2-Acetylpyridine- and 2-benzoylpyridine-derived hydrazones and their gallium(III) complexes are highly cytotoxic to glioma cells

2-Acetylpyridine-phenylhydrazone (H2AcPh), its para-chlorophenylhydrazone (H2AcpClPh) and para-nitrophenylhydrazone (H2AcpNO(2)Ph) analogues, the corresponding 2-benzoylpyridine-derived hydrazones (H2BzPh, H2BzpClPh and H2BzpNO(2)Ph) and their gallium(III) complexes were assayed for their cytotoxic activity against U87 (expressing wild-type p53 protein) and T98 (expressing mutant p53 protein) glioma cells. IC50 values against both glioma cells and against the MRC5 (human fetal lung fibroblast) lineage were obtained for the hydrazones, but not for their gallium(III) complexes, due to their low solubility. Hydrazones were highly cytotoxic at nanomolar doses against U87 and T98 cells. The therapeutic indexes (TI = IC50MRC5/IC50glioma) were 2-660 for T98 cells and 28-5000 for U87 cells, indicating that the studied hydrazones could be good antitumor drug candidates to treat brain tumors. (C) 2012 Elsevier Masson SAS. All rights reserved.

Field dependent transition to the non-linear regime in magnetic hyperthermia experiments: Comparison between maghemite, copper, zinc, nickel and cobalt ferrite nanoparticles of similar sizes

Further advances in magnetic hyperthermia might be limited by biological constraints, such as using sufficiently low frequencies and low field amplitudes to inhibit harmful eddy currents inside the patient's body. These incite the need to optimize the heating efficiency of the nanoparticles, referred to as the specific absorption rate (SAR). Among the several properties currently under research, one of particular importance is the transition from the linear to the non-linear regime that takes place as the field amplitude is increased, an aspect where the magnetic anisotropy is expected to play a fundamental role. In this paper we investigate the heating properties of cobalt ferrite and maghemite nanoparticles under the influence of a 500 kHz sinusoidal magnetic field with varying amplitude, up to 134 Oe. The particles were characterized by TEM, XRD, FMR and VSM, from which most relevant morphological, structural and magnetic properties were inferred. Both materials have similar size distributions and saturation magnetization, but strikingly different magnetic anisotropies. From magnetic hyperthermia experiments we found that, while at low fields maghemite is the best nanomaterial for hyperthermia applications, above a critical field, close to the transition from the linear to the non-linear regime, cobalt ferrite becomes more efficient. The results were also analyzed with respect to the energy conversion efficiency and compared with dynamic hysteresis simulations. Additional analysis with nickel, zinc and copper-ferrite nanoparticles of similar sizes confirmed the importance of the magnetic anisotropy and the damping factor. Further, the analysis of the characterization parameters suggested core-shell nanostructures, probably due to a surface passivation process during the nanoparticle synthesis. Finally, we discussed the effect of particle-particle interactions and its consequences, in particular regarding discrepancies between estimated parameters and expected theoretical predictions. Copyright 2012 Author(s). This article is distributed under a Creative Commons Attribution 3.0 Unported License. [http://dx.doi. org/10.1063/1.4739533]

Synthesis, Biological Evaluation, And Molecular Modeling of Chalcone Derivatives As Potent Inhibitors of Mycobacterium tuberculosis Protein Tyrosine Phosphatases (PtpA and PtpB)

Tuberculosis (TB) is a major infectious disease caused by Mycobacterium tuberculosis (Mtb). According to the World Health Organization (WHO), about 1.8 million people die from TB and 10 million new cases are recorded each year. Recently, a new series of naphthylchalcones has been identified as inhibitors of Mtb protein tyrosine phosphatases (PTPs). In this work, 100 chalcones were designed, synthesized, and investigated for their inhibitory properties against MtbPtps. Structure-activity relationships (SAR) were developed, leading to the discovery of new potent inhibitors with IC50 values in the low-micromolar range. Kinetic studies revealed competitive inhibition and high selectivity toward the Mtb enzymes. Molecular modeling investigations were carried out with the aim of revealing the most relevant structural requirements underlying the binding affinity and selectivity of this series of inhibitors as potential anti-TB drugs.

