Razvoj matriksnih sustava za transdermalnu isporuku pentazocina: In vitro/in vivo ispitivanje

The present study aimed to develop hydroxypropyl methylcellulose based transdermal delivery of pentazocine. In formulations containing lower proportions of polymer, the drug released followed the Higuchi kinetics while, with an increase in polymer content, it followed the zero-order release kinetics. Release exponent (n) values imply that the release of pentazocine from matrices was non-Fickian. FT-IR, DSC and XRD studies indicated no interaction between drug and polymer. The in vitro dissolution rate constant, dissolution half-life and pharmacokinetic parameters (Cmax, tmax, AUC(s), t1/2, Kel, and MRT) were evaluated statistically by two-way ANOVA. A significant difference was observed between but not within the tested products. Statistically, a good correlation was found between per cent of drug absorbed from patches vs. Cmax, and AUC(s). A good correlation was also observed when per cent drug released was correlated with the blood drug concentration obtained at the same time point. The results of this study indicate that the polymeric matrix films of pentazocine hold potential for transdermal drug delivery.U radu je opisan razvoj transdermalnih sustava na bazi hidroksipropil metilceluloze za isporuku pentazocina. U pripravcima koji sadrže manje udjele polimera, otpuštanje lijeka slijedilo je Higuchijevu kinetiku. Međutim, ako je udio polimera veći oslobađanje je najbolje odgovaralo kinetici nultog reda. Vrijednost eksponenta n implicira da oslobađanje pentazocina iz matriksa nije po Fickovom zakonu. FT-IR, DSC i X RD studije ukazuju da nema interakcije između ljekovite tvari i polimera. In vitro konstanta oslobađanja, poluvrijeme oslobađanja i farmakokinetički parametri (Cmax, tmax, AUC(s), t1/2, Kel, i MRT) procijenjeni su statistički koristeći ANOVA program. Značajna razlika primijećena je između, ali ne i unutar testiranih pripravaka. Pronađena je dobra korelacija između lijeka apsorbiranog iz flastera i Cmax i AUC(s) te oslobođenog lijeka i koncentracije lijeka u krvi. Rezultati ukazuju da su polimerni matriksni filmovi pentazocina potencijalno dobri sustavi za transdermalnu primjenu lijeka

Nucleation of the electroactive γ phase and enhancement of the optical transparency in low filler content poly(vinylidene)/clay nanocomposites

Poly(vinylidene fluoride), PVDF, based nanocomposites with different clays structures have been processed by solvent casting and melt crystallisation. Depending on the melting temperature of the polymer, the nanocomposite recrystalises in the electroactive or non electroactive β-phase of the polymer. This fact is related to the thermal behaviour of the clay. For montmorillonite clay, the full crystallisation of the electroactiveγ-phase occurs for clay contents lower than 0.5 wt%, allowing the nanocomposites to maintain the mechanical properties of the polymer matrix. The electroactivity of the material has been proven by measuring the piezoelectric d33 response of the material. The obtained value of d33 is -7 pC/N, lower than in β-PVDF obtained by mechanical stretching, but still among the largest coefficients obtained for polymers. Further, the optical transmittance in the visible range is strongly enhanced with respect to the transmittance of the pure polymer. Finally, it is demonstrated that the nucleation of the β-phase can be also obtained in other clays, such as in kaolinite and laponite.Fundação para a Ciência e a Tecnologia (FCT) - NANO/NMed-SD/0156/2007, PTDC/CTM/69316/2006, PTDC/CTM-NAN/112574/2009, SFRH/BD/62507/2009.FEDER funds through the "Programa Operacional Factores de Competitividade – COMPETECOST Action MP1003, the ‘European Scientific Network for Artificial Muscles’ (ESNAM)

Chaperones convert the energy from ATP into the nonequilibrium stabilization of native proteins.

