3 years. Notably, eight of the 10 patients were rubbing their bodies with nylon towels or sponges placed in the bathrooms during bathing. Pseudomonas aeruginosa was isolated from the nylon towels used in two of the two patients examined. Discontinued use of nylon towels resulted in prompt resolution of PF and no recurrence in all cases. Our observation suggests that rubbing the skin with nylon towels contaminated with P. aeruginosa was a major cause of PF in a Japanese population. © 2014 Japanese Dermatological Association.

Preference for Solitude, Social Isolation, Suicidal Ideation, and Self-Harm in Adolescents.

PubMed

Endo, Kaori; Ando, Shuntaro; Shimodera, Shinji; Yamasaki, Syudo; Usami, Satoshi; Okazaki, Yuji; Sasaki, Tsukasa; Richards, Marcus; Hatch, Stephani; Nishida, Atsushi

2017-08-01

Social isolation is associated with suicidal ideation (SI) and self-harm (SH) among adolescents. However, the association between preference for solitude (PfS), SI, and SH is unknown. The prevalence of adolescents who have both of PfS and social isolation and the risks for SI and SH among them are also unknown. Information on PfS, social isolation, SI, and SH was collected in a large-scale school-based survey on adolescents, using a self-report questionnaire. Associations between PfS, SI, and SH were examined by logistic regression analysis. The interactions between PfS and social isolation on SI and SH were also investigated. The odds of SI and SH were examined for groups defined by presence of PfS and social isolation. Responses from 17,437 students (89.3% of relevant classes) were available. After adjusting for demographic characteristics and social isolation, PfS was associated with increased odds of SI (odds ratio [OR] = 3.1) and SH (OR = 1.9). There was no interaction between PfS and social isolation on SI and SH. After adjusting for demographic characteristics, the odds for SI (OR = 8.6) and SH (OR = 3.8) were highest among adolescents with both PfS and social isolation (8.4% of all respondents). PfS was associated with increased odds of SI and SH in adolescents. No interaction effect between PfS and social isolation on SI and SH was found, but adolescents with PfS and social isolation had the highest risk for SI and SH. Parents and professionals should pay attention to suicide risk in adolescents with PfS. Copyright © 2017 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.

Progress with Plasmodium falciparum sporozoite (PfSPZ)-based malaria vaccines.

PubMed

Richie, Thomas L; Billingsley, Peter F; Sim, B Kim Lee; James, Eric R; Chakravarty, Sumana; Epstein, Judith E; Lyke, Kirsten E; Mordmüller, Benjamin; Alonso, Pedro; Duffy, Patrick E; Doumbo, Ogobara K; Sauerwein, Robert W; Tanner, Marcel; Abdulla, Salim; Kremsner, Peter G; Seder, Robert A; Hoffman, Stephen L

2015-12-22

Sanaria Inc. has developed methods to manufacture, purify and cryopreserve aseptic Plasmodium falciparum (Pf) sporozoites (SPZ), and is using this platform technology to develop an injectable PfSPZ-based vaccine that provides high-grade, durable protection against infection with Pf malaria. Several candidate vaccines are being developed and tested, including PfSPZ Vaccine, in which the PfSPZ are attenuated by irradiation, PfSPZ-CVac, in which fully infectious PfSPZ are attenuated in vivo by concomitant administration of an anti-malarial drug, and PfSPZ-GA1, in which the PfSPZ are attenuated by gene knockout. Forty-three research groups in 15 countries, organized as the International PfSPZ Consortium (I-PfSPZ-C), are collaborating to advance this program by providing intellectual, clinical, and financial support. Fourteen clinical trials of these products have been completed in the USA, Europe and Africa, two are underway and at least 12 more are planned for 2015-2016 in the US (four trials), Germany (2 trials), Tanzania, Kenya, Mali, Burkina Faso, Ghana and Equatorial Guinea. Sanaria anticipates application to license a first generation product as early as late 2017, initially to protect adults, and a year later to protect all persons >6 months of age for at least six months. Improved vaccine candidates will be advanced as needed until the following requirements have been met: long-term protection against natural transmission, excellent safety and tolerability, and operational feasibility for population-wide administration. Here we describe the three most developed whole PfSPZ vaccine candidates, associated clinical trials, initial plans for licensure and deployment, and long-term objectives for a final product suitable for mass administration to achieve regional malaria elimination and eventual global eradication. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Progress with Plasmodium falciparum sporozoite (PfSPZ)-based malaria vaccines

PubMed Central

Richie, Thomas L.; Billingsley, Peter F.; Sim, B. Kim Lee; James, Eric R.; Chakravarty, Sumana; Epstein, Judith E.; Lyke, Kirsten E.; Mordmüller, Benjamin; Alonso, Pedro; Duffy, Patrick E.; Doumbo, Ogobara K.; Sauerwein, Robert W.; Tanner, Marcel; Abdulla, Salim; Kremsner, Peter G.; Seder, Robert A.; Hoffman, Stephen L.

2016-01-01

Sanaria Inc. has developed methods to manufacture, purify and cryopreserve aseptic Plasmodium falciparum (Pf) sporozoites (SPZ), and is using this platform technology to develop an injectable PfSPZ-based vaccine that provides high-grade, durable protection against infection with Pf malaria. Several candidate vaccines are being developed and tested, including PfSPZ Vaccine, in which the PfSPZ are attenuated by irradiation, PfSPZ-CVac, in which fully infectious PfSPZ are attenuated in vivo by concomitant administration of an anti-malarial drug, and PfSPZ-GA1, in which the PfSPZ are attenuated by gene knockout. Forty-three research groups in 15 countries, organized as the International PfSPZ Consortium (I-PfSPZ-C), are collaborating to advance this program by providing intellectual, clinical, and financial support. Fourteen clinical trials of these products have been completed in the USA, Europe and Africa, two are underway and at least 12 more are planned for 2015–2016 in the US (four trials), Germany (2 trials), Tanzania, Kenya, Mali, Burkina Faso, Ghana and Equatorial Guinea. Sanaria anticipates application to license a first generation product as early as late 2017, initially to protect adults, and a year later to protect all persons >6 months of age for at least six months. Improved vaccine candidates will be advanced as needed until the following requirements have been met: long-term protection against natural transmission, excellent safety and tolerability, and operational feasibility for population-wide administration. Here we describe the three most developed whole PfSPZ vaccine candidates, associated clinical trials, initial plans for licensure and deployment, and long-term objectives for a final product suitable for mass administration to achieve regional malaria elimination and eventual global eradication. PMID:26469720

Electrically heated particulate filter using catalyst striping

DOEpatents

Gonze, Eugene V; Paratore, Jr., Michael J; Ament, Frank

2013-07-16

An exhaust system that processes exhaust generated by an engine is provided. The system generally includes a particulate filter (PF) that filters particulates from the exhaust wherein an upstream end of the PF receives exhaust from the engine. A grid of electrically resistive material is applied to an exterior upstream surface of the PF and selectively heats exhaust passing through the grid to initiate combustion of particulates within the PF. A catalyst coating is applied to the PF that increases a temperature of the combustion of the particulates within the PF.

Comparison of diagnostic value of indirect immunofluorescence assay and desmoglein ELISA in the diagnosis of pemphigus.

PubMed

Marinović, Branka; Fabris, Zrinka; Lipozencić, Jasna; Stulhofer Buzina, Daska; Lakos Jukić, Ines

2010-01-01

Pemphigus vulgaris (PV) and pemphigus foliaceus (PF) are autoimmune blistering diseases characterized by intraepidermal separation as the result of autoantibodies directed to desmoglein 1 and desmoglein 3, adhesion molecules that have a pathogenic role in blister formation. Both PV and PF are diagnosed according to clinical picture, histopathologic, immunopathologic and molecular biologic features. In the present study, the value of indirect immunofluorescence (IIF) and enzyme linked immunosorbent assay (ELISA) for desmoglein 1 (Dsg 1) and desmoglein 3 (Dsg 3) at baseline visit was compared. The study was performed as a retrospective study that included 22 patients, 19 of them with PV and three with PF. Patient sera were tested with IIF and Dsg 1 and Dsg 3 ELISA. In the group of 19 PV patients, 12 patients had positive IIF, Dsg 3 and Dsg 1 ELISA; two had positive IIF and positive anti Dsg 3 but negative anti Dsg 1; three had negative IIF but positive both Dsg 1 and Dsg 3 antibodies; and two had negative IIF and Dsg 1 but positive Dsg 3 antibodies. In the group of PF patients, all three patients had positive IIF, positive Dsg 1 ELISA and negative Dsg 3 ELISA. Results of our study supported previous reports confirming Dsg 1 and Dsg 3 ELISA to be a sensitive and specific tool for the diagnosis of PV and PF.

24-Hour Efficacy and Ocular Surface Health with Preservative-Free Tafluprost Alone and in Conjunction with Preservative-Free Dorzolamide/Timolol Fixed Combination in Open-Angle Glaucoma Patients Insufficiently Controlled with Preserved Latanoprost Monotherapy.

PubMed

Konstas, Anastasios-Georgios; Boboridis, Konstadinos G; Kapis, Paraskevas; Marinopoulos, Konstantinos; Voudouragkaki, Irini C; Panayiotou, Dimitrios; Mikropoulos, Dimitrios G; Pagkalidou, Eirini; Haidich, Anna-Bettina; Katsanos, Andreas; Quaranta, Luciano

2017-01-01

The aim of the present study was to evaluate the 24-h efficacy, tolerability, and ocular surface health with preservative-free (PF) tafluprost and a PF triple drug regimen comprising tafluprost and dorzolamide/timolol fixed combination (DTFC) in open-angle glaucoma patients who were insufficiently controlled with preserved branded or generic latanoprost monotherapy and who exhibited signs or symptoms of ocular surface disease (OSD). Prospective, observer-masked, crossover, comparison. Eligible consecutive open-angle glaucoma patients were randomized to either PF tafluprost or the triple PF regimen for 3 months. They were then crossed over to the opposite therapy for another 3 months. At the end of the latanoprost run-in period and after each PF treatment period, patients underwent habitual 24-h intraocular pressure (IOP) monitoring with Goldmann tonometry in the sitting position (at 10:00, 14:00, 18:00, and 22:00) and Perkins tonometry in the supine position (at 02:00 and 06:00). Tolerability and selected ocular surface parameters were evaluated at baseline and the end of each treatment period. Forty-three open-angle glaucoma patients completed the trial. Mean 24-h IOP on preserved latanoprost was 22.2 ± 3.9 mmHg. Compared with latanoprost monotherapy, PF tafluprost obtained a greater reduction in mean, peak, and fluctuation of 24-h IOP including the 02:00 and 06:00 time points (P < 0.05). With the exception of 24-h fluctuation, the triple PF regimen provided significantly lower IOP parameters than latanoprost or PF tafluprost (P < 0.001). Finally, PF tafluprost therapy displayed significantly improved tear film break-up times (6.7 vs 6.0 s), corneal staining (1.3 vs 2.2), and Schirmer I test results (9.1 vs 8.2 mm) compared with the preserved latanoprost baseline (all P < 0.01). The triple PF regimen demonstrated similar tear film break-up times (6.1 vs 6.0 s) and Schirmer I test results (8.2 vs 8.2 mm) to latanoprost, but revealed a significant improvement in the corneal stain test (1.7 vs 2.2; P < 0.001). In this trial PF tafluprost therapy provided statistically greater 24-h efficacy and improved tolerability compared with preserved latanoprost. The combination of PF tafluprost and PF dorzolamide/timolol fixed combination was statistically and clinically more efficacious than both monotherapies and demonstrated similar ocular surface characteristics to preserved latanoprost monotherapy. ClinicalTrials.gov (NCT02802137). Santen.

Plasma Free Hemoglobin Generation Using the EOS PMP™ Oxygenator and the CentriMag® Blood Pump.

PubMed

Hodge, Ashley B; Deitemyer, Matthew A; Duffy, Victoria L; Tumin, Dmitry; Garbin, Dorothy A; Nicol, Kathleen K; Hayes, Don; Cismowski, Mary J; Yates, Andrew R

2018-06-01

Hemolysis is a known consequence of extracorporeal membrane oxygenation (ECMO) resulting from shear force within the different components of the extracorporeal circuit. The primary aim of this study was to evaluate the EOS PMP ™ oxygenator for generation of plasma free hemoglobin (PfHg) over 24 hours at nominal operating range flow rates. The EOS ECMO ™ (LivaNova, Inc.; formerly Sorin, Arvada, CO) is equipped with a plasma tight polymethylpentene (PMP) hollow fiber oxygenator. We hypothesized that PfHg generation would be elevated in circuits with higher flow rates, because of the significant pressure drop across the oxygenator according to manufacturer provided flow charts. Generated PfHg concentrations were compared with PfHg concentrations from blood not exposed to an ECMO circuit. The secondary aim was to evaluate circuit flow-rate-induced changes in platelet count and platelet function over 24 hours. Circuits contained a CentriMag ® (St. Jude Medical, St. Paul, MN) blood pump and an EOS ECMO PMP ™ oxygenator. Circuits in triplicate were run continuously for 24 hours at three flow rates [1, 3, and 5 liters per minute {LPM}]. PfHg was analyzed at baseline, 6, 12, 18, and 24 hours. Platelet count and function were measured at baseline and 24 hours. Concentrations of PfHg at baseline for circuits operating at 1, 3, and 5 LPM were 24.4 ± 4.0, 38.4 ± 28.6, and 26.7 ± 6.9 mg/dL, respectively. PfHg concentrations after 24 hours were statistically compared for the three flow rates using analysis of variance; PfHg concentrations at 1 LPM (181.4 ± 29.1 mg/dL), 3 LPM (145.9 ± 8.7 mg/dL), and 5 LPM (100.1 ± 111.3 mg/dL) circuits. The F -test was not statistically significant ( p = .632), indicating that PfHg generation at 24 hours was similar among the three flow rates. Excessive hemolysis using PfHg levels in the EOS PMP ™ membrane oxygenator was not observed.

Phase I Clinical Trial of a Recombinant Blood Stage Vaccine Candidate for Plasmodium falciparum Malaria Based on MSP1 and EBA175

PubMed Central

Chitnis, Chetan E.; Mukherjee, Paushali; Mehta, Shantanu; Yazdani, Syed Shams; Dhawan, Shikha; Shakri, Ahmad Rushdi; Bharadwaj, Rukmini; Gupta, Puneet Kumar; Hans, Dhiraj; Mazumdar, Suman; Singh, Bijender; Kumar, Sanjeev; Pandey, Gaurav; Parulekar, Varsha; Imbault, Nathalie; Shivyogi, Preethi; Godbole, Girish; Mohan, Krishna; Leroy, Odile; Singh, Kavita; Chauhan, Virander S.

2015-01-01

Background A phase I randomised, controlled, single blind, dose escalation trial was conducted to evaluate safety and immunogenicity of JAIVAC-1, a recombinant blood stage vaccine candidate against Plasmodium falciparum malaria, composed of a physical mixture of two recombinant proteins, PfMSP-119, the 19 kD conserved, C-terminal region of PfMSP-1 and PfF2 the receptor-binding F2 domain of EBA175. Method Healthy malaria naïve Indian male subjects aged 18–45 years were recruited from the volunteer database of study site. Fifteen subjects in each cohort, randomised in a ratio of 2:1 and meeting the protocol specific eligibility criteria, were vaccinated either with three doses (10μg, 25μg and 50μg of each antigen) of JAIVAC-1 formulated with adjuvant Montanide ISA 720 or with standard dosage of Hepatitis B vaccine. Each subject received the assigned vaccine in the deltoid muscle of the upper arms on Day 0, Day 28 and Day 180. Results JAIVAC-1 was well tolerated and no serious adverse event was observed. All JAIVAC-1 subjects sero-converted for PfF2 but elicited poor immune response to PfMSP-119. Dose-response relationship was observed between vaccine dose of PfF2 and antibody response. The antibodies against PfF2 were predominantly of IgG1 and IgG3 isotype. Sera from JAIVAC-1 subjects reacted with late schizonts in a punctate pattern in immunofluorescence assays. Purified IgG from JAIVAC-1 sera displayed significant growth inhibitory activity against Plasmodium falciparum CAMP strain. Conclusion Antigen PfF2 should be retained as a component of a recombinant malaria vaccine but PfMSP-119 construct needs to be optimised to improve its immunogenicity. Trial Registration Clinical Trial Registry, India CTRI/2010/091/000301 PMID:25927360

Phase feeding in a big-bird production scenario: effect on growth performance, yield, and fillet dimension.

PubMed

Brewer, V B; Owens, C M; Emmert, J L

2012-05-01

Phase feeding (PF) has been effective at maintaining broiler growth while reducing production cost, but the effect on different broiler strains and sex has not been assessed. An experiment was conducted using 4 commercial broiler strains grown up to 63 d of age (n = 1,440), comparing a PF approach to an industry-type diet. At d 17, birds began either the industry or PF regimen. The industry regimen consisted of average industry nutrient levels with periods from 17 to 32 d, 32 to 40 d, 40 to 49 d, and 49 d to the end of trial. For PF, diets were prepared that contained Lys, sulfur amino acids, and Thr levels matching the predicted requirements for birds at the beginning (high nutrient density) and end (low nutrient density) of PF. Pelleted high and low nutrient density diets were blended to produce rations containing amino acid levels that matched the predicted PF requirements over 2-d intervals. Weight gain, feed intake, and feed efficiency were calculated through d 58. Birds were commercially processed at 59, 61, or 63 d; yield and fillet dimensions were measured. Phase feeding did not effect weight gain or feed intake of broilers during the overall growth period (17-58 d). For most strains, PF did not effect final BW, yield, or fillet dimensions. However, strain and sex had greater effects on growth performance, yields, and fillet dimensions. Strains B and D had greater breast yield than strains A and C. Reduced feed costs ($0.01 to $0.04 per kilogram of gain, depending on strain) were observed for all strains with PF for the overall growth period (17-58 d). Therefore, potential savings on feed costs are possible for all strains used in this study with the incorporation of the PF regimen.

Psychometric properties of the PROMIS Physical Function item bank in patients receiving physical therapy.

PubMed

Crins, Martine H P; van der Wees, Philip J; Klausch, Thomas; van Dulmen, Simone A; Roorda, Leo D; Terwee, Caroline B

2018-01-01

The Patient-Reported Outcomes Measurement Information System (PROMIS) is a universally applicable set of instruments, including item banks, short forms and computer adaptive tests (CATs), measuring patient-reported health across different patient populations. PROMIS CATs are highly efficient and the use in practice is considered feasible with little administration time, offering standardized and routine patient monitoring. Before an item bank can be used as CAT, the psychometric properties of the item bank have to be examined. Therefore, the objective was to assess the psychometric properties of the Dutch-Flemish PROMIS Physical Function item bank (DF-PROMIS-PF) in Dutch patients receiving physical therapy. Cross-sectional study. 805 patients >18 years, who received any kind of physical therapy in primary care in the past year, completed the full DF-PROMIS-PF (121 items). Unidimensionality was examined by Confirmatory Factor Analysis and local dependence and monotonicity were evaluated. A Graded Response Model was fitted. Construct validity was examined with correlations between DF-PROMIS-PF T-scores and scores on two legacy instruments (SF-36 Health Survey Physical Functioning scale [SF36-PF10] and the Health Assessment Questionnaire Disability-Index [HAQ-DI]). Reliability (standard errors of theta) was assessed. The results for unidimensionality were mixed (scaled CFI = 0.924, TLI = 0.923, RMSEA = 0.045, 1th factor explained 61.5% of variance). Some local dependence was found (8.2% of item pairs). The item bank showed a broad coverage of the physical function construct (threshold-parameters range: -4.28-2.33) and good construct validity (correlation with SF36-PF10 = 0.84 and HAQ-DI = -0.85). Furthermore, the DF-PROMIS-PF showed greater reliability over a broader score-range than the SF36-PF10 and HAQ-DI. The psychometric properties of the DF-PROMIS-PF item bank are sufficient. The DF-PROMIS-PF can now be used as short forms or CAT to measure the level of physical function of physiotherapy patients.

Use of PROMIS for Patients Undergoing Primary Total Shoulder Arthroplasty.

PubMed

Dowdle, S Blake; Glass, Natalie; Anthony, Chris A; Hettrich, Carolyn M

2017-09-01

The Patient-Reported Outcomes Measurement Information System (PROMIS) consists of question banks for health domains through computer adaptive testing (CAT). For patients with glenohumeral arthritis, (1) there would be high correlation between traditional patient-reported outcome (PRO) measures and the PROMIS upper extremity item bank (PROMIS UE) and PROMIS physical function CAT (PROMIS PF CAT), and (2) PROMIS PF CAT would not demonstrate ceiling effects. Cohort study (diagnosis); Level of evidence, 3. Sixty-one patients with glenohumeral osteoarthritis were included. Each patient completed the American Shoulder and Elbow Surgeons (ASES) assessment form, Marx Shoulder Activity Scale, Short Form-36 physical function scale (SF-36 PF), EuroQol 5 Dimensions (EQ-5D) questionnaire, Western Ontario Osteoarthritis Shoulder (WOOS) index, PROMIS PF CAT, and the PROMIS UE. Correlation was defined as high (>0.7), moderate (0.4-0.6), or weak (0.2-0.3). Significant floor and ceiling effects were present if more than 15% of individuals scored the lowest or highest possible total score on any PRO. The PROMIS PF demonstrated excellent correlation with the SF-36 PF ( r = 0.81, P < .0001) and good correlation with the ASES ( r = 0.62, P < .0001), EQ-5D ( r = 0.64, P < .001), and WOOS index ( r = 0.51, P < .01). The PROMIS PF demonstrated low correlation with the Marx scale ( r = 0.29, P = .02). The PROMIS UE demonstrated good correlation with the ASES ( r = 0.55, P < .0001), SF-36 ( r = 0.53, P < .01), EQ-5D ( r = 0.48, P < .01), and WOOS ( r = 0.34, P <.01), and poor correlation with the Marx scale ( r = 0.06, P = .62). There were no ceiling or floor effects observed. The mean number of items administered by the PROMIS PRO was 4. These data suggest that for a patient population with operative shoulder osteoarthritis, PROMIS UE and PROMIS PF CAT may be valid alternative PROs. Additionally, PROMIS PF CAT offers a decreased question burden with no ceiling effects.

Multifunctional (3-in-1) cancer theranostics applications of hydroxyquinoline-appended polyfluorene nanoparticles† †Electronic supplementary information (ESI) available: Synthesis, characterization, stability, optical properties, imaging, drug delivery, etc. See DOI: 10.1039/c7sc03321d

PubMed Central

Chowdhury, Sayan Roy; Mukherjee, Sudip; Das, Sourav

2017-01-01

The accumulation of fluorescent hydroxyquinoline-affixed polyfluorene (PF-HQ) nanoparticles and their utility for multi-color bio-imaging and drug delivery for cancer treatment are reported. The formation of nanoparticles (PF-HQ) containing hydrophobic pockets via three-dimensional growth of a polymeric backbone in a higher water fraction (THF : H2O = 1 : 9) was observed. The nanoparticles showed incredible dual-state optical and fluorescence properties, which were further explored in multi-color cell imaging in both cancer and normal cells. The cell viability assay in various normal cells confirmed the biocompatible nature of PF-HQ, which was further supported by an ex vivo (chick chorioallantoic membrane assay) model. This encouraged us to fabricate PF-HQ-based new drug delivery systems (DDS: PF-HQ–DOX) upon conjugation with the FDA-approved anti-cancer drug doxorubicin (DOX) by filling the hydrophobic pockets of the polymer nanoparticles. The enhanced anti-cancer activity of the DDS (PF-HQ–DOX) compared with that of free DOX was observed in mouse melanoma cancer cells (B16F10) and a subcutaneous mouse (C57BL6/J) melanoma tumor model upon administration of PF-HQ–DOX. Ex vivo biodistribution studies using a fluorescence quantification method demonstrated the enhanced accumulation of DOX in tumor tissues in the PF-HQ–DOX-treated group compared to that of the free drug, signifying the drug delivery efficacy of the delivery system by a passive targeting manner. Based on the above biological data (in vitro and in the pre-clinical model), these robust and versatile fluorescent hydroxyquinoline-affixed polyfluorene (PF-HQ) nanoparticles could be effectively utilized for multifunctional biomedical applications (as they are biocompatible and can be used for bio-imaging and as a drug delivery vehicle). PMID:29568419

Relationships between salivary free testosterone and the expression of force and power in elite athletes.

PubMed

Crewther, B T; Kilduff, L P; Cook, C J; Cunningham, D J; Bunce, P; Bracken, R M; Gaviglio, C M

2012-04-01

This study examined the predictive relationships between the salivary free testosterone (T) concentrations of elite athletes and the expression of force and power. A group of elite male rugby players (N.=64) were assessed for peak force (PF), peak rate of force development (PRFD), force at 100 milliseconds (F100 ms) and 250 milliseconds (F250 ms) during an isometric mid-thigh pull (IMTP), and/or peak power (PP) and height during a countermovement jump (CMJ). Saliva samples were collected before testing and assayed for free T. Relationships between individual T concentrations and performance were assessed as a pooled group and 4 sub-groups of equal size. As pooled data sets, none of the IMTP and CMJ performance variables were significantly correlated with free T in either the PF or PP groups (r=0.01-0.23). The PF and PP abilities of the 4 sub-groups were significantly different, so that PF1>PF2>PF3>PF4 (P<0.001) and PP1>PP2>PP3>PP4 (P<0.01). When the 4 sub-groups were analysed, the T concentrations of the PF4 group were significantly (P<0.05-0.01) correlated to PRFD (r=0.69) and F100 ms (r=0.55) during the IMTP, as was F100 ms in the PF1 group (r=0.66). In the PP1 group, free T also correlated to CMJ height (r=0.62). The key conclusion is that the expression of force and power in an elite athletic group may be dependent, to some extent, on individual variation in salivary free T concentrations and existing strength or power levels. The current results also confirm that the grouping of elite athletes of mixed strength or power ability may bias predictive results in a manner not reflective of sub-groups within this population.

Taxane-cisplatin-fluorouracil as induction chemotherapy for advanced head and neck cancer: a meta-analysis of the 5-year efficacy and safety.

PubMed

Qian, Xu; Ma, Chenming; Hoffmann, Thomas K; Kaufmann, Andreas M; Albers, Andreas E

2015-01-01

The objective of this study was to compare the efficacy and safety of taxane (docetaxel or paclitaxel), cisplatin, and fluorouracil (Tax-PF) with cisplatin plus fluorouracil (PF) regimen by a meta-analysis of data retrieved from the literature. Seven randomized clinical trials were identified, which included patients with advanced head and neck cancer who underwent induction chemotherapy with either a Tax-PF or PF protocol. The outcomes included the 3-year and 5-year overall survival (OS) and progression-free survival (PFS), overall response rate (ORR) and different types of adverse events. The 3-year OS rate (HR: 1.14; 95% CI: 1.03 to 1.25; P = 0.008), 3-year PFS rate (HR: 1.24; 95% CI: 1.08 to 1.43; P = 0.002), 5-year OS rate (HR: 1.30; 95% CI, 1.09 to 1.55;P = 0.003), 5-year PFS rate (HR: 1.39; 95% CI, 1.14 to 1.70; P = 0.001) and ORR to chemotherapy (OR 1.66; 95% CI, 1.35 to 2.05; P < 0.001) of the patients in the Tax-PF group were statistically superior to those in the PF group. In terms of toxicities, the incidence of febrile neutropenia (OR 2.36; 95% CI, 1.62 to 3.46; P < 0.001), alopecia (OR 8.22; 95% CI, 3.99 to 16.92; P < 0.001), diarrhea (OR 1.57; 95% CI, 1.05 to 2.36; P = 0.03) and leukopenia (OR 2.79; 95% CI, 1.86 to 4.21; P < 0.001) was higher in the Tax-PF group. The Tax-PF induction chemotherapy improved PFS and OS, and the ORR was better as compared to PF-based therapy regimens at the cost of a higher incidence of adverse events.

Iron excess in recreational marathon runners.

PubMed

Mettler, S; Zimmermann, M B

2010-05-01

Iron deficiency and anemia may impair athletic performance, and iron supplements are commonly consumed by athletes. However, iron overload should be avoided because of the possible long-term adverse health effects. We investigated the iron status of 170 male and female recreational runners participating in the Zürich marathon. Iron deficiency was defined either as a plasma ferritin (PF) concentration <15 microg/l (iron depletion) or as the ratio of the concentrations of transferrin receptor (sTfR) to PF (sTfR:log(PF) index) of > or =4.5 (functional iron deficiency). After excluding subjects with elevated C-reactive protein concentrations, iron overload was defined as PF >200 microg/l. Iron depletion was found in only 2 out of 127 men (1.6% of the male study population) and in 12 out of 43 (28.0%) women. Functional iron deficiency was found in 5 (3.9%) and 11 (25.5%) male and female athletes, respectively. Body iron stores, calculated from the sTfR/PF ratio, were significantly higher (P<0.001) among male compared with female marathon runners. Median PF among males was 104 microg/l, and the upper limit of the PF distribution in males was 628 microg/l. Iron overload was found in 19 out of 127 (15.0%) men but only 2 out of 43 in women (4.7%). Gender (male sex), but not age, was a predictor of higher PF (P<0.001). Iron depletion was present in 28% of female runners but in <2% of males, whereas one in six male runners had signs of iron overload. Although iron supplements are widely used by athletes in an effort to increase performance, our findings indicate excess body iron may be common in male recreational runners and suggest supplements should only be used if tests of iron status indicate deficiency.

Diagnostic accuracy of serum miR-122 and miR-199a in women with endometriosis.

PubMed

Maged, Ahmed M; Deeb, Wesam S; El Amir, Azza; Zaki, Sherif S; El Sawah, Heba; Al Mohamady, Maged; Metwally, Ahmed A; Katta, Maha A

2018-04-01

To evaluate the value of serum microRNA-122 (miR-122) and miR-199a as reliable noninvasive biomarkers in the diagnosis of endometriosis. During 2015-2016, at a teaching hospital in Egypt, a prospective cohort study was conducted on 45 women with pelvic endometriosis and 35 women who underwent laparoscopy for pelvic pain but were not diagnosed with endometriosis. Blood and peritoneal fluid (PF) samples were collected; interleukin-6 (IL-6) was detected by enzyme-linked immunosorbent assay and miR-122 and miR-199a expression was measured by quantitative real-time polymerase chain reaction. The serum and PF levels of IL-6, miR-122, and miR-199a were significantly higher in women with endometriosis than in controls (P<0.001 for all comparisons). Serum miR-122 expression was positively correlated with serum IL-6 (r=0.597), PF IL-6 (r=0.603), PF miR-122 (r=0.934), serum miR-199a (r=0.727), and PF miR-199a (r=0.653). Serum miR-199a expression was positively correlated with serum IL-6 (r=0.677), PF IL-6 (r=0.678), PF miR-122 (r=0.744), and PF miR-199a (r=0.932). Serum miR-122 and miR-199a had a sensitivity of 95.6% and 100.0%, and a specificity of 91.4% and 100%, respectively, for the detection of endometriosis. Serum miR-122 and miR-199a were significantly increased in endometriosis, indicating that these microRNAs might serve as biomarkers for the diagnosis of endometriosis. © 2017 International Federation of Gynecology and Obstetrics.

Psyllium husk fiber supplementation to the diets rich in soybean or coconut oil: hypocholesterolemic effect in healthy humans.

PubMed

Ganji, V; Kies, C V

1996-03-01

The objective of this study was to investigate the effect of psyllium husk fiber supplementation to the diets of soybean and coconut oil on serum lipids in normolipidemic humans. A 28-day study was divided into four 7-day experimental periods. Dietary periods were soybean oil (SO), soybean oil plus psyllium fiber (SO + PF), coconut oil (CO) and coconut oil plus psyllium fiber (CO + PF), and were arranged to a randomized cross over design. Ten subjects consumed controlled diet containing 30% fat calories (20% from test oils and 10% from controlled diet) and 20 g per day of psyllium during fiber supplementation periods. SO + PF diet significantly reduced serum cholesterol compared with SO diet (P < 0.001). CO + PF diet significantly reduced serum cholesterol compared with CO diet (P < 0.014). Hypocholesterolemic response was greater with SO + PF compared with CO + PF (0.36 mmol 1(-1) vs 0.31 mmol 1(-1)). Reductions in low-density lipoprotein (LDL) cholesterol and apolipoprotein (apo) B were parallel to reductions of serum cholesterol. SO diet decreased, while CO diet increased serum cholesterol, LDL cholesterol and apo B. Very-low density lipoprotein cholesterol, high-density lipoprotein cholesterol and apo A-1 were unaffected by psyllium fiber and saturation of fat. Reduction of serum cholesterol was due to reduction of LDL cholesterol. Psyllium fiber supplementation lowered serum cholesterol regardless of saturation level of dietary fat.

Binding and Inhibition of Spermidine Synthase from Plasmodium falciparum and Implications for In Vitro Inhibitor Testing

PubMed Central

Sprenger, Janina; Carey, Jannette; Svensson, Bo; Wengel, Verena

2016-01-01

The aminopropyltransferase spermidine synthase (SpdS) is a promising drug target in cancer and in protozoan diseases including malaria. Plasmodium falciparum SpdS (PfSpdS) transfers the aminopropyl group of decarboxylated S-adenosylmethionine (dcAdoMet) to putrescine or to spermidine to form spermidine or spermine, respectively. In an effort to understand why efficient inhibitors of PfSpdS have been elusive, the present study uses enzyme activity assays and isothermal titration calorimetry with verified or predicted inhibitors of PfSpdS to analyze the relationship between binding affinity as assessed by KD and inhibitory activity as assessed by IC50. The results show that some predicted inhibitors bind to the enzyme with high affinity but are poor inhibitors. Binding studies with PfSpdS substrates and products strongly support an ordered sequential mechanism in which the aminopropyl donor (dcAdoMet) site must be occupied before the aminopropyl acceptor (putrescine) site can be occupied. Analysis of the results also shows that the ordered sequential mechanism adequately accounts for the complex relationship between IC50 and KD and may explain the limited success of previous efforts at structure-based inhibitor design for PfSpdS. Based on PfSpdS active-site occupancy, we suggest a classification of ligands that can help to predict the KD−IC50 relations in future design of new inhibitors. The present findings may be relevant for other drug targets that follow an ordered sequential mechanism. PMID:27661085

Extracts Obtained from Pterocarpus angolensis DC and Ziziphus mucronata Exhibit Antiplasmodial Activity and Inhibit Heat Shock Protein 70 (Hsp70) Function.

PubMed

Zininga, Tawanda; Anokwuru, Chinedu P; Sigidi, Muendi T; Tshisikhawe, Milingoni P; Ramaite, Isaiah I D; Traoré, Afsatou N; Hoppe, Heinrich; Shonhai, Addmore; Potgieter, Natasha

2017-07-28

Malaria parasites are increasingly becoming resistant to currently used antimalarial therapies, therefore there is an urgent need to expand the arsenal of alternative antimalarial drugs. In addition, it is also important to identify novel antimalarial drug targets. In the current study, extracts of two plants, Pterocarpus angolensis and Ziziphus mucronata were obtained and their antimalarial functions were investigated. Furthermore, we explored the capability of the extracts to inhibit Plasmodium falciparum heat shock protein 70 (Hsp70) function. Heat shock protein 70 (Hsp70) are molecular chaperones whose function is to facilitate protein folding. Plasmodium falciparum the main agent of malaria, expresses two cytosol-localized Hsp70s: PfHsp70-1 and PfHsp70-z. The PfHsp70-z has been reported to be essential for parasite survival, while inhibition of PfHsp70-1 function leads to parasite death. Hence both PfHsp70-1 and PfHsp70-z are potential antimalarial drug targets. Extracts of P. angolensis and Z. mucronata inhibited the basal ATPase and chaperone functions of the two parasite Hsp70s. Furthermore, fractions of P. angolensis and Z. mucronata inhibited P. falciparum 3D7 parasite growth in vitro. The extracts obtained in the current study exhibited antiplasmodial activity as they killed P. falciparum parasites maintained in vitro. In addition, the findings further suggest that some of the compounds in P. angolensis and Z. mucronata may target parasite Hsp70 function.

Nuclear factor of activated T cells (NFAT) in pearl oyster Pinctada fucata: molecular cloning and functional characterization.

PubMed

Huang, Xian-De; Wei, Guo-jian; Zhang, Hua; He, Mao-Xian

2015-01-01

Nuclear factor of activated T cells (NFAT) plays an important role in nonimmune cells and also in T cells and many other cells of the immune system, by regulating the expression of a variety of genes involved in the immune response, organ development, developmental apoptosis and angiogenesis. In the present study, the NFAT homology gene, PfNFAT, from the pearl oyster Pinctada fucata was cloned and its genomic structure and promoter were analyzed. PfNFAT encodes a putative protein of 1226 amino acids, and contains a highly conserved Rel homology region (RHR) with DNA-binding specificity, and a regulatory domain (NFAT homology region, NHR) containing a potent transactivation domain (TAD). The PfNFAT gene consists of 12 exons and 11 introns, and its promoter contains potential binding sites for transcription factors such as NF-κB (Nuclear factor κB), STATx (signal transducer and activator of transcription), AP-1 (activator protein-1) and Sox-5/9 (SRY type HMG box-5/9), MyoD (Myogenic Differentiation Antigen) and IRF (Interferon regulatory factor). Comparison and phylogenetic analysis revealed that PfNFAT shows high identity with other invertebrate NFAT, and clusters with the NFAT5 subgroup. Furthermore, gene expression analysis revealed that PfNFAT is involved in the immune response to lipopolysaccharide (LPS) and Polyinosinic-polycytidylic acid (poly I:C) stimulation and in the nucleus inserting operation. The study of PfNFAT may increase understanding of molluscan innate immunity. Copyright © 2014 Elsevier Ltd. All rights reserved.