The relationship between gamma Cassiopeiae's X-ray emission and its circumstellar environment

gamma Cas is the prototypical classical Be star and is recently best known for its variable hard X-ray emission. To elucidate the reasons for this emission, we mounted a multiwavelength campaign in 2010 centered around four XMM-Newton observations. The observational techniques included long baseline optical interferometry (LBOI) from two instruments at CHARA, photometry carried out by an automated photometric telescope and H alpha observations. Because gamma Cas is also known to be in a binary, we measured radial velocities from the H alpha line and redetermined its period as 203.55 +/- 0.20 days and its eccentricity as near zero. The LBOI observations suggest that the star's decretion disk was axisymmetric in 2010, has an system inclination angle near 45 degrees, and a larger radius than previously reported. In addition, the Be star began an "outburst" at the beginning of our campaign, made visible by a brightening and reddening of the disk during our campaign and beyond. Our analyses of the new high resolution spectra disclosed many attributes also found from spectra obtained in 2001 (Chandra) and 2004 (XMM-Newton). As well as a dominant hot (approximate to 14 keV) thermal component, the familiar attributes included: (i) a fluorescent feature of Fe K even stronger than observed at previous times; (ii) strong lines of N VII and Ne XI lines indicative of overabundances; and (iii) a subsolar Fe abundance from K-shell lines but a solar abundance from L-shell ions. We also found that two absorption columns are required to fit the continuum. While the first one maintained its historical average of 1 x 10(21) cm(-2), the second was very large and doubled to 7.4 x 10(23) cm(-2) during our X-ray observations. Although we found no clear relation between this column density and orbital phase, it correlates well with the disk brightening and reddening both in the 2010 and earlier observations. Thus, the inference from this study is that much (perhaps all?) of the X-ray emission from this source originates behind matter ejected by gamma Cas into our line of sight.

Beyond the diffraction limit of optical/IR interferometers I. Angular diameter and rotation parameters of Achernar from differential phases

Context. Spectrally resolved long-baseline optical/IR interferometry of rotating stars opens perspectives to investigate their fundamental parameters and the physical mechanisms that govern their interior, photosphere, and circumstellar envelope structures. Aims. Based on the signatures of stellar rotation on observed interferometric wavelength-differential phases, we aim to measure angular diameters, rotation velocities, and orientation of stellar rotation axes. Methods. We used the AMBER focal instrument at ESO-VLTI in its high-spectral resolution mode to record interferometric data on the fast rotator Achernar. Differential phases centered on the hydrogen Br gamma line (K band) were obtained during four almost consecutive nights with a continuous Earth-rotation synthesis during similar to 5h/night, corresponding to similar to 60 degrees position angle coverage per baseline. These observations were interpreted with our numerical code dedicated to long-baseline interferometry of rotating stars. Results. By fitting our model to Achernar's differential phases from AMBER, we could measure its equatorial radius R-eq = 11.6 +/- 0.3 R-circle dot, equatorial rotation velocity V-eq = 298 +/- 9 km s(-1), rotation axis inclination angle i = 101.5 +/- 5.2 degrees, and rotation axis position angle (from North to East) PA(rot) = 34.9 +/- 1.6 degrees. From these parameters and the stellar distance, the equatorial angular diameter circle divide(eq) of Achernar is found to be 2.45 +/- 0.09 mas, which is compatible with previous values derived from the commonly used visibility amplitude. In particular, circle divide(eq) and PA(rot) measured in this work with VLTI/AMBER are compatible with the values previously obtained with VLTI/VINCI. Conclusions. The present paper, based on real data, demonstrates the super-resolution potential of differential interferometry for measuring sizes, rotation velocities, and orientation of rotating stars in cases where visibility amplitudes are unavailable and/or when the star is partially or poorly resolved. In particular, we showed that differential phases allow the measurement of sizes up to similar to 4 times smaller than the diffraction-limited angular resolution of the interferometer.