During and after protein translation, molecular chaperones require ATP hydrolysis to favor the native folding of their substrates and, under stress, to avoid aggregation and revert misfolding. Why do some chaperones need ATP, and what are the consequences of the energy contributed by the ATPase cycle? Here, we used biochemical assays and physical modeling to show that the bacterial chaperones GroEL (Hsp60) and DnaK (Hsp70) both use part of the energy from ATP hydrolysis to restore the native state of their substrates, even under denaturing conditions in which the native state is thermodynamically unstable. Consistently with thermodynamics, upon exhaustion of ATP, the metastable native chaperone products spontaneously revert to their equilibrium non-native states. In the presence of ATPase chaperones, some proteins may thus behave as open ATP-driven, nonequilibrium systems whose fate is only partially determined by equilibrium thermodynamics

Modulation of EEG spectral edge frequency during patterned pneumatic oral stimulation in preterm infants

Background—Stimulation of the nervous system plays a central role in brain development and neurodevelopmental outcome. Thalamocortical and corticocortical development is diminished in premature infants and correlated to electroencephalography (EEG) progression. The purpose of this study was to determine the effects of orocutaneous stimulation on the modulation of spectral edge frequency, fc=90% (SEF-90) derived from EEG recordings in preterm infants. Methods—Twenty two preterm infants were randomized to experimental and control conditions. Pulsed orocutaneous stimulation was presented during gavage feedings begun at around 32 weeks postmenstrual age (PMA). The SEF-90 was derived from 2-channel EEG recordings. Results—Compared to the control condition, the pulsed orocutaneous stimulation produced a significant reorganization of SEF-90 in the left (p = 0.005) and right (p \u3c 0.0001) hemispheres. Notably, the left and right hemisphere showed a reversal in the polarity of frequency shift, demonstrating hemispheric asymmetry in the frequency domain. Pulsed orocutaneous stimulation also produced a significant pattern of short term cortical adaptation and a long term neural adaptation manifest as a 0.5 Hz elevation in SEF-90 after repeated stimulation sessions. Conclusion—This is the first study to demonstrate the modulating effects of a servo-controlled oral somatosensory input on the spectral features of EEG activity in preterm infants