Performance of Paracheck™-Pf, SD Bioline malaria Ag-Pf and SD Bioline malaria Ag-Pf/pan for diagnosis of falciparum malaria in the Central African Republic

PubMed Central

2014-01-01

Background Rapid diagnostic tests (RDTs) are the current complement to microscopy for ensuring prompt malaria treatment. We determined the performance of three candidate RDTs (Paracheck™-Pf, SD Bioline malaria Ag-Pf and SD Bioline malaria Ag-Pf/pan) for rapid diagnosis of malaria in the Central African Republic. Methods Blood samples from consecutive febrile patients who attended for laboratory analysis of malaria at the three main health centres of Bangui were screened by microscopy and the RDTs. Two reference standards were used to assess the performance of the RDTs: microscopy and, a combination of microscopy plus nested PCR for slides reported as negative, on the assumption that negative results by microscopy were due to sub-patent parasitaemia. Results We analysed 436 samples. Using the combined reference standard of microscopy + PCR, the sensitivity of Paracheck™-Pf was 85.7% (95% CI, 80.8–89.8%), that of SD Bioline Ag-Pf was 85.4% (95% CI, 80.5–90.7%), and that of SD Bioline Ag-Pf/pan was 88.2% (95% CI, 83.2–92.0%). The tests performed less well in cases of low parasitaemia; however, the sensitivity was > 95% at > 500 parasites/μl. Conclusions Overall, SD Bioline malaria Ag-Pf and SD Bioline malaria Ag-Pf/pan performed slightly better than Paracheck™-Pf. Use of RDTs with reinforced microscopy practice and laboratory quality assurance should improve malaria treatment in the Central African Republic. PMID:24568311

Imaging of plantar fascia disorders: findings on plain radiography, ultrasound and magnetic resonance imaging.

PubMed

Draghi, Ferdinando; Gitto, Salvatore; Bortolotto, Chandra; Draghi, Anna Guja; Ori Belometti, Gioia

2017-02-01

Plantar fascia (PF) disorders commonly cause heel pain and disability in the general population. Imaging is often required to confirm diagnosis. This review article aims to provide simple and systematic guidelines for imaging assessment of PF disease, focussing on key findings detectable on plain radiography, ultrasound and magnetic resonance imaging (MRI). Sonographic characteristics of plantar fasciitis include PF thickening, loss of fibrillar structure, perifascial collections, calcifications and hyperaemia on Doppler imaging. Thickening and signal changes in the PF as well as oedema of adjacent soft tissues and bone marrow can be assessed on MRI. Radiographic findings of plantar fasciitis include PF thickening, cortical irregularities and abnormalities in the fat pad located deep below the PF. Plantar fibromatosis appears as well-demarcated, nodular thickenings that are iso-hypoechoic on ultrasound and show low-signal intensity on MRI. PF tears present with partial or complete fibre interruption on both ultrasound and MRI. Imaging description of further PF disorders, including xanthoma, diabetic fascial disease, foreign-body reactions and plantar infections, is detailed in the main text. Ultrasound and MRI should be considered as first- and second-line modalities for assessment of PF disorders, respectively. Indirect findings of PF disease can be ruled out on plain radiography. Teaching Points • PF disorders commonly cause heel pain and disability in the general population.• Imaging is often required to confirm diagnosis or reveal concomitant injuries.• Ultrasound and MRI respectively represent the first- and second-line modalities for diagnosis.• Indirect findings of PF disease can be ruled out on plain radiography.

Does Sequence Matter? Productive Failure and Designing Online Authentic Learning for Process Engineering

ERIC Educational Resources Information Center

Lai, Polly K.; Portolese, Alisha; Jacobson, Michael J.

2017-01-01

This paper presents a study that applied both "productive failure" (PF) and "authentic learning" instructional approaches in online learning activities for early-career process engineers' professional development. This study compares participants learning with either a PF (low-to-high [LH]) or a more traditional (high-to-low)…

High sensitivity and specificity of a new functional flow cytometry assay for clinically significant heparin-induced thrombocytopenia antibodies.

PubMed

Garritsen, H S; Probst-Kepper, M; Legath, N; Eberl, W; Samaniego, S; Woudenberg, J; Schuitemaker, J H N; Kroll, H; Gurney, D A; Moore, G W; Zehnder, J L

2014-04-01

Heparin-induced thrombocytopenia (HIT) is a life-threatening condition, in which the anticoagulant heparin, platelet factor 4 (PF4), and platelet-activating antibodies form complexes with prothrombotic properties. Laboratory tests to support clinical diagnosis are subdivided into functional, platelet activation assays, which lack standardization, or immunological assays, which have moderate specificity toward HIT. In this study, clinical performance of HITAlert, a novel in vitro diagnostic (IVD) registered platelet activation assay, was tested in a large cohort of HIT-suspected patients and compared with immunological assays. From 346 HIT-suspected patients (single center), clinical data including 4T pretest probability results, citrated platelet-poor plasmas, and sera were collected, allowing direct comparison of clinical observations with HITAlert results. HITAlert performance was compared with PF4 IgG ELISA (246 patients, three centers) and PF4 PaGIA (298 patients, single center). HITAlert showed high sensitivity (88.2%) and specificity (99.1%) when compared with clinical diagnosis. Agreement of HITAlert with PF4 ELISA- and PF4 PaGIA-positive patients is low (52.7 and 23.2%, respectively), while agreement with PF4 IgG ELISA- and PF4 PaGIA-negative patients is very high (98.1 and 99.1%, respectively). HITAlert performance is excellent when compared with clinical HIT diagnosis, making it a suitable assay for rapid testing of platelet activation due to anticoagulant therapy. © 2013 John Wiley & Sons Ltd.

What Influences Parents' Fear about Children's Independent Mobility? Evidence from a State-Wide Survey of Australian Parents.

PubMed

Bennetts, Shannon K; Cooklin, Amanda R; Crawford, Sharinne; D'Esposito, Fabrizio; Hackworth, Naomi J; Green, Julie; Matthews, Jan; Strazdins, Lyndall; Zubrick, Stephen R; Nicholson, Jan M

2018-03-01

To identify factors associated with generalized and stranger-specific parental fear (PF) about children's independent mobility (CIM), a critical aspect of physical activity. Cross-sectional survey; random sampling frame, minimum quotas of fathers, rural residents. State of Victoria, Australia. Parents of children aged 9 to 15 years (n = 1779), 71% response rate. Validated measures of PF and fear of strangers (FoS); parent, child, social, and environmental factors. Unadjusted and adjusted linear regression stratified by child age (9-10; 11-13; 14-15). Adjusted models explained a substantial proportion of variance across all age groups (PF: 33.6%-36.7%; FoS: 39.1%-44.0%). Perceived disapproval from others was consistently associated with both outcomes (PF: β =.11 to 23, p ≤ .05; FoS: β =.17-.21, p ≤ .001) as was parents' perception of children's competence to travel safely (PF: β = -.24 to -.11, p ≤ .05; FoS: β = -.16 to -.13, p ≤ .01). Factors associated with FoS included having a female child (β = -.21 to -.13, p ≤ .001), language other than English (β = .09 to.11, p ≤ .01), and low levels of parent education (β = -.14 to -08, p ≤ .05). The current study suggests that social norms, child competence, and perceptions about the benefits of CIM underpin PF. This evidence informs the development of interventions to reduce PF and promote CIM and children's physical activity.

Plate fixation versus intramedullary fixation for midshaft clavicle fractures: Meta-analysis of complications and functional outcomes.

PubMed

Xiao, Hao; Gao, Hengbo; Zheng, Tuokang; Zhao, Jianhui; Tian, Yingping

2016-04-01

This analysis critically compares publications discussing complications and functional outcomes of plate fixation (PF) versus intramedullary fixation (IF) for midshaft clavicle fractures. Relevant studies published between January 1990 and October 2014, without language restrictions, were identified in database searches of PubMed®, Medline®, Embase and the Chinese National Knowledge Infrastructure (CNKI). Studies that compared postoperative complications and functional outcomes between PF and IF for midshaft clavicle fractures, and provided sufficient data for analysis, were included in this meta-analysis. After strict evaluation, 12 studies were included in this meta-analysis. Studies encompassed 462 participants in the PF group and 440 in the IF group. Study participants were followed up for ≥1 year. Outcomes were superior with IF compared with PF in terms of shoulder constant score at 6-month follow-up, fewer symptomatic hardware complications, lower rate of refracture after hardware removal and less hypertrophic scarring. In other aspects, such as functional recovery at 12-months and 24-months, Disability of Arm, Shoulder and Hand (DASH) questionnaire results at 12-month follow-up, shoulder motion range, rates of superficial infection, temporary brachial plexus lesion, nonunion, malunion, delayed union, implant failure and need for major revision, both techniques were similar. Findings of this meta-analysis suggest that, in many respects, IF was superior to PF for the management of midshaft clavicle fractures. This finding could aid surgeons in making decisions on the optimum internal fixation pattern for midshaft clavicular fractures. © The Author(s) 2016.

A Weighted Measurement Fusion Particle Filter for Nonlinear Multisensory Systems Based on Gauss–Hermite Approximation

PubMed Central

Li, Yun

2017-01-01

We addressed the fusion estimation problem for nonlinear multisensory systems. Based on the Gauss–Hermite approximation and weighted least square criterion, an augmented high-dimension measurement from all sensors was compressed into a lower dimension. By combining the low-dimension measurement function with the particle filter (PF), a weighted measurement fusion PF (WMF-PF) is presented. The accuracy of WMF-PF appears good and has a lower computational cost when compared to centralized fusion PF (CF-PF). An example is given to show the effectiveness of the proposed algorithms. PMID:28956862

n-p Short-Range Correlations from (p,2p+n) Measurements

NASA Astrophysics Data System (ADS)

Tang, A.; Watson, J. W.; Aclander, J.; Alster, J.; Asryan, G.; Averichev, Y.; Barton, D.; Baturin, V.; Bukhtoyarova, N.; Carroll, A.; Gushue, S.; Heppelmann, S.; Leksanov, A.; Makdisi, Y.; Malki, A.; Minina, E.; Navon, I.; Nicholson, H.; Ogawa, A.; Panebratsev, Yu.; Piasetzky, E.; Schetkovsky, A.; Shimanskiy, S.; Zhalov, D.

2003-01-01

We studied the 12C(p,2p+n) reaction at beam momenta of 5.9, 8.0, and 9.0 GeV/c. For quasielastic (p,2p) events pf, the momentum of the knocked-out proton before the reaction, was compared (event by event) with pn, the coincident neutron momentum. For |pn|>kF=0.220 GeV/c (the Fermi momentum) a strong back-to-back directional correlation between pf and pn was observed, indicative of short-range n-p correlations. From pn and pf we constructed the distributions of c.m. and relative motion in the longitudinal direction for correlated pairs. We also determined that 49±13% of events with |pf|>kF had directionally correlated neutrons with |pn|>kF.

Effects of Inter- and Intra-aggregate Pore Space on the Soil-Gas Diffusivity Behavior in Unsaturated, Undisturbed Volcanic Ash Soils

NASA Astrophysics Data System (ADS)

Resurreccion, A. C.; Kawamoto, K.; Komatsu, T.; Moldrup, P.

2006-12-01

Volcanic ash soils (Andisols) have a unique dual porosity structure that results in good drainage and high soil- water retention. Despite of the complicated and highly developed soil structure, recent studies have reported a simple, highly linear relation between the soil-gas diffusion coefficient, Dp, and the soil-air content, ɛ, for several Japanese Andisols. In this study, we explain the linear Dp(ɛ) behavior from the effects of the inter- and intra-aggregate pore-size distributions. We couple the bimodal van Genuchten soil-water retention model with a general Dp(ɛ) model, ɛ^{X}, allowing the tortuosity- connectivity factor X to vary with pF (= log(-ψ; the soil-water matric potential in cm H2O)). Measured data suggest that the tortuosity-connectivity parameter X is at the minimum at pF 3 (where X ~ 2, following Buckingham, 1904), equal to the water retention point where a separation of inter- and intra-aggregate effects on Dp is observed. At pF < 3, the X values increased as pF decreased because of inactive/remote air-filled pore space entrapped by the inter-connected water films between inter-aggregate pore spaces. At pF > 3, X increased to a high value at very dry conditions due to remote air-filled space inside the intra-aggregate pores. By combining the complex dual porosity soil-water retention model with the power- law gas diffusivity model using a parabolic X(pF) function, the surprisingly simple linear behavior of Dp with ɛ was captured while the variation of Dp with pF followed a dual s-shaped curve similar to the water retention curve. A simple linear model to predict Dp(ɛ) is suggested, with slope C and threshold soil-air content, ɛth, calculated from the power-law model ɛ^{X} at pF 2 (near field capacity) and at pF 4.1 (near wilting point) using the same X value (= 2.3) at both pF in agreement with measured data. This linear Dp(ɛ) model performed better, especially at dry conditions, compared to the traditionally-used predictive models when tested against several independent Andisol datasets from literature.

Development of a parent version of the Manchester-Minneapolis quality of life survey for use by parents and carers of UK children: MMQL-UK (PF)

PubMed Central

Hutchings, Hayley A; Upton, Penney; Cheung, Wai-Yee; Maddocks, Alison; Eiser, Christine; Williams, John G; Russell, Ian T; Jackson, Sonia; Jenney, Meriel EM

2008-01-01

Background Although it is now widely endorsed that children should as far as possible rate their own health related quality of life (HRQL), there are situations where proxy information on child HRQL may be useful, especially where a child is too ill or young to provide their own HRQL assessment. There is limited availability of generic HRQL scales that have a parallel child and parent version and that are reliable, valid, brief, comprehensible and suitable for use in UK populations. The aims of this study were therefore to develop and validate a parent version of the anglicised Manchester-Minneapolis Quality of Life child form (MMQL-UK (CF)) and to determine the level of association between the child and parent versions of this form. Methods This study was undertaken concurrently with the anglicisation and validation of the MMQL, a measure of HRQL developed for use with children in North America. At that time, no parent version existed, so the MMQL form for children (MMQL-UK (CF)) was used as the basis for the development of the MMQL-UK parent form (PF). The sample included a control group of healthy children and their parents and five exemplar groups; children diagnosed with asthma, diabetes or inflammatory bowel disease and their parents, children in remission from cancer and their parents and children in public care and their carers. Consistency of the MMQL-UK (PF) components were assessed by calculating Cronbach's alpha. Validation of the parent questionnaire was undertaken by comparing MMQL-UK (PF) component scores with comparable components on the proxy PedsQL™ quality of life scales, comparing MMQL-UK (PF) component scores between parents of healthy and chronic disease children and by comparison of component scores from children and their parents or carers. Reproducibility and responsiveness were assessed by retesting parents by follow-up questionnaires. Results A total of 874 children (completing MMQL-UK (CF)) and 572 parents or carers (completing MMQL-UK (PF)) took part in the study. The internal consistency of all the MMQL-UK (PF) components exceeding the accepted criterion of 0.70 and the construct validity was good with moderate correlations being evident between comparable components of the MMQL-UK (PF) and the proxy PedsQL™. Discriminant validity was demonstrated with significant differences being identified between parents of healthy children and those with chronic conditions. Intra-class correlations exceeded 0.65 for all MMQL-UK (PF) components demonstrating good reproducibility. Weak to moderate levels of responsiveness were demonstrated for all but social functioning. The MMQL-UK (PF) showed moderate parent-child correlation with the MMQL-UK (CF) for all components. The best correlations were seen for those components measuring the same construct (Pearson's r ranged from 0.31 to 0.61, p < 0.01 for equivalent components). Conclusion The MMQL-UK (PF) showed moderate to good correlations with the MMQL-UK (CF) component scores. The MMQL-UK (PF) will be of use when comparing child and parent/carer perception of the impact of a child's condition on their HRQL or where the child is too ill or young to provide their own report. PMID:18307771

Primordial Magnetic Field Effects on the CMB and Large-Scale Structure

DOE PAGES

Yamazaki, Dai G.; Ichiki, Kiyotomo; Kajino, Toshitaka; ...

2010-01-01

Mmore » agnetic fields are everywhere in nature, and they play an important role in every astronomical environment which involves the formation of plasma and currents. It is natural therefore to suppose that magnetic fields could be present in the turbulent high-temperature environment of the big bang. Such a primordial magnetic field (PF) would be expected to manifest itself in the cosmic microwave background (CB) temperature and polarization anisotropies, and also in the formation of large-scale structure. In this paper, we summarize the theoretical framework which we have developed to calculate the PF power spectrum to high precision. Using this formulation, we summarize calculations of the effects of a PF which take accurate quantitative account of the time evolution of the cutoff scale. We review the constructed numerical program, which is without approximation, and an improvement over the approach used in a number of previous works for studying the effect of the PF on the cosmological perturbations. We demonstrate how the PF is an important cosmological physical process on small scales. We also summarize the current constraints on the PF amplitude B λ and the power spectral index n B which have been deduced from the available CB observational data by using our computational framework.« less

Independent and joint associations of physical activity and fitness with fibromyalgia symptoms and severity: The al-Ándalus project.

PubMed

Segura-Jiménez, Víctor; Soriano-Maldonado, Alberto; Estévez-López, Fernando; Álvarez-Gallardo, Inmaculada C; Delgado-Fernández, Manuel; Ruiz, Jonatan R; Aparicio, Virginia A

2017-08-01

We examined independent and joint associations of objectively measured physical activity (PA) and physical fitness (PF) with pain, fatigue and the overall impact of fibromyalgia in 386 fibromyalgia women aged 51.2 ± 7.6 years. Levels of PA (light, moderate and vigorous) and PF were measured with triaxial accelerometry and the Senior Fitness Test, respectively. We used the Short-Form health survey-36 pain sub-scale and the Multidimensional Fatigue Inventory to assess pain and multiple dimensions of fatigue, respectively. The impact of fibromyalgia was studied with the Revised Fibromyalgia Impact Questionnaire (FIQR). Both, total PA and global PF were independently associated with pain pressure threshold, SF-36 pain, reduced activity, reduced motivation and FIQR total score (all, P ≤ 0.027). The associations between total PA and symptoms were weaker than those observed between global PF and symptoms. Overall, unfit patients with low PA showed a worse profile that fit patients with high PA (all, P ≤ 0.001). In summary, PA and PF are independently associated with pain, fatigue and the overall impact of fibromyalgia in women. Although PF presented greater associations with symptoms, the results suggest that both being physically active and keep adequate fitness levels might be convenient for fibromyalgia women.

Direct effect of plasma permeability factors from patients with idiopatic FSGS on nephrin and podocin expression in human podocytes.

PubMed

Doublier, Sophie; Musante, Luca; Lupia, Enrico; Candiano, Giovanni; Spatola, Tiziana; Caridi, Gianluca; Zennaro, Cristina; Carraro, Michele; Ghiggeri, Gian Marco; Camussi, Giovanni

2005-07-01

The presence of circulating plasma factors (PF) altering renal permeability to proteins has been previously described in patients with focal segmental glomerulosclerosis (FSGS). Since these patients show reduced nephrin and podocin expression at renal biopsy, we evaluated the effect of serum and PF from patients with FSGS on nephrin and podocin expression in human podocytes. We studied 7 sera from patients with steroid-resistant FSGS, 3 from patients with nephrotic syndrome caused by non-immune disease, and 6 from healthy subjects. PF was prepared from plasmapheresis eluates of 2 patients with post-transplant recurrence of FSGS. Purification procedure was based on protein A Sepharose chromatography and differential precipitation in ammonium sulphate. Nephrin and podocin expression was semi-quantitatively evaluated by immunofluorescence. We found that serum and PF from FSGS patients rapidly induced redistribution and loss of nephrin in podocytes. This effect was associated with cytoskeleton redistribution and inhibited by cytochalasin B and sodium azide. On the contrary, podocin expression was unchanged after incubation with serum and PF from FSGS patients for short periods, but markedly reduced at 24 h. Our results demonstrate that serum and PF from FSGS patients may directly affect nephrin and podocin in human podocytes, thus providing new insights into the mechanisms causing proteinuria in FSGS.

Membrane and luminal proteins reach the apicoplast by different trafficking pathways in the malaria parasite Plasmodium falciparum

PubMed Central

Chaudhari, Rahul; Dey, Vishakha; Narayan, Aishwarya; Sharma, Shobhona

2017-01-01

The secretory pathway in Plasmodium falciparum has evolved to transport proteins to the host cell membrane and to an endosymbiotic organelle, the apicoplast. The latter can occur via the ER or the ER-Golgi route. Here, we study these three routes using proteins Erythrocyte Membrane Protein-1 (PfEMP1), Acyl Carrier Protein (ACP) and glutathione peroxidase-like thioredoxin peroxidase (PfTPxGl) and inhibitors of vesicular transport. As expected, the G protein-dependent vesicular fusion inhibitor AlF4− and microtubule destabilizing drug vinblastine block the trafficking of PfEMP-1, a protein secreted to the host cell membrane. However, while both PfTPxGl and ACP are targeted to the apicoplast, only ACP trafficking remains unaffected by these treatments. This implies that G protein-dependent vesicles do not play a role in classical apicoplast protein targeting. Unlike the soluble protein ACP, we show that PfTPxGl is localized to the outermost membrane of the apicoplast. Thus, the parasite apicoplast acquires proteins via two different pathways: first, the vesicular trafficking pathway appears to handle not only secretory proteins, but an apicoplast membrane protein, PfTPxGl; second, trafficking of apicoplast luminal proteins appear to be independent of G protein-coupled vesicles. PMID:28462015

Membrane and luminal proteins reach the apicoplast by different trafficking pathways in the malaria parasite Plasmodium falciparum.

PubMed

Chaudhari, Rahul; Dey, Vishakha; Narayan, Aishwarya; Sharma, Shobhona; Patankar, Swati

2017-01-01

The secretory pathway in Plasmodium falciparum has evolved to transport proteins to the host cell membrane and to an endosymbiotic organelle, the apicoplast. The latter can occur via the ER or the ER-Golgi route. Here, we study these three routes using proteins Erythrocyte Membrane Protein-1 (PfEMP1), Acyl Carrier Protein (ACP) and glutathione peroxidase-like thioredoxin peroxidase (PfTPx Gl ) and inhibitors of vesicular transport. As expected, the G protein-dependent vesicular fusion inhibitor AlF 4 - and microtubule destabilizing drug vinblastine block the trafficking of PfEMP-1, a protein secreted to the host cell membrane. However, while both PfTPx Gl and ACP are targeted to the apicoplast, only ACP trafficking remains unaffected by these treatments. This implies that G protein-dependent vesicles do not play a role in classical apicoplast protein targeting. Unlike the soluble protein ACP, we show that PfTPx Gl is localized to the outermost membrane of the apicoplast. Thus, the parasite apicoplast acquires proteins via two different pathways: first, the vesicular trafficking pathway appears to handle not only secretory proteins, but an apicoplast membrane protein, PfTPx Gl ; second, trafficking of apicoplast luminal proteins appear to be independent of G protein-coupled vesicles.

External Versus Internal Pancreatic Duct Drainage for the Early Efficacy After Pancreaticoduodenectomy: A Retrospectively Comparative Study.

PubMed

Wang, Gang; Li, Le; Ma, Yuan; Qu, Feng-Zhi; Zhu, Hong; Lv, Jia-Chen; Jia, Yue-Hui; Wu, Lin-Feng; Sun, Bei

2016-08-01

To compare the early efficacy of external versus internal pancreatic duct drainage after pancreaticoduodenectomy (PD), providing clinical evidence for selecting the optimal approach to pancreatic duct drainage. The clinical data of 395 consecutive patients undergoing PD from 2006 to 2013 were analyzed retrospectively. All the patients were divided into external and internal drainage group. Intraoperative blood loss, surgery duration, postoperative hospitalization duration, mortality rate, PF, and other complications were compared between the two groups. The perioperative relative risk factors that might induce PF were analyzed. External drainage significantly reduced the incidences of post-PD PF, delayed gastric emptying, abdominal infection, bowel obstruction, overall complications, and shortened the healing time of PF (p < .05). The univariate analysis showed that the pancreatic duct drainage method, body mass index (BMI), preoperative serum bilirubin level, perioperative blood transfusion, pancreaticojejunostomy approach, pancreatic texture, pancreatic duct diameter, and primary disease differed markedly between the two groups (p < .05). A multivariate analysis revealed that BMI ≥ 25 kg/m(2), internal pancreatic duct drainage, pancreatic duct diameter <3 mm, soft pancreatic texture, and ampullary disease were independent risk factors for PF. External pancreatic duct drainage can effectively reduce the morbidity of PF and overall complications after PD.

Structural dynamics of Casein Kinase I (CKI) from malarial parasite Plasmodium falciparum (Isolate 3D7): Insights from theoretical modelling and molecular simulations.

PubMed

Dehury, Budheswar; Behera, Santosh Kumar; Mahapatra, Namita

2017-01-01

The protein kinases (PKs), belonging to serine/threonine kinase (STKs), are important drug targets for a wide spectrum of diseases in human. Among protein kinases, the Casein Kinases (CKs) are vastly expanded in various organisms, where, the malarial parasite Plasmodium falciparum possesses a single member i.e., PfCKI, which can phosphorylate various proteins in parasite extracts in vitro condition. But, the structure-function relationship of PfCKI and dynamics of ATP binding is yet to be understood. Henceforth, an attempt was made to study the dynamics, stability, and ATP binding mechanisms of PfCKI through computational modelling, docking, molecular dynamics (MD) simulations, and MM/PBSA binding free energy estimation. Bi-lobed catalytic domain of PfCKI shares a high degree of secondary structure topology with CKI domains of rice, human, and mouse indicating co-evolution of these kinases. Molecular docking study revealed that ATP binds to the active site where the glycine-rich ATP-binding motif (G16-X-G18-X-X-G21) along with few conserved residues plays a crucial role maintaining stability of the complex. Structural superposition of PfCKI with close structural homologs depicted that the location and length of important loops are different, indicating the dynamic properties of these loops among CKIs, which is consistent with principal component analysis (PCA). PCA displayed that the overall global motion of ATP-bound form is comparatively higher than that of apo form. The present study provides insights into the structural features of PfCKI, which could contribute towards further understanding of related protein structures, dynamics of catalysis and phosphorylation mechanism in these important STKs from malarial parasite in near future. Copyright © 2016 Elsevier Inc. All rights reserved.

Bilateral comparison of 10 pF and 100 pF standards (ongoing BIPM key comparisons BIPM.EM-K14.a and 14.b) between the NIS (Egypt) and the BIPM

NASA Astrophysics Data System (ADS)

Gournay, Pierre; Helmy, M.; Raouf, A.; Hamed, Heba A. M.; Eliwa Gad, A.

2017-01-01

This report presents the results of a bilateral comparison of 10 pF and 100 pF capacitance standards between the NIS (Egypt) and the BIPM carried out in 2016. The comparison at 10 pF forms part of the ongoing BIPM key comparison BIPM.EM-K14.a and that at 100 pF of the ongoing BIPM key comparison BIPM.EM-K14.b. The BIPM is the pilot laboratory for both of these comparisons. Two 10 pF and 100 pF travelling standards belonging to the BIPM were used in this comparison carried out with an 'A-B-A' pattern of measurements. The standards were measured first at the BIPM for a period of about one month, then for a similar period at the NIS, and finally again at the BIPM. The measurand was the two terminal-pair capacitance at a frequency of either 1000 Hz or 1592 Hz, for a measuring rms voltage of 15 V at 10 pF and 10 V at 100 pF. One of the 10 pF travelling standards had to be eliminated from the comparison due to a bistable behaviour, possibly due to transportation. The results from the NIS and the BIPM at both 1000 Hz and 1592 Hz were found to be in good agreement, with a difference smaller than the relative expanded uncertainty (95 % confidence, k = 2) of about 0.72 × 10-6 at 10 pF and about 0.65 × 10-6 at 100 pF. Main text To reach the main text of this paper, click on Final Report. Note that this text is that which appears in Appendix B of the BIPM key comparison database kcdb.bipm.org/. The final report has been peer-reviewed and approved for publication by the CCEM, according to the provisions of the CIPM Mutual Recognition Arrangement (CIPM MRA).

Sulfonamide inhibition studies of the η-class carbonic anhydrase from the malaria pathogen Plasmodium falciparum.

PubMed

Vullo, Daniela; Del Prete, Sonia; Fisher, Gillian M; Andrews, Katherine T; Poulsen, Sally-Ann; Capasso, Clemente; Supuran, Claudiu T

2015-02-01

The η-carbonic anhydrases (CAs, EC 4.2.1.1) were recently discovered as the sixth genetic class of this metalloenzyme superfamily, and are so far known only in protozoa, including various Plasmodium species, the causative agents of malaria. We report here an inhibition study of the η-CA from Plasmodium falciparum (PfCA) against a panel of sulfonamides and one sulfamate compound, some of which are clinically used. The strongest inhibitors identified were ethoxzolamide and sulthiame, with KIs of 131-132 nM, followed by acetazolamide, methazolamide and hydrochlorothiazide (KIs of 153-198 nM). Brinzolamide, topiramate, zonisamide, indisulam, valdecoxib and celecoxib also showed significant inhibitory action against PfCA, with KIs ranging from 217 to 308 nM. An interesting observation was that the more efficient PfCA inhibitors are representative of several scaffolds and chemical classes, including benzene sulfonamides, monocyclic/bicyclic heterocyclic sulfonamides and compounds with a more complex scaffold (i.e., the sugar sulfamate derivative, topiramate, and the coxibs, celecoxib and valdecoxib). A comprehensive inhibition study of small molecules for η-CAs is needed as a first step towards assessing PfCA as a druggable target. The present work identifies the first known η-CA inhibitors and provides a platform for the development of next generation novel PfCA inhibitors. Copyright © 2014 Elsevier Ltd. All rights reserved.

Efficacy of texture, shape, and intensity feature fusion for posterior-fossa tumor segmentation in MRI.

PubMed

Ahmed, Shaheen; Iftekharuddin, Khan M; Vossough, Arastoo

2011-03-01

Our previous works suggest that fractal texture feature is useful to detect pediatric brain tumor in multimodal MRI. In this study, we systematically investigate efficacy of using several different image features such as intensity, fractal texture, and level-set shape in segmentation of posterior-fossa (PF) tumor for pediatric patients. We explore effectiveness of using four different feature selection and three different segmentation techniques, respectively, to discriminate tumor regions from normal tissue in multimodal brain MRI. We further study the selective fusion of these features for improved PF tumor segmentation. Our result suggests that Kullback-Leibler divergence measure for feature ranking and selection and the expectation maximization algorithm for feature fusion and tumor segmentation offer the best results for the patient data in this study. We show that for T1 and fluid attenuation inversion recovery (FLAIR) MRI modalities, the best PF tumor segmentation is obtained using the texture feature such as multifractional Brownian motion (mBm) while that for T2 MRI is obtained by fusing level-set shape with intensity features. In multimodality fused MRI (T1, T2, and FLAIR), mBm feature offers the best PF tumor segmentation performance. We use different similarity metrics to evaluate quality and robustness of these selected features for PF tumor segmentation in MRI for ten pediatric patients.

RTS,S/AS01 malaria vaccine mismatch observed among Plasmodium falciparum isolates from southern and central Africa and globally.

PubMed

Pringle, Julia C; Carpi, Giovanna; Almagro-Garcia, Jacob; Zhu, Sha Joe; Kobayashi, Tamaki; Mulenga, Modest; Bobanga, Thierry; Chaponda, Mike; Moss, William J; Norris, Douglas E

2018-04-26

The RTS,S/AS01 malaria vaccine encompasses the central repeats and C-terminal of Plasmodium falciparum circumsporozoite protein (PfCSP). Although no Phase II clinical trial studies observed evidence of strain-specific immunity, recent studies show a decrease in vaccine efficacy against non-vaccine strain parasites. In light of goals to reduce malaria morbidity, anticipating the effectiveness of RTS,S/AS01 is critical to planning widespread vaccine introduction. We deep sequenced C-terminal Pfcsp from 77 individuals living along the international border in Luapula Province, Zambia and Haut-Katanga Province, the Democratic Republic of the Congo (DRC) and compared translated amino acid haplotypes to the 3D7 vaccine strain. Only 5.2% of the 193 PfCSP sequences from the Zambia-DRC border region matched 3D7 at all 84 amino acids. To further contextualize the genetic diversity sampled in this study with global PfCSP diversity, we analyzed an additional 3,809 Pfcsp sequences from the Pf3k database and constructed a haplotype network representing 15 countries from Africa and Asia. The diversity observed in our samples was similar to the diversity observed in the global haplotype network. These observations underscore the need for additional research assessing genetic diversity in P. falciparum and the impact of PfCSP diversity on RTS,S/AS01 efficacy.

DPF heater attachment mechanisms

DOEpatents

Gonze, Eugene V [Pinckney, MI; Ament, Frank [Troy, MI

2011-04-26

An exhaust filter system includes a particulate filter (PF) that is disposed downstream from an engine. The PF filters particulates within an exhaust from the engine. A heating element heats particulate matter in the PF. A fastener limits expansion movement of the heating element relative to the PF.

Paeoniflorin improves cardiac function and decreases adverse postinfarction left ventricular remodeling in a rat model of acute myocardial infarction.

PubMed

Chen, Hengwen; Dong, Yan; He, Xuanhui; Li, Jun; Wang, Jie

2018-01-01

Paeoniflorin (PF) is the active component of Paeonia lactiflora Pall. or Paeonia veitchii Lynch. This study was, therefore, aimed to evaluate the improvement and mechanism of the PF on ventricular remodeling in rats with acute myocardial infarction (AMI). In this study, AMI model was established by ligating the anterior descending coronary artery in Wistar rats. After 4 weeks gavage of PF, the apparent signs and the left ventricle weight index of Wistar rats were observed. The left ventricular ejection fraction (LVEF) was evaluated by Doppler ultrasonography. Changes in cardiac morphology were observed by pathologic examination, and apoptosis was observed by the terminal deoxynucleotidyl transferase dUTP nick end labeling assay. In addition, enzyme-linked immunosorbent assay was used to detect the expression of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) interleukin-10 (IL-10) and brain natriuretic peptide (BNP). Immunohistochemistry and Western blot method were applied to detect Caspase-3 and Caspase-9. Compared with the model control, the survival conditions of rats in all treatment groups were generally improved after PF treatment. LVEF was significantly increased, and both left ventricular end-diastolic inner diameter and left ventricular end-systolic inner diameter were significantly reduced. Moreover, pathologic examination showed that the myocardium degeneration of the rats treated with PF was decreased, including neater arrangement, more complete myofilament, more uniform gap and less interstitial collagen fibers. Furthermore, the mitochondrial structure of cardiomyocytes was significantly improved. The ultrastructure was clear, and the arrangement of myofilament was more regular. Also, the expression of Caspase-3 and Caspase-9 was inhibited, and apoptosis was obviously reduced in the PF treatment groups. BNP, TNF-α and IL-6 were also decreased and IL-10 was increased in the treated rats. PF could significantly improve the LVEF of rats. It decreased adverse left ventricular remodeling after myocardial infarction in rat models. The potential mechanism could be that PF decreased and inhibited BNP, TNF-α and IL-6, increased IL-10 and further inhibited the expression of Caspase-3 and Caspase-9, thus promoting ventricular remodeling.

Unique Cardiac Purkinje Fiber Transient Outward Current β-Subunit Composition

PubMed Central

Xiao, Ling; Koopmann, Tamara T.; Ördög, Balázs; Postema, Pieter G.; Verkerk, Arie O.; Iyer, Vivek; Sampson, Kevin J.; Boink, Gerard J.J.; Mamarbachi, Maya A.; Varro, Andras; Jordaens, Luc; Res, Jan; Kass, Robert S.; Wilde, Arthur A.; Bezzina, C.R.; Nattel, Stanley

2015-01-01

Rationale A chromosomal haplotype producing cardiac overexpression of dipeptidyl peptidase-like protein-6 (DPP6) causes familial idiopathic ventricular fibrillation. The molecular basis of transient outward current (Ito) in Purkinje fibers (PFs) is poorly understood. We hypothesized that DPP6 contributes to PF Ito and that its overexpression might specifically alter PF Ito properties and repolarization. Objective To assess the potential role of DPP6 in PF Ito. Methods and Results Clinical data in 5 idiopathic ventricular fibrillation patients suggested arrhythmia origin in the PF-conducting system. PF and ventricular muscle Ito had similar density, but PF Ito differed from ventricular muscle in having tetraethylammonium sensitivity and slower recovery. DPP6 overexpression significantly increased, whereas DPP6 knockdown reduced, Ito density and tetraethylammonium sensitivity in canine PF but not in ventricular muscle cells. The K+-channel interacting β-subunit K+-channel interacting protein type-2, essential for normal expression of Ito in ventricular muscle, was weakly expressed in human PFs, whereas DPP6 and frequenin (neuronal calcium sensor-1) were enriched. Heterologous expression of Kv4.3 in Chinese hamster ovary cells produced small Ito; Ito amplitude was greatly enhanced by coexpression with K+-channel interacting protein type-2 or DPP6. Coexpression of DPP6 with Kv4.3 and K+-channel interacting protein type-2 failed to alter Ito compared with Kv4.3/K+-channel interacting protein type-2 alone, but DPP6 expression with Kv4.3 and neuronal calcium sensor-1 (to mimic PF Ito composition) greatly enhanced Ito compared with Kv4.3/neuronal calcium sensor-1 and recapitulated characteristic PF kinetic/pharmacological properties. A mathematical model of cardiac PF action potentials showed that Ito enhancement can greatly accelerate PF repolarization. Conclusions These results point to a previously unknown central role of DPP6 in PF Ito, with DPP6 gain of function selectively enhancing PF current, and suggest that a DPP6-mediated PF early-repolarization syndrome might be a novel molecular paradigm for some forms of idiopathic ventricular fibrillation. PMID:23532596

International journal of computational fluid dynamics real-time prediction of unsteady flow based on POD reduced-order model and particle filter

NASA Astrophysics Data System (ADS)

Kikuchi, Ryota; Misaka, Takashi; Obayashi, Shigeru

2016-04-01

An integrated method consisting of a proper orthogonal decomposition (POD)-based reduced-order model (ROM) and a particle filter (PF) is proposed for real-time prediction of an unsteady flow field. The proposed method is validated using identical twin experiments of an unsteady flow field around a circular cylinder for Reynolds numbers of 100 and 1000. In this study, a PF is employed (ROM-PF) to modify the temporal coefficient of the ROM based on observation data because the prediction capability of the ROM alone is limited due to the stability issue. The proposed method reproduces the unsteady flow field several orders faster than a reference numerical simulation based on Navier-Stokes equations. Furthermore, the effects of parameters, related to observation and simulation, on the prediction accuracy are studied. Most of the energy modes of the unsteady flow field are captured, and it is possible to stably predict the long-term evolution with ROM-PF.

