Free 2-propen-1-amine Derivative And Inclusion Complexes With β-cyclodextrin: Scanning Electron Microscopy, Dissolution, Cytotoxicity And Antimycobacterial Activity

Inclusion complexes and physical mixtures of isomeric mixture of E/Z (50:50) of 3-(4′-bromo-[1,1′-biphenyl]-4-yl)-3-(4-bromophenyl)-N,N- dimethyl-2-propen-1-amine (BBAP) and β-cyclodextrin (β-CD) in the molar proportion of 1:1 and 1:2 were analyzed by scanning electron microscopy. The dissolution behavior of BBAP and of the inclusion complexes were also evaluated for six hours. By scanning electron microscopy (SEM), it was possible to observe an inclusion complex formed between BBAP and β-CD by co-evaporation, either in the molar proportion of 1:1 or 1:2. In the physical mixtures, no complex was observed as previously detected by physicochemical analysis. The dissolution studies showed that the inclusion complexes BBAP/β-CD 1:1 and 1:2 released respectively 49.07 ± 1.48 and 40.26 ± 3.90% of BBAP during six hours. Free BBAP was less soluble than the inclusion complex and reached 9.00 ± 0.75% of dissolution. Biological assays, such as cytotoxicity to J774 macrophages and to a permanent lung fibroblast cell line (V79), indicated that the BBAP does not exhibit any additional toxic effect with the β-CD complexes. However, the complexes were less cytotoxic to V79 cells than the free form. The BBAP/β-CD inclusion complexes were more effective (MIC) than the free compound on several mycobacteria strains. Similar behavior was observed for BBAP/β-CD complexes and rifampicin, a front-line antitubercular drug, on M. tuberculosis H37Rv growing inside J774 macrophages.155682689Bibby, D.C., Davies, N.M., Tucker, I.G., (2000) Int. J. Pharm., 197, p. 1De Souza, A.O., Sato, D.N., Aily, D.C.G., Durán, N., (1998) J. Antimicrob. Chemother., 42, p. 407Pereira, D.G., De Castro, S.L., Durán, N., (1998) Acta Tropica, 69, p. 205De Souza, A.O., Santos Júnior, R.R., Ferreira-Júlio, J.F., Rodrigues, J.A., Melo, P.S., Haun, M., Sato, D.N., Durán, N., (2001) Eur. J. Med. Chem., 36, p. 843De Souza, A.O., Hemerly, F.P., Busollo, A.C., Melo, P.S., Machado, G.M.C., Miranda, C.C., Santa-Rita, R.M., Durán, N., (2002) J. Antimicrob. Chemother., 50, p. 629De Conti, R., Gimenez, S.M.N., Haun, M., Pilli, R.A., De Castro, S.L., Durán, N., (1996) Eur. J. Med. Chem., 31, p. 915De Souza, A.O., Santos Jr., R.R., Sato, D.N., Lima, H.O.S., Andrade-Santana, M.H., Alderete, J.B., Faljoni-Alario, A., Durán, N., (2000) Abstracts of the 29 a Reunião Anual Da Sociedade Brasileira de Bioquímica, , Caxambu, BrazilHiguchi, T., Connors, K.A., (1965) Adv. Anal. Chem. Instrum., 4, p. 117Collins, L.A., Franzblau, S.G., (1997) Antimicrob. Agents Chemother., 41, p. 1004Oh, Y.K., Nix, D.E., Straubinger, R.M., (1995) Antimicrob Agents Chemother., 39, p. 2104Cingi, M.R., De Angelis, I., Fortunati, E., Reggiani, D., Bianchi, V., Tiozzo, R., Zucco, F., (1991) Toxicol. In Vitro, 5, p. 119Denizot, F., Lang, R., (1986) J. Immun. Methods, 89, p. 271Borenfreund, E., Puerner, J.A., (1984) J. Tiss. Cult. Meth., 9, p. 7Melo, P.S., Maria, S.S., Vidal, B.C., Haun, M., Durán, N., (2000) In Vitro Cell Rev. Biol. Animal, 36, p. 539Melo, P.S., Durán, N., Haun, M., (2001) Toxicology, 159, p. 135Shrivastava, R., John, G.W., Rispat, G., Chevalier, A., Massingham, R., (1991) ATLA - Alt. Lab. Anim., 19, p. 39

Electromagnetic-field quantization and spontaneous decay in left-handed media

We present a quantization scheme for the electromagnetic field interacting with atomic systems in the presence of dispersing and absorbing magnetodielectric media, including left-handed material having negative real part of the refractive index. The theory is applied to the spontaneous decay of a two-level atom at the center of a spherical free-space cavity surrounded by magnetodielectric matter of overlapping band-gap zones. Results for both big and small cavities are presented, and the problem of local-field corrections within the real-cavity model is addressed.Comment: 15 pages, 5 figures, RevTe