Data-driven modeling of electron recoil nucleation in PICO C3F8 bubble chambers

[EN] The primary advantage of moderately superheated bubble chamber detectors is their simultaneous sensitivity to nuclear recoils from weakly interacting massive particle (WIMP) dark matter and insensitivity to electron recoil backgrounds. A comprehensive analysis of PICO gamma calibration data demonstrates for the first time that electron recoils in C3F8 scale in accordance with a new nucleation mechanism, rather than one driven by a hot spike as previously supposed. Using this semiempirical model, bubble chamber nucleation thresholds may be tuned to be sensitive to lower energy nuclear recoils while maintaining excellent electron recoil rejection. The PICO-40L detector will exploit this model to achieve thermodynamic thresholds as low as 2.8 keV while being dominated by single-scatter events from coherent elastic neutrino-nucleus scattering of solar neutrinos. In one year of operation, PICO-401, can improve existing leading limits from PICO on spin-dependent WIMP-proton coupling by nearly an order of magnitude for WIMP masses greater than 3 GeV c(-2) and will have the ability to surpass all existing non-xenon bounds on spin-independent WIMP-nucleon coupling for WIMP masses from 3 to 40 GeV c(-2).The PICO Collaboration wishes to thank SNOLAB and its staff for support through underground space, logistical and technical services. SNOLAB operations are supported by the Canada Foundation for Innovation and the Province of Ontario Ministry of Research and Innovation, with underground access provided by Vale at the Creighton mine site. We wish to acknowledge the support of the Natural Sciences and Engineering Research Council of Canada (NSERC) and the Canada Foundation for Innovation (CFI) for funding. We acknowledge the support from National Science Foundation (NSF) (Grants No. 0919526, No. 1506337, No. 1242637, No. 1205987, and No. 1806722). We acknowledge that this work is supported by the U.S. Department of Energy (DOE) Office of Science, Office of High Energy Physics (under Award No. DE-SC-0012161), by DGAPA-UNAM (PAPIIT No. IA100118) and Consejo Nacional de Ciencia y Tecnología (CONACyT, M¿exico, Grants No. 252167 and No. A1-S-8960), by the Department of Atomic Energy (DAE), Government of India, under the Centre for AstroParticle Physics II project (CAPP-II) at the Saha Institute of Nuclear Physics (SINP), European Regional Development Fund¿Project ¿Engineering Applications of Microworld Physics¿ (Project No. CZ.02.1.01/0.0/0.0/ 16_019/0000766), and the Spanish Ministerio de Ciencia, Innovación y Universidades (Red Consolider MultiDark, Grant No. FPA2017-90566-REDC). This work is partially supported by the Kavli Institute for Cosmological Physics at the University of Chicago through NSF Grant No. 1125897, and an endowment from the Kavli Foundation and its founder Fred Kavli. We also wish to acknowledge the support from Fermi National Accelerator Laboratory under Contract No. DE-AC02-07CH11359, and Pacific Northwest National Laboratory, which is operated by Battelle for the U.S. Department of Energy under Contract No. DE-AC05- 76RL01830. We also thank Compute Canada [75] and the Center for Advanced Computing, ACENET, Calcul Qu¿ebec, Compute Ontario, and WestGrid for computational support.Amole, C.; Ardid Ramírez, M.; Arnquist, I.; Asner, DM.; Baxter, D.; Behnke, E.; Bressler, M.... (2019). Data-driven modeling of electron recoil nucleation in PICO C3F8 bubble chambers. Physical Review D: covering particles, fields, gravitation, and cosmology. 100(8):1-18. https://doi.org/10.1103/PhysRevD.100.082006S1181008Amole, C., Ardid, M., Arnquist, I. J., Asner, D. M., Baxter, D., Behnke, E., … Chen, C. J. (2019). Dark matter search results from the complete exposure of the PICO-60 C3F8 bubble chamber. 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Il Nuovo Cimento A, 107(2), 291-298. doi:10.1007/bf02781560Amole, C., Ardid, M., Asner, D. M., Baxter, D., Behnke, E., Bhattacharjee, P., … Broemmelsiek, D. (2016). Dark matter search results from the PICO-60CF3Ibubble chamber. Physical Review D, 93(5). doi:10.1103/physrevd.93.052014Amole, C., Ardid, M., Arnquist, I. J., Asner, D. M., Baxter, D., Behnke, E., … Campion, P. (2017). Dark Matter Search Results from the PICO−60 C3F8 Bubble Chamber. Physical Review Letters, 118(25). doi:10.1103/physrevlett.118.251301Amole, C., Ardid, M., Arnquist, I. J., Asner, D. M., Baxter, D., Behnke, E., … Brice, S. J. (2016). Improved dark matter search results from PICO-2L Run 2. Physical Review D, 93(6). doi:10.1103/physrevd.93.061101Amole, C., Ardid, M., Asner, D. M., Baxter, D., Behnke, E., Bhattacharjee, P., … Broemmelsiek, D. (2015). Dark Matter Search Results from the PICO-2LC3F8Bubble Chamber. Physical Review Letters, 114(23). doi:10.1103/physrevlett.114.231302Hasert, F. 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Nuclear Instruments and Methods in Physics Research Section A: Accelerators, Spectrometers, Detectors and Associated Equipment, 513(3), 550-558. doi:10.1016/j.nima.2003.06.012Archambault, S., Aubin, F., Auger, M., Beleshi, M., Behnke, E., … Behnke, J. (2011). New insights into particle detection with superheated liquids. New Journal of Physics, 13(4), 043006. doi:10.1088/1367-2630/13/4/043006Glaser, D. A. (1954). Progress report on the development of bubble chambers. Il Nuovo Cimento, 11(S2), 361-368. doi:10.1007/bf02781098Fabian, B. N., Place, R. L., Riley, W. A., Sims, W. H., & Kenney, V. P. (1963). Density of Particle Tracks in the Hydrogen Bubble Chamber. Review of Scientific Instruments, 34(5), 484-495. doi:10.1063/1.1718415Willis, W. J., Fowler, E. C., & Rahm, D. C. (1957). Bubble Density in a Propane Bubble Chamber. Physical Review, 108(4), 1046-1047. doi:10.1103/physrev.108.1046Hahn, B., & Hugentobler, E. (1960). 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Physical Review Letters, 114(14). doi:10.1103/physrevlett.114.141301Ruppin, F., Billard, J., Figueroa-Feliciano, E., & Strigari, L. (2014). Complementarity of dark matter detectors in light of the neutrino background. Physical Review D, 90(8). doi:10.1103/physrevd.90.083510Felizardo, M., Girard, T. A., Morlat, T., Fernandes, A. C., Ramos, A. R., Marques, J. G., … Marques, R. (2014). The SIMPLE Phase II dark matter search. Physical Review D, 89(7). doi:10.1103/physrevd.89.072013Adrián-Martínez, S., Albert, A., André, M., Anton, G., Ardid, M., Aubert, J.-J., … Basa, S. (2016). Limits on dark matter annihilation in the sun using the ANTARES neutrino telescope. Physics Letters B, 759, 69-74. doi:10.1016/j.physletb.2016.05.019Adrián-Martínez, S., Albert, A., André, M., Anton, G., Ardid, M., Aubert, J.-J., … Basa, S. (2016). A search for Secluded Dark Matter in the Sun with the ANTARES neutrino telescope. Journal of Cosmology and Astroparticle Physics, 2016(05), 016-016. doi:10.1088/1475-7516/2016/05/016Aprile, E., Aalbers, J., Agostini, F., Alfonsi, M., Althueser, L., Amaro, F. D., … Bauermeister, B. (2018). Dark Matter Search Results from a One Ton-Year Exposure of XENON1T. Physical Review Letters, 121(11). doi:10.1103/physrevlett.121.111302Akerib, D. S., Alsum, S., Araújo, H. M., Bai, X., Bailey, A. J., Balajthy, J., … Biesiadzinski, T. P. (2017). Results from a Search for Dark Matter in the Complete LUX Exposure. Physical Review Letters, 118(2). doi:10.1103/physrevlett.118.021303Agnes, P., Albuquerque, I. F. M., Alexander, T., Alton, A. K., Araujo, G. R., Asner, D. M., … Batignani, G. (2018). Low-Mass Dark Matter Search with the DarkSide-50 Experiment. Physical Review Letters, 121(8). doi:10.1103/physrevlett.121.081307Agnes, P., Albuquerque, I. F. M., Alexander, T., Alton, A. K., Araujo, G. R., Ave, M., … Biery, K. (2018). DarkSide-50 532-day dark matter search with low-radioactivity argon. Physical Review D, 98(10). doi:10.1103/physrevd.98.102006Agnese, R., Anderson, A. J., Aralis, T., Aramaki, T., Arnquist, I. J., Baker, W., … Bauer, D. A. (2018). Low-mass dark matter search with CDMSlite. Physical Review D, 97(2). doi:10.1103/physrevd.97.022002Agnese, R., Aramaki, T., Arnquist, I. J., Baker, W., Balakishiyeva, D., Banik, S., … Binder, T. (2018). Results from the Super Cryogenic Dark Matter Search Experiment at Soudan. Physical Review Letters, 120(6). doi:10.1103/physrevlett.120.061802Hehn, L., Armengaud, E., Arnaud, Q., Augier, C., Benoît, A., Bergé, L., … Yakushev, E. (2016). Improved EDELWEISS-III sensitivity for low-mass WIMPs using a profile likelihood approach. The European Physical Journal C, 76(10). doi:10.1140/epjc/s10052-016-4388-yTolman, R. C. (1949). The Effect of Droplet Size on Surface Tension. The Journal of Chemical Physics, 17(3), 333-337. doi:10.1063/1.1747247Kirkwood, J. 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Performance and Stability of Pearl Millet Varieties for Grain Yield and Micronutrients in Arid and Semi-Arid Regions of India