A Plasma Focus Device with a 2-MA Discharge Current as a Hard X-Ray Source

NASA Astrophysics Data System (ADS)

Yurkov, D. I.; Dulatov, A. K.; Lemeshko, B. D.; Andreev, D. A.; Golikov, A. V.; Mikhailov, Yu. V.; Prokuratov, I. A.; Selifanov, A. N.; Fatiev, T. S.

2018-04-01

A device based on a pulsed current generator with capacitive energy storage loaded on a plasma focus (PF) chamber is described. The device provides a discharge current amplitude of up to 2 MA in the PF chamber at a stored energy in the capacitor bank of up to 150 kJ. The PF chamber is designed to study hard X-ray (HXR) emission. It has windows for output of HXR emission in the cathode direction, as well as a special insert for output of HXR emission into the anode cavity. A study of operation of the chamber as a part of the setup with the use of various X-ray targets on the anode has been carried out. At a discharge current of 1.5MA, an HXR pulse with an average duration of 16 ns and energy spectrum from 10 to 200 keV, which provides an absorbed dose in the irradiated samples on the order of 1 Sv, is generated in the PF chamber.

[Application of the Polish version of CHQ-PF28 questionnaire in two population studies carried out in 2003 and 2008].

PubMed

Małkowska-Szkutnik, Agnieszka; Tabak, Izabela; Mazur, Joanna

2010-01-01

To conduct a psychometric analysis of the Polish version of the CHQ-PF28 questionnaire for measuring the health-related quality of life (HRQL) of children and adolescents, on the basis of two population studies carried out in 2003 and 2008. The CHQ-PF28 questionnaire was completed by parents of 1093 adolescents surveyed in 2003 and by parents of 605 adolescents surveyed in 2008. The average age of children was similar (13.4 yrs). An exploratory and confirmatory factor analysis was carried out on a combined sample from those studies. The HRQL profile of adolescents displaying and not displaying health problems, was compared. Mean standardized quality of life scores were calculated for all 13 partial dimensions and a two summary dimensions of physical and psychosocial health where high CHQ score always means better quality of life. In the 2003 study, the mean scores of partial scales ranged between 59.78 (SD = 20.39) for the scale of family coherence and 97.07 (SD = 11.88) for the scale of emotional limitations in playing social roles. In the 2008 study, mean scores for the same subscales were as follows: 59.17 (SD = 19.50) and 96.17 (SD = 14,45). It was concluded that parents assessed children's psychosocial health as worse than their children's physical health. In girls, higher mean scores were noted in the scales of self-esteem and behavioural disorders; in boys, higher mean scores were recorded in the scale of pain sensation. The reliability of partial scales was measured using alpha-Cronbach, which only for four scales was above 0.7. Six items were identified, which severely impair psychometric characteristics of the Polish version of the CHQ-PF28. A clear link was found between mean CHQ-PF28 indeces and the results of screening tests which identify physical and mental health abnormalities, such as the SDQ (Strengths and Difficulties Questionnaire), as well as the CSHCN (Children with Special Health Care Needs) test. The Polish version of the CHQ-PF28 questionnaire has satisfactory psychometric characteristics. A wider use of the CHQ-PF28 in clinical research and population studies in Poland is fully justified. However, we would suggest implementing its abbreviated version, excluding items, which may affect the reliability and validity of the subscales and of the overall research tool.

Profile of Instrumentation Laboratory's HemosIL® AcuStar HIT-Ab(PF4-H) assay for diagnosis of heparin-induced thrombocytopenia.

PubMed

Nagler, Michael; Cuker, Adam

2017-05-01

Immunoassays play an essential role in the diagnosis of heparin-induced thrombocytopenia (HIT). The objective of this article is to review HemosIL® AcuStar HIT-Ab(PF4-H) (Instrumentation Laboratory, Bedford, MA, USA), a new chemiluminescent immunoassay for HIT. Areas covered: The authors searched the published literature for evaluation studies of HemosIL® AcuStar HIT-Ab(PF4-H) and sought information from the manufacturer. In this paper, the authors discuss the analytical principle and technical aspects of the assay; describe its diagnostic performance in validation studies; report on its reproducibility, cost-effectiveness, and regulatory status; and discuss the implications of the assay on clinical practice and means of integrating it in diagnostic pathways. HemosIL® AcuStar HIT-Ab(PF4-H) is compared with other rapid assays and widely used enzyme-linked immunoassays for the diagnosis of HIT. Expert commentary: HemosIL® AcuStar HIT-Ab(PF4-H) is automatable, can be performed 24 h per day, offers a rapid turnaround time, and appears to have favorable diagnostic accuracy, particularly at thresholds above that listed in the label. These advantages could lead to improved patient outcomes through rapid provision of results at the point of care, enhancing the accuracy of initial diagnosis.

Mechanism of artemisinin resistance for malaria PfATP6 L263 mutations and discovering potential antimalarials: An integrated computational approach

NASA Astrophysics Data System (ADS)

Nagasundaram, N.; George Priya Doss, C.; Chakraborty, Chiranjib; Karthick, V.; Thirumal Kumar, D.; Balaji, V.; Siva, R.; Lu, Aiping; Ge, Zhang; Zhu, Hailong

2016-07-01

Artemisinin resistance in Plasmodium falciparum threatens global efforts in the elimination or eradication of malaria. Several studies have associated mutations in the PfATP6 gene in conjunction with artemisinin resistance, but the underlying molecular mechanism of the resistance remains unexplored. Associated mutations act as a biomarker to measure the artemisinin efficacy. In the proposed work, we have analyzed the binding affinity and efficacy between PfATP6 and artemisinin in the presence of L263D, L263E and L263K mutations. Furthermore, we performed virtual screening to identify potential compounds to inhibit the PfATP6 mutant proteins. In this study, we observed that artemisinin binding affinity with PfATP6 gets affected by L263D, L263E and L263K mutations. This in silico elucidation of artemisinin resistance enhanced the identification of novel compounds (CID: 10595058 and 10625452) which showed good binding affinity and efficacy with L263D, L263E and L263K mutant proteins in molecular docking and molecular dynamics simulations studies. Owing to the high propensity of the parasite to drug resistance the need for new antimalarial drugs will persist until the malarial parasites are eventually eradicated. The two compounds identified in this study can be tested in in vitro and in vivo experiments as possible candidates for the designing of new potential antimalarial drugs.

Docking Based 3D-QSAR Study of Tricyclic Guanidine Analogues of Batzelladine K as anti-malarial agents

NASA Astrophysics Data System (ADS)

Ahmed, Nafees; Anwar, Sirajudheen; Thet Htar, Thet

2017-06-01

The Plasmodium falciparum Lactate Dehydrogenase enzyme (PfLDH) catalyzes inter-conversion of pyruvate to lactate during glycolysis producing the energy required for parasitic growth. The PfLDH has been studied as a potential molecular target for development of anti-malarial agents. In an attempt to find the potent inhibitor of PfLDH, we have used Discovery studio to perform molecular docking in the active binding pocket of PfLDH by CDOCKER, followed by three-dimensional quantitative structure-activity relationship (3D-QSAR) studies of tricyclic guanidine batzelladine compounds, which were previously synthesized in our laboratory. Docking studies showed that there is a very strong correlation between in silico and in vitro results. Based on docking results, a highly predictive 3D-QSAR model was developed with q2 of 0.516. The model has predicted r2 of 0.91 showing that predicted IC50 values are in good agreement with experimental IC50 values. The results obtained from this study revealed the developed model can be used to design new anti-malarial compounds based on tricyclic guanidine derivatives and to predict activities of new inhibitors.

Docking Based 3D-QSAR Study of Tricyclic Guanidine Analogues of Batzelladine K As Anti-Malarial Agents.

PubMed

Ahmed, Nafees; Anwar, Sirajudheen; Thet Htar, Thet

2017-01-01

The Plasmodium falciparum Lactate Dehydrogenase enzyme ( Pf LDH) catalyzes inter-conversion of pyruvate to lactate during glycolysis producing the energy required for parasitic growth. The Pf LDH has been studied as a potential molecular target for development of anti-malarial agents. In an attempt to find the potent inhibitor of Pf LDH, we have used Discovery studio to perform molecular docking in the active binding pocket of Pf LDH by CDOCKER, followed by three-dimensional quantitative structure-activity relationship (3D-QSAR) studies of tricyclic guanidine batzelladine compounds, which were previously synthesized in our laboratory. Docking studies showed that there is a very strong correlation between in silico and in vitro results. Based on docking results, a highly predictive 3D-QSAR model was developed with q 2 of 0.516. The model has predicted r 2 of 0.91 showing that predicted IC 50 values are in good agreement with experimental IC 50 values. The results obtained from this study revealed the developed model can be used to design new anti-malarial compounds based on tricyclic guanidine derivatives and to predict activities of new inhibitors.

Docking Based 3D-QSAR Study of Tricyclic Guanidine Analogues of Batzelladine K As Anti-Malarial Agents

PubMed Central

Ahmed, Nafees; Anwar, Sirajudheen; Thet Htar, Thet

2017-01-01

The Plasmodium falciparum Lactate Dehydrogenase enzyme (PfLDH) catalyzes inter-conversion of pyruvate to lactate during glycolysis producing the energy required for parasitic growth. The PfLDH has been studied as a potential molecular target for development of anti-malarial agents. In an attempt to find the potent inhibitor of PfLDH, we have used Discovery studio to perform molecular docking in the active binding pocket of PfLDH by CDOCKER, followed by three-dimensional quantitative structure-activity relationship (3D-QSAR) studies of tricyclic guanidine batzelladine compounds, which were previously synthesized in our laboratory. Docking studies showed that there is a very strong correlation between in silico and in vitro results. Based on docking results, a highly predictive 3D-QSAR model was developed with q2 of 0.516. The model has predicted r2 of 0.91 showing that predicted IC50 values are in good agreement with experimental IC50 values. The results obtained from this study revealed the developed model can be used to design new anti-malarial compounds based on tricyclic guanidine derivatives and to predict activities of new inhibitors. PMID:28664157

The Clp Chaperones and Proteases of the Human Malaria Parasite Plasmodium falciparum

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

M El Bakkouri; A Pow; A Mulichak

The Clpchaperones and proteases play an important role in protein homeostasis in the cell. They are highly conserved across prokaryotes and found also in the mitochondria of eukaryotes and the chloroplasts of plants. They function mainly in the disaggregation, unfolding and degradation of native as well as misfolded proteins. Here, we provide a comprehensive analysis of the Clpchaperones and proteases in the humanmalariaparasitePlasmodiumfalciparum. The parasite contains four Clp ATPases, which we term PfClpB1, PfClpB2, PfClpC and PfClpM. One PfClpP, the proteolytic subunit, and one PfClpR, which is an inactive version of the protease, were also identified. Expression of all Clpchaperonesmore » and proteases was confirmed in blood-stage parasites. The proteins were localized to the apicoplast, a non-photosynthetic organelle that accommodates several important metabolic pathways in P. falciparum, with the exception of PfClpB2 (also known as Hsp101), which was found in the parasitophorous vacuole. Both PfClpP and PfClpR form mostly homoheptameric rings as observed by size-exclusion chromatography, analytical ultracentrifugation and electron microscopy. The X-ray structure of PfClpP showed the protein as a compacted tetradecamer similar to that observed for Streptococcus pneumoniae and Mycobacterium tuberculosis ClpPs. Our data suggest the presence of a ClpCRP complex in the apicoplast of P. falciparum.« less

Determination of PF-04928473 in human plasma using liquid chromatography with tandem mass spectrometry

PubMed Central

Jain, Lokesh; Gardner, Erin R.; Venitz, Jürgen; Giaccone, Giuseppe; Houk, Brett E.; Figg, William D.

2010-01-01

A simple, rapid and sensitive liquid chromatography/tandem mass spectrometric (LC/MS/MS) analytical method was developed for quantification of Hsp90 inhibitor PF-04928473 in human plasma, following administration of its prodrug, PF-04929113. Sample processing involved protein precipitation by addition of 0.4 mL of methanol containing internal standard (PF-04972487) to 50 μL volume of plasma sample. Chromatographic separation of PF-04928473 and PF-04972487 was achieved on a Phenomenex® Luna C18(2) (2.0×50 mm, 5 μm) column using a gradient elution method with mobile phase solvents: methanol containing 0.1% formic acid and 0.1% formic acid at a flow rate of 0.25 mL/min. Detection was performed in electrospray positive ionization mode, monitoring the ion transitions from m/z 465.1→350.1 (PF-04928473) and m/z 447.0→329.1 (PF-04972487). The retention times for PF-04928473 and PF-04972487 were 1.86 and 2.85 minutes, respectively. Calibration curves were generated in the range of 2–2000 ng/mL. The accuracy and precision ranged from 94.1–99.0% and 86.7–97.6%, respectively, which were calculated using quality control samples of three different concentrations analyzed in quintuplicate on four different days. PMID:20951100

A synthetic study and characterization of the Pt(II) complexes with bipyridines back-born system.

PubMed

Jo, Woongkyu; Son, Seokhwan; Jo, Hyeongjun; Kim, Byeongcheol; Kwak, Cheehun; Jung, Sangchul; Lee, Jihoon; Ahn, Hogeun; Chung, Minchul

2014-08-01

The reaction of platinum [Pt(5,5-dmbpy)]Cl2 (5,5-dmbpy = 5,5'-dimethyl-2,2'-bipyridine) with 4,4'-dimethyl-2,2'-bipyridine (4,4-dmbpy), [Pt(dbbpy)]Cl2 (dbbpy = 4,4'-dibutyl-2,2'-bipyridine), [Pt(dpbpy)]Cl2 (dpbpy = 4,4'-dipentyl-2,2'-bipyridine) with 5,5'-dimethyl-2,2'-bipyridine (5,5-dmbpy) affords the following complexes: [(4,4-dmbpy)Pt(5,5-dmbpy)][PF6]2 (1) and [(dbbpy)Pt(5,5-dmbpy)][PF6]2 (2), [(dpbpy)Pt(5,5-dmbpy)][PF6]2 (3), [(5,5-dmbpy)Pt(5,5-dmbpy)][PF6]2 (4). This study was synthesized new platinum complex compounds utilizing ligand of 5,5'-Dimethyl-2,2'-dipyridyl System. To study the chemical composition was used 1H(13C)-NMR, UV-vis, Spectro photometer and Measurements about optical physics and chemical properties were measured to use spectrofluorometer. UV-vis absorption area was measured 310 nm to 383 nm and luminous wavelength was measured 390 nm to 419 nm.

The mechanical and thermal characteristics of phenolic foam reinforced with kaolin powder and glass fiber fabric

NASA Astrophysics Data System (ADS)

Xiao, Wenya; Huang, Zhixiong; Ding, Jie

2017-12-01

In this work, kaolin powder and glass fiber fabric were added to PF in order to improve its thermal stability and mechanical property. Micro-structures of carbonized PF with kaolin powder were inspected by scanning electron microscopy (SEM) to demonstrate the filler’s pinning effect. SEM results illustrated modified PF had well morphology after high-temperature heat treatment. The Fourier transform infrared spectrometer (FTIR) test was carried out and found that kaolin powder only physically dispersed in PF. The compression test and thermal weight loss test were done on two groups of modified PF (Group A: add powder and fabric; Group B: add powder only). Results showed that all modified PF were better than pure PF, while foams with powder and fabric showed better mechanical characteristic and thermal stability compared with foams with powder only.

Synchrotron-based X-ray Fluorescence Microscopy in Conjunction with Nanoindentation to Study Molecular-Scale Interactions of Phenol-Formaldehyde in Wood Cell Walls

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

Jakes, Joseph E.; Hunt, Chris G.; Yelle, Daniel J.

Understanding and controlling molecular-scale interactions between adhesives and wood polymers are critical to accelerate the development of improved adhesives for advanced wood-based materials. The submicrometer resolution of synchrotron-based X-ray fluorescence microscopy (XFM) was found capable of mapping and quantifying infiltration of Br-labeled phenolformaldehyde (BrPF) into wood cell walls. Cell wall infiltration of five BrPF adhesives with different average molecular weights (MWs) was mapped. Nanoindentation on the same cell walls was performed to assess the effects of BrPF infiltration on cell wall hygromechanical properties. For the same amount of weight uptake, lower MW BrPF adhesives were found to be more effectivemore » at decreasing moisture-induced mechanical softening. This greater effectiveness of lower MW phenolic adhesives likely resulted from their ability to more intimately associate with water sorption sites in the wood polymers. Evidence also suggests that a BrPF interpenetrating polymer network (IPN) formed within the wood polymers, which might also decrease moisture sorption by mechanically restraining wood polymers during swelling.« less

Structure-based drug design studies of the interactions of ent-kaurane diterpenes derived from Wedelia paludosa with the Plasmodium falciparum sarco/endoplasmic reticulum Ca²⁺-ATPase PfATP6.

PubMed

Guimarães, Daniel Silqueira Martins; Fonseca, Amanda Luisa da; Batista, Ronan; Comar Junior, Moacyr; Oliveira, Alaíde Braga de; Taranto, Alex Gutterres; Varotti, Fernando de Pilla

2015-04-01

Malaria is responsible for more deaths around the world than any other parasitic disease. Due to the emergence of strains that are resistant to the current chemotherapeutic antimalarial arsenal, the search for new antimalarial drugs remains urgent though hampered by a lack of knowledge regarding the molecular mechanisms of artemisinin resistance. Semisynthetic compounds derived from diterpenes from the medicinal plant Wedelia paludosa were tested in silico against the Plasmodium falciparum Ca2+-ATPase, PfATP6. This protein was constructed by comparative modelling using the three-dimensional structure of a homologous protein, 1IWO, as a scaffold. Compound 21 showed the best docking scores, indicating a better interaction with PfATP6 than that of thapsigargin, the natural inhibitor. Inhibition of PfATP6 by diterpene compounds could promote a change in calcium homeostasis, leading to parasite death. These data suggest PfATP6 as a potential target for the antimalarial ent-kaurane diterpenes.

Pyrolysis of oil palm mesocarp fiber and palm frond in a slow-heating fixed-bed reactor: A comparative study.

PubMed

Kabir, G; Mohd Din, A T; Hameed, B H

2017-10-01

Oil palm mesocarp fiber (OPMF) and palm frond (PF) were respectively devolatilized by pyrolysis to OPMF-oil and PF-oil bio-oils and biochars, OPMF-char and PF-char in a slow-heating fixed-bed reactor. In particular, the OPMF-oil and PF-oil were produced to a maximum yield of 48wt% and 47wt% bio-oils at 550°C and 600°C, respectively. The high heating values (HHVs) of OPMF-oil and PF-oil were respectively found to be 23MJ/kg and 21MJ/kg, whereas 24.84MJ/kg and 24.15MJ/kg were for the corresponding biochar. The HHVs of the bio-oils and biochars are associated with low O/C ratios to be higher than those of the corresponding biomass. The Fourier transform infrared spectra and peak area ratios highlighted the effect of pyrolysis temperatures on the bio-oil compositions. The bio-oils are pervaded with numerous oxygenated carbonyl and aromatic compounds as suitable feedstocks for renewable fuels and chemicals. Copyright © 2017 Elsevier Ltd. All rights reserved.

Phenol-Formaldehyde Resin for Optical-Chemical Temperature Sensing.

PubMed

Claucherty, Steven; Sakaue, Hirotaka

2018-05-30

The application of phenol-formaldehyde (PF) resin as an optical temperature sensor is investigated. Recent developments in optical luminescent sensors allow for global measurements to be made over the surface of a test article, extending beyond conventional point measurements. Global temperature distributions are particularly helpful when validating computational models or when mapping temperature over complex geometries, and can be used to calculate surface heat flux values. Temperature-sensitive paint (TSP) is a novel chemical approach to obtaining these global temperature measurements, but there are still challenges to overcome to make it a reliable tool. A sensor with a wide range of temperature sensitivity is desired to provide the maximum amount of utility, especially for tests spanning large temperature gradients. Naturally luminescent materials such as PF resin provide an attractive alternative to chemical sensor coatings, and PF resin is studied for this reason. Static tests of different PF resin samples are conducted using two binder materials to strengthen the material: cloth and paper. The material shows temperature sensitivities up to -0.8%/K, demonstrating the usefulness of PF resin as a temperature sensor.

Survival of porcine reproductive and respiratory syndrome virus in houseflies.

PubMed

Otake, Satoshi; Dee, Scott A; Moon, Roger D; Rossow, Kurt D; Trincado, Carlos; Farnham, MacDonald; Pijoan, Carlos

2003-07-01

The objectives of the study were to determine the duration of porcine reproductive and respiratory syndrome virus (PRRSV) survival in houseflies (Musca domestica Linnaeus) following feeding on an infected pig, and to determine whether the virus was present on the exterior surface or within the internal viscera of the fly. A total of 210 laboratory-colonized houseflies were allowed to feed to repletion on a pig, experimentally infected with PRRSV on day 7 postinoculation, and then maintained alive under laboratory conditions (27 degrees C). Two subsets (A and B) of 30 flies were collected at each of the following sampling points; 0, 6, and 12 hours post feeding (pf). Subset A contained an extra group of 30 flies collected at 24 hours pf due to the availability of extra flies. Flies in subset A were processed as whole fly homogenates, while the exterior surface washes and digestive organs were collected from flies in subset B. Whole fly homogenates, collected at 0, 6, and 12 hours pf, were positive by both polymerase chain reaction (PCR) and swine bioassay. Digestive organs, collected at 0 and 12 hours pf, were positive by PCR and swine bioassay. The PRRSV RNA was detected by PCR from the exterior surface wash of subset B flies collected at 0, 6, and 12 hours pf; however, only the subset collected at 0 hour pf was swine bioassay-positive. This study indicates that infectious PRRSV can survive within the intestinal tract of houseflies for up to 12 hours following feeding on an infected pig, but only for a short period on the exterior surface of the flies.

Signal intensity of the pancreas on magnetic resonance imaging: Prediction of postoperative pancreatic fistula after a distal pancreatectomy using a triple-row stapler.

PubMed

Arai, Takuma; Kobayashi, Akira; Yokoyama, Takahide; Ohya, Ayumi; Fujinaga, Yasunari; Shimizu, Akira; Motoyama, Hiroaki; Furusawa, Norihiko; Sakai, Hiroshi; Uehara, Takeshi; Kadoya, Masumi; Miyagawa, Shin-Ichi

2015-01-01

The aim of this study was to evaluate the impact of the pancreatic signal intensity (SI) on magnetic resonance imaging (MRI) findings for predicting the development of pancreatic fistula (PF) after a distal pancreatectomy (DP) involving a triple-row stapler closure. A multivariate logistic regression analysis was used to identify risk factors for clinical PF, as defined by the International Study Group on Pancreatic Fistula grade B or C. The pancreas-to-muscle SI ratio was evaluated using fat-suppressed T1-weighted MRI. Of the 41 enrolled patients, 8 (19.5%) developed clinical PF. The pancreatic thickness (≥15 mm) and SI ratio (≥1.3) were identified as independent predictors of clinical PF in a multivariate analysis. Clinical PF was observed in one patient with a thick pancreas and a low SI ratio (14.3%), whereas it was observed in 60% of the patients with a thick pancreas and a high SI ratio. The area under the receiver operating characteristic curve for a predictive model consisting of the two factors was 0.87 (95% confidence interval, 0.75 to 0.99), the level of which tended to be greater than that for pancreatic thickness alone (0.81, p = 0.09). The SI ratio as evaluated using MRI might be useful for predicting clinical PF in patients with the pancreatic thickness ≥15 mm after DP involving a stapler closure. Copyright © 2015 IAP and EPC. Published by Elsevier B.V. All rights reserved.

Radiation induced pulmonary fibrosis as a model of progressive fibrosis: Contributions of DNA damage, inflammatory response and cellular senescence genes.

PubMed

Beach, Tyler A; Johnston, Carl J; Groves, Angela M; Williams, Jacqueline P; Finkelstein, Jacob N

2017-04-01

Purpose/Aim of Study: Studies of pulmonary fibrosis (PF) have resulted in DNA damage, inflammatory response, and cellular senescence being widely hypothesized to play a role in the progression of the disease. Utilizing these aforementioned terms, genomics databases were interrogated along with the term, "pulmonary fibrosis," to identify genes common among all 4 search terms. Findings were compared to data derived from a model of radiation-induced progressive pulmonary fibrosis (RIPF) to verify that these genes are similarly expressed, supporting the use of radiation as a model for diseases involving PF, such as human idiopathic pulmonary fibrosis (IPF). In an established model of RIPF, C57BL/6J mice were exposed to 12.5 Gy thorax irradiation and sacrificed at 24 hours, 1, 4, 12, and 32 weeks following exposure, and lung tissue was compared to age-matched controls by RNA sequencing. Of 176 PF associated gene transcripts identified by database interrogation, 146 (>82%) were present in our experimental model, throughout the progression of RIPF. Analysis revealed that nearly 85% of PF gene transcripts were associated with at least 1 other search term. Furthermore, of 22 genes common to all four terms, 16 were present experimentally in RIPF. This illustrates the validity of RIPF as a model of progressive PF/IPF based on the numbers of transcripts reported in both literature and observed experimentally. Well characterized genes and proteins are implicated in this model, supporting the hypotheses that DNA damage, inflammatory response and cellular senescence are associated with the pathogenesis of PF.

Interaction of proflavin with aromatic amines in homogeneous and micellar media: Photoinduced electron transfer probed by magnetic field effect

NASA Astrophysics Data System (ADS)

Chakraborty, Brotati; Basu, Samita

2010-02-01

Photoinduced electron transfer (PET) between proflavin (PF +) and two aromatic amines viz., dimethylaniline (DMA) and 4,4'-bis(dimethylamino)diphenylmethane (DMDPM) is studied in homogeneous and heterogeneous media using steady-state as well as time-resolved fluorescence spectroscopy and laser flash photolysis with an associated magnetic field. Ionic micelles have been used to study the effect of charge of proflavin on PET with amines. Magnetic field effect on PET reactions reveals that the parent spin-state of precursors of PET for DMA-PF + system is singlet while for DMDPM-PF + system is triplet, implying that the dynamics of PET is influenced by the structure of the donor.

Syntheses, structures and redox properties of some complexes containing the Os(dppe)Cp* fragment, including [{Os(dppe)Cp*}2(mu-C triple bondCC triple bond C)].

PubMed

Bruce, Michael I; Costuas, Karine; Davin, Thomas; Halet, Jean-François; Kramarczuk, Kathy A; Low, Paul J; Nicholson, Brian K; Perkins, Gary J; Roberts, Rachel L; Skelton, Brian W; Smith, Mark E; White, Allan H

2007-12-14

The sequential conversion of [OsBr(cod)Cp*] (9) to [OsBr(dppe)Cp*] (10), [Os([=C=CH2)(dppe)Cp*]PF6 ([11]PF6), [Os(C triple bond CH)(dppe)Cp*] (12), [{Os(dppe)Cp*}2{mu-(=C=CH-CH=C=)}][PF6]2 ([13](PF6)2) and finally [{Os(dppe)Cp*}(2)(mu-C triple bond CC triple bond C)] (14) has been used to make the third member of the triad [{M(dppe)Cp*}2(mu-C triple bond CC triple bond C)] (M = Fe, Ru, Os). The molecular structures of []PF6, 12 and 14, together with those of the related osmium complexes [Os(NCMe)(dppe)Cp*]PF6 ([15]PF6) and [Os(C triple bond CPh)(dppe)Cp*] (16), have been determined by single-crystal X-ray diffraction studies. Comparison of the redox properties of 14 with those of its iron and ruthenium congeners shows that the first oxidation potential E1 varies as: Fe approximately Os < Ru. Whereas the Fe complex has been shown to undergo three sequential 1-electron oxidation processes within conventional electrochemical solvent windows, the Ru and Os compounds undergo no fewer than four sequential oxidation events giving rise to a five-membered series of redox related complexes [{M(dppe)Cp*}2(mu-C4)]n+ (n = 0, 1, 2, 3 and 4), the osmium derivatives being obtained at considerably lower potentials than the ruthenium analogues. These results are complimented by DFT and DT DFT calculations.

Modification of adenylate cyclase by photoaffinity analogs of forskolin

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

Ho, L.T.; Nie, Z.M.; Mende, T.J.

1989-01-01

Photoaffinity labeling analogs of the adenylate cyclase activator forskolin (PF) have been synthesized, purified and tested for their effect on preparations of membrane-bound, Lubrol solubilized and forskolin affinity-purified adenylate cyclase (AC). All analogs of forskolin significantly activated AC. However, in the presence of 0.1 to 0.3 microM forskolin, the less active forskolin photoaffinity probes at 100 microM caused inhibition. This inhibition was dose-dependent for PF, suggesting that PF may complete with F for the same binding site(s). After cross-linking (125I)PF-M to either membrane or Lubrol-solubilized AC preparations by photolysis, a radiolabeled 100-110 kDa protein band was observed after autoradiography followingmore » SDS-PAGE. F at 100 microM blocked the photoradiolabeling of this protein. Radioiodination of forskolin-affinity purified AC showed several protein bands on autoradiogram, however, only one band (Mr = 100-110 kDa) was specifically labeled by (125I)PF-M following photolysis. The photoaffinity-labeled protein of 100-110 kDa of AC preparation of rat adipocyte may be the catalytic unit of adenylate cyclase of rat adipocyte itself as supported by the facts that (a) no other AC-regulatory proteins are known to be of this size, (b) the catalytic unit of bovine brain enzyme is in the same range and (c) this PF specifically stimulates AC activity when assayed alone, and weekly inhibits forskolin-activation of cyclase. These studies indicate that radiolabeled PF probes may be useful for photolabeling and detecting the catalytic unit of adenylate cyclase.« less

Elimination of radiocontrast agent diatrizoic acid by photo-Fenton process and enhanced treatment by coupling with electro-Fenton process.

PubMed

Bocos, Elvira; Oturan, Nihal; Pazos, Marta; Sanromán, M Ángeles; Oturan, Mehmet A

2016-10-01

The removal of radiocontrast agent diatrizoic acid (DIA) from water was performed using photo-Fenton (PF) process. First, the effect of H2O2 dosage on mineralization efficiency was determined using ultraviolet (UV) irradiation. The system reached a maximum mineralization degree of 60 % total organic carbon (TOC) removal at 4 h with 20 mM initial H2O2 concentration while further concentration values led to a decrease in TOC abatement efficiency. Then, the effect of different concentrations of Fenton's reagents was studied for homogeneous Fenton process. Obtained results revealed that 0.25 mM Fe(3+) and 20 mM H2O2 were the best conditions, achieving 80 % TOC removal efficiency at 4 h treatment. Furthermore, heterogeneous PF treatment was developed using iron-activated carbon as catalyst. It was demonstrated that this catalyst is a promising option, reaching 67 % of TOC removal within 4 h treatment without formation of iron leachate in the medium. In addition, two strategies of enhancement for process efficiency are proposed: coupling of PF with electro-Fenton (EF) process in two ways: photoelectro-Fenton (PEF) or PF followed by EF (PF-EF) treatments, achieving in both cases the complete mineralization of DIA solution within only 2 h. Finally, the Microtox tests revealed the formation of more toxic compounds than the initial DIA during PF process, while, it was possible to reach total mineralization by both proposed alternatives (PEF or PF-EF) and thus to remove the toxicity of DIA solution.

Transcriptional and Biochemical Analysis of Starch Metabolism in the Hyperthermophilic Archaeon Pyrococcus furiosus

PubMed Central

Lee, Han-Seung; Shockley, Keith R.; Schut, Gerrit J.; Conners, Shannon B.; Montero, Clemente I.; Johnson, Matthew R.; Chou, Chung-Jung; Bridger, Stephanie L.; Wigner, Nathan; Brehm, Scott D.; Jenney, Francis E.; Comfort, Donald A.; Kelly, Robert M.; Adams, Michael W. W.

2006-01-01

Pyrococcus furiosus utilizes starch and its degradation products, such as maltose, as primary carbon sources, but the pathways by which these α-glucans are processed have yet to be defined. For example, its genome contains genes proposed to encode five amylolytic enzymes (including a cyclodextrin glucanotransferase [CGTase] and amylopullulanase), as well as two transporters for maltose and maltodextrins (Mal-I and Mal-II), and a range of intracellular enzymes have been purified that reportedly metabolize maltodextrins and maltose. However, precisely which of these enzymes are involved in starch processing is not clear. In this study, starch metabolism in P. furiosus was examined by biochemical analyses in conjunction with global transcriptional response data for cells grown on a variety of glucans. In addition, DNA sequencing led to the correction of two key errors in the genome sequence, and these change the predicted properties of amylopullulanase (now designated PF1935*) and CGTase (PF0478*). Based on all of these data, a pathway is proposed that is specific for starch utilization that involves one transporter (Mal-II [PF1933 to PF1939]) and only three enzymes, amylopullulanase (PF1935*), 4-α-glucanotransferase (PF0272), and maltodextrin phosphorylase (PF1535). Their expression is upregulated on starch, and together they generate glucose and glucose-1-phosphate, which then feed into the novel glycolytic pathway of this organism. In addition, the results indicate that several hypothetical proteins encoded by three gene clusters are also involved in the transport and processing of α-glucan substrates by P. furiosus. PMID:16513741

Effect of retorque on loosening torque of prosthetic screws under two levels of fit of implant-supported dentures.

PubMed

Spazzin, Aloísio Oro; Henrique, Guilherme Elias Pessanha; Nóbilo, Mauro Antônio de Arruda; Consani, Rafael Leonardo Xediek; Correr-Sobrinho, Lourenço; Mesquita, Marcelo Ferraz

2010-01-01

This study evaluated the influence of retorque on loosening torque (Lt) of prosthetic screws in implant-supported dentures with different fit levels. Ten mandibular implant-supported dentures were fabricated and then 20 cast models were then prepared using prosthetic structures to create 2 fit levels: passive fit (Pf) and misfit (Mf). Two tightening techniques were also evaluated: initial torque only (T1); and initial torque and retorque after 10 min (T2). Gold or titanium screws were used, resulting in 4 groups to each one: Pf/T1, Pf/T2, Mf/T1, Mf/T2. The Lt was measured 24 h after the tightening torque using digital torque meter. Data were analyzed statistically by two-way ANOVA and Tukey's test (alpha=0.05), separately for each screw material. For titanium screws, no significant difference (p>0.05) was found between Pf/T1 and Pf/T2, or between Pf/T2 and Mf/T2. However, statistically significant difference (p<0.05) was found between Pf/T1 and Mf/T1, and between Mf/T1 and Mf/T2. Mf reduced the Lt using T1, while and T2 increased the Lt for Mf. Retorque and fit were shown to have no significant influence on the Lt of the gold screws. Retorque application made insignificant the misfit effect on the Lt of the titanium screws, suggesting that this procedure should be performed routinely during the screw tightening in multi-unit dentures.

Interstrain Differences in CO2-Induced Pulmonary Hemorrhage in Mice.

PubMed

Fisher, Suhrim; Burgess, Winona L; Hines, Kenneth D; Mason, Gary L; Owiny, James R

2016-11-01

Carbon dioxide is the most commonly used gas for euthanasia of rodents. The current AVMA Guidelines recommend slowly filling the container with CO2 (SF) and now indicate that the practice of placing conscious animals in containers prefilled with CO2 (PF) is unacceptable. An investigator noted pulmonary hemorrhage (PH) in BALB/c mice euthanized by SF that was not observed after PF. Here we evaluated whether the air-displacement rate (SF compared with PF) influenced the development of PH or nasal hemorrhage (NH) in 2 commonly used mouse strains. In addition, we investigated the prevalence of PH and NH in mice euthanized by isoflurane overdose (IO). Male and female (age groups, 6 wk and 6 mo) BALB/c and C57BL/6 mice were euthanized by SF or PF. In addition, 6-mo-old BALB/c male mice were euthanized by IO. Lung, nasal turbinates, brain, and reproductive organs were collected for gross and histologic evaluation and scored for degree of hemorrhage (score, 0 to 3). Severity of hemorrhage did not differ according to mouse age or sex. PH in BALB/c mice was more severe after SF than PF, and SF and PF induced more severe PH in BALB/c than in C57BL/6 mice. PH in 6-mo-old male BALB/c mice was more severe after SF than IO. Neither SF, PF, nor IO influenced the prevalence of NH in any group. This study demonstrates that the method of euthanasia may need to be altered depending on the mouse strain used.

