Aromatic nitro substitution reaction between 4-nitro-N-n-butyl-1,8-naphthalimide and n-heptanethiol in water-methanol binary mixtures

The second-order rate constants of thiolysis by n-heptanethiol on 4-nitro-N-n-butyl-1,8-naphthalimide (4NBN) are strongly affected by the water-methanol binary mixture composition reaching its maximum at around 50% mole fraction. In parallel solvent effects on 4NBN absorption molar extinction coefficient also shows a maximum at this composition region. From the spectroscopic study of reactant and product and the known H-bond capacity of the mixture a rationalization that involves specific solvent H-donor interaction with the nitro group is proposed to explain the kinetic data. Present findings also show a convenient methodology to obtain strongly fluorescent imides, valuable for peptide and analogs labeling as well as for thio-naphthalimide derivatives preparations. Copyright (C) 2008 John Wiley & Sons, Ltd.

On the evection resonance and its connection to the stability of outer satellites

In terms of stability around the primary, it is widely known that the semimajor axis of the retrograde satellites is much larger than the corresponding semimajor axis of the prograde satellites. Usually this conclusion is obtained numerically, since precise analytical derivation is far from being easy, especially, in the case of two or more disturbers. Following the seminal idea that what is unstable in the restricted three-body problem is also unstable in the general N-body problem, we present a simplified model which allows us to derive interesting resonant configurations. These configurations are responsible for cumulative perturbations which can give birth to strong instability that may cause the ejection of the satellite. Then we obtain, analytically, approximate bounds of the stability of prograde and retrograde satellites. Although we recover quite well previous results of other authors, we comment very briefly some weakness of these bounds. Copyright (c) 2008 Tadashi Yokoyama et al.

Effects of lycopene, synbiotic and their association on early biomarkers of rat colon carcinogenesis

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Dynamics of a spacecraft and normalization around Lagrangian points in the Neptune-Triton system

The problem of a spacecraft orbiting the Neptune-Triton system is presented. The new ingredients in this restricted three body problem are the Neptune oblateness and the high inclined and retrograde motion of Triton. First we present some interesting simulations showing the role played by the oblateness on a Neptune's satellite, disturbed by Triton. We also give an extensive numerical exploration in the case when the spacecraft orbits Triton, considering Sun, Neptune and its planetary oblateness as disturbers. In the plane a x I (a = semi-major axis, I = inclination), we give a plot of the stable regions where the massless body can survive for thousand of years. Retrograde and direct orbits were considered and as usual, the region of stability is much more significant for the case of direct orbit of the spacecraft (Triton's orbit is retrograde). Next we explore the dynamics in a vicinity of the Lagrangian points. The Birkhoff normalization is constructed around L-2, followed by its reduction to the center manifold. In this reduced dynamics, a convenient Poincare section shows the interplay of the Lyapunov and halo periodic orbits, Lissajous and quasi-halo tori as well as the stable and unstable manifolds of the planar Lyapunov orbit. To show the effect of the oblateness, the planar Lyapunov family emanating from the Lagrangian points and three-dimensional halo orbits are obtained by the numerical continuation method. Published by Elsevier Ltd. on behalf of COSPAR.

Variation of the Equator due to a Highly Inclined and Eccentric Disturber

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Urocortin in the central nervous system of a primate (Cebus apella): Sequencing, immunohistochemical, and hybridization histochemical characterization

The urocortin (UCN)-like immunoreactivity and UCN mRNA distribution in various regions of the nonprimate mammalian brain have been reported. However, the Edinger-Westphal nucleus (EW) appears to be the only brain site where UCN expression is conserved across species. Although UCN peptides are present throughout vertebrate phylogeny, the functional roles of both UCN and EW remain poorly understood. Therefore, a study focused on UCN system organization in the primate brain is warranted. By using immunohistochemistry (single and double labeling) and in situ hybridization, we have characterized the organization of UCN-expressing cells and fibers in the central nervous system and pituitary of the capuchin monkey (Cebus apella). In addition, the sequence of the prepro-UCN was determined to establish the level of structural conservation relative to the human sequence. To understand the relationship of acetylcholine cells in the EW, a colocalization study comparing choline acetyltransferase (ChAT) and UCN was also performed. The cloned monkey prepro-UCN is 95% identical to the human preprohormone across the matched sequences. By using an antiserum raised against rat UCN and a probe generated from human cDNA, we found that the EW is the dominant site for UCN expression, although UCN mRNA is also expressed in spinal cord lamina IX. Labeled axons and terminals were distributed diffusely throughout many brain regions and along the length of the spinal cord. of particular interest were UCN-immunoreactive inputs to the medial preoptic area, the paraventricular nucleus of the hypothalamus, the oral part of the spinal trigeminal nucleus, the flocculus of the cerebellum, and the spinal cord laminae VII and X. We found no UCN hybridization signal in the pituitary. In addition, we observed no colocalization between ChAT and UCN in EW neurons. Our results support the hypothesis that the UCN system might participate in the control of autonomic, endocrine, and sensorimotor functions in primates.