Pearl millet [Pennisetum glaucum (L.) R. Br.] is grown under both arid and semi-arid conditions in India, where other cereals are hard to grow. Pearl millet cultivars, hybrids, and OPVs (open pollinated varieties) are tested and released by the All India Coordinated Research Project on Pearl Millet (AICRP-PM) across three zones (A1, A, and B) that are classified based on rainfall pattern. Except in locations with extreme weather conditions, hybrids dominate pearl millet growing areas, which can be attributed to hybrid vigor and the active role of the private sector. The importance of OPVs cannot be ruled out, owing to wider adaptation, lower input cost, and timely seed availability to subsidiary farmers cultivating this crop. This study was conducted to scrutinize the presently used test locations for evaluation of pearl millet OPVs across India, identify the best OPVs across locations, and determine the variation in grain Fe and Zn contents across locations in these regions. Six varieties were evaluated across 20 locations in A1 and A (pooled as A) and B zones along with three common checks and additional three zonal adapted checks in the respective zones during the 2019 rainy season. Recorded data on yield and quality traits were analyzed using genotype main effects and genotype × environment interaction biplot method. The genotype × environment (G × E) interaction was found to be highly significant for all the grain yield and agronomic traits and for both micronutrients (iron and zinc). However, genotypic effect (G) was four (productive tillers) to 49 (grain Fe content) times that of G × E interaction effect for various traits across zones that show the flexibility of OPVs. Ananthapuramu is the ideal test site for selecting pearl millet cultivars effectively for adaptation across India, while Ananthapuramu, Perumallapalle, and Gurugram can also be used as initial testing locations. OPVs MP 599 and MP 600 are identified as ideal genotypes, because they showed higher grain and fodder yields and stability compared with other cultivars. Iron and zinc concentration showed highly significant positive correlation (across environment = 0.83; p < 0.01), indicating possibility of simultaneous effective selection for both traits. Three common checks were found to be significantly low yielders than the test entries or zonal checks in individual zones and across India, indicating the potential of genetic improvement through OPVs