Times to pain relief and pain freedom with rizatriptan 10 mg and other oral triptans

PubMed Central

Ng-Mak, D S; Hu, X H; Chen, Y; Ma, L; Solomon, G

2007-01-01

Background: In the clinical trial setting, oral rizatriptan 10 mg has greater efficacy than other oral triptans in freedom from migraine headache pain 2 h after dosing. Objective: The study objective is to compare the effectiveness of rizatriptan 10 mg and other oral triptans for acute migraine attack in a naturalistic setting. Methods: A total of 673 patients took rizatriptan 10 mg or their usual-care oral triptans for two migraine attacks in a sequential, cross-over manner and recorded outcomes using a diary and a stopwatch. Mean and median times to pain relief (PR) and pain freedom (PF) for rizatriptan and other oral triptans were compared. The effect of rizatriptan on times to PR and PF, adjusting for potential confounding factors (treatment sequence, treatment order and use of rescue medication), was computed via a Cox proportional hazard model. Results: Significantly, more patients taking rizatriptan achieved both PR and PF within 2 h after dosing than other oral triptans. Times to PR and PF were shorter with rizatriptan than with other oral triptans (median time to PR: 45 vs. 52 min, p < 0.0001; median time to PF: 100 vs. 124 min, p < 0.0001). The adjusted proportional hazard ratios (rizatriptan vs. other oral triptans) for times to PR and PF were 1.32 (95% CI: 1.22–1.44) and 1.27 (95% CI: 1.16–1.39) respectively. Conclusion: The times to PR and PF in a ‘naturalistic’ setting were significantly shorter for patients treating a migraine attack with rizatriptan 10 mg than with other oral triptans. PMID:17537184

Genetics of human body size and shape: body proportions and indices.

PubMed

Livshits, Gregory; Roset, A; Yakovenko, K; Trofimov, S; Kobyliansky, E

2002-01-01

The study of the genetic component in morphological variables such as body height and weight, head and chest circumference, etc. has a rather long history. However, only a few studies investigated body proportions and configuration. The major aim of the present study was to evaluate the extent of the possible genetic effects on the inter-individual variation of a number of body configuration indices amenable to clear functional interpretation. Two ethnically different pedigree samples were used in the study: (1) Turkmenians (805 individuals) from Central Asia, and (2) Chuvasha (732 individuals) from the Volga riverside, Russian Federation. To achieve the aim of the present study we proposed three new indices, which were subjected to a statistical-genetic analysis using modified version of "FISHER" software. The proposed indices were: (1) an integral index of torso volume (IND#1), an index reflecting a predisposition of body proportions to maintain a balance in a vertical position (IND#2), and an index of skeletal extremities volume (IND#3). Additionally, the first two principal factors (PF1 and PF2) obtained on 19 measurements of body length and breadth were subjected to genetic analysis. Variance decomposition analysis that simultaneously assess the contribution of gender, age, additive genetic effects and effects of environment shared by the nuclear family members, was applied to fit variation of the above three indices, and PF1 and PF2. The raw familial correlation of all study traits and in both samples showed: (1) all marital correlations did not differ significantly from zero; (2) parent-offspring and sibling correlations were all positive and statistically significant. The parameter estimates obtained in variance analyses showed that from 40% to 75% of inter-individual variation of the studied traits (adjusted for age and sex) were attributable to genetic effects. For PF1 and PF2 in both samples, and for IND#2 (in Chuvasha pedigrees), significant common sib environmental effects were also detectable. Genetic factors substantially influence inter-individual differences in body shape and configuration in two studied samples. However, further studies are needed to clarify the extent of pleiotropy and epigenetic effects on various facets of the human physique.

Performance of PROMIS Instruments in Patients With Shoulder Instability.

PubMed

Anthony, Chris A; Glass, Natalie A; Hancock, Kyle; Bollier, Matt; Wolf, Brian R; Hettrich, Carolyn M

2017-02-01

Shoulder instability is a relatively common condition occurring in 2% of the population. PROMIS (Patient-Reported Outcome Measurement Information System) was developed by the National Institutes of Health in an effort to advance patient-reported outcome (PRO) instruments by developing question banks for major health domains. To compare PROMIS instruments to current PRO instruments in patients who would be undergoing operative intervention for recurrent shoulder instability. Cohort study (diagnosis); Level of evidence, 2. A total of 74 patients with a primary diagnosis of shoulder instability who would be undergoing surgery were asked to fill out the American Shoulder and Elbow Surgeons shoulder assessment form (ASES), Marx shoulder activity scale (Marx), Short Form-36 Health Survey Physical Function subscale (SF-36 PF), Western Ontario Shoulder Instability Index (WOSI), PROMIS physical function computer adaptive test (PF CAT), and PROMIS upper extremity item bank (UE). Correlation between PRO instruments was defined as excellent (>0.7), excellent-good (0.61-0.7), good (0.4-0.6), and poor (0.2-0.3). Utilization of the PROMIS UE demonstrated excellent correlation with the SF-36 PF ( r = 0.78, P < .01) and ASES ( r = 0.71, P < .01); there was excellent-good correlation with the EQ-5D ( r = 0.66, P < .01), WOSI ( r = 0.63, P < .01), and PROMIS PF CAT ( r = 0.63, P < .01). Utilization of the PROMIS PF CAT demonstrated excellent correlation with the SF-36 PF ( r = 0.72, P < .01); there was excellent-good correlation with the ASES ( r = 0.67, P < .01) and PROMIS UE ( r = 0.63, P < .01). When utilizing the PROMIS UE, ceiling effects were present in 28.6% of patients aged 18 to 21 years. Patients, on average, answered 4.6 ± 1.8 questions utilizing the PROMIS PF CAT. The PROMIS UE and PROMIS PF CAT demonstrated good to excellent correlation with common shoulder and upper extremity PRO instruments as well as the SF-36 PF in patients with shoulder instability. In patients aged ≤21 years, there were significant ceiling effects utilizing the PROMIS UE. While the PROMIS PF CAT appears appropriate for use in adults of any age, our findings demonstrate that the PROMIS UE has significant ceiling effects in patients with shoulder instability who are ≤21 years old, and we do not recommend use of the PROMIS UE in this population.

Electrically heated particulate filter regeneration using hydrocarbon adsorbents

DOEpatents

Gonze, Eugene V [Pinckney, MI; Ament, Frank [Troy, MI

2011-02-01

An exhaust system that processes exhaust generated by an engine is provided. The system generally includes a particulate filter (PF) that filters particulates from the exhaust wherein an upstream end of the PF receives exhaust from the engine. A grid of electrically resistive material selectively heats exhaust passing through the upstream end to initiate combustion of particulates within the PF. A hydrocarbon adsorbent coating applied to the PF releases hydrocarbons into the exhaust to increase a temperature of the combustion of the particulates within the PF.

Longitudinal estimation of Plasmodium falciparum prevalence in relation to malaria prevention measures in six sub-Saharan African countries.

PubMed

Drakeley, Chris; Abdulla, Salim; Agnandji, Selidji Todagbe; Fernandes, José Francisco; Kremsner, Peter; Lell, Bertrand; Mewono, Ludovic; Bache, Bache Emmanuel; Mihayo, Michael Gabriel; Juma, Omar; Tanner, Marcel; Tahita, Marc Christian; Tinto, Halidou; Diallo, Salou; Lompo, Palpouguini; D'Alessandro, Umberto; Ogutu, Bernhards; Otieno, Lucas; Otieno, Solomon; Otieno, Walter; Oyieko, Janet; Asante, Kwaku Poku; Dery, Dominic Bon-Ereme; Adjei, George; Adeniji, Elisha; Atibilla, Dorcas; Owusu-Agyei, Seth; Greenwood, Brian; Gesase, Samwel; Lusingu, John; Mahende, Coline; Mongi, Robert; Segeja, Method; Adjei, Samuel; Agbenyega, Tsiri; Agyekum, Alex; Ansong, Daniel; Bawa, John Tanko; Boateng, Harry Owusu; Dandalo, Léonard; Escamilla, Veronica; Hoffman, Irving; Maenje, Peter; Martinson, Francis; Carter, Terrell; Leboulleux, Didier; Kaslow, David C; Usuf, Effua; Pirçon, Jean-Yves; Bahmanyar, Edith Roset

2017-10-27

Plasmodium falciparum prevalence (PfPR) is a widely used metric for assessing malaria transmission intensity. This study was carried out concurrently with the RTS,S/AS01 candidate malaria vaccine Phase III trial and estimated PfPR over ≤ 4 standardized cross-sectional surveys. This epidemiology study (NCT01190202) was conducted in 8 sites from 6 countries (Burkina Faso, Gabon, Ghana, Kenya, Malawi, and Tanzania), between March 2011 and December 2013. Participants were enrolled in a 2:1:1 ratio according to age category: 6 months-4 years, 5-19 years, and ≥ 20 years, respectively, per year and per centre. All sites carried out surveys 1-3 while survey 4 was conducted only in 3 sites. Surveys were usually performed during the peak malaria parasite transmission season, in one home visit, when medical history and malaria risk factors/prevention measures were collected, and a blood sample taken for rapid diagnostic test, microscopy, and haemoglobin measurement. PfPR was estimated by site and age category. Overall, 6401 (survey 1), 6411 (survey 2), 6400 (survey 3), and 2399 (survey 4) individuals were included in the analyses. In the 6 months-4 years age group, the lowest prevalence (assessed using microscopy) was observed in 2 Tanzanian centres (4.6% for Korogwe and 9.95% for Bagamoyo) and Lambaréné, Gabon (6.0%), while the highest PfPR was recorded for Nanoro, Burkina Faso (52.5%). PfPR significantly decreased over the 3 years in Agogo (Ghana), Kombewa (Kenya), Lilongwe (Malawi), and Bagamoyo (Tanzania), and a trend for increased PfPR was observed over the 4 surveys for Kintampo, Ghana. Over the 4 surveys, for all sites, PfPR was predominantly higher in the 5-19 years group than in the other age categories. Occurrence of fever and anaemia was associated with high P. falciparum parasitaemia. Univariate analyses showed a significant association of anti-malarial treatment in 4 surveys (odds ratios [ORs]: 0.52, 0.52, 0.68, 0.41) and bed net use in 2 surveys (ORs: 0.63, 0.68, 1.03, 1.78) with lower risk of malaria infection. Local PfPR differed substantially between sites and age groups. In children 6 months-4 years old, a significant decrease in prevalence over the 3 years was observed in 4 out of the 8 study sites. Trial registration Clinical Trials.gov identifier: NCT01190202:NCT. GSK Study ID numbers: 114001.

Carotid plaque-thickness and common carotid IMT show additive value in cardiovascular risk prediction and reclassification.

PubMed

Amato, Mauro; Veglia, Fabrizio; de Faire, Ulf; Giral, Philippe; Rauramaa, Rainer; Smit, Andries J; Kurl, Sudhir; Ravani, Alessio; Frigerio, Beatrice; Sansaro, Daniela; Bonomi, Alice; Tedesco, Calogero C; Castelnuovo, Samuela; Mannarino, Elmo; Humphries, Steve E; Hamsten, Anders; Tremoli, Elena; Baldassarre, Damiano

2017-08-01

Carotid plaque size and the mean common carotid intima-media thickness measured in plaque-free areas (PF CC-IMT mean ) have been identified as predictors of vascular events (VEs), but their complementarity in risk prediction and stratification is still unresolved. The aim of this study was to evaluate the independence of carotid plaque thickness and PF CC-IMT mean in cardiovascular risk prediction and risk stratification. The IMPROVE-study is a European cohort (n = 3703), where the thickness of the largest plaque detected in the whole carotid tree was indexed as cIMT max . PF CC-IMT mean was also assessed. Hazard Ratios (HR) comparing the top quartiles of cIMT max and PF CC-IMT mean versus their respective 1-3 quartiles were calculated using Cox regression. After a 36.2-month follow-up, there were 215 VEs (125 coronary, 73 cerebral and 17 peripheral). Both cIMT max and PF CC-IMT mean were mutually independent predictors of combined-VEs, after adjustment for center, age, sex, risk factors and pharmacological treatment [HR (95% CI) = 1.98 (1.47, 2.67) and 1.68 (1.23, 2.29), respectively]. Both variables were independent predictors of cerebrovascular events (ischemic stroke, transient ischemic attack), while only cIMT max was an independent predictor of coronary events (myocardial infarction, sudden cardiac death, angina pectoris, angioplasty, coronary bypass grafting). In reclassification analyses, PF CC-IMT mean significantly adds to a model including both Framingham Risk Factors and cIMT max (Integrated Discrimination Improvement; IDI = 0.009; p = 0.0001) and vice-versa (IDI = 0.02; p < 0.0001). cIMT max and PF CC-IMT mean are independent predictors of VEs, and as such, they should be used as additive rather than alternative variables in models for cardiovascular risk prediction and reclassification. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Kinetics of B cell responses to Plasmodium falciparum erythrocyte membrane protein 1 in Ghanaian women naturally exposed to malaria parasites.

PubMed

Ampomah, Paulina; Stevenson, Liz; Ofori, Michael F; Barfod, Lea; Hviid, Lars

2014-06-01

Naturally acquired protective immunity to Plasmodium falciparum malaria takes years to develop. It relies mainly on Abs, particularly IgG specific for Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) proteins on the infected erythrocyte surface. It is only partially understood why acquisition of clinical protection takes years to develop, but it probably involves a range of immune-evasive parasite features, not least of which are PfEMP1 polymorphism and clonal variation. Parasite-induced subversion of immunological memory and expansion of "atypical" memory B cells may also contribute. In this first, to our knowledge, longitudinal study of its kind, we measured B cell subset composition, as well as PfEMP1-specific Ab levels and memory B cell frequencies, in Ghanaian women followed from early pregnancy up to 1 y after delivery. Cell phenotypes and Ag-specific B cell function were assessed three times during and after pregnancy. Levels of IgG specific for pregnancy-restricted, VAR2CSA-type PfEMP1 increased markedly during pregnancy and declined after delivery, whereas IgG levels specific for two PfEMP1 proteins not restricted to pregnancy did not. Changes in VAR2CSA-specific memory B cell frequencies showed typical primary memory induction among primigravidae and recall expansion among multigravidae, followed by contraction postpartum in all. No systematic changes in the frequencies of memory B cells specific for the two other PfEMP1 proteins were identified. The B cell subset analysis confirmed earlier reports of high atypical memory B cell frequencies among residents of P. falciparum-endemic areas, and indicated an additional effect of pregnancy. Our study provides new knowledge regarding immunity to P. falciparum malaria and underpins efforts to develop PfEMP1-based vaccines against this disease. Copyright © 2014 by The American Association of Immunologists, Inc.

Quantitative detection of PfHRP2 in saliva of malaria patients in the Philippines

PubMed Central

2012-01-01

Background Malaria is a global health priority with a heavy burden of fatality and morbidity. Improvements in field diagnostics are needed to support the agenda for malaria elimination. Saliva has shown significant potential for use in non-invasive diagnostics, but the development of off-the-shelf saliva diagnostic kits requires best practices for sample preparation and quantitative insight on the availability of biomarkers and the dynamics of immunoassay in saliva. This pilot study measured the levels of the PfHRP2 in patient saliva to inform the development of salivary diagnostic tests for malaria. Methods Matched samples of blood and saliva were collected between January and May, 2011 from eight patients at Palawan Baptist Hospital in Roxas, Palawan, Philippines. Parasite density was determined from thick-film blood smears. Concentrations of PfHRP2 in saliva of malaria-positive patients were measured using a custom chemiluminescent ELISA in microtitre plates. Sixteen negative-control patients were enrolled at UCLA. A substantive difference between this protocol and previous related studies was that saliva samples were stabilized with protease inhibitors. Results Of the eight patients with microscopically confirmed P. falciparum malaria, seven tested positive for PfHRP2 in the blood using rapid diagnostic test kits, and all tested positive for PfHRP2 in saliva. All negative-control samples tested negative for salivary PfHRP2. On a binary-decision basis, the ELISA agreed with microscopy with 100 % sensitivity and 100 % specificity. Salivary levels of PfHRP2 ranged from 17 to 1,167 pg/mL in the malaria-positive group. Conclusion Saliva is a promising diagnostic fluid for malaria when protein degradation and matrix effects are mitigated. Systematic quantitation of other malaria biomarkers in saliva would identify those with the best clinical relevance and suitability for off-the-shelf diagnostic kits. PMID:22631858

Biomechanical Evaluation of an Injectable and Biodegradable Copolymer P(PF-co-CL) in a Cadaveric Vertebral Body Defect Model

PubMed Central

Fang, Zhong; Giambini, Hugo; Zeng, Heng; Camp, Jon J.; Dadsetan, Mahrokh; Robb, Richard A.; An, Kai-Nan; Yaszemski, Michael J.

2014-01-01

A novel biodegradable copolymer, poly(propylene fumarate-co-caprolactone) [P(PF-co-CL)], has been developed in our laboratory as an injectable scaffold for bone defect repair. In the current study, we evaluated the ability of P(PF-co-CL) to reconstitute the load-bearing capacity of vertebral bodies with lytic lesions. Forty vertebral bodies from four fresh-frozen cadaveric thoracolumbar spines were used for this study. They were randomly divided into four groups: intact vertebral body (intact control), simulated defect without treatment (negative control), defect treated with P(PF-co-CL) (copolymer group), and defect treated with poly(methyl methacrylate) (PMMA group). Simulated metastatic lytic defects were made by removing a central core of the trabecular bone in each vertebral body with an approximate volume of 25% through an access hole in the side of the vertebrae. Defects were then filled by injecting either P(PF-co-CL) or PMMA in situ crosslinkable formulations. After the spines were imaged with quantitative computerized tomography, single vertebral body segments were harvested for mechanical testing. Specimens were compressed until failure or to 25% reduction in body height and ultimate strength and elastic modulus of each specimen were then calculated from the force–displacement data. The average failure strength of the copolymer group was 1.83 times stronger than the untreated negative group and it closely matched the intact vertebral bodies (intact control). The PMMA-treated vertebrae, however, had a failure strength 1.64 times larger compared with the intact control. The elastic modulus followed the same trend. This modulus mismatch between PMMA-treated vertebrae and the host vertebrae could potentially induce a fracture cascade and degenerative changes in adjacent intervertebral discs. In contrast, P(PF-co-CL) restored the mechanical properties of the treated segments similar to the normal, intact, vertebrae. Therefore, P(PF-co-CL) may be a suitable alternative to PMMA for vertebroplasty treatment of vertebral bodies with lytic defects. PMID:24256208

Performance of two rapid diagnostic tests for malaria diagnosis at the China-Myanmar border area

PubMed Central

2013-01-01

Background Rapid diagnostic tests (RDTs) have become an essential tool in the contemporary malaria control and management programmes in the world. This study aims to evaluate the performance of two commonly used RDTs for malaria diagnosis in the China-Myanmar border area. Methods A total 606 febrile patients in the China-Myanmar border were recruited to this study and were diagnosed for malaria infections by microscopy, two RDTs tests (Pf/Pan device, and Pv/Pf device) and nested PCR. Results Malaria parasites were found in 143 patients by microscopy, of which 51, 73, and 19 were Plasmodium falciparum, Plasmodium vivax and P. falciparum/P. vivax mixed infections, respectively. Compared to microscopy, the sensitivity of the Pf/Pan device was 88.6% for P. falciparum and 69.9% for P. vivax with the specificity of 90.4%. For a subset of 350 patients, the sensitivity of the Pf/Pan device and Pv/Pf device for detection of P. falciparum was 87.5% and 91.7%, respectively; and for detection of P. vivax was 72.0% and 73.8%, respectively. The specificity of the Pf/Pan device and Pv/Pf device was 94.3% and 96.5%, respectively. Nested PCR detected malaria parasites in 174 of 606 samples, of which 67, 79, two and 26 were P. falciparum, P. vivax, P. ovale and P. falciparum/P. vivax mixed infections, respectively. Compared to nested PCR, all other methods had sensitivity below 80%, suggesting that a significant number of cases were missed. Conclusions Compared to PCR, both microscopy and RDTs had lower sensitivities. RDTs had similar performance to microscopy for P. falciparum diagnosis, but performed worse for P. vivax diagnosis. Other RDT products should be selected with higher sensitivity (and good specificity) for both P. falciparum and P. vivax diagnosis. PMID:23433230

Comparison of an IgG-Specific Enzyme-Linked Immunosorbent Assay Cutoff of 0.4 Versus 0.8 and 1.0 Optical Density Units for Heparin-Induced Thrombocytopenia.

PubMed

Ritchie, Brianne M; Connors, Jean M; Sylvester, Katelyn W

2017-04-01

Previous studies have demonstrated optimized diagnostic accuracy in utilizing higher antiheparin-platelet factor 4 (PF4) enzyme-linked immunosorbent assay (ELISA) optical density (OD) thresholds for diagnosing heparin-induced thrombocytopenia (HIT). We describe the incidence of positive serotonin release assay (SRA) results, as well as performance characteristics, for antiheparin-PF4 ELISA thresholds ≥0.4, ≥0.8, and ≥1.0 OD units in the diagnosis of HIT at our institution. Following institutional review board approval, we conducted a single-center retrospective chart review on adult inpatients with a differential diagnosis of HIT evaluated by both antiheparin-PF4 ELISA and SRA from 2012 to 2014. The major endpoints were to assess incidence of positive SRA results, sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy at antiheparin-PF4 ELISA values ≥0.4 OD units when compared to values ≥0.8 and ≥1.0 OD units. Clinical characteristics, including demographics, laboratory values, clinical and safety outcomes, length of stay, and mortality, were collected. A total of 140 patients with 140 antiheparin-PF4 ELISA and SRA values were evaluated, of which 23 patients were SRA positive (16.4%) and 117 patients were SRA negative (83.6%). We identified a sensitivity of 91.3% versus 82.6% and 73.9%, specificity of 61.5% versus 87.2% and 91.5%, PPV of 31.8% versus 55.9% and 63.0%, NPV of 97.3% versus 96.2% and 94.7%, and accuracy of 66.4% versus 86.4% and 88.6% at antiheparin-PF4 ELISA thresholds ≥0.4, ≥0.8, and ≥1.0 OD units, respectively. Our study suggests an increased antiheparin-PF4 ELISA threshold of 0.8 or 1.0 OD units enhances specificity, PPV, and accuracy while maintaining NPV with decreased sensitivity.

Plate fixation versus intramedullary fixation for midshaft clavicle fractures: Meta-analysis of complications and functional outcomes

PubMed Central

Xiao, Hao; Gao, Hengbo; Zheng, Tuokang; Zhao, Jianhui

2016-01-01

Objective This analysis critically compares publications discussing complications and functional outcomes of plate fixation (PF) versus intramedullary fixation (IF) for midshaft clavicle fractures. Methods Relevant studies published between January 1990 and October 2014, without language restrictions, were identified in database searches of PubMed®, Medline®, Embase and the Chinese National Knowledge Infrastructure (CNKI). Studies that compared postoperative complications and functional outcomes between PF and IF for midshaft clavicle fractures, and provided sufficient data for analysis, were included in this meta-analysis. Results After strict evaluation, 12 studies were included in this meta-analysis. Studies encompassed 462 participants in the PF group and 440 in the IF group. Study participants were followed up for ≥1 year. Outcomes were superior with IF compared with PF in terms of shoulder constant score at 6-month follow-up, fewer symptomatic hardware complications, lower rate of refracture after hardware removal and less hypertrophic scarring. In other aspects, such as functional recovery at 12-months and 24-months, Disability of Arm, Shoulder and Hand (DASH) questionnaire results at 12-month follow-up, shoulder motion range, rates of superficial infection, temporary brachial plexus lesion, nonunion, malunion, delayed union, implant failure and need for major revision, both techniques were similar. Conclusions Findings of this meta-analysis suggest that, in many respects, IF was superior to PF for the management of midshaft clavicle fractures. This finding could aid surgeons in making decisions on the optimum internal fixation pattern for midshaft clavicular fractures. PMID:26880791

Preventing Gut Leakiness and Endotoxemia Contributes to the Protective Effect of Zinc on Alcohol-Induced Steatohepatitis in Rats123

PubMed Central

Zhong, Wei; Li, Qiong; Sun, Qian; Zhang, Wenliang; Zhang, Jiayang; Sun, Xinguo; Yin, Xinmin; Zhang, Xiang; Zhou, Zhanxiang

2015-01-01

Background: Zinc deficiency has been well documented in alcoholic liver disease. Objective: This study was undertaken to determine whether dietary zinc supplementation provides beneficial effects in treating alcohol-induced gut leakiness and endotoxemia. Methods: Male Sprague Dawley rats were divided into 3 groups and pair-fed (PF) Lieber-DeCarli liquid diet for 8 wk: 1) control (PF); 2) alcohol-fed (AF; 5.00–5.42% wt:vol ethanol); and 3) AF with zinc supplementation (AF/Zn) at 220 ppm zinc sulfate heptahydrate. The PF and AF/Zn groups were pair-fed with the AF group. Hepatic inflammation and endotoxin signaling were determined by immunofluorescence and quantitative polymerase chain reaction (qPCR). Alterations in intestinal tight junctions and aldehyde dehydrogenases were assessed by qPCR and Western blot analysis. Results: The AF rats had greater macrophage activation and cytokine production (P < 0.05) in the liver compared with the PF rats, whereas the AF/Zn rats showed no significant differences (P > 0.05). Plasma endotoxin concentrations of the AF rats were 136% greater than those of the PF rats, whereas the AF/Zn rats did not differ from the PF rats. Ileal permeability was 255% greater in the AF rats and 19% greater in the AF/Zn rats than in the PF rats. The AF group had reduced intestinal claudin-1, occludin, and zona occludens-1 (ZO-1) expression, and the AF/Zn group had upregulated claudin-1 and ZO-1 expression (P < 0.05) compared with the PF group. The intestinal epithelial expression and activity of aldehyde dehydrogenases were elevated (P < 0.05) in the AF/Zn rats compared with those of the AF rats. Furthermore, the ileal expression and function of hepatocyte nuclear factor 4α, which was impaired in the AF group, was significantly elevated in the AF/Zn group compared with the PF group. Conclusions: The results demonstrate that attenuating hepatic endotoxin signaling by preserving the intestinal barrier contributes to the protective effect of zinc on alcohol-induced steatohepatitis in rats. PMID:26468492

The 16PF Tradition in Contemporary Personality Assessment.

ERIC Educational Resources Information Center

Krug, Samuel E.

The 16 Personality Factor Questionnaire (16PF), which is reviewed historically in this essay, represents a unique and significant chapter in the history of personality assessment. During the first 20 years of its existence, the 16PF underwent numerous revisions and restandardizations. During that period, R. B. Cattell, the creator of the 16PF,…

A sugar phosphatase regulates the methylerythritol phosphate (MEP) pathway in malaria parasites

PubMed Central

Edwards, Rachel L.; Kelly, Megan L.; Hodge, Dana M.; Tolia, Niraj H.; Odom, Audrey R.

2014-01-01

Isoprenoid biosynthesis through the methylerythritol phosphate (MEP) pathway generates commercially important products and is a target for antimicrobial drug development. MEP pathway regulation is poorly understood in microorganisms. We employ a forward genetics approach to understand MEP pathway regulation in the malaria parasite, Plasmodium falciparum. The antimalarial fosmidomycin inhibits the MEP pathway enzyme deoxyxylulose 5-phosphate reductoisomerase (DXR). Fosmidomycin-resistant P. falciparum are enriched for changes in the PF3D7_1033400 locus (hereafter referred to as PfHAD1), encoding a homologue of haloacid dehalogenase (HAD)-like sugar phosphatases. We describe the structural basis for loss-of-function PfHAD1 alleles and find that PfHAD1 dephosphorylates a variety of sugar phosphates, including glycolytic intermediates. Loss of PfHAD1 is required for fosmidomycin resistance. Parasites lacking PfHAD1 have increased MEP pathway metabolites, particularly the DXR substrate, deoxyxylulose 5-phosphate. PfHAD1 therefore controls substrate availability to the MEP pathway. Because PfHAD1 has homologs in plants and bacteria, other HAD proteins may be MEP pathway regulators. PMID:25058848

Plasmodium falciparum erythrocyte membrane protein-1 specifically suppresses early production of host interferon-gamma.

PubMed

D'Ombrain, Marthe C; Voss, Till S; Maier, Alexander G; Pearce, J Andrew; Hansen, Diana S; Cowman, Alan F; Schofield, Louis

2007-08-16

Plasmodium falciparum erythrocyte membrane protein-1 (PfEMP-1) is a variable antigen expressed by P. falciparum, the malarial parasite. PfEMP-1, present on the surface of infected host erythrocytes, mediates erythrocyte binding to vascular endothelium, enabling the parasite to avoid splenic clearance. In addition, PfEMP-1 is proposed to regulate host immune responses via interactions with the CD36 receptor on antigen-presenting cells. We investigated the immunoregulatory function of PfEMP-1 by comparing host cell responses to erythrocytes infected with either wild-type parasites or transgenic parasites lacking PfEMP-1. We showed that PfEMP-1 suppresses the production of the cytokine interferon-gamma by human peripheral blood mononuclear cells early after exposure to P. falciparum. Suppression of this rapid proinflammatory response was CD36 independent and specific to interferon-gamma production by gammadelta-T, NK, and alphabeta-T cells. These data demonstrate a parasite strategy for downregulating the proinflammatory interferon-gamma response and further establish transgenic parasites lacking PfEMP-1 as powerful tools for elucidating PfEMP-1 functions.

Investigation on Polylactide (PLA)/Poly(butylene adipate-co-terephthalate) (PBAT)/Bark Flour of Plane Tree (PF) Eco-Composites

PubMed Central

Dou, Qiang; Cai, Jun

2016-01-01

Polylactide (PLA)/poly(butylene adipate-co-terephthalate) (PBAT)/bark flour of plane tree (PF) eco-composites were prepared via melt blending. The morphologies, mechanical properties, crystal structures and melting and crystallization behaviors of the eco-composites were investigated by means of scanning electron microscopy (SEM), mechanical tests, polarized light microscopy (PLM), wide angle X-ray diffraction (WAXD) and differential scanning calorimetry (DSC), respectively. It is shown that the interfacial adhesion between PLA matrix and PF is weak and the mechanical properties of PLA/PF eco-composites are poor. The titanate treatment improves the adhesion between the matrix and the filler and enhances the stiffness of the eco-composites. The toughness is improved by PBAT and ductile fractured surfaces can be found. The spherulitic size of PLA is decreased by the addition of PF. The α crystalline form of PLA remains in the composites. Compared with PF, T-PF (PF treated by a titanate coupling agent) and PBAT have negative effects on the crystallization of PLA. PMID:28773515

Interaction of PF4 (CXCL4) with the vasculature: a role in atherosclerosis and angiogenesis.

PubMed

Aidoudi, Sallouha; Bikfalvi, Andreas

2010-11-01

Platelet factor-4 (PF4), a platelet-derived chemokine, has two important functions in the vasculature. It has a pro-atherogenic role while also having anti-angiogenic effects. The activity of platelet factor-4 (PF4), unlike other chemokines that bind to specific receptors, depends on its unusually high affinity for proteoglycans and other negatively charged molecules. High affinity for heparan sulfates was thought to be central to all of PF4's biological functions. However, other mechanisms have been described such as direct growth factor binding, activation of the CXCR3B chemokine receptor isoform that is present in some vascular cells or binding to lipoprotein-related protein-1 (LRP1). Furthermore, PF4 also binds to integrins with affinities similar to matrix molecules. These interactions may explain the effects of PF4 in healthy and pathological tissues. However, the mechanisms involved in PF4's activity are complex and may depend on a given tissue or localisation. Overall, while much is already known about PF4, its specific role in atherosclerosis and angiogenesis remains still to be clarified.

A homeodomain transcription factor gene, PfMSX, activates expression of Pif gene in the pearl oyster Pinctada fucata.

PubMed

Zhao, Mi; He, Maoxian; Huang, Xiande; Wang, Qi

2014-01-01

We reported pearl oyster Pinctada fucata cDNA and genomic characterization of a new homeobox-containing protein, PfMSX. The PfMSX gene encodes a transcription factor that was localized to the nucleus. Analyses of PfMSX mRNA in tissues and developmental stages showed high expressions in mantle or D-shaped larvae. In electrophoretic mobility shift assays (EMSAs) PfMSX binded to MSX consensus binding sites in the 5' flanking region of the Pif promoter. In co-transfection experiment PfMSX transactivated reporter constructs containing Pif promoter sequences, and mutation of the MSX-binding sites attenuated transactivation. A knockdown experiment using PfMSX dsRNA showed decreased Pif mRNA and unregular crystallization of the nacreous layer using scanning electron microscopy. Our results suggested that PfMSX was a conserved homeodomain transcription factor gene, which can activate Pif gene expression through MSX binding site, and was then involved in the mineralization process in pearl oyster Pinctada fucata. Our data provided important clues about mechanisms regulating biomineralization in pearl oyster.

A Homeodomain Transcription Factor Gene, PfMSX, Activates Expression of Pif Gene in the Pearl Oyster Pinctada fucata

PubMed Central

Zhao, Mi; He, Maoxian; Huang, Xiande; Wang, Qi

2014-01-01

We reported pearl oyster Pinctada fucata cDNA and genomic characterization of a new homeobox-containing protein, PfMSX. The PfMSX gene encodes a transcription factor that was localized to the nucleus. Analyses of PfMSX mRNA in tissues and developmental stages showed high expressions in mantle or D-shaped larvae. In electrophoretic mobility shift assays (EMSAs) PfMSX binded to MSX consensus binding sites in the 5′ flanking region of the Pif promoter. In co-transfection experiment PfMSX transactivated reporter constructs containing Pif promoter sequences, and mutation of the MSX-binding sites attenuated transactivation. A knockdown experiment using PfMSX dsRNA showed decreased Pif mRNA and unregular crystallization of the nacreous layer using scanning electron microscopy. Our results suggested that PfMSX was a conserved homeodomain transcription factor gene, which can activate Pif gene expression through MSX binding site, and was then involved in the mineralization process in pearl oyster Pinctada fucata. Our data provided important clues about mechanisms regulating biomineralization in pearl oyster. PMID:25099698

Iron stores of breastfed infants during the first year of life.

PubMed

Ziegler, Ekhard E; Nelson, Steven E; Jeter, Janice M

2014-05-21

The birth iron endowment provides iron for growth in the first months of life. We describe the iron endowment under conditions of low dietary iron supply. Subjects were infants participating in a trial of Vitamin D supplementation from 1 to 9 months. Infants were exclusively breastfed at enrollment but could receive complementary foods from 4 months but not formula. Plasma ferritin (PF) and transferrin receptor (TfR) were determined at 1, 2, 4, 5.5, 7.5, 9 and 12 months. At 1 month PF ranged from 38 to 752 µg/L and was only weakly related to maternal PF. PF declined subsequently and flattened out at 5.5 months. PF of females was significantly higher than PF of males except at 12 months. TfR increased with age and was inversely correlated with PF. PF and TfR tracked strongly until 9 months. Iron deficiency (PF < 10 µg/L) began to appear at 4 months and increased in frequency until 9 months. Infants with ID were born with low iron endowment. We concluded that the birth iron endowment is highly variable in size and a small endowment places infants at risk of iron deficiency before 6 months. Boys have smaller iron endowments and are at greater risk of iron deficiency than girls.

Efficacy and tolerability of a new synergized pyrethrins thermofobic foam in comparison with benzyl benzoate in the treatment of scabies in convicts: the ISAC study (Studio Della scabbia in ambiente carcerario).

PubMed

Biele, M; Campori, G; Colombo, R; De Giorgio, G; Frascione, P; Sali, R; Starnini, G; Milani, M

2006-07-01

Scabies is a very common skin infection in convicts. The SIMSPE Society (Società Italiana di Medicina e Sanità Penitenziaria) has organized and conducted a multicentre, randomized, comparative, parallel group, investigator-blinded trial to evaluate the efficacy and tolerability of synergized pyrethrins foam (PF) in comparison with benzyl benzoate (BB) lotion. A total of 240 convicted patients, enrolled in eight National Jail Institutions, with a clinical diagnosis of scabies, were treated with PF (n = 120) for three consecutive days or BB (n = 120) for five consecutive days. Primary study endpoints were the clinical cure rate and the local tolerability. Secondary endpoints were clinical evolution of scabietic lesions and itching intensity. Study outcomes were assessed using appropriate semiquantitative scores at baseline and after 2 and 4 weeks. A second treatment cycle was applied if after 2 weeks the patient was not judged clinically cured. At week 2, a total of 75% (95% CI: 66-82%) and 71% (95% CI: 62-78%) of patients showed a complete clinical cure rate in the PF and BB groups, respectively. At week 4, the percentage of totally cured patients increased up to 95% (95% CI: 89-97%) and 91% (95% CI: 83-94%) in the PF and BB groups, respectively (P = NS between groups). At week 4, 5% in the PF group and 9% in the BB group complained of itching. Burning and irritation after treatment applications were more common in the BB group in comparison with the PF group. The tolerability score was better in the PF group in comparison with to BB group (2.9 vs. 2.2; P = 0.0001). A total of 95% of patients in the PV group had a good tolerability score (i.e. = 3) in comparison with 41% in the BB group. Our results show that a 3-day treatment with pyrethrins thermofobic foam is at least as effective as a 5-day treatment with benzyl benzoate lotion in convicted subjects with scabies. The foam formulation is better tolerated than the benzyl benzoate lotion.