Nonlinear Integer Programming

Research efforts of the past fifty years have led to a development of linear integer programming as a mature discipline of mathematical optimization. Such a level of maturity has not been reached when one considers nonlinear systems subject to integrality requirements for the variables. This chapter is dedicated to this topic. The primary goal is a study of a simple version of general nonlinear integer problems, where all constraints are still linear. Our focus is on the computational complexity of the problem, which varies significantly with the type of nonlinear objective function in combination with the underlying combinatorial structure. Numerous boundary cases of complexity emerge, which sometimes surprisingly lead even to polynomial time algorithms. We also cover recent successful approaches for more general classes of problems. Though no positive theoretical efficiency results are available, nor are they likely to ever be available, these seem to be the currently most successful and interesting approaches for solving practical problems. It is our belief that the study of algorithms motivated by theoretical considerations and those motivated by our desire to solve practical instances should and do inform one another. So it is with this viewpoint that we present the subject, and it is in this direction that we hope to spark further research.Comment: 57 pages. To appear in: M. J\"unger, T. Liebling, D. Naddef, G. Nemhauser, W. Pulleyblank, G. Reinelt, G. Rinaldi, and L. Wolsey (eds.), 50 Years of Integer Programming 1958--2008: The Early Years and State-of-the-Art Surveys, Springer-Verlag, 2009, ISBN 354068274

Update on the correlation of the highest energy cosmic rays with nearby extragalactic matter

Data collected by the Pierre Auger Observatory through 31 August 2007 showed evidence for anisotropy in the arrival directions of cosmic rays above the Greisen-Zatsepin-Kuz'min energy threshold, \nobreak{$6\times 10^{19}$eV}. The anisotropy was measured by the fraction of arrival directions that are less than $3.1^\circ$ from the position of an active galactic nucleus within 75 Mpc (using the V\'eron-Cetty and V\'eron $12^{\rm th}$ catalog). An updated measurement of this fraction is reported here using the arrival directions of cosmic rays recorded above the same energy threshold through 31 December 2009. The number of arrival directions has increased from 27 to 69, allowing a more precise measurement. The correlating fraction is $(38^{+7}_{-6})$, compared with $21$ expected for isotropic cosmic rays. This is down from the early estimate of $(69^{+11}_{-13})$. The enlarged set of arrival directions is examined also in relation to other populations of nearby extragalactic objects: galaxies in the 2 Microns All Sky Survey and active galactic nuclei detected in hard X-rays by the Swift Burst Alert Telescope. A celestial region around the position of the radiogalaxy Cen A has the largest excess of arrival directions relative to isotropic expectations. The 2-point autocorrelation function is shown for the enlarged set of arrival directions and compared to the isotropic expectation.Comment: Accepted for publication in Astroparticle Physics on 31 August 201

The Fluorescence Detector of the Pierre Auger Observatory

The Pierre Auger Observatory is a hybrid detector for ultra-high energy cosmic rays. It combines a surface array to measure secondary particles at ground level together with a fluorescence detector to measure the development of air showers in the atmosphere above the array. The fluorescence detector comprises 24 large telescopes specialized for measuring the nitrogen fluorescence caused by charged particles of cosmic ray air showers. In this paper we describe the components of the fluorescence detector including its optical system, the design of the camera, the electronics, and the systems for relative and absolute calibration. We also discuss the operation and the monitoring of the detector. Finally, we evaluate the detector performance and precision of shower reconstructions.Comment: 53 pages. Submitted to Nuclear Instruments and Methods in Physics Research Section

Advanced functionality for radio analysis in the Offline software framework of the Pierre Auger Observatory

The advent of the Auger Engineering Radio Array (AERA) necessitates the development of a powerful framework for the analysis of radio measurements of cosmic ray air showers. As AERA performs "radio-hybrid" measurements of air shower radio emission in coincidence with the surface particle detectors and fluorescence telescopes of the Pierre Auger Observatory, the radio analysis functionality had to be incorporated in the existing hybrid analysis solutions for fluoresence and surface detector data. This goal has been achieved in a natural way by extending the existing Auger Offline software framework with radio functionality. In this article, we lay out the design, highlights and features of the radio extension implemented in the Auger Offline framework. Its functionality has achieved a high degree of sophistication and offers advanced features such as vectorial reconstruction of the electric field, advanced signal processing algorithms, a transparent and efficient handling of FFTs, a very detailed simulation of detector effects, and the read-in of multiple data formats including data from various radio simulation codes. The source code of this radio functionality can be made available to interested parties on request.Comment: accepted for publication in NIM A, 13 pages, minor corrections to author list and references in v

Search for First Harmonic Modulation in the Right Ascension Distribution of Cosmic Rays Detected at the Pierre Auger Observatory

We present the results of searches for dipolar-type anisotropies in different energy ranges above $2.5\times 10^{17}$ eV with the surface detector array of the Pierre Auger Observatory, reporting on both the phase and the amplitude measurements of the first harmonic modulation in the right-ascension distribution. Upper limits on the amplitudes are obtained, which provide the most stringent bounds at present, being below 2% at 99% $C.L.$ for EeV energies. We also compare our results to those of previous experiments as well as with some theoretical expectations.Comment: 28 pages, 11 figure