Conservation of the S10-spc-α Locus within Otherwise Highly Plastic Genomes Provides Phylogenetic Insight into the Genus Leptospira

S10-spc-α is a 17.5 kb cluster of 32 genes encoding ribosomal proteins. This locus has an unusual composition and organization in Leptospira interrogans. We demonstrate the highly conserved nature of this region among diverse Leptospira and show its utility as a phylogenetically informative region. Comparative analyses were performed by PCR using primer sets covering the whole locus. Correctly sized fragments were obtained by PCR from all L. interrogans strains tested for each primer set indicating that this locus is well conserved in this species. Few differences were detected in amplification profiles between different pathogenic species, indicating that the S10-spc-α locus is conserved among pathogenic Leptospira. In contrast, PCR analysis of this locus using DNA from saprophytic Leptospira species and species with an intermediate pathogenic capacity generated varied results. Sequence alignment of the S10-spc-α locus from two pathogenic species, L. interrogans and L. borgpetersenii, with the corresponding locus from the saprophyte L. biflexa serovar Patoc showed that genetic organization of this locus is well conserved within Leptospira. Multilocus sequence typing (MLST) of four conserved regions resulted in the construction of well-defined phylogenetic trees that help resolve questions about the interrelationships of pathogenic Leptospira. Based on the results of secY sequence analysis, we found that reliable species identification of pathogenic Leptospira is possible by comparative analysis of a 245 bp region commonly used as a target for diagnostic PCR for leptospirosis. Comparative analysis of Leptospira strains revealed that strain H6 previously classified as L. inadai actually belongs to the pathogenic species L. interrogans and that L. meyeri strain ICF phylogenetically co-localized with the pathogenic clusters. These findings demonstrate that the S10-spc-α locus is highly conserved throughout the genus and may be more useful in comparing evolution of the genus than loci studied previously