New activity in the large circumstellar disk of the Be-shell star 48 Librae

Aims. Spectroscopic, polarimetric, and high spectral resolution interferometric data covering the period 1995-2011 are analyzed to document the transition into a new phase of circumstellar disk activity in the classical Be-shell star 48 Lib. The objective is to use this broad data set to additionally test disk oscillations as the basic underlying dynamical process. Methods. The long-term disk evolution is described using the V/R ratio of the violet and red emission components of H alpha and Br gamma, radial velocities and profiles of He I and optical metal shell lines, as well as multi-band BVRI polarimetry. Single-epoch broad-band and high-resolution interferometric visibilities and phases are discussed with respect to a classical disk model and the given baseline orientations. Results. Spectroscopic signatures of disk asymmetries in 48 Lib vanished in the late nineties but recovered some time between 2004 and 2007, as shown by a new large-amplitude and long-duration V/R cycle. Variations in the radial velocity and line profile of conventional shell lines correlate with the V/R behavior. They are shared by narrow absorption cores superimposed on otherwise seemingly photospheric He I lines, which may form in high-density gas at the inner disk close to the photosphere. Large radial velocity variations continued also during the V/R-quiet years, suggesting that V/R may not always be a good indicator of global density waves in the disk. The comparison of the polarization after the recovery of the V/R activity shows a slight increase, while the polarization angle has been constant for more than 20 years, placing tight limits on any 3-D precession or warping of the disk. The broad H-band interferometry gives a disk diameter of (1.72 +/- 0.2) mas (equivalent to 15 stellar radii), position angle of the disk (50 +/- 9)degrees and a relatively low disk flattening of 1.66 +/- 0.3. Within the errors the same disk position angle is derived from polarimetric observations and from photocenter shifts across Br gamma. The high-resolution interferometric visibility and phase profiles show a double or even multiple-component structure. A preliminary estimate based on the size of the Br gamma emitting region indicates a large diameter for the disk (tens of stellar radii). Overall, no serious contradiction between the observations and the disk-oscillation model could be construed.

Decisions on Temporal Sampling Protocol Influence the Detection of Ecological Patterns

Within-site variability in species detectability is a problem common to many biodiversity assessments and can strongly bias the results. Such variability can be caused by many factors, including simple counting inaccuracies, which can be solved by increasing sample size, or by temporal changes in species behavior, meaning that the way the temporal sampling protocol is designed is also very important. Here we use the example of mist-netted tropical birds to determine how design decisions in the temporal sampling protocol can alter the data collected and how these changes might affect the detection of ecological patterns, such as the species-area relationship (SAR). Using data from almost 3400 birds captured from 21,000 net-hours at 31 sites in the Brazilian Atlantic Forest, we found that the magnitude of ecological trends remained fairly stable, but the probability of detecting statistically significant ecological patterns varied depending on sampling effort, time of day and season in which sampling was conducted. For example, more species were detected in the wet season, but the SAR was strongest in the dry season. We found that the temporal distribution of sampling effort was more important than its total amount, discovering that similar ecological results could have been obtained with one-third of the total effort, as long as each site had been equally sampled over 2 yr. We discuss that projects with the same sampling effort and spatial design, but with different temporal sampling protocol are likely to report different ecological patterns, which may ultimately lead to inappropriate conservation strategies.

A simple method to measure critical angles for high-sensitivity differential refractometry

A total internal reflection-based differencial refractometer, capable of measuring the real and imaginary parts of the complex refractive index in real time, is presented. The device takes advantage of the phase difference acquired by s- and p-polarized light to generate an easily detectable minimum at the reflected profile. The method allows to sensitively measuring transparent and turbid liquid samples. (C)2012 Optical Society of America

Optimization of anti-Trypanosoma cruzi oxadiazoles leads to identification of compounds with efficacy in infected mice

We recently showed that oxadiazoles have anti-Trypanosoma cruzi activity at micromolar concentrations. These compounds are easy to synthesize and show a number of clear and interpretable structure-activity relationships (SAR), features that make them attractive to pursue potency enhancement. We present here the structural design, synthesis, and anti-T. cruzi evaluation of new oxadiazoles denoted 5a-h and 6a-h. The design of these compounds was based on a previous model of computational docking of oxadiazoles on the T. cruzi protease cruzain. We tested the ability of these compounds to inhibit catalytic activity of cruzain, but we found no correlation between the enzyme inhibition and the antiparasitic activity of the compounds. However, we found reliable SAR data when we tested these compounds against the whole parasite. While none of these oxadiazoles showed toxicity for mammalian cells, oxadiazoles 6c (fluorine), 6d (chlorine), and 6e (bromine) reduced epimastigote proliferation and were cidal for trypomastigotes of T. cruzi Y strain. Oxadiazoles 6c and 6d have IC50 of 9.5 +/- 2.8 and 3.5 +/- 1.8 mu M for trypomastigotes, while Benznidazole, which is the currently used drug for Chagas disease treatment, showed an IC50 of 11.3 +/- 2.8 mu M. Compounds 6c and 6d impair trypomastigote development and invasion in macrophages, and also induce ultrastructural alterations in trypomastigotes. Finally, compound 6d given orally at 50 mg/kg substantially reduces the parasitemia in T. cruzi-infected BALB/c mice. Our drug design resulted in potency enhancement of oxadiazoles as anti-Chagas disease agents, and culminated with the identification of oxadiazole 6d, a trypanosomicidal compound in an animal model of infection. (C) 2012 Elsevier Ltd. All rights reserved.