The Clp Chaperones and Proteases of the Human Malaria Parasite Plasmodium falciparum

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

Bakkouri, Majida El; Pow, Andre; Mulichak, Anne

The Clp chaperones and proteases play an important role in protein homeostasis in the cell. They are highly conserved across prokaryotes and found also in the mitochondria of eukaryotes and the chloroplasts of plants. They function mainly in the disaggregation, unfolding and degradation of native as well as misfolded proteins. Here, we provide a comprehensive analysis of the Clp chaperones and proteases in the human malaria parasite Plasmodium falciparum. The parasite contains four Clp ATPases, which we term PfClpB1, PfClpB2, PfClpC and PfClpM. One PfClpP, the proteolytic subunit, and one PfClpR, which is an inactive version of the protease, weremore » also identified. Expression of all Clp chaperones and proteases was confirmed in blood-stage parasites. The proteins were localized to the apicoplast, a non-photosynthetic organelle that accommodates several important metabolic pathways in P. falciparum, with the exception of PfClpB2 (also known as Hsp101), which was found in the parasitophorous vacuole. Both PfClpP and PfClpR form mostly homoheptameric rings as observed by size-exclusion chromatography, analytical ultracentrifugation and electron microscopy. The X-ray structure of PfClpP showed the protein as a compacted tetradecamer similar to that observed for Streptococcus pneumoniae and Mycobacterium tuberculosis ClpPs. Our data suggest the presence of a ClpCRP complex in the apicoplast of P. falciparum.« less

Systematic review: plantar fasciitis and prolonged weight bearing.

PubMed

Waclawski, E R; Beach, J; Milne, A; Yacyshyn, E; Dryden, D M

2015-03-01

Plantar fasciitis (PF) is one of the most common causes of foot pain. Work can involve factors that may predispose to foot pain. To systematically review the evidence of the association between weight bearing (walking or standing) and PF among workers. Literature search of relevant indexing databases from inception to May 2012, grey literature, websites of relevant organizations and reference lists for all identified articles. Two reviewers independently selected studies for full review, assessed methodological quality and graded evidence. Findings were summarized qualitatively. Four studies were included; all were assessed as high or unclear risk of bias. Three studies were case-control studies; two used clinic populations and one used volunteers. The other study was cross-sectional involving the workforce of an assembly plant. A number of associations between PF and risk factors were identified including sex, obesity, foot biomechanics and job factors (e.g. job tenure). Two case-control studies and the cross-sectional study found an association with weight bearing, but the assessment of weight bearing varied (e.g. time on feet, time walking or standing). There was low-quality evidence to confirm a causal relationship (Royal College of General Practitioners (RCGP) * grade). This systematic review found low-quality evidence of an association between PF and weight-bearing tasks such as walking and standing on hard surfaces. The only occupations specifically identified as having higher risk were those associated with the engine assembly plant. Further research is required to fully determine the association between weight bearing and PF. © The Author 2015. Published by Oxford University Press on behalf of the Society of Occupational Medicine. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Effects of peritoneal fluid from endometriosis patients on interferon-gamma-induced protein-10 (CXCL10) and interleukin-8 (CXCL8) released by neutrophils and CD4+ T cells.

PubMed

Kim, Ji-Yeon; Lee, Dong-Hyung; Joo, Jong-Kil; Jin, Jun-O; Wang, Ji-Won; Hong, Young-Seoub; Kwak, Jong-Young; Lee, Kyu-Sup

2009-09-01

Intraperitoneal immuno-inflammatory changes may be associated with the pathogenesis of endometriosis. We evaluated the effects of peritoneal fluid obtained from patients with endometriosis (ePF) on the release of interferon-gamma-induced protein-10 (IP-10/CXCL10) and interleukin-8 (IL-8/CXCL8) by neutrophils, CD4(+) T cells, and monocytes. Neutrophils, CD4(+) T cells, and monocytes were cultured with ePF and the chemokine levels in the supernatants were then measured using enzyme-linked immunosorbent assay. The addition of ePF to cultures of CD4(+) T cells led to a significant increase in the release of IP-10 when compared with control PF without endometriosis (cPF). There was a positive correlation between the levels of IL-8 and IP-10 in ePF (R = 0.89, P = 0.041), but not between the levels of IP-10 and IL-8 released by neutrophils, CD4(+) T cells, and monocytes. The levels of IP-10 in ePF were positively correlated with the release of IP-10 by ePF-treated neutrophils (R = 0.89, P < 0.001), CD4(+) T cells (R = 0.93, P < 0.001), and monocytes (R = 0.70, P = 0.01). Moreover, the addition of ePF significantly enhanced the interferon-gamma-induced release of IP-10 by nuetrophils and CD4(+) T cells. These findings suggest that neutrophils and T cells release differential levels of IP-10 and IL-8 in response to stimulation with ePF, and that these cells are a major source of IP-10 in the PF of endometriosis patients.

Somatic cells initiate primordial follicle activation and govern the development of dormant oocytes in mice.

PubMed

Zhang, Hua; Risal, Sanjiv; Gorre, Nagaraju; Busayavalasa, Kiran; Li, Xin; Shen, Yan; Bosbach, Benedikt; Brännström, Mats; Liu, Kui

2014-11-03

The majority of oocytes in the mammalian ovary are dormant oocytes that are enclosed in primordial follicles by several somatic cells, which we refer to as primordial follicle granulosa cells (pfGCs). Very little is known, however, about how the pfGCs control the activation of primordial follicles and the developmental fates of dormant oocytes. By targeting molecules in pfGCs with several mutant mouse models, we demonstrate that the somatic pfGCs initiate the activation of primordial follicles and govern the quiescence or awakening of dormant oocytes. Inhibition of mTORC1 signaling in pfGCs prevents the differentiation of pfGCs into granulosa cells, and this arrests the dormant oocytes in their quiescent states, leading to oocyte death. Overactivation of mTORC1 signaling in pfGCs accelerates the differentiation of pfGCs into granulosa cells and causes premature activation of all dormant oocytes and primordial follicles. We further show that pfGCs trigger the awakening of dormant oocytes through KIT ligand (KITL), and we present an essential communication network between the somatic cells and germ cells that is based on signaling between the mTORC1-KITL cascade in pfGCs and KIT-PI3K signaling in oocytes. Our findings provide a relatively complete picture of how mammalian primordial follicles are activated. The microenvironment surrounding primordial follicles can activate mTORC1-KITL signaling in pfGCs, and these cells trigger the awakening of dormant oocytes and complete the process of follicular activation. Such communication between the microenvironment, somatic cells, and germ cells is essential to maintaining the proper reproductive lifespan in mammals. Copyright © 2014 Elsevier Ltd. All rights reserved.

Effectiveness of Personalized Feedback Alone or Combined with Peer Support to Improve Physical Activity in Sedentary Older Malays with Type 2 Diabetes: A Randomized Controlled Trial.

PubMed

Sazlina, Shariff-Ghazali; Browning, Colette Joy; Yasin, Shajahan

2015-01-01

Regular physical activity is an important aspect of self-management among older people with type 2 diabetes but many remain inactive. Interventions to improve physical activity levels have been studied but few studies have evaluated the effects of personalized feedback (PF) or peer support (PS); and there was no study on older people of Asian heritage. Hence, this trial evaluated whether PF only or combined with PS improves physical activity among older Malays with type 2 diabetes (T2DM) compared to usual care only. A three-arm randomized controlled trial was conducted in a primary healthcare clinic in Malaysia. Sixty-nine sedentary Malays aged 60 years and older with T2DM who received usual diabetes care were randomized to PF or PS interventions or as controls for 12 weeks with follow-ups at weeks 24 and 36. Intervention groups performed unsupervised walking activity and received written feedback on physical activity. The PS group also received group and telephone contacts from trained peer mentors. The primary outcome was pedometer steps. Secondary outcomes were self-reported physical activity, cardiovascular risk factors, cardiorespiratory fitness, balance, quality of life, and psychosocial wellbeing. Fifty-two (75.4%) completed the 36-week study. The PS group showed greater daily pedometer readings than the PF and controls (p = 0.001). The PS group also had greater improvement in weekly duration (p < 0.001) and frequency (p < 0.001) of moderate intensity physical activity, scores on the Physical Activity Scale for Elderly (p = 0.003), 6-min walk test (p < 0.001), and social support from friends (p = 0.032) than PF and control groups. The findings suggest that PF combined with PS in older Malays with T2DM improved their physical activity levels, cardiorespiratory fitness, and support from friends. Current Controlled Trials ISRCTN71447000.

Assessment of psychotropic-like properties of a probiotic formulation (Lactobacillus helveticus R0052 and Bifidobacterium longum R0175) in rats and human subjects.

PubMed

Messaoudi, Michaël; Lalonde, Robert; Violle, Nicolas; Javelot, Hervé; Desor, Didier; Nejdi, Amine; Bisson, Jean-François; Rougeot, Catherine; Pichelin, Matthieu; Cazaubiel, Murielle; Cazaubiel, Jean-Marc

2011-03-01

In a previous clinical study, a probiotic formulation (PF) consisting of Lactobacillus helveticus R0052 and Bifidobacterium longum R0175 (PF) decreased stress-induced gastrointestinal discomfort. Emerging evidence of a role for gut microbiota on central nervous system functions therefore suggests that oral intake of probiotics may have beneficial consequences on mood and psychological distress. The aim of the present study was to investigate the anxiolytic-like activity of PF in rats, and its possible effects on anxiety, depression, stress and coping strategies in healthy human volunteers. In the preclinical study, rats were daily administered PF for 2 weeks and subsequently tested in the conditioned defensive burying test, a screening model for anti-anxiety agents. In the clinical trial, volunteers participated in a double-blind, placebo-controlled, randomised parallel group study with PF administered for 30 d and assessed with the Hopkins Symptom Checklist (HSCL-90), the Hospital Anxiety and Depression Scale (HADS), the Perceived Stress Scale, the Coping Checklist (CCL) and 24 h urinary free cortisol (UFC). Daily subchronic administration of PF significantly reduced anxiety-like behaviour in rats (P < 0·05) and alleviated psychological distress in volunteers, as measured particularly by the HSCL-90 scale (global severity index, P < 0·05; somatisation, P < 0·05; depression, P < 0·05; and anger-hostility, P < 0·05), the HADS (HADS global score, P < 0·05; and HADS-anxiety, P < 0·06), and by the CCL (problem solving, P < 0·05) and the UFC level (P < 0·05). L. helveticus R0052 and B. longum R0175 taken in combination display anxiolytic-like activity in rats and beneficial psychological effects in healthy human volunteers.

Personality assessment in aviation : an analysis of the item ambiguity characteristics of the 16PF and MMPI.

DOT National Transportation Integrated Search

1971-07-01

Devices such as the 16PF and MMPI have been widely employed in the evaluation of personnel in aviation settings. The present study investigated the problem of item ambiguity (the degree to which an item elicits multiple interpretation) which may limi...

The effect of zinc limitation on the transcriptome of Pseudomonas protegens Pf-5

USDA-ARS?s Scientific Manuscript database

Zinc is an important nutrient but can be lacking in some soil environments, influencing the physiology of soil-dwelling bacteria. Hence, we studied the global effect of zinc limitation on the transcriptome of the rhizosphere biocontrol strain Pseudomonas protegens Pf-5. We observed that the expressi...

Insights into the activity of maturation inhibitor PF-46396 on HIV-1 clade C.

PubMed

Ghimire, Dibya; Timilsina, Uddhav; Srivastava, Tryambak Pratap; Gaur, Ritu

2017-03-02

HIV maturation inhibitors are an emerging class of anti-retroviral compounds that inhibit the viral protease-mediated cleavage of the Gag, CA-SP1 (capsid-spacer peptide 1) peptide to mature CA. The first-in-class maturation inhibitor bevirimat (BVM) displayed potent activity against HIV-1 clade B but was ineffective against other HIV-1 clades including clade C. Another pyridone-based maturation inhibitor, PF-46396 displayed potent activity against HIV-1 clade B. In this study, we aimed at determining the activity of PF-46396 against HIV-1 clade C. We employed various biochemical and virological assays to demonstrate that PF-46396 is effective against HIV-1 clade C. We observed a dose dependent accumulation of CA-SP1 intermediate in presence of the compound. We carried out mutagenesis in the CA- SP1 region of HIV-1 clade C Gag and observed that the mutations conferred resistance against the compound. Many mutations inhibited Gag processing thereby reducing virus release in the absence of the compound. However, presence of PF-46396 rescued these defects and enhanced virus release, replication capacity and infectivity of HIV-1 clade C. These results put together identify PF-46396 as a broadly active maturation inhibitor against HIV-1 clade B and C and help in rational designing of novel analogs with reduced toxicity and increased efficacy for its potential use in clinics.

Pea Fiber and Wheat Bran Fiber Show Distinct Metabolic Profiles in Rats as Investigated by a 1H NMR-Based Metabolomic Approach

PubMed Central

Liu, Guangmang; Xiao, Liang; Fang, Tingting; Cai, Yimin; Jia, Gang; Zhao, Hua; Wang, Jing; Chen, Xiaoling; Wu, Caimei

2014-01-01

This study aimed to examine the effect of pea fiber (PF) and wheat bran fiber (WF) supplementation in rat metabolism. Rats were assigned randomly to one of three dietary groups and were given a basal diet containing 15% PF, 15% WF, or no supplemental fiber. Urine and plasma samples were analyzed by NMR-based metabolomics. PF significantly increased the plasma levels of 3-hydroxybutyrate, and myo-inositol as well as the urine levels of alanine, hydroxyphenylacetate, phenylacetyglycine, and α-ketoglutarate. However, PF significantly decreased the plasma levels of isoleucine, leucine, lactate, and pyruvate as well as the urine levels of allantoin, bile acids, and trigonelline. WF significantly increased the plasma levels of acetone, isobutyrate, lactate, myo-inositol, and lipids as well as the urine levels of alanine, lactate, dimethylglycine, N-methylniconamide, and α-ketoglutarate. However, WF significantly decreased the plasma levels of amino acids, and glucose as well as the urine levels of acetate, allantoin, citrate, creatine, hippurate, hydroxyphenylacetate, and trigonelline. Results suggest that PF and WF exposure can promote antioxidant activity and can exhibit common systemic metabolic changes, including lipid metabolism, energy metabolism, glycogenolysis and glycolysis metabolism, protein biosynthesis, and gut microbiota metabolism. PF can also decrease bile acid metabolism. These findings indicate that different fiber diet may cause differences in the biofluid profile in rats. PMID:25541729

Facile synthesis of a novel magnesium amino-tris-(methylenephosphonate)-reduced graphene oxide hybrid and its high performance in mechanical strength, thermal stability, smoke suppression and flame retardancy in phenolic foam.

PubMed

Liu, Lei; Wang, Zhengzhou

2018-05-26

This study presents a one-step synthesis of a magnesium amino-tris-(methylenephosphonate) (Mg-AMP)-reduced graphene oxide (Mg-rGO) hybrid involving graphene oxide (GO) reduction and growth in situ of Mg-AMP nanoparticles in the absence of a reducing agent. Mg-rGO was characterized by X-ray diffraction, X-ray photoelectron and Fourier-transform infrared spectroscopies, transmission electronic microscopy, and thermogravimetric analysis (TGA). Mg-rGO was then used to prepare flame-retardant and toughened phenolic (PF) foam. This additive was found to enhance the compressive and flexural strengths of PF foam as well as to reduce its high friability and brittleness. The limiting oxygen index of the foam with 4 phr Mg-rGO (sample PF/4Mg-rGO) increased to 41.5%, compared with the 38% of untreated foam; the peak heat release rate and total heat release of sample PF/4Mg-rGO were decreased by 28.7 and 18.4%, respectively. Also, the total smoke release and peak CO production rate of PF/4Mg-rGO were reduced by 52.5 and 38.1%, respectively. TGA results indicated that Mg-rGO clearly improved the thermal stability of PF foam. Copyright © 2018 Elsevier B.V. All rights reserved.

Phosphorylated and Nonphosphorylated PfMAP2 Are Localized in the Nucleus, Dependent on the Stage of Plasmodium falciparum Asexual Maturation

PubMed Central

Dahalan, Farah Aida; Sidek, Hasidah Mohd; Murtey, Mogana Das; Embi, Mohammed Noor; Ibrahim, Jamaiah; Fei Tieng, Lim; Zakaria, Nurul Aiezzah

2016-01-01

Plasmodium falciparum mitogen-activated protein (MAP) kinases, a family of enzymes central to signal transduction processes including inflammatory responses, are a promising target for antimalarial drug development. Our study shows for the first time that the P. falciparum specific MAP kinase 2 (PfMAP2) is colocalized in the nucleus of all of the asexual erythrocytic stages of P. falciparum and is particularly elevated in its phosphorylated form. It was also discovered that PfMAP2 is expressed in its highest quantity during the early trophozoite (ring form) stage and significantly reduced in the mature trophozoite and schizont stages. Although the phosphorylated form of the kinase is always more prevalent, its ratio relative to the nonphosphorylated form remained constant irrespective of the parasites' developmental stage. We have also shown that the TSH motif specifically renders PfMAP2 genetically divergent from the other plasmodial MAP kinase activation sites using Neighbour Joining analysis. Furthermore, TSH motif-specific designed antibody is crucial in determining the location of the expression of the PfMAP2 protein. However, by using immunoelectron microscopy, PPfMAP2 were detected ubiquitously in the parasitized erythrocytes. In summary, PfMAP2 may play a far more important role than previously thought and is a worthy candidate for research as an antimalarial. PMID:27525262

Highly expressed EGFR in pearl sac may facilitate the pearl formation in the pearl oyster, Pinctada fucata.

PubMed

Zhu, Wenjie; Fan, Sigang; Huang, Guiju; Zhang, Dongling; Liu, Baosuo; Bi, Xiaomin; Yu, Dahui

2015-07-25

Epidermal growth factor receptor (EGFR) plays an important role in cell growth, proliferation, differentiation and migration. Yet whether it functions in pearl formation or not is not reported. In this study, EGFR was cloned from the pearl oyster Pinctada fucata (named as Pf-EGFR) and its expression profiles were investigated. The cDNA was 2156bp long with an ORF of 1017bp encoding 338 amino acid residues. The deduced polypeptide contained an L domain and a cysteine-rich domain, consistent with the characteristics of ErbB family. The sequence of Pf-EGFR shared 22.78-56.71% identity with other EGFRs. The genomic sequence of Pf-EGFR consisted of six exons and five introns, being 5190bp in total length, and expressed in all the tested tissues with a higher expression level in the pearl sac (P<0.05). In situ hybridization showed that Pf-EGFR was specifically expressed on both the inner side of the outer fold and the outer side of the inner fold of the mantle, as well as on the whole pearl sac including the connective tissues. In addition, Pf-EGFR was markedly increased at larval metamorphosis, significantly higher than other development periods (P<0.05). These results indicated that the Pf-EGFR may facilitate pearl formation as well as larval metamorphosis. Copyright © 2015 Elsevier B.V. All rights reserved.

Gut morphology and hepatic oxidative status of European sea bass (Dicentrarchus labrax) juveniles fed plant feedstuffs or fishmeal-based diets supplemented with short-chain fructo-oligosaccharides and xylo-oligosaccharides.

PubMed

Guerreiro, Inês; Couto, Ana; Pérez-Jiménez, Amalia; Oliva-Teles, Aires; Enes, Paula

2015-12-28

The effects of short-chain fructo-oligosaccharides (scFOS) and xylo-oligosaccharides (XOS) on gut morphology and hepatic oxidative status were studied in European sea bass juveniles weighing 60 g. Fish were fed diets including fishmeal (FM diets) or plant feedstuffs (PF diets; 30 FM:70 PF) as main protein sources (control diets). Four other diets were formulated similar to the control diets but including 1 % scFOS or 1 % XOS. At the end of the trial, fish fed PF-based diets presented histomorphological alterations in the distal intestine, whereas only transient alterations were observed in the pyloric caeca. Comparatively to fish fed FM-based diets, fish fed PF diets had higher liver lipid peroxidation (LPO), superoxide dismutase (SOD) and catalase (CAT) activities, and lower glutathione peroxidase, glutathione reductase and glucose 6-phosphate dehydrogenase activities. In fish fed the PF diets, prebiotic supplementation decreased SOD activity and XOS supplementation further decreased CAT activity. In fish fed the FM diets, XOS supplementation promoted a reduction of all antioxidant enzyme activities. Overall, dietary XOS and scFOS supplementation had only minor effects on gut morphology or LPO levels. However, dietary XOS reduced antioxidant enzymatic activity in both PF and FM diets, which indicate a positive effect on reduction of hepatic reactive oxygen species production.

Structural Plasticity of Malaria Dihydroorotate Dehydrogenase Allows Selective Binding of Diverse Chemical Scaffolds

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

Deng, Xiaoyi; Gujjar, Ramesh; El Mazouni, Farah

Malaria remains a major global health burden and current drug therapies are compromised by resistance. Plasmodium falciparum dihydroorotate dehydrogenase (PfDHODH) was validated as a new drug target through the identification of potent and selective triazolopyrimidine-based DHODH inhibitors with anti-malarial activity in vivo. Here we report x-ray structure determination of PfDHODH bound to three inhibitors from this series, representing the first of the enzyme bound to malaria specific inhibitors. We demonstrate that conformational flexibility results in an unexpected binding mode identifying a new hydrophobic pocket on the enzyme. Importantly this plasticity allows PfDHODH to bind inhibitors from different chemical classes andmore » to accommodate inhibitor modifications during lead optimization, increasing the value of PfDHODH as a drug target. A second discovery, based on small molecule crystallography, is that the triazolopyrimidines populate a resonance form that promotes charge separation. These intrinsic dipoles allow formation of energetically favorable H-bond interactions with the enzyme. The importance of delocalization to binding affinity was supported by site-directed mutagenesis and the demonstration that triazolopyrimidine analogs that lack this intrinsic dipole are inactive. Finally, the PfDHODH-triazolopyrimidine bound structures provide considerable new insight into species-selective inhibitor binding in this enzyme family. Together, these studies will directly impact efforts to exploit PfDHODH for the development of anti-malarial chemotherapy.« less

A theoretical and shock tube kinetic study on hydrogen abstraction from phenyl formate.

PubMed

Ning, Hongbo; Liu, Dapeng; Wu, Junjun; Ma, Liuhao; Ren, Wei; Farooq, Aamir

2018-06-12

The hydrogen abstraction reactions of phenyl formate (PF) by different radicals (H/O(3P)/OH/HO2) were theoretically investigated. We calculated the reaction energetics for PF + H/O/OH using the composite method ROCBS-QB3//M06-2X/cc-pVTZ and that for PF + HO2 at the M06-2X/cc-pVTZ level of theory. The high-pressure limit rate constants were calculated using the transition state theory in conjunction with the 1-D hindered rotor approximation and tunneling correction. Three-parameter Arrhenius expressions of rate constants were provided over the temperature range of 500-2000 K. To validate the theoretical calculations, the overall rate constants of PF + OH → Products were measured in shock tube experiments at 968-1128 K and 1.16-1.25 atm using OH laser absorption. The predicted overall rate constants agree well with the shock tube data (within 15%) over the entire experimental conditions. Rate constant analysis indicates that the H-abstraction at the formic acid site dominates the PF consumption, whereas the contribution of H-abstractions at the aromatic ring increases with temperature. Additionally, comparisons of site-specific H-abstractions from PF with methyl formate, ethyl formate, benzene, and toluene were performed to understand the effects of the aromatic ring and side-chain substituent on H-abstraction rate constants.

Advancing Global Health through Development and Clinical Trials Partnerships: A Randomized, Placebo-Controlled, Double-Blind Assessment of Safety, Tolerability, and Immunogenicity of PfSPZ Vaccine for Malaria in Healthy Equatoguinean Men

PubMed Central

Olotu, Ally; Urbano, Vicente; Hamad, Ali; Eka, Martin; Chemba, Mwajuma; Nyakarungu, Elizabeth; Raso, Jose; Eburi, Esther; Mandumbi, Dolores O.; Hergott, Dianna; Maas, Carl D.; Ayekaba, Mitoha O.; Milang, Diosdado N.; Rivas, Matilde R.; Schindler, Tobias; Embon, Oscar M.; Ruben, Adam J.; Saverino, Elizabeth; Abebe, Yonas; KC, Natasha; James, Eric R.; Murshedkar, Tooba; Manoj, Anita; Chakravarty, Sumana; Li, Minglin; Adams, Matthew; Schwabe, Christopher; Segura, J. Luis; Daubenberger, Claudia; Tanner, Marcel; Richie, Thomas L.; Billingsley, Peter F.; Lee Sim, B. Kim; Abdulla, Salim; Hoffman, Stephen L.

2018-01-01

Abstract. Equatorial Guinea (EG) has implemented a successful malaria control program on Bioko Island. A highly effective vaccine would be an ideal complement to this effort and could lead to halting transmission and eliminating malaria. Sanaria® PfSPZ Vaccine (Plasmodium falciparum sporozoite Vaccine) is being developed for this purpose. To begin the process of establishing the efficacy of and implementing a PfSPZ Vaccine mass vaccination program in EG, we decided to conduct a series of clinical trials of PfSPZ Vaccine on Bioko Island. Because no clinical trial had ever been conducted in EG, we first successfully established the ethical, regulatory, quality, and clinical foundation for conducting trials. We now report the safety, tolerability, and immunogenicity results of the first clinical trial in the history of the country. Thirty adult males were randomized in the ratio 2:1 to receive three doses of 2.7 × 105 PfSPZ of PfSPZ Vaccine (N = 20) or normal saline placebo (N = 10) by direct venous inoculation at 8-week intervals. The vaccine was safe and well tolerated. Seventy percent, 65%, and 45% of vaccinees developed antibodies to Plasmodium falciparum (Pf) circumsporozoite protein (PfCSP) by enzyme-linked immunosorbent assay, PfSPZ by automated immunofluorescence assay, and PfSPZ by inhibition of sporozoite invasion assay, respectively. Antibody responses were significantly lower than responses in U.S. adults who received the same dosage regimen, but not significantly different than responses in young adult Malians. Based on these results, a clinical trial enrolling 135 subjects aged 6 months to 65 years has been initiated in EG; it includes PfSPZ Vaccine and first assessment in Africa of PfSPZ-CVac. ClinicalTrials.gov identifier: NCT02418962. PMID:29141739

Bilateral comparison of 10 pF and 100 pF standards (ongoing BIPM key comparisons BIPM.EM-K14.a and 14.b) between the NMISA (South Africa) and the BIPM

NASA Astrophysics Data System (ADS)

Gournay, Pierre; Khoza, Michael

2017-01-01

This report presents the results of a bilateral comparison of 10 pF and 100 pF capacitance standards between the NMISA (South Africa) and the BIPM carried out in 2016. The comparison at 10 pF forms part of the ongoing BIPM key comparison BIPM.EM-K14.a and that at 100 pF of the ongoing BIPM key comparison BIPM.EM-K14.b. The BIPM is the pilot laboratory for both of these comparisons. Two 10 pF and 100 pF travelling standards belonging to the BIPM were used in this comparison carried out with an 'A-B-A' pattern of measurements. The standards were measured first at the BIPM for a period of about one month, then for a similar period at the NMISA, and finally again at the BIPM. The measurand was the two terminal-pair capacitance at a frequency of either 1000 Hz or 1592 Hz, for a measuring rms voltage of 15 V at 10 pF and 10 V at 100 pF. One of the 10 pF travelling standards had to be eliminated from the comparison due to a bistable behaviour, possibly due to transportation. The results from the NMISA and the BIPM at both 1000 Hz and 1592 Hz were found to be in good agreement, with a difference smaller than the relative expanded uncertainty (95 % confidence, k = 2) of maximum value 0.33 × 10-6 at 10 pF and 0.24 × 10-6 at 100 pF (and 1000 Hz in both cases). Main text To reach the main text of this paper, click on Final Report. Note that this text is that which appears in Appendix B of the BIPM key comparison database kcdb.bipm.org/. The final report has been peer-reviewed and approved for publication by the CCEM, according to the provisions of the CIPM Mutual Recognition Arrangement (CIPM MRA).

A new world malaria map: Plasmodium falciparum endemicity in 2010.

PubMed

Gething, Peter W; Patil, Anand P; Smith, David L; Guerra, Carlos A; Elyazar, Iqbal R F; Johnston, Geoffrey L; Tatem, Andrew J; Hay, Simon I

2011-12-20

Transmission intensity affects almost all aspects of malaria epidemiology and the impact of malaria on human populations. Maps of transmission intensity are necessary to identify populations at different levels of risk and to evaluate objectively options for disease control. To remain relevant operationally, such maps must be updated frequently. Following the first global effort to map Plasmodium falciparum malaria endemicity in 2007, this paper describes the generation of a new world map for the year 2010. This analysis is extended to provide the first global estimates of two other metrics of transmission intensity for P. falciparum that underpin contemporary questions in malaria control: the entomological inoculation rate (PfEIR) and the basic reproductive number (PfR). Annual parasite incidence data for 13,449 administrative units in 43 endemic countries were sourced to define the spatial limits of P. falciparum transmission in 2010 and 22,212 P. falciparum parasite rate (PfPR) surveys were used in a model-based geostatistical (MBG) prediction to create a continuous contemporary surface of malaria endemicity within these limits. A suite of transmission models were developed that link PfPR to PfEIR and PfR and these were fitted to field data. These models were combined with the PfPR map to create new global predictions of PfEIR and PfR. All output maps included measured uncertainty. An estimated 1.13 and 1.44 billion people worldwide were at risk of unstable and stable P. falciparum malaria, respectively. The majority of the endemic world was predicted with a median PfEIR of less than one and a median PfRc of less than two. Values of either metric exceeding 10 were almost exclusive to Africa. The uncertainty described in both PfEIR and PfR was substantial in regions of intense transmission. The year 2010 has a particular significance as an evaluation milestone for malaria global health policy. The maps presented here contribute to a rational basis for control and elimination decisions and can serve as a baseline assessment as the global health community looks ahead to the next series of milestones targeted at 2015.

What are the concerns and goals of women attending a urogynaecology clinic? Content analysis of free-text data from an electronic pelvic floor assessment questionnaire (ePAQ-PF).

PubMed

Gray, Thomas; Strickland, Scarlett; Pooranawattanakul, Sarita; Li, Weiguang; Campbell, Patrick; Jones, Georgina; Radley, Stephen

2018-06-27

Understanding patients' concerns and goals is essential for providing individualised care in urogynaecology. The study objectives were to undertake a content analysis of free-text concerns and goals recorded by patients using an electronic pelvic-floor questionnaire (ePAQ-PF) and measure how these related to self-reported symptom and health-related quality-of-life (HRQOL) data also recorded using ePAQ-PF. A total of 1996 consenting patients completed ePAQ-PF. Content analysis was undertaken of free-text responses to the item: 'Considering the issues that currently concern you the most, what do you hope to achieve from any help, advice or treatment?' Key content themes were identified by the lead researcher, and three researchers read and coded all recorded responses. Student's t test was used to compare ePAQ-PF domain scores for patients reporting concerns in the relevant domain with those who did not. In total, 63% of participants who completed the questionnaire, recorded at least one free-text item. Content analysis identified 1560 individual concerns coding into the 19 ePAQ-PF domains. Symptom scores were significantly higher for patients reporting free-text concerns in 18 domains (p < 0.05). Additional concerns relating specifically to body image were recorded by 11% of patients. Key areas of importance emerging for personal goals included cure/improvement, better understanding, incontinence pad use, sexual function and surgery. Free-text reporting in ePAQ-PF is utilised by patients and facilitates self-expression and discussion of issues impacting on HRQOL. The significant relationship between recorded free-text concerns and ePAQ-PF domain scores suggests convergent validity for the instrument. Development and psychometric testing of a domain to assess body image is proposed.

KBE009: An antimalarial bestatin-like inhibitor of the Plasmodium falciparum M1 aminopeptidase discovered in an Ugi multicomponent reaction-derived peptidomimetic library.

PubMed

González-Bacerio, Jorge; Maluf, Sarah El Chamy; Méndez, Yanira; Pascual, Isel; Florent, Isabelle; Melo, Pollyana M S; Budu, Alexandre; Ferreira, Juliana C; Moreno, Ernesto; Carmona, Adriana K; Rivera, Daniel G; Alonso Del Rivero, Maday; Gazarini, Marcos L

2017-09-01

Malaria is a global human parasitic disease mainly caused by the protozoon Plasmodium falciparum. Increased parasite resistance to current drugs determines the relevance of finding new treatments against new targets. A novel target is the M1 alanyl-aminopeptidase from P. falciparum (PfA-M1), which is essential for parasite development in human erythrocytes and is inhibited by the pseudo-peptide bestatin. In this work, we used a combinatorial multicomponent approach to produce a library of peptidomimetics and screened it for the inhibition of recombinant PfA-M1 (rPfA-M1) and the in vitro growth of P. falciparum erythrocytic stages (3D7 and FcB1 strains). Dose-response studies with selected compounds allowed identifying the bestatin-based peptidomimetic KBE009 as a submicromolar rPfA-M1 inhibitor (K i =0.4μM) and an in vitro antimalarial compound as potent as bestatin (IC 50 =18μM; without promoting erythrocyte lysis). At therapeutic-relevant concentrations, KBE009 is selective for rPfA-M1 over porcine APN (a model of these enzymes from mammals), and is not cytotoxic against HUVEC cells. Docking simulations indicate that this compound binds PfA-M1 without Zn 2+ coordination, establishing mainly hydrophobic interactions and showing a remarkable shape complementarity with the active site of the enzyme. Moreover, KBE009 inhibits the M1-type aminopeptidase activity (Ala-7-amido-4-methylcoumarin substrate) in isolated live parasites with a potency similar to that of the antimalarial activity (IC 50 =82μM), strongly suggesting that the antimalarial effect is directly related to the inhibition of the endogenous PfA-M1. These results support the value of this multicomponent strategy to identify PfA-M1 inhibitors, and make KBE009 a promising hit for drug development against malaria. Copyright © 2017 Elsevier Ltd. All rights reserved.

Toward the Elucidation of the Competing Role of Evaporation and Thermal Decomposition in Ionic Liquids: A Multitechnique Study of the Vaporization Behavior of 1-Butyl-3-methylimidazolium Hexafluorophosphate under Effusion Conditions.

PubMed

Volpe, V; Brunetti, B; Gigli, G; Lapi, A; Vecchio Ciprioti, S; Ciccioli, A

2017-11-16

The evaporation/decomposition behavior of the imidazolium ionic liquid 1-butyl-3-methylimidazolium hexafluorophosphate (BMImPF 6 ) was investigated in the overall temperature range 425-551 K by means of the molecular-effusion-based techniques Knudsen effusion mass loss (KEML) and Knudsen effusion mass spectrometry (KEMS), using effusion orifices of different size (from 0.2 to 3 mm in diameter). Specific effusion fluxes measured by KEML were found to depend markedly on the orifice size, suggesting the occurrence of a kinetically delayed evaporation/decomposition process. KEMS experiments revealed that other species are present in the vapor phase besides the intact ion pair BMImPF 6 (g) produced by the simple evaporation BMImPF 6 (l) = BMImPF 6 (g), with relative abundances depending on the orifice size-the larger the orifice, the larger the contribution of the BMImPF 6 (g) species. By combining KEML and KEMS results, the conclusion is drawn that in the investigated temperature range, when small effusion orifices are used, a significant part of the mass loss/volatility of BMImPF 6 is due to molecular products formed by decomposition/dissociation processes rather than to evaporated intact ion pairs. Additional experiments performed by nonisothermal thermogravimetry-differential thermal analysis (TG-DTA) further support the evidence of simultaneous evaporation/decomposition, although the conventional decomposition temperature derived from TG curves is much higher than the temperatures covered in effusion experiments. Partial pressures of the BMImPF 6 (g) species were derived from KEMS spectra and analyzed by second- and third-law methods giving a value of Δ evap H 298K ° = 145.3 ± 2.9 kJ·mol -1 for the standard evaporation enthalpy of BMImPF 6 . A comparison is done with the behavior of the 1-butyl-3-methylimidazolium bis(trifluoromethyl)sulfonylimide (BMImNTf 2 ) ionic liquid.

Performance of the PROMIS in Patients After Anterior Cruciate Ligament Reconstruction

PubMed Central

Scott, Elizabeth J.; Westermann, Robert; Glass, Nathalie A.; Hettrich, Carolyn; Wolf, Brian R.; Bollier, Matthew J.

2018-01-01

Background: The Patient-Reported Outcomes Measurement Information System (PROMIS) is designed to advance patient-reported outcome (PRO) instruments by utilizing question banks for major health domains. Purpose: To compare the responsiveness and construct validity of the PROMIS physical function computer adaptive test (PF CAT) with current PRO instruments for patients before and up to 2 years after anterior cruciate ligament (ACL) reconstruction. Study Design: Cohort study (diagnosis); Level of evidence, 2. Methods: Initially, 157 patients completed the PROMIS PF CAT, Short Form–36 Health Survey (SF-36 physical function [PF] and general health [GH]), Marx Activity Rating Scale (MARS), Knee injury and Osteoarthritis Outcome Score (KOOS activities of daily living [ADL], sport, and quality of life [QOL]), and EuroQol–5 dimensions questionnaire (EQ-5D) at 6 weeks, 6 months, and 2 years after ACL reconstruction. Correlations between instruments, ceiling and floor effects, effect sizes (Cohen d), and standardized response means to describe responsiveness were evaluated. Subgroup analyses compared participants with and without additional arthroscopic procedures using linear mixed models. Results: At baseline, 6 weeks, and 6 months, the PROMIS PF CAT showed excellent or excellent-good correlations with the SF-36 PF (r = 0.75-0.80, P < .01), KOOS-ADL (r = 0.63-0.70, P < .01), and KOOS-sport (r = 0.32-0.69, P < .01); excellent-good correlation with the EQ-5D (r = 0.60-0.71, P < .01); and good correlation with the KOOS-QOL (r = 0.52-0.58, P < .01). As expected, there were poor correlations with the MARS (r = 0.00-0.24, P < .01) and SF-36 GH (r = 0.16-0.34, P < .01 ). At 2 years, the PROMIS PF CAT showed good to excellent correlations with all PRO instruments (r = 0.42-0.72, P < .01), including the MARS (r = 0.42, P < .01), indicating frequent return to preinjury function. The PROMIS PF CAT had the fewest ceiling or floor effects of all instruments tested, and patients answered, on average, 4 questions. There was no significant difference in baseline physical function scores between subgroups; at follow-up, all groups showed improvements in scores that were not statistically different. Conclusion: The PROMIS PF CAT is a valid tool to assess outcomes after ACL reconstruction up to 2 years after surgery, demonstrating the highest responsiveness to change with the fewest ceiling and floor effects and a low time burden among all instruments tested. The PROMIS PF CAT is a beneficial alternative for assessing physical function in adults before and after ACL reconstruction. PMID:29854864

Translating exercise interventions to an in-home setting for seniors: preliminary impact on physical activity and function.