Dark Matter Search Results from the PICO-60C(3)F(8) Bubble Chamber

[EN] New results are reported from the operation of the PICO-60 dark matter detector, a bubble chamber filled with 52 kg of C3F8 located in the SNOLAB underground laboratory. As in previous PICO bubble chambers, PICO-60 C3F8 exhibits excellent electron recoil and alpha decay rejection, and the observed multiple-scattering neutron rate indicates a single-scatter neutron background of less than one event per month. A blind analysis of an efficiency-corrected 1167-kg day exposure at a 3.3-keV thermodynamic threshold reveals no single-scattering nuclear recoil candidates, consistent with the predicted background. These results set the most stringent direct-detection constraint to date on the weakly interacting massive particle (WIMP)-proton spin-dependent cross section at 3.4 x 10(-41) cm(2) for a 30-GeVc(-2) WIMP, more than 1 order of magnitude improvement from previous PICO results.The PICO Collaboration wishes to thank SNOLAB and its staff for support through underground space, logistical, and technical services. SNOLAB operations are supported by the Canada Foundation for Innovation and the Province of Ontario Ministry of Research and Innovation, with underground access provided by Vale at the Creighton mine site. We are grateful to Kristian Hahn and Stanislava Sevova of Northwestern University and Bjorn Penning of the University of Bristol for their assistance and useful discussion. We wish to acknowledge the support of the Natural Sciences and Engineering Research Council of Canada (NSERC) and the Canada Foundation for Innovation (CFI) for funding. We acknowledge the support from National Science Foundation (NSF) (Grants No. 0919526, No. 1506337, No. 1242637, and No. 1205987). We acknowledge that this work is supported by the U.S. Department of Energy (DOE) Office of Science, Office of High Energy Physics (under Award No. DE-SC-0012161), by a DOE Office of Science Graduate Student Research (SCGSR) award, by Direccion General Asuntos del Personal Academico, Universidad Nacional Autonoma de Mexico (DGAPA-UNAM) through the grant Programa de Apoyo a Proyectos de Investigacion e Innovacion Tecnologica (PAPIIT) No. IA100316 and by Consejo Nacional de Ciencia y Tecnologia (CONACyT) (Mexico) through Grant No. 252167, by the Department of Atomic Energy (DAE), the Government of India, under the Center of AstroParticle Physics II project (CAPP-II) at Saha Institute of Nuclear Physics (SINP), by the Czech Ministry of Education, Youth and Sports (Grant No. LM2015072), and by the Spanish Ministerio de Economia y Competitividad, Consolider MultiDark (Grant No. CSD2009-00064). This work is partially supported by the Kavli Institute for Cosmological Physics at the University of Chicago through NSF Grant No. 1125897, and an endowment from the Kavli Foundation and its founder Fred Kavli. We also wish to acknowledge the support from Fermi National Accelerator Laboratory under Contract No. De-AC02-07CH11359, and Pacific Northwest National Laboratory, which is operated by Battelle for the U.S. Department of Energy under Contract No. DE-AC05-76RL01830. We also thank Compute Canada and the Center for Advanced Computing, ACENET, Calcul Quebec, Compute Ontario, and WestGrid for the computational support.Amole, C.; Ardid Ramírez, M.; Arnquist, I.; Asner, DM.; Baxter, D.; Behnke, E.; Bhattacharjee, P.... (2017). Dark Matter Search Results from the PICO-60C(3)F(8) Bubble Chamber. Physical Review Letters. 118(25). https://doi.org/10.1103/PhysRevLett.118.251301S11825Olive, K. A. (2014). Review of Particle Physics. 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