Influence of different routes of flush perfusion on the distribution of lung preservation solutions in parenchyma and airways

Objective: The present study was performed to investigate the influence of different routes of perfusion on the distribution of the preservation solutions in the lung parenchyma and upper airways. Methods: Pigs were divided into four groups: control (n = 6), pulmonary artery (PA) (n = 6), simultaneous PA + bronchial artery (BA) (n = 8), and retrograde delivery (n = 6). After preparation and cannulation, cardioplegia solution and Euro- Collins solution (ECS) for lung preservation were given simultaneously. After removal of the heart, the double lung bloc was harvested. Following parameters were assessed: total and regional perfusion (dye-labeled microspheres), tissue water content, PA, aorta, left atrial and left ventricular pressures, cardiac output and lung temperature. Results: Our data show that flow of the ECS in lung parenchyma did not reach control values (9.4 ± 1.0 ml/min per g lung wet weight) regardless of the route of delivery (PA 6.3 ± 1.5, PA + BA 4.8 ± 0.9, retrograde 2.7 ± 0.9 ml/min per g lung wet weight). However, flow in the proximal and distal trachea were significantly increased by PA + BA delivery (0.970 ± 0.4, respectively, 0.380 ± 0.2 ml/min per g) in comparison with PA (0.023 ± 0.007, respectively, 0.024 ± 0.070 ml/min per g), retrograde (0.009 ± 0.003, respectively, 0.021 ± 0.006 ml/min per g) and control experiments (0.125 ± 0.0018, respectively, 0.105 ± 0.012 ml/g per min). Similarly the highest flow rates in the right main bronchus were achieved by PA + BA delivery (1.04 ± 0.4 ml/min per g) in comparison with 0.11 ± 0.03 in control, 0.033 ± 0.008 in PA, and 0.019 ± 0.005 ml/min per g in retrograde group. Flows in the left main bronchus were 0.09 ± 0.02 ml/min per g in control, 0.045 ± 0.012 ml/min per g in PA, and 0.027 ± 0.006 ml/min per g in retrograde group. The flow rates were significantly (P = 0.001) increased by PA + BA delivery of the storage solution (0.97 ± 0.3 ml/min per g). Conclusions: Our data show that the distribution of ECS for lung preservation is significantly improved in airway tissues (trachea and bronchi) if a simultaneous PA + BA delivery is used.

An interplanetary mission to Neptune system: Gravitational capture and maneuvers around triton

The gravitational capture was initially used to understand the capture of planetary satellites. However, in the 90's decade, this phenomenon was applied in spacecraft trajectories. Belbruno and Miller studied missions in the Earth-Moon system that uses this technique to save fuel during the insertion of the spacecraft in its final orbit around the Moon. Using a parameter defined as twice the two-body energy of the planet-particle system, Yamakawa also studied the gravitational capture in the Earth-Moon system. In the present paper, this technique is used to study a mission that goes to the Neptune system and perform a gravitational capture in the satellite Triton. The results show direct and retrograde trajectories, for different values of the initial conditions.