Two-degree-of-freedom vortex-induced vibration of circular cylinders with very low aspect ratio and small mass ratio

The investigation of vortex-induced vibration on very short cylinders with two degrees of freedom has drawn the attention of a large number of researchers. Some investigations on such a problem are carried out in order to have a better understanding of the physics involved in vortex-induced motions of floating bodies such as offshore platforms. In this paper, experiments were carried out in a recirculating water channel over the range of Reynolds number 6000

Glaciers and climate in northern Sweden during the 19th and 20th century

Our understanding of the climate of northern Sweden during the late Holocene is largely dependent on proxy-data series. These datasets remain spatially and temporally sparse and instrumental series are rare prior to the mid 19th century. Nevertheless, the glaciology and paleo-glaciology of the region has a strong potential significance for the exploration of climate change scenarios, past and future. The aim of this thesis is to investigate the 19th and 20th century climate in the northern Swedish mountain range. This provides a good opportunity to analyse the natural variability of the climate before the onset of the industrial epoch. Developing a temporal understanding of fluctuations in glacier front positions and glacier mass balance that is linked to a better understanding of their interaction and relative significance to climate is fundamental in the assessment of past climate. I have chosen to investigate previously unexplored temperature data from northern Sweden from between 1802 and 1860 and combined it with a temperature series from a synoptic station in Haparanda, which began operation in 1859, in order to create a reliable long temperature series for the period 1802 to 2002. I have also investigated two different glaciers, Pårteglaciären and Salajekna, which are located in different climatic environments. These glaciers have, from a Swedish perspective, long observational records. Furthermore, I have investigated a recurring jökulhlaup at the glacier Sälkaglaciären in order to analyse glacier-climate relationships with respect to the jökulhlaups. A number of datasets are presented, including: glacier frontal changes, in situ and photogrammetric mass balance data, in situ and satellite radar interferometry measurements of surface velocity, radar measurements, ice volume data and a temperature series. All these datasets are analysed in order to investigate the response of the glaciers to climatic stimuli, to attribute specific behaviour to particular climates and to analyse the 19th and 20th century glacier/climate relationships in northern Sweden. The 19th century was characterized by cold conditions in northern Sweden, particularly in winter. Significant changes in the amplitude of the annual temperature cycle are evident. Through the 19th century there is a marked decreasing trend in the amplitude of the data, suggesting a change towards a prevalence of maritime (westerly) air masses, something which has characterised the 20th century. The investigations on Salajekna support the conclusion that the major part of the 19th century was cold and dry. The 19th century advance of Salajekna was probably caused by colder climate in the late 18th and early 19th centuries, coupled with a weakening of the westerly airflow. The investigations on Pårteglaciären show that the glacier has a response time of ~200 years. It also suggests that there was a relatively high frequency of easterly winds providing the glacier with winter precipitation during the 19th century. Glaciers have very different response times and are sensitive to different climatic parameters. Glaciers in rather continental areas of the Subarctic and Arctic can have very long response times because of mass balance considerations and not primarily the glacier dynamics. This is of vital importance for analyzing Arctic and Subarctic glacier behaviour in a global change perspective. It is far from evident that the behaviour of the glacier fronts today reflects the present climate.

Guida, Linguistica generale, a.a. 2006-07

Questa Guida è stata fatta dalla docente con la collaborazione degli studenti che hanno seguito il corso di Linguistica generale nell'a.a. 2006-07. Una copia cartacea è depositata presso la Biblioteca del Dipartimento di Studi Linguistici e Orientali, via Zamboni 33. Verso la fine delle lezioni dell'a.a. 2007-08 sarà stilata una Guida corrispondente agli argomenti trattati durante il corso e al programma per l'esame di Linguistica generale.

Aspetti -emici e aspetti -etici del fenomeno della "quantità vocalica" nei dialetti dell'Italia settentrionale.

Nel file mancano le figure di cui sarà distribuita fotocopia durante le lezioni.