PubMed

Dondzila, Christopher J; Swartz, Ann M; Keenan, Kevin G; Harley, Amy E; Azen, Razia; Strath, Scott J

2016-12-01

The purpose of this study is to investigate whether an in-home, individually tailored intervention is efficacious in promoting increases in physical activity (PA) and improvements in physical functioning (PF) in low-active older adults. Participants were randomized to two groups for the 8-week intervention. The enhanced physical activity (EPA) group received individualized exercise programming, including personalized step goals and a resistance band training program, and the standard of care (SoC) group received a general activity goal. Pre- and post-intervention PF measures included choice step reaction time, knee extension/flexion strength, hand grip strength, and 8 ft up and go test completion time. Thirty-nine subjects completed this study (74.6 ± 6.4 years). Significant increases in steps/day were observed for both the EPA and SoC groups, although the improvements in the EPA group were significantly higher when including only those who adhered to weekly step goals. Both groups experienced significant PF improvements, albeit greater in the EPA group for the 8 ft up and go test and knee extension strength. A low cost, in-home intervention elicited improvements in both PA and PF. Future research is warranted to expand upon the size and scope of this study, exploring dose thresholds (and time frames) for PA to improve PF and strategies to further bolster adherence rates to maximize intervention benefits.

Correlation of Resistance to Proflavine and Penicillin in Escherichia coli

PubMed Central

McKellar, Robin C.; McKenzie, Colin N.; Kushner, Donn J.

1976-01-01

A number of proflavine (PF)-resistant mutants of Escherichia coli B were also resistant to penicillin and cephalothin. Mutants resistant to 1.0 mM PF were 10 times more penicillin resistant than were the PF-susceptible, wild-type cells. Single-step mutants selected for resistance to either PF or penicillin were also resistant to the other drug. None of the resistant mutants tested possessed β-lactamase activity. These results suggest that resistance to PF and penicillin in E. coli B may be due to permeability changes in the cell envelope. PMID:791110

Large outbreak of Legionnaires' disease and Pontiac fever at a military base.

PubMed

Ambrose, J; Hampton, L M; Fleming-Dutra, K E; Marten, C; McClusky, C; Perry, C; Clemmons, N A; McCormic, Z; Peik, S; Mancuso, J; Brown, E; Kozak, N; Travis, T; Lucas, C; Fields, B; Hicks, L; Cersovsky, S B

2014-11-01

We investigated a mixed outbreak of Legionnaires' disease (LD) and Pontiac fever (PF) at a military base to identify the outbreak's environmental source as well as known legionellosis risk factors. Base workers with possible legionellosis were interviewed and, if consenting, underwent testing for legionellosis. A retrospective cohort study collected information on occupants of the buildings closest to the outbreak source. We identified 29 confirmed and probable LD and 38 PF cases. All cases were exposed to airborne pathogens from a cooling tower. Occupants of the building closest to the cooling tower were 6·9 [95% confidence interval (CI) 2·2-22·0] and 5·5 (95% CI 2·1-14·5) times more likely to develop LD and PF, respectively, than occupants of the next closest building. Thorough preventive measures and aggressive responses to outbreaks, including searching for PF cases in mixed legionellosis outbreaks, are essential for legionellosis control.

Investigation of the biological properties of Cinnulin PF in the context of diabetes: mechanistic insights by genome-wide mRNA-Seq analysis.

PubMed

Rafehi, Haloom; Ververis, Katherine; Balcerczyk, Aneta; Ziemann, Mark; Ooi, Jenny; Hu, Sean; Kwa, Faith A A; Loveridge, Shanon J; Georgiadis, George T; El-Osta, Assam; Karagiannis, Tom C

2012-01-01

The accumulating evidence of the beneficial effects of cinnamon (Cinnamomum burmanni) in type-2 diabetes, a chronic age-associated disease, has prompted the commercialisation of various supplemental forms of the spice. One such supplement, Cinnulin PF(®), represents the water soluble fraction containing relatively high levels of the double-linked procyanidin type-A polymers of flavanoids. The overall aim of this study was to utilize genome-wide mRNA-Seq analysis to characterise the changes in gene expression caused by Cinnulin PF in immortalised human keratinocytes and microvascular endothelial cells, which are relevant with respect to diabetic complications. In summary, our findings provide insights into the mechanisms of action of Cinnulin PF in diabetes and diabetic complications. More generally, we identify relevant candidate genes which could provide the basis for further investigation.

Simulation of human plasma concentration-time profiles of the partial glucokinase activator PF-04937319 and its disproportionate N-demethylated metabolite using humanized chimeric mice and semi-physiological pharmacokinetic modeling.

PubMed

Kamimura, Hidetaka; Ito, Satoshi; Chijiwa, Hiroyuki; Okuzono, Takeshi; Ishiguro, Tomohiro; Yamamoto, Yosuke; Nishinoaki, Sho; Ninomiya, Shin-Ichi; Mitsui, Marina; Kalgutkar, Amit S; Yamazaki, Hiroshi; Suemizu, Hiroshi

2017-05-01

1. The partial glucokinase activator N,N-dimethyl-5-((2-methyl-6-((5-methylpyrazin-2-yl)carbamoyl)benzofuran-4-yl)oxy)pyrimidine-2-carboxamide (PF-04937319) is biotransformed in humans to N-methyl-5-((2-methyl-6-((5-methylpyrazin-2-yl)carbamoyl)benzofuran-4-yl)oxy)pyrimidine-2-carboxamide (M1), accounting for ∼65% of total exposure at steady state. 2. As the disproportionately abundant nature of M1 could not be reliably predicted from in vitro metabolism studies, we evaluated a chimeric mouse model with humanized liver on TK-NOG background for its ability to retrospectively predict human disposition of PF-04937319. Since livers of chimeric mice were enlarged by hyperplasia and contained remnant mouse hepatocytes, hepatic intrinsic clearances normalized for liver weight, metabolite formation and liver to plasma concentration ratios were plotted against the replacement index by human hepatocytes and extrapolated to those in the virtual chimeric mouse with 100% humanized liver. 3. Semi-physiological pharmacokinetic analyses using the above parameters revealed that simulated concentration curves of PF-04937319 and M1 were approximately superimposed with the observed clinical data in humans. 4. Finally, qualitative profiling of circulating metabolites in humanized chimeric mice dosed with PF-04937319 or M1 also revealed the presence of a carbinolamide metabolite, identified in the clinical study as a human-specific metabolite. The case study demonstrates that humanized chimeric mice may be potentially useful in preclinical discovery towards studying disproportionate or human-specific metabolism of drug candidates.

The Exported Chaperone PfHsp70x Is Dispensable for the Plasmodium falciparum Intraerythrocytic Life Cycle.

PubMed

Cobb, David W; Florentin, Anat; Fierro, Manuel A; Krakowiak, Michelle; Moore, Julie M; Muralidharan, Vasant

2017-01-01

Export of parasite proteins into the host erythrocyte is essential for survival of Plasmodium falciparum during its asexual life cycle. While several studies described key factors within the parasite that are involved in protein export, the mechanisms employed to traffic exported proteins within the host cell are currently unknown. Members of the Hsp70 family of chaperones, together with their Hsp40 cochaperones, facilitate protein trafficking in other organisms, and are thus likely used by P. falciparum in the trafficking of its exported proteins. A large group of Hsp40 proteins is encoded by the parasite and exported to the host cell, but only one Hsp70, P. falciparum Hsp70x (PfHsp70x), is exported with them. PfHsp70x is absent in most Plasmodium species and is found only in P. falciparum and closely related species that infect apes. Herein, we have utilized clustered regularly interspaced short palindromic repeat (CRISPR)/Cas9 genome editing in P. falciparum to investigate the essentiality of PfHsp70x. We show that parasitic growth was unaffected by knockdown of PfHsp70x using both the dihydrofolate reductase (DHFR)-based destabilization domain and the glmS ribozyme system. Similarly, a complete gene knockout of PfHsp70x did not affect the ability of P. falciparum to proceed through its intraerythrocytic life cycle. The effect of PfHsp70x knockdown/knockout on the export of proteins to the host red blood cell (RBC), including the critical virulence factor P. falciparum erythrocyte membrane protein 1 (PfEMP1), was tested, and we found that this process was unaffected. These data show that although PfHsp70x is the sole exported Hsp70, it is not essential for the asexual development of P. falciparum . IMPORTANCE Half of the world's population lives at risk for malaria. The intraerythrocytic life cycle of Plasmodium spp. is responsible for clinical manifestations of malaria; therefore, knowledge of the parasite's ability to survive within the erythrocyte is needed to combat the deadliest agent of malaria, P. falciparum . An outstanding question in the field is how P. falciparum undertakes the essential process of trafficking its proteins within the host cell. In most organisms, chaperones such as Hsp70 are employed in protein trafficking. Of the Plasmodium species causing human disease, the chaperone PfHsp70x is unique to P. falciparum , and it is the only parasite protein of its kind exported to the host (S. Külzer et al., Cell Microbiol 14:1784-1795, 2012). This has placed PfHsp70x as an ideal target to inhibit protein trafficking and kill the parasite. However, we show that PfHsp70x is not required for export of parasite effectors and it is not essential for parasite survival inside the RBC.

Comparative analysis of virulence traits between a Legionella feeleii strain implicated in Pontiac fever and a strain that caused Legionnaires' disease.

PubMed

Wang, Changle; Saito, Mitsumasa; Tanaka, Tamami; Amako, Kazunobu; Yoshida, Shin-ichi

2015-12-01

Legionella strains of the same species and serogroup are known to cause Legionnaires' disease (a potentially fatal atypical pneumonia) or Pontiac fever (a mild, flu-like disease), but the bacterial factors that define these dramatic differences in pathology have not been elucidated. To gain a better understanding of these factors, we compared the characteristics of Legionella feeleii strains that were isolated from either a sample of freshwater implicated in an outbreak of Pontiac fever (ATCC 35072, serogroup 1, LfPF), or a patient with Legionnaires' disease (ATCC 38549, serogroup 2, LfLD). Growth of LfPF and LfLD in BYE broth was slower than the positive control, Legionella pneumophila strain JR32. However, LfLD grew faster than LfPF at 42 °C. After in vitro infection to J774 murine or U937 human macrophage cell lines and A549 human lung epithelial cell line, LfLD showed a higher cell infection rate, stronger internalization by host cells, and greater cytotoxicity than that of LfPF. Large amounts of IL-6 and IL-8 were secreted by human host cells after infection with LfLD, but not with LfPF. LfLD possessed mono-polar flagellum while LfPF was unflagellated. When LfLD was cultured at 25, 30 and 37 °C, the bacteria had higher motility rate at lower temperatures. Based on our results, this is the first study that showed distinct characteristics between LfPF and LfLD, which may give important leads in elucidating differences in their virulence. Copyright © 2015 Elsevier Ltd. All rights reserved.

The sanitation situation: a case study.

PubMed

Ali, S

1993-10-15

In India, interviews with and observations of members of 100 households with a latrine were done in the towns of Satna and Khandwa, in Madhya Pradesh State, to examine the sanitation situation, to evaluate the maintenance and performance of the 2 pit pour-flush water seal (PF) latrines of poor households, and to recommend actions to improve the sanitation situation. The upper caste Hindus and Muslims tended to use the PF latrines, while the low caste Hindus tended not to use them. Few dry latrines existed in Satna. More than 75% of the households used the PF latrines, especially in Khandwa. The latrines generally were in disrepair, because more families did not receive either instruction or back-up latrine maintenance. Other apparent reasons for poor maintenance were limited water, illiteracy, limited knowledge of how the PF latrine works, poor construction, excreta adhering to the squatting pan, rain entering the leach pits through the squatting pan causing overflow of the pits contents, clogged outlets and Y-junctions, difficulty in emptying the pits, and collapsed brick drains. Children did not use the latrines in more than 50% of households were the latrines were used. Uncomfortable seats were the reason the children chose to defecate in the open. These findings led the author to recommend that the government adopt laws addressing sanitation in low-cost housing settlements, slums, and other areas. A PF latrine must be constructed for each new building. Dry or bucket latrines must be connected to sewers, if available. Leach pits must be constructed for converting latrines into PF latrines. There should be a ban on new dry or bucket latrines. The government should provide the local authorities the power to enforce these regulations. PF latrines should be free for the poor.

Development and Validation of a Portable and Inexpensive Tool to Measure the Drop Vertical Jump Using the Microsoft Kinect V2.

PubMed

Gray, Aaron D; Willis, Brad W; Skubic, Marjorie; Huo, Zhiyu; Razu, Swithin; Sherman, Seth L; Guess, Trent M; Jahandar, Amirhossein; Gulbrandsen, Trevor R; Miller, Scott; Siesener, Nathan J

Noncontact anterior cruciate ligament (ACL) injury in adolescent female athletes is an increasing problem. The knee-ankle separation ratio (KASR), calculated at initial contact (IC) and peak flexion (PF) during the drop vertical jump (DVJ), is a measure of dynamic knee valgus. The Microsoft Kinect V2 has shown promise as a reliable and valid marker-less motion capture device. The Kinect V2 will demonstrate good to excellent correlation between KASR results at IC and PF during the DVJ, as compared with a "gold standard" Vicon motion analysis system. Descriptive laboratory study. Level 2. Thirty-eight healthy volunteer subjects (20 male, 18 female) performed 5 DVJ trials, simultaneously measured by a Vicon MX-T40S system, 2 AMTI force platforms, and a Kinect V2 with customized software. A total of 190 jumps were completed. The KASR was calculated at IC and PF during the DVJ. The intraclass correlation coefficient (ICC) assessed the degree of KASR agreement between the Kinect and Vicon systems. The ICCs of the Kinect V2 and Vicon KASR at IC and PF were 0.84 and 0.95, respectively, showing excellent agreement between the 2 measures. The Kinect V2 successfully identified the KASR at PF and IC frames in 182 of 190 trials, demonstrating 95.8% reliability. The Kinect V2 demonstrated excellent ICC of the KASR at IC and PF during the DVJ when compared with the Vicon system. A customized Kinect V2 software program demonstrated good reliability in identifying the KASR at IC and PF during the DVJ. Reliable, valid, inexpensive, and efficient screening tools may improve the accessibility of motion analysis assessment of adolescent female athletes.

Biomechanical analysis of suture locations of the distal plantar fascia in partial foot.

PubMed

Guo, Jun-Chao; Wang, Li-Zhen; Mo, Zhong-Jun; Chen, Wei; Fan, Yu-Bo

2015-12-01

The aim of this study was to evaluate the rationality of the suture locations of distal plantar fascia (DPF) after foot amputation to avoid the risk factors of re-amputation or plantar fasciitis. The tensile strain of plantar fascia (PF) in the different regions was measured by uni-axial tensile experiment. A three-dimensional (3D) finite element model was also developed to simulate tensile behaviour of PF in weight bearing conditions. The model includes 12 bones, ligaments, PF, cartilage and soft tissues. Four suture location models for the DPF were considered: the fourth and fifth DPF were sutured on the third metatarsal, the cuboid, and both the third metatarsal and the cuboid, and one un-sutured model. The peak tensile strain of the first, second and third PF was 0.134, 0.128 and 0.138 based on the mechanical test, respectively. The fourth and fifth DPF sutured at the cuboid and the third metatarsal could offer more favourable outcomes. The peak strain of 4.859 × 10(-2), 2.347 × 10(-2) and 1.364 × 10(-2) in the first, second and third PF showed the least outcomes in stance phase. Also, peak strain and stress of the residual PF reduced to 4.859 × 10(-2) and 1.834 MPa, respectively. The stress region was redistributed on the mid-shaft of the first and third PF and the peak stress of medial cuneiform bone evidently decreased. The fourth and fifth DPF suture at the third metatarsal and cuboid was appropriate for the partial foot. The findings are expected to suggest optimal surgical plan of the DPF suture and guide further therapeutic planning of partial foot patients.

Disinhibition of perifornical hypothalamic neurones activates noradrenergic neurones and blocks pontine carbachol-induced REM sleep-like episodes in rats

PubMed Central

Lu, Jackie W; Fenik, Victor B; Branconi, Jennifer L; Mann, Graziella L; Rukhadze, Irma; Kubin, Leszek

2007-01-01

Studies in behaving animals suggest that neurones located in the perifornical (PF) region of the posterior hypothalamus promote wakefulness and suppress sleep. Among such cells are those that synthesize the excitatory peptides, orexins (ORX). Lack of ORX, or their receptors, is associated with narcolepsy/cataplexy, a disorder characterized by an increased pressure for rapid eye movement (REM) sleep. We used anaesthetized rats in which pontine microinjections of a cholinergic agonist, carbachol, can repeatedly elicit REM sleep-like episodes to test whether activation of PF cells induced by antagonism of endogenous, GABAA receptor-mediated, inhibition suppresses the ability of the brainstem to generate REM sleep-like state. Microinjections of the GABAA receptor antagonist, bicuculline (20 nl, 1 mm), into the PF region elicited cortical and hippocampal activation, increased the respiratory rate and hypoglossal nerve activity, induced c-fos expression in ORX and other PF neurones, and increased c-fos expression in pontine A7 and other noradrenergic neurones. The ability of pontine carbachol to elicit any cortical, hippocampal or brainstem component of the REM sleep-like response was abolished during the period of bicuculline-induced activation. The activating and REM sleep-suppressing effect of PF bicuculline was not attenuated by systemic administration of the ORX type 1 receptor antagonist, SB334867. Thus, activation of PF neurones that are endogenously inhibited by GABAA receptors is sufficient to turn off the brainstem REM sleep-generating network; the effect is, at least in part, due to activation of pontine noradrenergic neurones, but is not mediated by ORX type 1 receptors. A malfunction of the pathway that originates in GABAA receptor-expressing PF neurones may cause narcolepsy/cataplexy. PMID:17495048

The effects of slight pressure oscillations in the far infrasound frequency range on the pars flaccida in gerbil and rabbit ears.

PubMed

Didyk, L A; Bogdanov, V B; Lysenko, V A; Didyk, N P; Gorgo, Yu P; Dirckx, J J J

2007-01-01

This study was designed to clarify whether the pars flaccida (PF) as a flexible part of the tympanic membrane is capable of reacting to pressure oscillations (PO) with amplitudes and frequencies typical for natural atmospheric pressure fluctuations in the far infrasound frequency range (APF). If so, the PF mechanical reactions to APF might be involved in the overall physiologic regulation processes, which make organisms susceptible to APF. The displacements of the PF in response to PO were measured in vitro in ears of gerbils and rabbits by means of laser Doppler vibrometry. The index of the PF reactivity (R(a)) was determined as the ratio of the amplitude of the PF oscillations (PFO) to the amplitude of the PO. All kinds of PO applied caused PFO. The amplitude of the PFO increased when the amplitude of the PO was increased. In gerbils, a decrease in R(a) with the increase in amplitude of the PO was observed. In the range of PO lowest amplitudes (4-20 Pa) R(a) proved to be 1.4 times higher than in the range of highest amplitudes (90-105 Pa). Considering that the natural APF are usually within the range of +/-20 Pa, this fact points to an important contribution of the PF to the pressure dynamics in the middle ear (ME) of gerbils. In rabbit ears, R(a) was lower and recovery from plastic deformation was slower than in gerbils. Our findings are in line with the suggestion that the PF might play an important role in respect of adaptation to natural APF.

Protein-Induced Fluorescence Enhancement Based Detection of Plasmodium falciparum Glutamate Dehydrogenase Using Carbon Dot Coupled Specific Aptamer.

PubMed

Singh, Naveen Kumar; Chakma, Babina; Jain, Priyamvada; Goswami, Pranab

2018-06-11

A novel 90-mer long ssDNA aptamer (NG3) covering a 40-mer random region targeting Plasmodium falciparum glutamate dehydrogenase ( PfGDH) developed through systematic evolution of ligands by exponential enrichment (SELEX) technique. The binding affinity of the aptamer to PfGDH discerned by circular dichroism (CD) was 0.5 ± 0.04 μM. The specificity of the aptamer toward the target was confirmed by gel electrophoresis and CD studies. The presence of two quadruplex forming regions, two big and four small stem loop structures with a δG of -7.99 kcal mol -1 for NG3 were deduced by computational studies. The spherical carbon dots (Cdots) of size 2-4 nm, synthesized by pyrolysis method using l-glutamate as a substrate were covalently linked to the amine modified aptamer. The Cdot with a band gap of 2.8 eV and a quantum yield of 34% produced fluorescence at ∼ λ 410 nm when excited at λ 320nm . The quantum yield of Cdot-aptamer assembly was increased up to 40% in the presence of the PfGDH in solution. A linear relationship with a dynamic range of 0.5 nM to 25 nM (R 2 = 0.98) and a limit of detection (LOD) of 0.48 nM was observed between the fluorescence intensity of the Cdots-aptamer conjugate and the concentration of PfGDH. The method could detect PfGDH with an LOD of 2.85 nM in diluted serum sample. This novel simple, sensitive and specific protein induced fluorescence enhancement based detection of PfGDH has a great potential to develop as a method for malaria detection.

Survival of porcine reproductive and respiratory syndrome virus in houseflies

PubMed Central

Otake, Satoshi; Dee, Scott A.; Moon, Roger D.; Rossow, Kurt D.; Trincado, Carlos; Farnham, MacDonald; Pijoan, Carlos

2003-01-01

The objectives of the study were to determine the duration of porcine reproductive and respiratory syndrome virus (PRRSV) survival in houseflies (Musca domestica Linnaeus) following feeding on an infected pig, and to determine whether the virus was present on the exterior surface or within the internal viscera of the fly. A total of 210 laboratory-colonized houseflies were allowed to feed to repletion on a pig, experimentally infected with PRRSV on day 7 postinoculation, and then maintained alive under laboratory conditions (27°C). Two subsets (A and B) of 30 flies were collected at each of the following sampling points; 0, 6, and 12 hours post feeding (pf). Subset A contained an extra group of 30 flies collected at 24 hours pf due to the availability of extra flies. Flies in subset A were processed as whole fly homogenates, while the exterior surface washes and digestive organs were collected from flies in subset B. Whole fly homogenates, collected at 0, 6, and 12 hours pf, were positive by both polymerase chain reaction (PCR) and swine bioassay. Digestive organs, collected at 0 and 12 hours pf, were positive by PCR and swine bioassay. The PRRSV RNA was detected by PCR from the exterior surface wash of subset B flies collected at 0, 6, and 12 hours pf; however, only the subset collected at 0 hour pf was swine bioassay-positive. This study indicates that infectious PRRSV can survive within the intestinal tract of houseflies for up to 12 hours following feeding on an infected pig, but only for a short period on the exterior surface of the flies. PMID:12889726

Comparative immunocytochemical study of FMRFamide neuronal system in the brain of Danio rerio and Acipenser ruthenus during development.

PubMed

Pinelli, C; D'Aniello, B; Sordino, P; Meyer, D L; Fiorentino, M; Rastogi, R K

2000-02-07

The distribution of FMRFamide-like immunoreactive (ir) neurons and fibers was investigated in the central nervous system of developing zebrafish and juvenile sturgeon (sterlet). Adult zebrafish was also studied. In zebrafish embryos FMRFamide-ir elements first appeared 30 h post-fertilization (PF). Ir somata were located in the olfactory placode and in the ventral diencephalon. FMRFamide-ir fibers originating from diencephalic neurons were found in the ventral telencephalon and in ventral portions of the brainstem. At 48 h PF, the ir perikarya in the olfactory placode displayed increased immunoreactivity and stained fibers emerged from the somata. At 60 h PF, bilaterally, clusters of FMRFamide-ir neurons were found along the rostro-caudal axis of the brain, from the olfactory placode to rostral regions of the ventro-lateral telencephalon. At 60 h PF, numerous ir fibers appeared in the dorsal telencephalon, optic lobes, optic nerves, and retina. Except for ir fibers in the hypophysis at the age of 72 h PF, and a few ir cells in the nucleus olfacto-retinalis (NOR) at the age of 2 months PF, no major re-organization was noted in subsequent ontogenetic stages. The number of stained NOR neurons increased markedly in sexually mature zebrafish. In adult zebrafish, other ir neurons were located in the dorsal zones of the periventricular hypothalamus and in components of the nervus terminalis. We are inclined to believe that neurons expressing FMRFamide originate in the olfactory placode and in the ventricular ependyma in the hypothalamus. On the same grounds, a dual origin of FMRFamide-ir neurons is inferred in the sturgeon, an ancestral bony fish: prior to the observation of ir cells in the nasal area and in the telencephalon stained neurons were noted in circumventricular hypothalamic regions.

Poly(I:C) adjuvant strongly enhances parasite-inhibitory antibodies and Th1 response against Plasmodium falciparum merozoite surface protein-1 (42-kDa fragment) in BALB/c mice.

PubMed

Mehrizi, Akram Abouie; Rezvani, Niloufar; Zakeri, Sedigheh; Gholami, Atefeh; Babaeekhou, Laleh

2018-04-01

Malaria vaccine development has been confronted with various challenges such as poor immunogenicity of malaria vaccine candidate antigens, which is considered as the main challenge. However, this problem can be managed using appropriate formulations of antigens and adjuvants. Poly(I:C) is a potent Th1 inducer and a human compatible adjuvant capable of stimulating both B- and T-cell immunity. Plasmodium falciparum merozoite surface protein 1 42 (PfMSP-1 42 ) is a promising vaccine candidate for blood stage of malaria that has faced several difficulties in clinical trials, mainly due to improper adjuvants. Therefore, in the current study, poly(I:C), as a potent Th1 inducer adjuvant, was evaluated to improve the immunogenicity of recombinant PfMSP-1 42 , when compared to CFA/IFA, as reference adjuvant. Poly(I:C) produced high level and titers of anti-PfMSP-1 42 IgG antibodies in which was comparable to CFA/IFA adjuvant. In addition, PfMSP-1 42 formulated with poly(I:C) elicited a higher ratio of IFN-γ/IL-4 (23.9) and IgG2a/IgG1 (3.77) with more persistent, higher avidity, and titer of IgG2a relative to CFA/IFA, indicating a potent Th1 immune response. Poly(I:C) could also help to induce anti-PfMSP-1 42 antibodies with higher growth-inhibitory activity than CFA/IFA. Altogether, the results of the current study demonstrated that poly(I:C) is a potent adjuvant that can be appropriate for being used in PfMSP-1 42 -based vaccine formulations.

Th1 immune response to Plasmodium falciparum recombinant thrombospondin-related adhesive protein (TRAP) antigen is enhanced by TLR3-specific adjuvant, poly(I:C) in BALB/c mice.

PubMed

Mehrizi, A A; Ameri Torzani, M; Zakeri, S; Jafary Zadeh, A; Babaeekhou, L

2018-07-01

Sporozoite-based malaria vaccines have provided a gold standard for malaria vaccine development, and thrombospondin-related adhesive protein (TRAP) serves as the main vaccine candidate antigen on sporozoites. As recombinant malaria vaccine candidate antigens are poorly immunogenic, additional appropriate immunostimulants, such as an efficient adjuvant, are highly essential to modulate Th1-cell predominance and also to induce a protective and long-lived immune response. In this study, polyinosinic:polycytidylic acid [poly(I:C)], the ligand of TLR3, was considered as the potential adjuvant for vaccines targeting stronger Th1-based immune responses. For this purpose, BALB/c mice were immunized with rPfTRAP delivered in putative poly(I:C) adjuvant, and humoural and cellular immune responses were determined in different immunized mouse groups. Delivery of rPfTRAP with poly(I:C) induced high levels and titres of persisted and also high-avidity anti-rPfTRAP IgG antibodies comparable to complete Freund's adjuvant (CFA)/incomplete Freund's adjuvant (IFA) adjuvant after the second boost. In addition, rPfTRAP formulated with poly(I:C) elicited a higher ratio of IFN-γ/IL-5, IgG2a/IgG1, and IgG2b/IgG1 than with CFA/IFA, indicating that poly(I:C) supports the induction of a stronger Th1-based immune response. This is a first time study which reveals the potential of rPfTRAP delivery in poly(I:C) to increase the level, avidity and durability of both anti-PfTRAP cytophilic antibodies and Th1 cytokines. © 2018 John Wiley & Sons Ltd.

Oxidation Sensitive Nociception Involved in Endometriosis Associated Pain

PubMed Central

Ray, Kristeena; Fahrmann, Johannes; Mitchell, Brenda; Paul, Dennis; King, Holly; Crain, Courtney; Cook, Carla; Golovko, Mikhail; Brose, Stephen; Golovko, Svetlana; Santanam, Nalini

2015-01-01

Endometriosis is a disease characterized by the growth of endometrial tissue outside the uterus and is associated with chronic pelvic pain. Peritoneal fluid (PF) of women with endometriosis is a dynamic milieu, rich in inflammatory markers and pain-inducing prostaglandins PGE2/PGF2α and lipid peroxides, and the endometriotic tissue is innervated with nociceptors. Our clinical study showed the abundance of oxidatively-modified lipoproteins in the PF of women with endometriosis and the ability of antioxidant supplementation to alleviate endometriosis-associated pain. We hypothesized that oxidatively-modified lipoproteins present in the PF are the major source of nociceptive molecules that play a key role in endometriosis-associated pain. In this study, PF obtained from women with endometriosis or control women were used for (i) the detection of lipoprotein derived oxidation-sensitive pain molecules, (ii) the ability of such molecules to induce nociception, and (iii) the ability of antioxidants to suppress this nociception. LC-MS/MS showed the generation of eicosanoids by oxidized-lipoproteins similar to that seen in the PF. The oxidatively-modified lipoproteins induced hypothermia (intra-cerebroventricular) in CD-1 mice and nociception in the Hargreaves paw-withdrawal latency assay in Sprague-Dawley rats. Antioxidants, vitamin-E and N-acetylcysteine and the NSAID, indomethacin suppressed the pain inducing ability of oxidatively-modified lipoproteins. Treatment of human endometrial cells with oxidatively-modified lipoproteins or PF from women with endometriosis showed up-regulation of similar genes belonging to the opioid and inflammatory pathways. Our finding that oxidatively-modified lipoproteins can induce nociception has a broader impact not only in the treatment of endometriosis-associated pain but also in other diseases associated with chronic pain. PMID:25599233

Psychometric functions for pure-tone frequency discrimination.

PubMed

Dai, Huanping; Micheyl, Christophe

2011-07-01

The form of the psychometric function (PF) for auditory frequency discrimination is of theoretical interest and practical importance. In this study, PFs for pure-tone frequency discrimination were measured for several standard frequencies (200-8000 Hz) and levels [35-85 dB sound pressure level (SPL)] in normal-hearing listeners. The proportion-correct data were fitted using a cumulative-Gaussian function of the sensitivity index, d', computed as a power transformation of the frequency difference, Δf. The exponent of the power function corresponded to the slope of the PF on log(d')-log(Δf) coordinates. The influence of attentional lapses on PF-slope estimates was investigated. When attentional lapses were not taken into account, the estimated PF slopes on log(d')-log(Δf) coordinates were found to be significantly lower than 1, suggesting a nonlinear relationship between d' and Δf. However, when lapse rate was included as a free parameter in the fits, PF slopes were found not to differ significantly from 1, consistent with a linear relationship between d' and Δf. This was the case across the wide ranges of frequencies and levels tested in this study. Therefore, spectral and temporal models of frequency discrimination must account for a linear relationship between d' and Δf across a wide range of frequencies and levels. © 2011 Acoustical Society of America

Total Glucosides of Danggui Buxue Tang Attenuate BLM-Induced Pulmonary Fibrosis via Regulating Oxidative Stress by Inhibiting NOX4

PubMed Central

Zhao, Ping; Zhou, Wen-Cheng; Li, De-Lin; Mo, Xiao-Ting; Xu, Liang; Li, Liu-Cheng; Cui, Wen-Hui; Gao, Jian

2015-01-01

Pulmonary fibrosis (PF) is a serious chronic lung disease with unknown pathogenesis. Researches have confirmed that oxidative stress which is regulated by NADPH oxidase-4 (NOX4), a main source of reactive oxygen species (ROS), is an important molecular mechanism underlying PF. Previous studies showed that total glucosides of Danggui Buxue Tang (DBTG), an extract from a classical traditional Chinese herbal formula, Danggui Buxue Tang (DBT), attenuated bleomycin-induced PF in rats. However, the mechanisms of DBTG are still not clear. We hypothesize that DBTG attenuates PF through regulating the level of oxidative stress by inhibiting NOX4. And we found that fibrosis indexes hydroxyproline (HYP) and type I collagen (Col-I) were lower in DBTG groups compared with the model group. In addition, the expression of transforming growth factor-β1 (TGF-β1) and expression of alpha smooth muscle actin (α-SMA) were also much more decreased than the model group. For oxidative stress indicators, DBTG blunted the decrease of superoxide dismutase (SOD) activity, total antioxidant capacity (T-AOC), and the increase in malondialdehyde (MDA), 8-iso-prostaglandin in lung homogenates. Treatment with DBTG restrained the expression of NOX4 compared to the model group. Present study confirms that DBTG inhibits BLM-induced PF by modulating the level of oxidative stress via suppressing NOX4. PMID:26347805

Performance of Rapid Diagnostic Tests for Imported Malaria in Clinical Practice: Results of a National Multicenter Study

PubMed Central

Houzé, Sandrine; Boutron, Isabelle; Marmorat, Anne; Dalichampt, Marie; Choquet, Christophe; Poilane, Isabelle; Godineau, Nadine; Le Guern, Anne-Sophie; Thellier, Marc; Broutier, Hélène; Fenneteau, Odile; Millet, Pascal; Dulucq, Stéphanie; Hubert, Véronique; Houzé, Pascal; Tubach, Florence; Le Bras, Jacques; Matheron, Sophie

2013-01-01

We compared the performance of four rapid diagnostic tests (RDTs) for imported malaria, and particularly Plasmodium falciparum infection, using thick and thin blood smears as the gold standard. All the tests are designed to detect at least one protein specific to P. falciparum ( Plasmodium histidine-rich protein 2 (PfHRP2) or Plasmodium LDH (PfLDH)) and one pan-Plasmodium protein (aldolase or Plasmodium LDH (pLDH)). 1,311 consecutive patients presenting to 9 French hospitals with suspected malaria were included in this prospective study between April 2006 and September 2008. Blood smears revealed malaria parasites in 374 cases (29%). For the diagnosis of P. falciparum infection, the three tests detecting PfHRP2 showed high and similar sensitivity (96%), positive predictive value (PPV) (90%) and negative predictive value (NPV) (98%). The PfLDH test showed lower sensitivity (83%) and NPV (80%), despite good PPV (98%). For the diagnosis of non-falciparum species, the PPV and NPV of tests targeting pLDH or aldolase were 94–99% and 52–64%, respectively. PfHRP2-based RDTs are thus an acceptable alternative to routine microscopy for diagnosing P. falciparum malaria. However, as malaria may be misdiagnosed with RDTs, all negative results must be confirmed by the reference diagnostic method when clinical, biological or other factors are highly suggestive of malaria. PMID:24098699

Electronic communication in phosphine substituted bridged dirhenium complexes - clarifying ambiguities raised by the redox non-innocence of the C4H2- and C4-bridges.