Leishmania amazonensis Promastigotes Present Two Distinct Modes of Nucleus and Kinetoplast Segregation during Cell Cycle

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

SEM Evaluation of the Interface Between Filling and Root- End Filling Materials

The aim of this ex vivo study was to evaluate, by scanning electron microscopy (SEM), the presence of gaps at the interface between filling material and three root-end filling materials. Thirty human upper molars disto-buccal roots were instrumented and filled with gutta-percha and eugenol-based sealer. The apicoectomy was performed 2mm from the apex and retrograde cavities were prepared with ultrasonic points (3mm in deep). The samples were divided into three experimental groups (n=10): Group Iwhite mineral trioxide aggregate (MTA); Group IISuper EBA; and Group IIIPortland cement. The root-end filling materials were inserted into the retocavities using a MTA carrier. After 48h, the roots were transversally sectioned in order to obtain the apical 5mm. Next, each specimen was prepared longitudinally with crescent granulation of abrasives water-wet sandpapers in order to expose the filling and root-end filling materials. Then, the specimens were subjected to slow dehydration with silica gel, mounted onto specific stubs and coated with paladium coverage for SEM analysis of the interface between filling and root-end filling materials. The percentage of gaps at the interfacial area was calculated by using Image Tool 3.0 software. Super EBA presented the higher percentage of gaps (1.5 +/- 0.67%), whereas MTA presented the lowest values (0.33 +/- 0.20%; p=0.0004). Despite the statistical differences observed between Super EBA and MTA, all the root-end filling materials presented great adaptation to the filling material, presenting small amount of gaps. SCANNING 36:252-257, 2014. (c) 2013 Wiley Periodicals, Inc.

Correlation between immunoexpression of BCL-2 protein family with apoptosis index, cellular proliferation and survival in colorectal carcinomas

Objectives: To evaluate the Bcl-2, Bax, Bad and Bak immunoexpression in tumor and nontumorous tissue of 130 patients with colorectal carcinoma submitted to surgery at São Paulo Hospital, EPM/ UNIFESP, from 2002 to 2005, and to correlate the immunoexpression data with the apoptotic index (AI, obtained by anti-cleaved caspase 3 and M30 labeling), cell proliferation score (CPS, obtained by Ki-67), immunoexpression of p53 and patient’s clinical prognosis. Results: Positive correlation was verified between Bcl-2 protein family in tumor and nontumor tissue. Only Bcl-2 protein correlated with IA and CPS in the tumor. Positive correlation was observed between pro- -apoptotic proteins and Bcl-2 protein. In the adjacent mucosa, Bcl-2 correlated with Ki-67 and p53, but not with IA. Carcinomas exhibited higher immunoexpression of CPS and IA markers. No correlation occurred between immunoexpression data and patient survival. Conclusion: Positive correlation was observed between the pro-apoptotic proteins of the Bcl-2 family and the anti-apoptotic protein Bcl-2. In the adjacent nontumor mucosa, Bcl-2 correlated with Ki-67 and p53, but not with AI. Carcinomas presented greater immunoexpression for CPS and AI markers; however immunoexpression of these markers was not correlated with patient survival.

Differential projections from the lateral habenula to the rostromedial tegmental nucleus and ventral tegmental area in the rat

The mesopontine rostromedial tegmental nucleus (RMTg) is a mostly ?-aminobutyric acid (GABA)ergic structure believed to be a node for signaling aversive events to dopamine (DA) neurons in the ventral tegmental area (VTA). The RMTg receives glutamatergic inputs from the lateral habenula (LHb) and sends substantial GABAergic projections to the VTA, which also receives direct projections from the LHb. To further specify the topography of LHb projections to the RMTg and VTA, small focal injections of the anterograde tracer Phaseolus vulgaris leucoagglutinin were aimed at different subdivisions of the LHb. The subnuclear origin of LHb inputs to the VTA and RMTg was then confirmed by injections of the retrograde tracer cholera toxin subunit b into the VTA or RMTg. Furthermore, we compared the topographic position of retrogradely labeled neurons in the RMTg resulting from VTA injections with that of anterogradely labeled axons emerging from the LHb. As revealed by anterograde and retrograde tracing, LHb projections were organized in a strikingly topographic manner, with inputs to the RMTg mostly arising from the lateral division of the LHb (LHbL), whereas inputs to the VTA mainly emerged from the medial division of the LHb (LHbM). In the RMTg, profusely branched LHb axons were found in close register with VTA projecting neurons and were frequently apposed to the latter. Overall, our findings demonstrate that LHb inputs to the RMTg and VTA arise from different divisions of the LHb and provide direct evidence for a disynaptic pathway that links the LHbL to the VTA via the RMTg. J. Comp. Neurol. 520:12781300, 2012. (C) 2011 Wiley Periodicals, Inc.

Cinnamic acid induces apoptotic cell death and cytoskeleton disruption in human melanoma cells

Anticancer activities of cinnamic acid derivatives include induction of apoptosis by irreversible DNA damage leading to cell death. The present work aimed to compare the cytotoxic and genotoxic potential of cinnamic acid in human melanoma cell line (HT-144) and human melanocyte cell line derived from blue nevus (NGM). Viability assay showed that the IC50 for HT-144 cells was 2.4 mM, while NGM cells were more resistant to the treatment. The growth inhibition was probably associated with DNA damage leading to DNA synthesis inhibition, as shown by BrdU incorporation assay, induction of nuclear aberrations and then apoptosis. The frequency of cell death caused by cinnamic acid was higher in HT-144 cells. Activated-caspase 3 staining showed apoptosis after 24 hours of treatment with cinnamic acid 3.2 mM in HT-144 cells, but not in NGM. We observed microtubules disorganization after cinnamic acid exposure, but this event and cell death seem to be independent according to M30 and tubulin labeling. The frequency of micronucleated HT-144 cells was higher after treatment with cinnamic acid (0.4 and 3.2 mM) when compared to the controls. Cinnamic acid 3.2 mM also increased the frequency of micronucleated NGM cells indicating genotoxic activity of the compound, but the effects were milder. Binucleation and multinucleation counting showed similar results. We conclude that cinnamic acid has effective antiproliferative activity against melanoma cells. However, the increased frequency of micronucleation in NGM cells warrants the possibility of genotoxicity and needs further investigation.