PubMed

Li, Yan; Blacque, Olivier; Fox, Thomas; Luber, Sandra; Polit, Walther; Winter, Rainer F; Venkatesan, Koushik; Berke, Heinz

2016-04-07

The mononuclear rhenium carbyne complex trans-[Re(C[triple bond, length as m-dash]CSiMe3)([triple bond, length as m-dash]C-Me)(PMe3)4][PF6] (2) was prepared in 90% yield by heating a mixture of the dinitrogen complex trans-[ReCl(N2)(PMe3)4] (1), TlPF6, and an excess of HC[triple bond, length as m-dash]CSiMe3. 2 could be deprotonated with KOtBu to the vinylidene complex trans-[Re(C[triple bond, length as m-dash]CSiMe3)([double bond, length as m-dash]C[double bond, length as m-dash]CH2)(PMe3)4] (3) in 98% yield. Oxidation of 3 with 1.2 equiv. of [Cp2Fe][PF6] at -78 °C gave the Cβ-C'β coupled dinuclear rhenium biscarbyne complex trans-[(Me3SiC[triple bond, length as m-dash]C)(PMe3)4Re[triple bond, length as m-dash]C-CH2-CH2-C[triple bond, length as m-dash]Re(PMe3)4(C[triple bond, length as m-dash]CSiMe3)][PF6]2 (5) in 92% yield. Deprotonation of 5 with an excess of KOtBu in THF produced the diamagnetic trans-[(Me3SiC[triple bond, length as m-dash]C)(PMe3)4Re[double bond, length as m-dash]C[double bond, length as m-dash]CH-CH[double bond, length as m-dash]C[double bond, length as m-dash]Re(PMe3)4(C[triple bond, length as m-dash]CSiMe3)] complex (E-6(S)) in 87% yield with an E-butadienediylidene bridge. Density functional theory (DFT) calculations of E-6(S) confirmed its singlet ground state. The Z-form of 6 (Z-6(S)) could not be observed, which is in accord with its DFT calculated 17.8 kJ mol(-1) higher energy. Oxidation of E-6 with 2 equiv. of [Cp2Fe][PF6] resulted in the stable diamagnetic dicationic trans-[(Me3SiC[triple bond, length as m-dash]C)(PMe3)4Re[triple bond, length as m-dash]C-CH[double bond, length as m-dash]CH-C[triple bond, length as m-dash]Re(PMe3)4(C[triple bond, length as m-dash]CSiMe3)][PF6]2 complex (E-6[PF6]2) with an ethylenylidene dicarbyne structure of the bridge. The paramagnetic mixed-valence (MV) complex E-6[PF6] was obtained by comproportionation of E-6(S) and E-6[PF6]2 or by oxidation of E-6(S) with 1 equiv. of [Cp2Fe][PF6]. The dicationic trans-[(Me3SiC[triple bond, length as m-dash]C)(PMe3)4Re[triple bond, length as m-dash]C-C[triple bond, length as m-dash]C-C[triple bond, length as m-dash]Re(PMe3)4(C[triple bond, length as m-dash]CSiMe3)][PF6]2 (7[PF6]2) complex, attributed a butynedi(triyl) bridge structure, was obtained by deprotonation of E-6[PF6]2 with KOtBu followed by oxidation with 2 equiv. of [Cp2Fe][PF6]. The neutral complex 7 could be accessed best by reduction of 7[PF6]2 with KH in the presence of 18-crown-6. According to DFT calculations 7 possesses two equilibrating electronic states: diamagnetic 7(S) and triplet 7(F) with ferromagnetically coupled spins. The latter is calculated to be 5.2 kcal mol(-1) lower in energy than 7(S). There is experimental evidence that 7(S) prevails in solution. 7 could not be isolated in the crystalline state and is unstable transforming mainly by H-abstraction to give E-6(S). UV-Vis-NIR spectroscopy for the dinuclear rhenium complexes E-6(S), E-6[PF6] and E-6[PF6]2, as well as EPR spectroscopic and variable-temperature magnetization measurements for the MV complex E-6[PF6] were also conducted. Spectro-electrochemical reduction studies on 7[PF6]2 allowed the characterization of the mono- and direduced forms of 7(+) and 7 by means of IR- and UV-Vis-NIR-spectroscopy and revealed the chemical fate of the higher reduced form.

The Crystal Structure of PF-8, the DNA Polymerase Accessory Subunit from Kaposi's Sarcoma-Associated Herpesvirus

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

Baltz, Jennifer L.; Filman, David J.; Ciustea, Mihai

2009-12-01

Kaposi's sarcoma-associated herpesvirus is an emerging pathogen whose mechanism of replication is poorly understood. PF-8, the presumed processivity factor of Kaposi's sarcoma-associated herpesvirus DNA polymerase, acts in combination with the catalytic subunit, Pol-8, to synthesize viral DNA. We have solved the crystal structure of residues 1 to 304 of PF-8 at a resolution of 2.8 {angstrom}. This structure reveals that each monomer of PF-8 shares a fold common to processivity factors. Like human cytomegalovirus UL44, PF-8 forms a head-to-head dimer in the form of a C clamp, with its concave face containing a number of basic residues that are predictedmore » to be important for DNA binding. However, there are several differences with related proteins, especially in loops that extend from each monomer into the center of the C clamp and in the loops that connect the two subdomains of each protein, which may be important for determining PF-8's mode of binding to DNA and to Pol-8. Using the crystal structures of PF-8, the herpes simplex virus catalytic subunit, and RB69 bacteriophage DNA polymerase in complex with DNA and initial experiments testing the effects of inhibition of PF-8-stimulated DNA synthesis by peptides derived from Pol-8, we suggest a model for how PF-8 might form a ternary complex with Pol-8 and DNA. The structure and the model suggest interesting similarities and differences in how PF-8 functions relative to structurally similar proteins.« less

Stimulation of ovarian stem cells by follicle stimulating hormone and basic fibroblast growth factor during cortical tissue culture.

PubMed

Parte, Seema; Bhartiya, Deepa; Manjramkar, Dhananjay D; Chauhan, Anahita; Joshi, Amita

2013-04-01

Cryopreserved ovarian cortical tissue acts as a source of primordial follicles (PF) which can either be auto-transplanted or cultured in vitro to obtain mature oocytes. This offers a good opportunity to attain biological parenthood to individuals with gonadal insufficiency including cancer survivors. However, role of various intra- and extra-ovarian factors during PF growth initiation still remain poorly understood. Ovarian biology has assumed a different dimension due to emerging data on presence of pluripotent very small embryonic-like stem cells (VSELs) and ovarian germ stem cells (OGSCs) in ovary surface epithelium (OSE) and the concept of postnatal oogenesis. The present study was undertaken to decipher effect of follicle stimulating hormone (FSH) and basic fibroblast growth factor (bFGF) on the growth initiation of PF during organ culture with a focus on ovarian stem cells. Serum-free cultures of marmoset (n=3) and human (young and peri-menopausal) ovarian cortical tissue pieces were established. Cortical tissue pieces stimulated with FSH (0.5 IU/ml) or bFGF (100 ng/ml) were collected on Day 3 for histological and molecular studies. Gene transcripts specific for pluripotency (Oct-4A, Nanog), early germ cells (Oct-4, c-Kit, Vasa) and to reflect PF growth initiation (oocyte-specific Gdf-9 and Lhx8, and granulosa cells specific Amh) were studied by q-RTPCR. A prominent proliferation of OSE (which harbors stem cells) and transition of PF to primary follicles was observed after FSH and bFGF treatment. Ovarian stem cells were found to be released on the culture inserts and retained the potential to spontaneously differentiate into oocyte-like structures in extended cultures. q-RTPCR analysis revealed an increased expression of gene transcripts specific for VSELs, OGSCs and early germ cells suggestive of follicular transition. The present study shows that both FSH and bFGF stimulate stem cells present in OSE and also lead to PF growth initiation. Thus besides being a source of PF, cryopreserved ovarian cortical tissue could also be a source of stem cells which retain the ability to spontaneously differentiate into oocyte-like structures in vitro. Results provide a paradigm shift in the basic understanding of FSH action and also offer a new perspective to the field of oncofertility research.

Pseudomonas protegens Pf-5 causes discoloration and pitting of mushroom caps due to the production of antifungal metabolites.

PubMed

Henkels, Marcella D; Kidarsa, Teresa A; Shaffer, Brenda T; Goebel, Neal C; Burlinson, Peter; Mavrodi, Dmitri V; Bentley, Michael A; Rangel, Lorena I; Davis, Edward W; Thomashow, Linda S; Zabriskie, T Mark; Preston, Gail M; Loper, Joyce E

2014-07-01

Bacteria in the diverse Pseudomonas fluorescens group include rhizosphere inhabitants known for their antifungal metabolite production and biological control of plant disease, such as Pseudomonas protegens Pf-5, and mushroom pathogens, such as Pseudomonas tolaasii. Here, we report that strain Pf-5 causes brown, sunken lesions on peeled caps of the button mushroom (Agaricus bisporus) that resemble brown blotch symptoms caused by P. tolaasii. Strain Pf-5 produces six known antifungal metabolites under the control of the GacS/GacA signal transduction system. A gacA mutant produces none of these metabolites and did not cause lesions on mushroom caps. Mutants deficient in the biosynthesis of the antifungal metabolites 2,4-diacetylphloroglucinol and pyoluteorin caused less-severe symptoms than wild-type Pf-5 on peeled mushroom caps, whereas mutants deficient in the production of lipopeptide orfamide A caused similar symptoms to wild-type Pf-5. Purified pyoluteorin and 2,4-diacetylphloroglucinol mimicked the symptoms caused by Pf-5. Both compounds were isolated from mushroom tissue inoculated with Pf-5, providing direct evidence for their in situ production by the bacterium. Although the lipopeptide tolaasin is responsible for brown blotch of mushroom caused by P. tolaasii, P. protegens Pf-5 caused brown blotch-like symptoms on peeled mushroom caps through a lipopeptide-independent mechanism involving the production of 2,4-diacetylphloroglucinol and pyoluteorin.

Dynamometer-based measure of spasticity confirms limited association between plantarflexor spasticity and walking function in persons with multiple sclerosis

PubMed Central

Kremer, Theodore R.; Van Dillen, Linda R.; Wagner, Joanne M.

2017-01-01

The literature shows inconsistent evidence regarding the association between clinically assessed plantarflexor (PF) spasticity and walking function in ambulatory persons with multiple sclerosis (pwMS). The use of a dynamometer-based spasticity measure (DSM) may help to clarify this association. Our cohort included 42 pwMS (27 female, 15 male; age: 42.9 +/− 10.2 yr) with mild clinical disability (Expanded Disability Status Scale score: 3.6 +/− 1.6). PF spasticity was assessed using a clinical measure, the modified Ashworth Scale (MAS), and an instrumented measure, the DSM. Walking function was assessed by the timed 25-foot walk test (T25FWT), the 6-minute walk test (6MWT), and the 12-item Multiple Sclerosis Walking Scale (MSWS-12). Spearman rho correlations were used to evaluate relationships between spasticity measures, measures of walking speed and endurance, and self-perceived limitations in walking. The correlation was small between PF spasticity and the T25FWT (PF maximum [Max] MAS rho = 0.27, PF Max DSM rho = 0.26), the 6MWT (PF Max MAS rho = −0.20, PF Max DSM rho = −0.21), and the MSWS-12 (PF Max MAS rho = 0.11, PF Max DSM rho = 0.26). Our results are similar to reports in other neurologic clinical populations, wherein spasticity has a limited association with walking dysfunction. PMID:25356797

Neutralization of Plasmodium falciparum merozoites by antibodies against PfRH5

PubMed Central

Douglas, Alexander D.; Williams, Andrew R.; Knuepfer, Ellen; Illingworth, Joseph J.; Furze, Julie M.; Crosnier, Cécile; Choudhary, Prateek; Bustamante, Leyla Y.; Zakutansky, Sara E.; Awuah, Dennis K.; Alanine, Daniel G. W.; Theron, Michel; Worth, Andrew; Shimkets, Richard; Rayner, Julian C.; Holder, Anthony A.; Wright, Gavin J.; Draper, Simon J.

2013-01-01

There is intense interest in induction and characterization of strain-transcending neutralizing antibody against antigenically variable human pathogens. We have recently identified the human malaria parasite Plasmodium falciparum reticulocyte-binding protein homologue 5 (PfRH5) as a target of broadly-neutralizing antibodies, but there is little information regarding the functional mechanism(s) of antibody-mediated neutralization. Here, we report that vaccine-induced polyclonal anti-PfRH5 antibodies inhibit the tight attachment of merozoites to erythrocytes, and are capable of blocking the interaction of PfRH5 with its receptor basigin. Furthermore, by developing anti-PfRH5 monoclonal antibodies (mAbs), we provide evidence that i) the ability to block the PfRH5-basigin interaction in vitro is predictive of functional activity, but absence of blockade does not predict absence of functional activity; ii) neutralizing mAbs bind spatially-related epitopes on the folded protein, involving at least two defined regions of the PfRH5 primary sequence; iii) a brief exposure window of PfRH5 is likely to necessitate rapid binding of antibody to neutralize parasites; and iv) intact bivalent IgG contributes to but is not necessary for parasite neutralization. These data provide important insight into the mechanisms of broadly-neutralizing anti-malaria antibodies and further encourage anti-PfRH5 based malaria prevention efforts. PMID:24293631

Cross-language categorization of French and German vowels by naive American listeners.

PubMed

Strange, Winifred; Levy, Erika S; Law, Franzo F

2009-09-01

American English (AE) speakers' perceptual assimilation of 14 North German (NG) and 9 Parisian French (PF) vowels was examined in two studies using citation-form disyllables (study 1) and sentences with vowels surrounded by labial and alveolar consonants in multisyllabic nonsense words (study 2). Listeners categorized multiple tokens of each NG and PF vowel as most similar to selected AE vowels and rated their category "goodness" on a nine-point Likert scale. Front, rounded vowels were assimilated primarily to back AE vowels, despite their acoustic similarity to front AE vowels. In study 1, they were considered poorer exemplars of AE vowels than were NG and PF back, rounded vowels; in study 2, front and back, rounded vowels were perceived as similar to each other. Assimilation of some front, unrounded and back, rounded NG and PF vowels varied with language, speaking style, and consonantal context. Differences in perceived similarity often could not be predicted from context-specific cross-language spectral similarities. Results suggest that listeners can access context-specific, phonetic details when listening to citation-form materials, but assimilate non-native vowels on the basis of context-independent phonological equivalence categories when processing continuous speech. Results are interpreted within the Automatic Selective Perception model of speech perception.

Cross-language categorization of French and German vowels by naïve American listeners

PubMed Central

Strange, Winifred; Levy, Erika S.; Law, Franzo F.

2009-01-01

American English (AE) speakers’ perceptual assimilation of 14 North German (NG) and 9 Parisian French (PF) vowels was examined in two studies using citation-form disyllables (study 1) and sentences with vowels surrounded by labial and alveolar consonants in multisyllabic nonsense words (study 2). Listeners categorized multiple tokens of each NG and PF vowel as most similar to selected AE vowels and rated their category “goodness” on a nine-point Likert scale. Front, rounded vowels were assimilated primarily to back AE vowels, despite their acoustic similarity to front AE vowels. In study 1, they were considered poorer exemplars of AE vowels than were NG and PF back, rounded vowels; in study 2, front and back, rounded vowels were perceived as similar to each other. Assimilation of some front, unrounded and back, rounded NG and PF vowels varied with language, speaking style, and consonantal context. Differences in perceived similarity often could not be predicted from context-specific cross-language spectral similarities. Results suggest that listeners can access context-specific, phonetic details when listening to citation-form materials, but assimilate non-native vowels on the basis of context-independent phonological equivalence categories when processing continuous speech. Results are interpreted within the Automatic Selective Perception model of speech perception. PMID:19739759

Structure and anticoagulant property of a sulfated polysaccharide isolated from the green seaweed Monostroma angicava.

PubMed

Li, Na; Liu, Xue; He, Xiaoxi; Wang, Shuyao; Cao, Sujian; Xia, Zheng; Xian, Huali; Qin, Ling; Mao, Wenjun

2017-03-01

An anticoagulant-active polysaccharide PF2 was extracted with boiling water from the green seaweed Monostroma angicava, further purified by anion-exchange and size-exclusion chromatography. PF2 was a rhamnan-type sulfated polysaccharide with molecular weight of about 88.1kDa. Results of chemical and spectroscopic analyses demonstrated that PF2 consisted of→3)-α-l-Rhap-(1→ and →2)-α-l-Rhap-(1→residues, with partially branches at C-2 of→3)-α-l-Rhap-(1→residues. Sulfate groups were substituted at C-3 of →2)-α-l-Rhap-(1→ residues. The sulfated polysaccharide PF2 had a high anticoagulant action, and the mechanism of anticoagulant activity mediated by PF2 was mainly attributed to strong potentiation thrombin by heparin cofactor II. PF2 also exhibited weak effect on antithrombin-dependent thrombin or factor Xa inhibition. The fibrin(ogen)olytic activity and thrombolytic activity of PF2 were also evaluated. The investigation revealed that PF2 was a novel sulfated rhamnan differing from previously described sulfated polysaccharides from green seaweed and could be a potential anticoagulant polysaccharide. Copyright © 2016 Elsevier Ltd. All rights reserved.

Massive remobilization of permafrost carbon during post-glacial warming

PubMed Central

Tesi, T.; Muschitiello, F.; Smittenberg, R. H.; Jakobsson, M.; Vonk, J. E.; Hill, P.; Andersson, A.; Kirchner, N.; Noormets, R.; Dudarev, O.; Semiletov, I.; Gustafsson, Ö

2016-01-01

Recent hypotheses, based on atmospheric records and models, suggest that permafrost carbon (PF-C) accumulated during the last glaciation may have been an important source for the atmospheric CO2 rise during post-glacial warming. However, direct physical indications for such PF-C release have so far been absent. Here we use the Laptev Sea (Arctic Ocean) as an archive to investigate PF-C destabilization during the last glacial–interglacial period. Our results show evidence for massive supply of PF-C from Siberian soils as a result of severe active layer deepening in response to the warming. Thawing of PF-C must also have brought about an enhanced organic matter respiration and, thus, these findings suggest that PF-C may indeed have been an important source of CO2 across the extensive permafrost domain. The results challenge current paradigms on the post-glacial CO2 rise and, at the same time, serve as a harbinger for possible consequences of the present-day warming of PF-C soils. PMID:27897191

Massive remobilization of permafrost carbon during post-glacial warming

NASA Astrophysics Data System (ADS)

Tesi, T.; Muschitiello, F.; Smittenberg, R. H.; Jakobsson, M.; Vonk, J. E.; Hill, P.; Andersson, A.; Kirchner, N.; Noormets, R.; Dudarev, O.; Semiletov, I.; Gustafsson, Ö.

2016-11-01

Recent hypotheses, based on atmospheric records and models, suggest that permafrost carbon (PF-C) accumulated during the last glaciation may have been an important source for the atmospheric CO2 rise during post-glacial warming. However, direct physical indications for such PF-C release have so far been absent. Here we use the Laptev Sea (Arctic Ocean) as an archive to investigate PF-C destabilization during the last glacial-interglacial period. Our results show evidence for massive supply of PF-C from Siberian soils as a result of severe active layer deepening in response to the warming. Thawing of PF-C must also have brought about an enhanced organic matter respiration and, thus, these findings suggest that PF-C may indeed have been an important source of CO2 across the extensive permafrost domain. The results challenge current paradigms on the post-glacial CO2 rise and, at the same time, serve as a harbinger for possible consequences of the present-day warming of PF-C soils.

PF-05231023, a long-acting FGF21 analogue, decreases body weight by reduction of food intake in non-human primates.

PubMed

Thompson, W Clayton; Zhou, Yingjiang; Talukdar, Saswata; Musante, Cynthia J

2016-08-01

PF-05231023, a long-acting FGF21 analogue, is a promising potential pharmacotherapy for the treatment of obesity and associated comorbidities. Previous studies have shown the potential of FGF21 and FGF21-like compounds to decrease body weight in mice, non-human primates, and humans; the precise mechanisms of action remain unclear. In particular, there have been conflicting reports on the degree to which FGF21-induced weight loss in non-human primates is attributable to a decrease in food intake versus an increase in energy expenditure. Here, we present a semi-mechanistic mathematical model of energy balance and body composition developed from similar work in mice. This model links PF-05231023 administration and washout to changes in food intake, which in turn drives changes in body weight. The model is calibrated to and compared with recently published data from cynomolgus macaques treated with PF-05231023, demonstrating its accuracy in describing pharmacotherapy-induced weight loss in these animals. The results are consistent with the hypothesis that PF-05231023 decreases body weight in cynomolgus macaques solely by a reduction in food intake, with no direct effect on energy expenditure.

Response of Cultured Neuronal Network Activity After High-Intensity Power Frequency Magnetic Field Exposure

PubMed Central

Saito, Atsushi; Takahashi, Masayuki; Makino, Kei; Suzuki, Yukihisa; Jimbo, Yasuhiko; Nakasono, Satoshi

2018-01-01

High-intensity and low frequency (1–100 kHz) time-varying electromagnetic fields stimulate the human body through excitation of the nervous system. In power frequency range (50/60 Hz), a frequency-dependent threshold of the external electric field-induced neuronal modulation in cultured neuronal networks was used as one of the biological indicator in international guidelines; however, the threshold of the magnetic field-induced neuronal modulation has not been elucidated. In this study, we exposed rat brain-derived neuronal networks to a high-intensity power frequency magnetic field (hPF-MF), and evaluated the modulation of synchronized bursting activity using a multi-electrode array (MEA)-based extracellular recording technique. As a result of short-term hPF-MF exposure (50–400 mT root-mean-square (rms), 50 Hz, sinusoidal wave, 6 s), the synchronized bursting activity was increased in the 400 mT-exposed group. On the other hand, no change was observed in the 50–200 mT-exposed groups. In order to clarify the mechanisms of the 400 mT hPF-MF exposure-induced neuronal response, we evaluated it after blocking inhibitory synapses using bicuculline methiodide (BMI); subsequently, increase in bursting activity was observed with BMI application, and the response of 400 mT hPF-MF exposure disappeared. Therefore, it was suggested that the response of hPF-MF exposure was involved in the inhibitory input. Next, we screened the inhibitory pacemaker-like neuronal activity which showed autonomous 4–10 Hz firing with CNQX and D-AP5 application, and it was confirmed that the activity was reduced after 400 mT hPF-MF exposure. Comparison of these experimental results with estimated values of the induced electric field (E-field) in the culture medium revealed that the change in synchronized bursting activity occurred over 0.3 V/m, which was equivalent to the findings of a previous study that used the external electric fields. In addition, the results suggested that the potentiation of neuronal activity after 400 mT hPF-MF exposure was related to the depression of autonomous activity of pacemaker-like neurons. Our results indicated that the synchronized bursting activity was increased by hPF-MF exposure (E-field: >0.3 V/m), and the response was due to reduced inhibitory pacemaker-like neuronal activity. PMID:29662453

Lethality and Developmental Delay of Drosophila melanogaster Following Ingestion of Selected Pseudomonas fluorescens Strains

USDA-ARS?s Scientific Manuscript database

Pseudomonas fluorescens secretes antimicrobial compounds that promote plant health and provide protection from pathogens. We used a non-invasive feeding assay to study the toxicity of P. fluorescens strains Pf0-1, SBW25, and Pf-5 to Drosophila melanogaster. The three strains of P. fluorescens varie...

Influence of Sky Conditions on Estimation of Photosynthetic Photon Flux Density for Agricultural Ecosystem

NASA Astrophysics Data System (ADS)

Yamashita, M.; Yoshimura, M.

2018-04-01

Photosynthetic photon flux density (PPFD: µmol m-2 s-1) is indispensable for plant physiology processes in photosynthesis. However, PPFD is seldom measured, so that PPFD has been estimated by using solar radiation (SR: W m-2) measured in world wide. In method using SR, there are two steps: first to estimate photosynthetically active radiation (PAR: W m-2) by the fraction of PAR to SR (PF) and second: to convert PAR to PPFD using the ratio of quanta to energy (Q / E: µmol J-1). PF and Q/E usually have been used as the constant values, however, recent studies point out that PF and Q / E would not be constants under various sky conditions. In this study, we use the numeric data of sky-conditions factors such cloud cover, sun appearance/hiding and relative sky brightness derived from whole-sky image processing and examine the influences of sky-conditions factors on PF and Q / E of global and diffuse PAR. Furthermore, we discuss our results by comparing with the existing methods.

About PF

MedlinePlus

... vapors that can cause PF (such as asbestos, coal, silica, and others) Some MEDICATIONS can cause PF. ... wide variety of inorganic dusts, including asbestos, silica, coal dust, beryllium, and hard metal dusts. Are there ...

Cost comparison of pressure ulcer preventive dressings: hydrocolloid dressing versus transparent polyurethane film.

PubMed

Dutra, R A A; Salomé, G M; Leal, L M F; Alves, M G; Moura, J P; Silva, A T; Pereira, V O S; de Brito, M J A; Ferreira, L M

2016-11-02

To evaluate and compare the costs of using a transparent polyurethane film (PF) and hydrocolloid dressing (HD) in the prevention of pressure ulcers (PUs). This descriptive, observational, longitudinal, comparative study was conducted in the intensive care units, coronary care unit and medical clinic of a charity hospital in Brazil. Data were collected during a 30-day study period, consisting of physical examination, assessment of risk factors for PU development and application of the Braden scale, which were performed at inclusion in the study and once daily during hospitalisation. Either PF or HD was applied bilaterally in the sacral and trochanteric regions for prevention of PUs in patients at a moderate to high risk of PUs according to the Braden scale, and costs of using PU preventive dressings were estimated. The mean total costs per dressing change per patient when using the HD and PF to prevent PUs were 413.60 BRL and 74.04 BRL, respectively. There were significant between-group differences in mean costs for all variables, except for saline solution and nurse-technician services. Results showed that the mean cost per dressing change per patient was lower when using the transparent PF than when using the HD.

Drugs and personality: comparison of drug users, nonusers, and other clinical groups on the 16PF.

PubMed

Spotts, J V; Shontz, F C

1991-10-01

This article reviews published 16PF research on drug users. It also compares the 16PF scores of a new sample of nonusers with scores of matched groups of heavy, chronic users of cocaine, amphetamine, opiates, and barbiturates/sedative hypnotics, as well as combined groups of stimulant users, depressant users, and a combined group of users of all substances. No significant differences were found among drug user groups, but the profile of the nonuser group was distinctive. K-Means Cluster Analyses, as well as Cattell's Similarity and Pearson Product Moment Correlation Coefficients, were used to compare profiles of these new samples with the 19 groups described in an earlier meta-analysis of published 16PF studies. Data from the new samples did not cluster with data from other published research, although certain specific similarities appeared in more detailed correlational analyses. Methodological problems are discussed, and it is recommended that in future studies drug user groups be more carefully selected and defined, sample descriptions be more thorough and complete, complete profile information be routinely provided, and efforts be made to explore the utility of the Cattell CAQ in studies of drug users/misusers.

Plantar fasciitis in athletes: diagnostic and treatment strategies. A systematic review

PubMed Central

Petraglia, Federica; Ramazzina, Ileana; Costantino, Cosimo

2017-01-01

Summary Background: Plantar fasciitis (PF) is reported in different sports mainly in running and soccer athletes. Purpose of this study is to conduct a systematic review of published literature concerning the diagnosis and treatment of PF in both recreational and élite athletes. The review was conducted and reported in accordance with the PRISMA statement. Methods: The following electronic databases were searched: PubMed, Cochrane Library and Scopus. As far as PF diagnosis, we investigated the electronic databases from January 2006 to June 2016, whereas in considering treatments all data in literature were investigated. Results: For both diagnosis and treatment, 17 studies matched inclusion criteria. The results have highlighted that the most frequently used diagnostic techniques were Ultrasonography and Magnetic Resonance Imaging. Conventional, complementary, and alternative treatment approaches were assessed. Conclusions: In reviewing literature, we were unable to find any specific diagnostic algorithm for PF in athletes, due to the fact that no different diagnostic strategies were used for athletes and non-athletes. As for treatment, a few literature data are available and it makes difficult to suggest practice guidelines. Specific studies are necessary to define the best treatment algorithm for both recreational and élite athletes. Level of evidence: Ib. PMID:28717618

QSAR study on the antimalarial activity of Plasmodium falciparum dihydroorotate dehydrogenase (PfDHODH) inhibitors.

PubMed

Hou, X; Chen, X; Zhang, M; Yan, A

2016-01-01

Plasmodium falciparum, the most fatal parasite that causes malaria, is responsible for over one million deaths per year. P. falciparum dihydroorotate dehydrogenase (PfDHODH) has been validated as a promising drug development target for antimalarial therapy since it catalyzes the rate-limiting step for DNA and RNA biosynthesis. In this study, we investigated the quantitative structure-activity relationships (QSAR) of the antimalarial activity of PfDHODH inhibitors by generating four computational models using a multilinear regression (MLR) and a support vector machine (SVM) based on a dataset of 255 PfDHODH inhibitors. All the models display good prediction quality with a leave-one-out q(2) >0.66, a correlation coefficient (r) >0.85 on both training sets and test sets, and a mean square error (MSE) <0.32 on training sets and <0.37 on test sets, respectively. The study indicated that the hydrogen bonding ability, atom polarizabilities and ring complexity are predominant factors for inhibitors' antimalarial activity. The models are capable of predicting inhibitors' antimalarial activity and the molecular descriptors for building the models could be helpful in the development of new antimalarial drugs.

Pfhrp2 and pfhrp3 polymorphisms in Plasmodium falciparum isolates from Dakar, Senegal: impact on rapid malaria diagnostic tests

PubMed Central

2013-01-01

Background An accurate diagnosis is essential for the rapid and appropriate treatment of malaria. The accuracy of the histidine-rich protein 2 (PfHRP2)-based rapid diagnostic test (RDT) Palutop+4® was assessed here. One possible factor contributing to the failure to detect malaria by this test is the diversity of the parasite PfHRP2 antigens. Methods PfHRP2 detection with the Palutop+4® RDT was carried out. The pfhrp2 and pfhrp3 genes were amplified and sequenced from 136 isolates of Plasmodium falciparum that were collected in Dakar, Senegal from 2009 to 2011. The DNA sequences were determined and statistical analyses of the variation observed between these two genes were conducted. The potential impact of PfHRP2 and PfHRP3 sequence variation on malaria diagnosis was examined. Results Seven P. falciparum isolates (5.9% of the total isolates, regardless of the parasitaemia; 10.7% of the isolates with parasitaemia ≤0.005% or ≤250 parasites/μl) were undetected by the PfHRP2 Palutop+4® RDT. Low parasite density is not sufficient to explain the PfHRP2 detection failure. Three of these seven samples showed pfhrp2 deletion (2.4%). The pfhrp3 gene was deleted in 12.8%. Of the 122 PfHRP2 sequences, 120 unique sequences were identified. Of the 109 PfHRP3 sequences, 64 unique sequences were identified. Using the Baker’s regression model, at least 7.4% of the P. falciparum isolates in Dakar were likely to be undetected by PfHRP2 at a parasite density of ≤250 parasites/μl (slightly lower than the evaluated prevalence of 10.7%). This predictive prevalence increased significantly between 2009 and 2011 (P = 0.0046). Conclusion In the present work, 10.7% of the isolates with a parasitaemia ≤0.005% (≤250 parasites/μl) were undetected by the PfHRP2 Palutop+4® RDT (7.4% by the predictive Baker’model). In addition, all of the parasites with pfhrp2 deletion (2.4% of the total samples) and 2.1% of the parasites with parasitaemia >0.005% and presence of pfhrp2 were not detected by PfHRP2 RDT. PfHRP2 is highly polymorphic in Senegal. Efforts should be made to more accurately determine the prevalence of non-sensitive parasites to pfHRP2. PMID:23347727

Metal complexes of fluorophosphines. 13. Reaction of fac-(CH/sub 3/CN)/sub 3/Mo(CO)/sub 3/ with (methylamino)bis(difluorophosphine). X-ray crystal structure analysis of a novel binuclear molybdenum fluorophosphine carbonyl complex with a bridging chlorine atom: (CO)/sub 2/Mo(/sup +/-CH/sub 3/N(PF/sub 2/)/sub 2/)/sub 2/(. mu. -PF/sub 2/)(. mu. -Cl)Mo(CO)(PF/sub 2/NHCH/sub 3/)

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

King, R.B.; Shimura, M.; Brown, G.M.

1984-01-01

Reaction of fac-(CH/sub 3/CN)/sub 3/Mo(CO)/sub 3/ with CH/sub 3/N(PF/sub 2/)/sub 2/ in acetonitrile solution at room temperature gives white, volatile, crystalline fac-(CH/sub 3/N(PF/sub 2/)/sub 2/)/sub 2/Mo(CO)/sub 3/, containing one monodentate and one bidentate CH/sub 3/N(PF/sub 2/)/sub 2/ ligand. The same reactants in boiling acetonitrile give yellow (CH/sub 3/N(PF/sub 2/)/sub 2/)/sub 4/Mo/sub 2/(CO)/sub 3/ in considerably better yield than the previously reported preparation of this binuclear complex from the cycloheptatriene complex C/sub 7/H/sub 8/Mo(CO)/sub 3/ and CH/sub 3/N(PF/sub 2/)/sub 2/ in boiling methylcyclohexane. Reaction in acetonitrile solution of fac-(CH/sub 3/CN)/sub 3/Mo(CO)/sub 3/ with CH/sub 3/N(PF/sub 2/)/sub 2/ containing about 0.2% HClmore » gives brown-red, volatile (CO)/sub 2/Mo(/sup +/-CH/sub 3/N(PF/sub 2/)/sub 2/)/sub 2/(..mu..-PF/sub 2/)(..mu..-Cl)-Mo(CO)(PF/sub 2/NHCH/sub 3/), whose composition and structure were established by single-crystal X-ray structure analysis. This novel quadruply bridged binuclear complex is obtained in considerably better yield from the reaction of (CH/sub 3/N(PF/sub 2/)/sub 2/)/sub 3/Mo/sub 2/(CO)/sub 5/ with ((C/sub 2/H/sub 5/)/sub 3/NH)Cl in acetonitirle solution. The complex has a Mo-Mo bond 2.975 A in length. Crystal data: monoclinic, space group P2/sub 1//c, a = 17.546 (4) A, b = 9.725 (2) A, c = 14.558 (3), ..beta.. = 107.20 (2)/sup 0/, Z = 4. 30 references, 2 figures, 3 tables.« less

Density functional theory study of homologous organometallic molecules of the [RhXL2]2 (X=Cl, Br, or I; L=CO, PH3, or PF3) type

NASA Astrophysics Data System (ADS)

Seuret, P.; Weber, J.; Wesolowski, T. A.

Density functional theory generalized gradient approximation calculations, which were tested in our previous detailed study of [RhCl(PF3)2]2 (Seuret et al., 2003, Phys. Chem. chem. Phys., 5, 268-274), were applied for a series of homologous organometallic compounds of the [RhXL2]2 (X = Cl, Br, or I; L = CO, PH3, or PF3) type. Various properties of the studied compounds were obtained. Optimized geometries of [RhCl(PH3)2]2 and [RhCl(CO)2]2 are in very good agreement with available experimental data. Geometries of other compounds as well as other properties (thermochemistry of selected fragmentation channels, barriers to structural changes, frontier orbitals) which are not available experimentally were predicted. All the considered compounds are not planar. Enforcing planarity of the central [RhX]2 moiety requires only a small energetic cost ranging from 2.2 to 3.9 kcal mol-1. The analysis of frontier orbitals indicates that the metals provide the most favourable site for the electrophilic attack in all considered compounds. The analysis of the shape of the lowest unoccupied molecular orbitals indicates that the halogens and ligands provide the most favourable site for the nucleophilic attack for [RhCl(CO)2]2 or [RhCl(PF3)2]. For [RhBr(PF3)2]2, [RhI(PF3)2]2 and [RhCl(PH3)2]2, the nucleophilic attack on the halogen is less probable. Except for [RhCl(CO)2]2, the least energetically expensive decomposition channel involves initial separation of ligands. For [RhCl(CO)2]2, its decomposition into the RhCl(CO)2 fragments was found to be the least energetically expensive fragmentation reaction which is probably one of the reasons for the known catalytic activity of this compound.

History of cigarette smoking in cognitively-normal elders is associated with elevated cerebrospinal fluid biomarkers of oxidative stress.

PubMed

Durazzo, Timothy C; Mattsson, Niklas; Weiner, Michael W; Korecka, Magdalena; Trojanowski, John Q; Shaw, Leslie M

2014-09-01

Cigarette smoking in adults is associated with abnormalities in brain neurobiology. Smoking-induced central nervous system oxidative stress (OxS) is a potential mechanism associated with these abnormalities. The goal of this study was to compare cognitively-normal elders on cerebrospinal fluid (CSF) levels of F2-isoprostane biomarkers of OxS. Elders with a lifetime history of smoking (smokers; n=50; 75±5 years of age; 34±28 pack-years; approximately 12% were actively smoking at the time of study) were compared to never-smokers (n=61; 76±6 years of age) on CSF iPF2α-III and 8,12, iso-iPF2α-VI F2-isoprostanes levels. F2-isoprostanes levels were quantitated with HPLC-atmospheric pressure chemical ionization-tandem mass spectrometry. Associations between F2-isoprostanes levels, hippocampal volumes, and cigarette exposure measures were also evaluated. Smokers showed higher iPF2α-III level than never-smokers. An age×smoking status interaction was observed for 8,12, iso-iPF2α-VI, where smokers demonstrate a significantly greater concentration with increasing age than never-smokers. In smokers only, higher 8,12, iso-iPF2α-VI concentration was associated with smaller hippocampal volume, and greater iPF2α-III level was related to greater pack years. This is the first study to demonstrate that a history of cigarette smoking in cognitively-normal elders was associated with significantly elevated CSF F2-isoprostane levels and greater age-related increases in F2-isoprostanes, and that higher F2-isoprostane levels in smokers were related to smaller hippocampal volume. These findings provide additional novel evidence that a history of chronic smoking during adulthood is associated with adverse effects on the human brain that are potentially enduring even with extended smoking cessation. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Correlation of Patient-Reported Outcomes Measurement Information System (PROMIS) scores with legacy patient-reported outcome scores in patients undergoing rotator cuff repair.

PubMed

Patterson, Brendan M; Orvets, Nathan D; Aleem, Alexander W; Keener, Jay D; Calfee, Ryan P; Nixon, Devon C; Chamberlain, Aaron M

2018-06-01

The Patient-Reported Outcomes Measurement Information System (PROMIS) is being used to assess outcomes in many patient populations despite limited validation. The purpose of this study was to investigate the relationship between American Shoulder and Elbow Surgeons (ASES) and Simple Shoulder Test (SST) scores and PROMIS Physical Function (PF) and Upper Extremity (UE) function scores collected preoperatively in patients undergoing rotator cuff repair. This cross-sectional study analyzed 164 consecutive patients undergoing arthroscopic rotator cuff repair. Study inclusion required preoperative completion of the ASES and SST evaluations, as well as the PROMIS PF, UE, and Pain Interference computerized adaptive tests. Descriptive statistics were produced, and Pearson correlation coefficients were calculated between each of the outcome measures. Average PROMIS UE scores indicated greater impairment than PROMIS PF scores (34 vs 44). Three percent of patients reached the PROMIS UE ceiling score of 56. PROMIS PF scores demonstrated a weak correlation with ASES scores (r = 0.43, P < .001) and a moderate correlation with SST scores (r = 0.51, P < .001). PROMIS UE scores demonstrated a moderate correlation with both ASES scores (r = 0.59, P < .001) and SST scores (r = 0.62, P < .001). PROMIS Pain Interference scores demonstrated weak negative correlations with both ASES scores (r = -0.43, P < .001) and SST scores (r = -0.41, P < .001). Patients answered fewer questions on average using the PROMIS PF and UE instruments as compared with the ASES and SST instruments. PROMIS UE scores indicate greater impairment and demonstrate a stronger correlation with the legacy shoulder scores than PROMIS PF scores in patients with symptomatic rotator cuff tears. PROMIS computerized adaptive tests allow for more efficient patient-reported outcome data collection compared with traditional outcome scores. Copyright © 2018 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Elsevier Inc. All rights reserved.

Atomic-scale to Meso-scale Simulation Studies of Thermal Ageing and Irradiation Effects in Fe- Cr Alloys

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

Stanley, Eugene; Liu, Li

In this project, we target at three primary objectives: (1) Molecular Dynamics (MD) code development for Fe-Cr alloys, which can be utilized to provide thermodynamic and kinetic properties as inputs in mesoscale Phase Field (PF) simulations; (2) validation and implementation of the MD code to explain thermal ageing and radiation damage; and (3) an integrated modeling platform for MD and PF simulations. These two simulation tools, MD and PF, will ultimately be merged to understand and quantify the kinetics and mechanisms of microstructure and property evolution of Fe-Cr alloys under various thermal and irradiation environments

Phosphorylation Determines the Calmodulin-mediated Ca2+ Response and Water Permeability of AQP0*

PubMed Central

Kalman, Katalin; Németh-Cahalan, Karin L.; Froger, Alexandrine; Hall, James E.

2008-01-01

In Xenopus oocytes, the water permeability of AQP0 (Pf) increases with removal of external calcium, an effect that is mediated by cytoplasmic calmodulin (CaM) bound to the C terminus of AQP0. To investigate the effects of serine phosphorylation on CaM-mediated Ca2+ regulation of Pf, we tested the effects of kinase activation, CaM inhibition, and a series of mutations in the C terminus CaM binding site. Calcium regulation of AQP0 Pf manifests four distinct phenotypes: Group 1, with high Pf upon removal of external Ca2+ (wild-type, S229N, R233A, S235A, S235K, K238A, and R241E); Group 2, with high Pf in elevated (5 mm) external Ca2+ (S235D and R241A); Group 3, with high Pf and no Ca2+ regulation (S229D, S231N, S231D, S235N, and S235N/I236S); and Group 4, with low Pf and no Ca2+ regulation (protein kinase A and protein kinase C activators, S229D/S235D and S235N/I236S). Within each group, we tested whether CaM binding mediates the phenotype, as shown previously for wild-type AQP0. In the presence of calmidazolium, a CaM inhibitor, S235D showed high Pf and no Ca2+ regulation, suggesting that S235D still binds CaM. Contrarily, S229D showed a decrease in recruitment of CaM, suggesting that S229D is unable to bind CaM. Taken together, our results suggest a model in which CaM acts as an inhibitor of AQP0 Pf. CaM binding is associated with a low Pf state, and a lack of CaM binding is associated with a high Pf state. Pathological conditions of inappropriate phosphorylation or calcium/CaM regulation could induce Pf changes contributing to the development of a cataract. PMID:18508773

Identification of Plasmodium falciparum reticulocyte binding protein homologue 5-interacting protein, PfRipr, as a highly conserved blood-stage malaria vaccine candidate.

PubMed

Ntege, Edward H; Arisue, Nobuko; Ito, Daisuke; Hasegawa, Tomoyuki; Palacpac, Nirianne M Q; Egwang, Thomas G; Horii, Toshihiro; Takashima, Eizo; Tsuboi, Takafumi

2016-11-04

Genetic variability in Plasmodium falciparum malaria parasites hampers current malaria vaccine development efforts. Here, we hypothesize that to address the impact of genetic variability on vaccine efficacy in clinical trials, conserved antigen targets should be selected to achieve robust host immunity across multiple falciparum strains. Therefore, suitable vaccine antigens should be assessed for levels of polymorphism and genetic diversity. Using a total of one hundred and two clinical isolates from a region of high malaria transmission in Uganda, we analyzed extent of polymorphism and genetic diversity in four recently reported novel blood-stage malaria vaccine candidate proteins: Rh5 interacting protein (PfRipr), GPI anchored micronemal antigen (PfGAMA), rhoptry-associated leucine zipper-like protein 1 (PfRALP1) and Duffy binding-like merozoite surface protein 1 (PfMSPDBL1). In addition, utilizing the wheat germ cell-free system, we expressed recombinant proteins for the four candidates based on P. falciparum laboratory strain 3D7 sequences, immunized rabbits to obtain specific antibodies (Abs) and performed functional growth inhibition assay (GIA). The GIA activity of the raised Abs was demonstrated using both homologous 3D7 and heterologous FVO strains in vitro. Both pfripr and pfralp1 are less polymorphic but the latter is comparatively more diverse, with varied number of regions having insertions and deletions, asparagine and 6-mer repeats in the coding sequences. Pfgama and pfmspdbl1 are polymorphic and genetically diverse among the isolates with antibodies against the 3D7-based recombinant PfGAMA and PfMSPDBL1 inhibiting merozoite invasion only in the 3D7 but not FVO strain. Moreover, although Abs against the 3D7-based recombinant PfRipr and PfRALP1 proteins potently inhibited merozoite invasion of both 3D7 and FVO, the GIA activity of anti-PfRipr was much higher than that of anti-PfRALP1. Thus, PfRipr is regarded as a promising blood-stage vaccine candidate for next-generation vaccines against P. falciparum. Copyright © 2016 Elsevier Ltd. All rights reserved.

Posterior fossa volume and response to suboccipital decompression in patients with Chiari I malformation.

PubMed

Badie, B; Mendoza, D; Batzdorf, U

1995-08-01

Smaller posterior fossa (PF) volume has been suggested to be one of the mechanisms responsible for tonsillar herniation through the foramen magnum in patients with Chiari I malformation (CM I). Although previous radiological analyses of the cranial anatomy have suggested a smaller PF volume in patients with CM I, the relationship of the PF volume to decompressive surgery has not been reported. We have measured the ratio of PF volume to supratentorial volume (PF ratio [PFR]) in 20 patients with CM I and 20 control patients by retrospectively studying their magnetic resonance images with a computerized image analyzer. The mean PFR in patients with CM I (with or without syringomyelia) was significantly smaller than for those in the control group (15.6 +/- 1.9 versus 17.5 +/- 1.2, P = 0.0008). Although PFR did not correlate with the extent of tonsillar herniation in patients with CM I, it did directly correlate with their age, i.e., younger patients with CM I (but not control patients) had smaller PFRs. All but three patients responded both clinically and radiographically to decompressive surgery. Those patients who did not benefit from surgical intervention had normal PFRs. We conclude that: 1) PFRs are smaller in most patients with CM I; 2) a smaller PF may be a primary cause of tonsillar herniation; 3) patients with CM I who have smaller PFRs tend to develop symptoms earlier than those with normal values; 4) patients with smaller PFRs tend to respond better to suboccipital decompression.

Hydrophobic task-specific ionic liquids: synthesis, properties and application for the capture of SO2.

PubMed

Tian, Shidong; Hou, Yucui; Wu, Weize; Ren, Shuhang; Qian, Jianguo

2014-08-15

The capture of SO2 by ionic liquids (ILs) has drawn much attention all over the world. However, ILs can absorb not only SO2 but also water from flue gas. The removal of water from ILs is necessary for reusing the absorbent. In order to reduce the energy costs of removing water, it would be helpful to weaken the interactions between ILs and water. In this work, two kinds of hydrophobic task-specific ILs, 1-(2-diethyl-aminoethyl)-3-methylimidazolium hexafluorophosphate ([Et2NEmim] [PF6]) and 1-(2-diethyl-aminoethyl)-1-methylpyrrolidinium hexafluorophosphate ([Et2NEmpyr][PF6]), were designed and synthesized. Thermal stability and physical properties of the ILs were studied. Furthermore, the application of the ILs for the capture of SO2 and the absorption mechanism were systematically investigated. It has been found that both of the ILs are immiscible with water, and [Et2NEmim][PF6] has much lower viscosity, much higher thermal stability and much higher SO2 absorption rate than [Et2NEmpyr][PF6]. [Et2NEmim][PF6] shows high SO2 absorption capacities up to 2.11 mol SO2 per mole IL (pure SO2) and 0.94 mol SO2 per mole IL (3% SO2) under hydrous conditions at 30 °C. The result suggests that [Et2NEmim][PF6] is a promising recyclable absorbent for the capture of SO2. Copyright © 2014 Elsevier B.V. All rights reserved.

Reliability of Various Measurement Stations for Determining Plantar Fascia Thickness and Echogenicity.

PubMed

Bisi-Balogun, Adebisi; Cassel, Michael; Mayer, Frank

2016-04-13

This study aimed to determine the relative and absolute reliability of ultrasound (US) measurements of the thickness and echogenicity of the plantar fascia (PF) at different measurement stations along its length using a standardized protocol. Twelve healthy subjects (24 feet) were enrolled. The PF was imaged in the longitudinal plane. Subjects were assessed twice to evaluate the intra-rater reliability. A quantitative evaluation of the thickness and echogenicity of the plantar fascia was performed using Image J, a digital image analysis and viewer software. A sonography evaluation of the thickness and echogenicity of the PF showed a high relative reliability with an Intra class correlation coefficient of ≥0.88 at all measurement stations. However, the measurement stations for both the PF thickness and echogenicity which showed the highest intraclass correlation coefficient (ICCs) did not have the highest absolute reliability. Compared to other measurement stations, measuring the PF thickness at 3 cm distal and the echogenicity at a region of interest 1 cm to 2 cm distal from its insertion at the medial calcaneal tubercle showed the highest absolute reliability with the least systematic bias and random error. Also, the reliability was higher using a mean of three measurements compared to one measurement. To reduce discrepancies in the interpretation of the thickness and echogenicity measurements of the PF, the absolute reliability of the different measurement stations should be considered in clinical practice and research rather than the relative reliability with the ICC.

Reliability of Various Measurement Stations for Determining Plantar Fascia Thickness and Echogenicity

PubMed Central

Bisi-Balogun, Adebisi; Cassel, Michael; Mayer, Frank

2016-01-01

This study aimed to determine the relative and absolute reliability of ultrasound (US) measurements of the thickness and echogenicity of the plantar fascia (PF) at different measurement stations along its length using a standardized protocol. Twelve healthy subjects (24 feet) were enrolled. The PF was imaged in the longitudinal plane. Subjects were assessed twice to evaluate the intra-rater reliability. A quantitative evaluation of the thickness and echogenicity of the plantar fascia was performed using Image J, a digital image analysis and viewer software. A sonography evaluation of the thickness and echogenicity of the PF showed a high relative reliability with an Intra class correlation coefficient of ≥0.88 at all measurement stations. However, the measurement stations for both the PF thickness and echogenicity which showed the highest intraclass correlation coefficient (ICCs) did not have the highest absolute reliability. Compared to other measurement stations, measuring the PF thickness at 3 cm distal and the echogenicity at a region of interest 1 cm to 2 cm distal from its insertion at the medial calcaneal tubercle showed the highest absolute reliability with the least systematic bias and random error. Also, the reliability was higher using a mean of three measurements compared to one measurement. To reduce discrepancies in the interpretation of the thickness and echogenicity measurements of the PF, the absolute reliability of the different measurement stations should be considered in clinical practice and research rather than the relative reliability with the ICC. PMID:27089369

Insights into the epidemiological link between biting flies and pemphigus foliaceus in southeastern Brazil.

PubMed

Vernal, Sebastian; Pepinelli, Mateus; Casanova, Claudio; Goulart, Thais M; Kim, Olivia; De Paula, Natalia A; Pinto, Mara C; Sá-Nunes, Anderson; Roselino, Ana Maria

2017-12-01

Black fly and sandfly bites are related to the endemicity of pemphigus foliaceus (PF); however, an immune reaction against the salivary proteins from these flies still requires confirmation in the case of PF patients living in southeastern Brazil. To georeference the distribution of Simuliidae (Diptera: Simuliidae) and Phlebotominae (Diptera: Psychodidae) and of PF cases in the northeastern region of São Paulo State, and to assess the humoral immune response against salivary gland extracts (SGEs) from biting flies in PF patients, relatives, and neighbours. PF patients' medical information recorded between 1965 and 2014 were obtained from the database of the University Hospital. Data on the distribution of fly species were collected from scientific reports and epidemiological databases. Spatial maps relating the distribution of biting flies with PF cases were plotted. Serum IgG antibodies against the SGEs from Simulium nigrimanum, Nyssomyia neivai, and Aedes aegypti (as control) were determined by ELISA. Two hundred and eighty-five PF cases were distributed in 60 municipalities with a prevalence of 57.5 per million inhabitants, revealing well-defined geographical clusters. S. nigrimanum and N. neivai specimens were registered in eight (13.3%) and 26 (43.3%) of these municipalities, respectively. PF patients, and their relatives presented higher levels of IgG against the SGEs of S. nigrimanum and N. neivai (P<0.001 for both), but not against the SGE from A. aegypti (P=0.115 and P=0.552, respectively), as compared to controls. IgG against the SGEs from S. nigrimanum and N. neivai but not against the SGE from A. aegypti correlated with levels of anti-Desmoglein 1 in PF patients (r=0.3848, P=0.039; and r=0.416, P=0.022, respectively). An epidemiological link between biting flies and PF in southeastern Brazil is proposed, implying a possible role of the salivary proteins from these flies in PF etiopathogenesis. Copyright © 2017 Elsevier B.V. All rights reserved.

Experimental study of the lifetime and phase transition in neutron-rich Zr 98 ,100 ,102

NASA Astrophysics Data System (ADS)

Ansari, S.; Régis, J.-M.; Jolie, J.; Saed-Samii, N.; Warr, N.; Korten, W.; Zielińska, M.; Salsac, M.-D.; Blanc, A.; Jentschel, M.; Köster, U.; Mutti, P.; Soldner, T.; Simpson, G. S.; Drouet, F.; Vancraeyenest, A.; de France, G.; Clément, E.; Stezowski, O.; Ur, C. A.; Urban, W.; Regan, P. H.; Podolyák, Zs.; Larijani, C.; Townsley, C.; Carroll, R.; Wilson, E.; Mach, H.; Fraile, L. M.; Paziy, V.; Olaizola, B.; Vedia, V.; Bruce, A. M.; Roberts, O. J.; Smith, J. F.; Scheck, M.; Kröll, T.; Hartig, A.-L.; Ignatov, A.; Ilieva, S.; Lalkovski, S.; Mǎrginean, N.; Otsuka, T.; Shimizu, N.; Togashi, T.; Tsunoda, Y.

2017-11-01

Rapid shape changes are observed for neutron-rich nuclei with A around 100. In particular, a sudden onset of ground-state deformation is observed in the Zr and Sr isotopic chains at N = 60: Low-lying states in N ≤58 nuclei are nearly spherical, while those with N ≥60 have a rotational character. Nuclear lifetimes as short as a few picoseconds can be measured using fast-timing techniques with LaBr3(Ce) scintillators, yielding a key ingredient in the systematic study of the shape evolution in this region. We used neutron-induced fission of 241Pu and 235U to study lifetimes of excited states in fission fragments in the A ˜100 region with the EXILL-FATIMA array located at the PF1B cold neutron beam line at the Institut Laue-Langevin. In particular, we applied the generalized centroid difference method to deduce lifetimes of low-lying states for the nuclei 98Zr (N = 58), 100Zr, and 102Zr (N ≥60 ). The results are discussed in the context of the presumed phase transition in the Zr chain by comparing the experimental transition strengths with the theoretical calculations using the interacting boson model and the Monte Carlo shell model.

Malaria Parasite-Infected Erythrocytes Secrete PfCK1, the Plasmodium Homologue of the Pleiotropic Protein Kinase Casein Kinase 1

PubMed Central

Dorin-Semblat, Dominique; Demarta-Gatsi, Claudia; Hamelin, Romain; Armand, Florence; Carvalho, Teresa Gil; Moniatte, Marc; Doerig, Christian

2015-01-01

Casein kinase 1 (CK1) is a pleiotropic protein kinase implicated in several fundamental processes of eukaryotic cell biology. Plasmodium falciparum encodes a single CK1 isoform, PfCK1, that is expressed at all stages of the parasite’s life cycle. We have previously shown that the pfck1 gene cannot be disrupted, but that the locus can be modified if no loss-of-function is incurred, suggesting an important role for this kinase in intra-erythrocytic asexual proliferation. Here, we report on the use of parasite lines expressing GFP- or His-tagged PfCK1 from the endogenous locus to investigate (i) the dynamics of PfCK1 localisation during the asexual cycle in red blood cells, and (ii) potential interactors of PfCK1, so as to gain insight into the involvement of the enzyme in specific cellular processes. Immunofluorescence analysis reveals a dynamic localisation of PfCK1, with evidence for a pool of the enzyme being directed to the membrane of the host erythrocyte in the early stages of infection, followed by a predominantly intra-parasite localisation in trophozoites and schizonts and association with micronemes in merozoites. Furthermore, we present strong evidence that a pool of enzymatically active PfCK1 is secreted into the culture supernatant, demonstrating that PfCK1 is an ectokinase. Our interactome experiments and ensuing kinase assays using recombinant PfCK1 to phosphorylate putative interactors in vitro suggest an involvement of PfCK1 in many cellular processes such as mRNA splicing, protein trafficking, ribosomal, and host cell invasion. PMID:26629826

PHISTc protein family members localize to different subcellular organelles and bind Plasmodium falciparum major virulence factor PfEMP-1.

PubMed

Kumar, Vikash; Kaur, Jasweer; Singh, Amrit P; Singh, Vineeta; Bisht, Anjali; Panda, Jiban J; Mishra, Prakash C; Hora, Rachna

2018-01-01

Plasmodium falciparum encodes a novel repertoire of the Plasmodium helical interspersed subtelomeric (PHIST) family of exported proteins, which play diverse roles in infected red blood cells, contributing to malaria pathogenesis. PHIST proteins are central to parasite biology and modify human erythrocytes by interacting with parasite and host proteins. Here, we have attempted to understand the localization and function of two unexplored proteins of the PHISTc subfamily, PFD1140w and PF11_0503, and compared these with a well-characterized member, PFI1780w. We demonstrate that Phist domains assume different oligomeric states owing to a distinct array of subunit interface residues. Colocalization of a Maurer's cleft signature protein, P. falciparum skeleton-binding protein-1 (PfSBP-1), and P. falciparum erythrocyte membrane protein-1 (PfEMP-1) revealed different subcellular destinations for these PHIST members. We further show the binding of recombinant PHIST proteins to the cytoplasmic tail of PfEMP-1 and a novel interaction with PfSBP-1. Interestingly, PFD1140w interacts with PfEMP-1 and PfSBP-1 simultaneously in vitro leading to formation of a complex. These two distant PHISTc members also bind PfEMP-1 on distinct sites, despite sharing the Phist domain. Our data re-emphasize a supportive role for PHIST proteins in cytoadhesion, and identify a new binding partner, PfSBP-1, for members of this family. This information therefore adds another chapter to the understanding of P. falciparum biology and highlights the significance of the unexplored PHIST family. © 2017 Federation of European Biochemical Societies.

Preferential flows and soil moistures on a Benggang slope: Determined by the water and temperature co-monitoring

NASA Astrophysics Data System (ADS)

Tao, Yu; He, Yangbo; Duan, Xiaoqian; Zou, Ziqiang; Lin, Lirong; Chen, Jiazhou

2017-10-01

Soil preferential flow (PF) has important effects on rainfall infiltration, moisture distribution, and hydrological and ecological process; but it is very difficult to monitor and characterize on a slope. In this paper, soil water and soil temperature at 20, 40, 60, 80 cm depths in six positions were simultaneously monitored at high frequency to confirm the occurrence of PF at a typical Benggang slope underlain granite residual deposits, and to determine the interaction of soil moisture distribution and Benggang erosion. In the presence of PF, the soil temperature was first (half to one hour) governed by the rainwater temperature, then (more than one hour) governed by the upper soil temperature; in the absence of PF (only matrix flow, MF), the soil temperature was initially governed by the upper soil temperature, then by the rainwater temperature. The results confirmed the water replacement phenomenon in MF, thus it can be distinguished from PF by additional temperature monitoring. It indicates that high frequency moisture and temperature monitoring can determine the occurrence of PF and reveal the soil water movement. The distribution of soil water content and PF on the different positions of the slope showed that a higher frequency of PF resulted in a higher variation of average of water content. The frequency of PF at the lower position can be three times as that of the upper position, therefore, the variation coefficient of soil water content increased from 4.67% to 12.68% at the upper position to 8.18%-33.12% at the lower position, where the Benggang erosion (soil collapse) was more possible. The results suggest strong relationships between PF, soil water variation, and collapse activation near the Benggang wall.

Sulfur mobilization for Fe-S cluster assembly by the essential SUF pathway in the Plasmodium falciparum apicoplast and its inhibition.

PubMed

Charan, Manish; Singh, Nidhi; Kumar, Bijay; Srivastava, Kumkum; Siddiqi, Mohammad Imran; Habib, Saman

2014-06-01

The plastid of the malaria parasite, the apicoplast, is essential for parasite survival. It houses several pathways of bacterial origin that are considered attractive sites for drug intervention. Among these is the sulfur mobilization (SUF) pathway of Fe-S cluster biogenesis. Although the SUF pathway is essential for apicoplast maintenance and parasite survival, there has been limited biochemical investigation of its components and inhibitors of Plasmodium SUFs have not been identified. We report the characterization of two proteins, Plasmodium falciparum SufS (PfSufS) and PfSufE, that mobilize sulfur in the first step of Fe-S cluster assembly and confirm their exclusive localization to the apicoplast. The cysteine desulfurase activity of PfSufS is greatly enhanced by PfSufE, and the PfSufS-PfSufE complex is detected in vivo. Structural modeling of the complex reveals proximal positioning of conserved cysteine residues of the two proteins that would allow sulfide transfer from the PLP (pyridoxal phosphate) cofactor-bound active site of PfSufS. Sulfide release from the l-cysteine substrate catalyzed by PfSufS is inhibited by the PLP inhibitor d-cycloserine, which forms an adduct with PfSufS-bound PLP. d-Cycloserine is also inimical to parasite growth, with a 50% inhibitory concentration close to that reported for Mycobacterium tuberculosis, against which the drug is in clinical use. Our results establish the function of two proteins that mediate sulfur mobilization, the first step in the apicoplast SUF pathway, and provide a rationale for drug design based on inactivation of the PLP cofactor of PfSufS. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

Tracking Glideosome-associated protein 50 reveals the development and organization of the inner membrane complex of Plasmodium falciparum.

PubMed

Yeoman, Jeffrey A; Hanssen, Eric; Maier, Alexander G; Klonis, Nectarios; Maco, Bohumil; Baum, Jake; Turnbull, Lynne; Whitchurch, Cynthia B; Dixon, Matthew W A; Tilley, Leann

2011-04-01

The most deadly of the human malaria parasites, Plasmodium falciparum, has different stages specialized for invasion of hepatocytes, erythrocytes, and the mosquito gut wall. In each case, host cell invasion is powered by an actin-myosin motor complex that is linked to an inner membrane complex (IMC) via a membrane anchor called the glideosome-associated protein 50 (PfGAP50). We generated P. falciparum transfectants expressing green fluorescent protein (GFP) chimeras of PfGAP50 (PfGAP50-GFP). Using immunoprecipitation and fluorescence photobleaching, we show that C-terminally tagged PfGAP50-GFP can form a complex with endogenous copies of the linker protein PfGAP45 and the myosin A tail domain-interacting protein (MTIP). Full-length PfGAP50-GFP is located in the endoplasmic reticulum in early-stage parasites and then redistributes to apical caps during the formation of daughter merozoites. In the final stage of schizogony, the PfGAP50-GFP profile extends further around the merozoite surface. Three-dimensional (3D) structured illumination microscopy reveals the early-stage IMC as a doubly punctured flat ellipsoid that separates to form claw-shaped apposed structures. A GFP fusion of PfGAP50 lacking the C-terminal membrane anchor is misdirected to the parasitophorous vacuole. Replacement of the acid phosphatase homology domain of PfGAP50 with GFP appears to allow correct trafficking of the chimera but confers a growth disadvantage.

Cloning, sequence determination, and regulation of the ribonucleotide reductase subunits from Plasmodium falciparum: a target for antimalarial therapy.

PubMed Central

Rubin, H; Salem, J S; Li, L S; Yang, F D; Mama, S; Wang, Z M; Fisher, A; Hamann, C S; Cooperman, B S

1993-01-01

Malaria remains a leading cause of morbidity and mortality worldwide, accounting for more than one million deaths annually. We have focused on the reduction of ribonucleotides to 2'-deoxyribonucleotides, catalyzed by ribonucleotide reductase, which represents the rate-determining step in DNA replication as a target for antimalarial agents. We report the full-length DNA sequence corresponding to the large (PfR1) and small (PfR2) subunits of Plasmodium falciparum ribonucleotide reductase. The small subunit (PfR2) contains the major catalytic motif consisting of a tyrosyl radical and a dinuclear Fe site. Whereas PfR2 shares 59% amino acid identity with human R2, a striking sequence divergence between human R2 and PfR2 at the C terminus may provide a selective target for inhibition of the malarial enzyme. A synthetic oligopeptide corresponding to the C-terminal 7 residues of PfR2 inhibits mammalian ribonucleotide reductase at concentrations approximately 10-fold higher than that predicted to inhibit malarial R2. The gene encoding the large subunit (PfR1) contains a single intron. The cysteines thought to be involved in the reduction mechanism are conserved. In contrast to mammalian ribonucleotide reductase, the genes for PfR1 and PfR2 are located on the same chromosome and the accumulation of mRNAs for the two subunits follow different temporal patterns during the cell cycle. Images Fig. 2 Fig. 4 Fig. 5 PMID:8415692

Validation of the Spanish Version of the Food Allergy Quality of Life Questionnaire-Parent Form (S-FAQLQ-PF).

PubMed

Manso, L; Pineda, R; Huertas, B; Fernández-Rivas, M; Diéguez, M C; Cerecedo, I; Muriel, A; Fernández, F B; DunnGalvin, A; Antolín-Amérigo, D; De la Hoz, B

2017-01-01

Food allergy is an emerging health problem. Several questionnaires can be used to establish health-related quality of life (HRQOL) in food allergy patients. Current questionnaires should be translated in such a way that they take account of the culture of the country in which they are to be used. Objective: To translate and perform a cross-sectional validation of the Food Allergy Quality of Life Questionnaire-Parent Form (FAQLQ-PF). The parents of 54 children diagnosed with food allergy were recruited to assess the Spanish version of the FAQLQ-PF (S-FQLQ-PF). The S-FQLQ-PF was translated into Spanish according to WHO guidelines (including a forward-backward translation). The statistical analysis showed that feasibility, reliability, and internal consistency were very good for the global S-FAQLQ-PF score and for the different domains. Assessment of construct validity indicated that S-FAQLQ-PF has reduced capacity for measurement of HRQOL in younger children. Cross-sectional validation of the S-FAQLQ-PF demonstrated that HRQOL of a Spanish pediatric population was affected by patient age, severity of symptoms, and number of reactions. HRQOL was not affected by sex, food implicated, number of foods implicated, ingestion of the implicated food, or presence of anaphylaxis. Translation into Spanish and cultural validation of the FAQLQ-PF demonstrated the influence of factors, such as patient age, severity of symptoms, and number of reactions on the HRQOL of a pediatric Spanish population.

Genetic diversity of Plasmodium falciparum histidine-rich protein 2 (PfHRP2) and its effect on the performance of PfHRP2-based rapid diagnostic tests.

PubMed

Baker, Joanne; McCarthy, James; Gatton, Michelle; Kyle, Dennis E; Belizario, Vicente; Luchavez, Jennifer; Bell, David; Cheng, Qin

2005-09-01

Rising costs of antimalarial agents are increasing the demand for accurate diagnosis of malaria. Rapid diagnostic tests (RDTs) offer great potential to improve the diagnosis of malaria, particularly in remote areas. Many RDTs are based on the detection of Plasmodium falciparum histidine-rich protein (PfHRP) 2, but reports from field tests have questioned their sensitivity and reliability. We hypothesize that the variability in the results of PfHRP2-based RDTs is related to the variability in the target antigen. We tested this hypothesis by examining the genetic diversity of PfHRP2, which includes numerous amino acid repeats, in 75 P. falciparum lines and isolates originating from 19 countries and testing a subset of parasites by use of 2 PfHRP2-based RDTs. We observed extensive diversity in PfHRP2 sequences, both within and between countries. Logistic regression analysis indicated that 2 types of repeats were predictive of RDT detection sensitivity (87.5% accuracy), with predictions suggesting that only 84% of P. falciparum parasites in the Asia-Pacific region are likely to be detected at densities < or = 250 parasites/microL. Our data also indicated that PfHRP3 may play a role in the performance of PfHRP2-based RDTs. These findings provide an alternative explanation for the variable sensitivity in field tests of malaria RDTs that is not due to the quality of the RDTs.

Extraction of tryptophan with ionic liquids studied with molecular dynamics simulations.

PubMed

Seduraman, Abirami; Wu, Ping; Klähn, Marco

2012-01-12

Extraction of amino acids from aqueous solutions with ionic liquids (ILs) in biphasic systems is analyzed with molecular dynamics (MD) simulations. Extraction of tryptophan (TRP) with the imidazolium-based ILs [C(4)mim][PF(6)], [C(8)mim][PF(6)], and [C(8)mim][BF(4)] are considered as model cases. Solvation free energies of TRP are calculated with MD simulations and thermodynamic integration in combination with an empirical force field, whose parametrization is based on the liquid-phase charge distribution of the ILs. Calculated solvation free energies reproduce successfully all observed experimental trends according to the previously reported partition of TRP between water and IL phases. Water is present in ILs as a cosolvent, due to direct contact with the aqueous phase during extraction, and is found to play a major role in the extraction of TRP. Water improves solvation of cationic TRP by 7.8 and 5.1 kcal/mol in [C(4)mim][PF(6)] and [C(8)mim][PF(6)], respectively, which is in the case of [C(4)mim][PF(6)] sufficient to extract TRP. Extraction in [C(8)mim][PF(6)] is not feasible, since the hydrophobic octyl groups of the cations limit the water concentration in the IL. The solvation of cationic TRP is 2.4 kcal/mol less favorable in [C(8)mim][PF(6)] than in [C(4)mim][PF(6)]. Water improves the solvation of TRP in ILs mostly through dipole-dipole interactions with the polar backbone of TRP. Extraction is most efficient with [C(8)mim][BF(4)], where hydrophilic BF(4)(-) anions substantially increase the water concentration in the IL. Additionally, stronger direct electrostatic interactions of TRP with BF(4)(-) anions improve its solvation in the IL further. The solvation of cationic TRP in [C(8)mim][BF(4)] is 3.4 kcal/mol more favorable than in [C(8)mim][PF(6)]. Overall, the extractive power of the ILs correlates with the water saturation concentration of the IL phase, which in turn is determined by the hydrophilicity of the constituting ions. The results of this work identify relations between the extraction performance of ILs and the basic chemical properties of the ions, which provide guidelines that could contribute to the design of improved novel ILs for amino acid extraction.

The predictive value of ePAQ in the urodynamic diagnoses-A prospective cohort study.

PubMed

McCooty, Shanteela; Nightingale, Peter; Latthe, Pallavi

2018-01-01

To assess whether the electronic Personal Assessment Questionnaire-Pelvic Floor (ePAQ-PF) had accuracy in predicting the urodynamic diagnoses of Detrusor Overactivity (DO) and/or Urodynamic Stress Incontinence (USI). Tertiary urogynaecology unit linked to an academic university teaching hospital. Consecutive women who presented with lower urinary tract symptoms (LUTS) and were booked to have urodynamic studies. Women completed an ePAQ-PF prior to having urodynamics (UDS) by clinicians who were blinded to the ePAQ-PF results while conducting this procedure. Receiver Operating Characteristics (ROC) curves were constructed for predictive accuracy of overactive bladder (OAB) score in DO and of stress urinary incontinence (SUI) score in USI. Prospective cohort study designed to meet the requirements of the standards for reporting of diagnostic accuracy (STARD). 390 women with a mean age of 54.2 (range 21-92) years were recruited. The majority (n = 294; 75%) were White Caucasian and had two children (n = 157; 40.3%). Of them, 67.2% (n = 262) had DO and USI was confirmed in 21.5% (n = 84). The area under the ROC curve for DO was 0.704 (95% confidence interval 0.650-0.759) and for USI it was 0.731 (95% confidence interval 0.652-0.778). The OAB and SUI scores on the ePAQ-PF demonstrated that they are fair predictors in diagnosing DO and USI. As the OAB and SUI score on ePAQ-PF increased so did the likelihood of DO (up to a score of 75) and USI on UDS. © 2017 Wiley Periodicals, Inc.

Higher body mass index is associated with plantar fasciopathy/'plantar fasciitis': systematic review and meta-analysis of various clinical and imaging risk factors.

PubMed

van Leeuwen, K D B; Rogers, J; Winzenberg, T; van Middelkoop, M

2016-08-01

What (risk) factors are associated with plantar fasciopathy (PF)? Systematic review with meta-analyses. Patients with PF. All factors described in prospective, case-control or cross-sectional observational studies. 51 included studies (1 prospective, 46 case-control and 4 cross-sectional studies) evaluated a total of 104 variables. Pooling was possible for 12 variables. Higher body mass index (BMI) (BMI>27, OR 3.7 (95% CI 2.93 to 5.62)) in patients with PF was the only significant clinical association, and its effect was the strongest in the non-athletic subgroup. In people with PF compared to controls, pooled imaging data demonstrated a significantly thicker, hypoechogenic plantar fascia with increased vascular signal and perifascial fluid collection. In addition, people with PF were more likely to have a thicker loaded and unloaded heel fat pat, and bone findings, including a subcalcaneal spur and increased Tc-99 uptake. No significant difference was found in the extension of the first metatarsophalangeal joint. We found a consistent clinical association between higher BMI and plantar fasciopathy. This association may differ between athletic and non-athletic subgroups. While consistent evidence supports a range of bone and soft tissue abnormalities, there is lack of evidence for the dogma of clinical and mechanical measures of foot and ankle function. Clinicians can use this information in shared decision-making. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

In silico screening for Plasmodium falciparum enoyl-ACP reductase inhibitors

NASA Astrophysics Data System (ADS)

Lindert, Steffen; Tallorin, Lorillee; Nguyen, Quynh G.; Burkart, Michael D.; McCammon, J. Andrew

2015-01-01

The need for novel therapeutics against Plasmodium falciparum is urgent due to recent emergence of multi-drug resistant malaria parasites. Since fatty acids are essential for both the liver and blood stages of the malarial parasite, targeting fatty acid biosynthesis is a promising strategy for combatting P. falciparum. We present a combined computational and experimental study to identify novel inhibitors of enoyl-acyl carrier protein reductase ( PfENR) in the fatty acid biosynthesis pathway. A small-molecule database from ChemBridge was docked into three distinct PfENR crystal structures that provide multiple receptor conformations. Two different docking algorithms were used to generate a consensus score in order to rank possible small molecule hits. Our studies led to the identification of five low-micromolar pyrimidine dione inhibitors of PfENR.

Renal targeted delivery of triptolide by conjugation to the fragment peptide of human serum albumin.

PubMed

Yuan, Zhi-xiang; Wu, Xiao-juan; Mo, Jingxin; Wang, Yan-li; Xu, Chao-qun; Lim, Lee Yong

2015-08-01

We have previously demonstrated that peptide fragments (PFs) of the human serum albumin could be developed as potential renal targeting carriers, in particular, the peptide fragment, PF-A299-585 (A299-585 representing the amino acid sequence of the human serum albumin). In this paper, we conjugated triptolide (TP), the anti-inflammatory Chinese traditional medicine, to PF-A299-585 via a succinic acid spacer to give TPS-PF-A299-585 (TP loading 2.2% w/w). Compared with the free TP, TPS-PF-A299-585 exhibited comparable anti-inflammatory activity in the lipopolysaccharide stimulated MDCK cells, but was significantly less cytotoxic than the free drug. Accumulation of TPS-PF-A299-585 in the MDCK cells in vitro and in rodent kidneys in vivo was demonstrated using FITC-labeled TPS-PF-A299-585. Renal targeting was confirmed in vivo in a membranous nephropathic (MN) rodent model, where optical imaging and analyses of biochemical markers were combined to show that TPS-PF-A299-585 was capable of alleviating the characteristic symptoms of MN. The collective data affirm PF-A299-585 to be a useful carrier for targeting TP to the kidney. Copyright © 2015 Elsevier B.V. All rights reserved.