Synthesis and surface modification of semiconductor nanocrystals

The last decade has witnessed an exponential growth of activities in the field of nanoscience and nanotechnology worldwide, driven both by the excitement of understanding new science and by the potential hope for applications and economic impacts. The largest activity in this field up to date has been in the synthesis and characterization of new materials consisting of particles with dimensions in the order of a few nanometers, so-called nanocrystalline materials. [1-8] Semiconductor nanomaterials such as III/V or II/VI compound semiconductors exhibit strong quantum confinement behavior in the size range from 1 to 10 nm. Therefore, preparation of high quality semiconductor nanocrystals has been a challenge for synthetic chemists, leading to the recent rapid progress in delivering a wide variety of semiconducting nanomaterials. Semiconductor nanocrystals, also called quantum dots, possess physical properties distinctly different from those of the bulk material. Typically, in the size range from 1 to 10 nm, when the particle size is changed, the band gap between the valence and the conduction band will change, too. In a simple approximation a particle in a box model has been used to describe the phenomenon[9]: at nanoscale dimensions the degenerate energy states of a semiconductor separate into discrete states and the system behaves like one big molecule. The size-dependent transformation of the energy levels of the particles is called “quantum size-effect”. Quantum confinement of both the electron and hole in all three dimensions leads to an increase in the effective bandgap of the material with decreasing crystallite size. Consequently, both the optical absorption and emission of semiconductor nanaocrystals shift to the blue (higher energies) as the size of the particles gets smaller. This color tuning is well documented for CdSe nanocrystals whose absorption and emission covers almost the whole visible spectral range. As particle sizes become smaller the ratio of surface atoms to those in the interior increases, which has a strong impact on particle properties, too. Prominent examples are the low melting point [8] and size/shape dependent pressure resistance [10] of semiconductor nanocrystals. Given the size dependence of particle properties, chemists and material scientists now have the unique opportunity to change the electronic and chemical properties of a material by simply controlling the particle size. In particular, CdSe nanocrystals have been widely investigated. Mainly due to their size-dependent optoelectronic properties [11, 12] and flexible chemical processibility [13], they have played a distinguished role for a number of seminal studies [11, 12, 14, 15]. Potential technical applications have been discussed, too. [8, 16-27] Improvement of the optoelectronic properties of semiconductor nanocrystals is still a prominent research topic. One of the most important approaches is fabricating composite type-I core-shell structures which exhibit improved properties, making them attractive from both a fundamental and a practical point of view. Overcoating of nanocrystallites with higher band gap inorganic materials has been shown to increase the photoluminescence quantum yields by eliminating surface nonradiative recombination sites. [28] Particles passivated with inorganic shells are more robust than nanocrystals covered by organic ligands only and have greater tolerance to processing conditions necessary for incorporation into solid state structures or for other applications. Some examples of core-shell nanocrystals reported earlier include CdS on CdSe [29], CdSe on CdS, [30], ZnS on CdS, [31] ZnS on CdSe[28, 32], ZnSe on CdSe [33] and CdS/HgS/CdS [34]. The characterization and preparation of a new core-shell structure, CdSe nanocrystals overcoated by different shells (CdS, ZnS), is presented in chapter 4. Type-I core-shell structures as mentioned above greatly improve the photoluminescence quantum yield and chemical and photochemical stability of nanocrystals. The emission wavelengths of type-I core/shell nanocrystals typically only shows a small red-shift when compared to the plain core nanocrystals. [30, 31, 35] In contrast to type-I core-shell nanocrystals, only few studies have been conducted on colloidal type-II core/shell structures [36-38] which are characterized by a staggered alignment of conduction and valence bands giving rise to a broad tunability of absorption and emission wavelengths, as was shown for CdTe/CdSe core-shell nanocrystals. [36] The emission of type-II core/shell nanocrystals mainly originates from the radiative recombination of electron-hole pairs across the core-shell interface leading to a long photoluminescence lifetime. Type-II core/shell nanocrystals are promising with respect to photoconduction or photovoltaic applications as has been discussed in the literature.[39] Novel type-II core-shell structures with ZnTe cores are reported in chapter 5. The recent progress in the shape control of semiconductor nanocrystals opens new fields of applications. For instance, rod shaped CdSe nanocrystals can enhance the photo-electro conversion efficiency of photovoltaic cells, [40, 41] and also allow for polarized emission in light emitting diodes. [42, 43] Shape control of anisotropic nanocrystals can be achieved by the use of surfactants, [44, 45] regular or inverse micelles as regulating agents, [46, 47] electrochemical processes, [48] template-assisted [49, 50] and solution-liquid-solution (SLS) growth mechnism. [51-53] Recently, formation of various CdSe nanocrystal shapes has been reported by the groups of Alivisatos [54] and Peng, [55] respectively. Furthermore, it has been reported by the group of Prasad [56] that noble metal nanoparticles can induce anisotropic growth of CdSe nanocrystals at lower temperatures than typically used in other methods for preparing anisotropic CdSe structures. Although several approaches for anisotropic crystal growth have been reported by now, developing new synthetic methods for the shape control of colloidal semiconductor nanocrystals remains an important goal. Accordingly, we have attempted to utilize a crystal phase control approach for the controllable synthesis of colloidal ZnE/CdSe (E = S, Se, Te) heterostructures in a variety of morphologies. The complex heterostructures obtained are presented in chapter 6. The unique optical properties of nanocrystals make them appealing as in vivo and in vitro fluorophores in a variety of biological and chemical investigations, in which traditional fluorescence labels based on organic molecules fall short of providing long-term stability and simultaneous detection of multiple emission colours [References]. The ability to prepare water soluble nanocrystals with high stability and quantum yield has led to promising applications in cellular labeling, [57, 58] deep-tissue imaging, [59, 60] and assay labeling [61, 62]. Furthermore, appropriately solubilized nanocrystals have been used as donors in fluorescence resonance energy transfer (FRET) couples. [63-65] Despite recent progress, much work still needs to be done to achieve reproducible and robust surface functionalization and develop flexible (bio-) conjugation techniques. Based on multi-shell CdSe nanocrystals, several new solubilization and ligand exchange protocols have been developed which are presented in chapter 7. The organization of this thesis is as follows: A short overview describing synthesis and properties of CdSe nanocrystals is given in chapter 2. Chapter 3 is the experimental part providing some background information about the optical and analytical methods used in this thesis. The following chapters report the results of this work: synthesis and characterization of type-I multi-shell and type-II core/shell nanocrystals are described in chapter 4 and chapter 5, respectively. In chapter 6, a high–yield synthesis of various CdSe architectures by crystal phase control is reported. Experiments about surface modification of nanocrystals are described in chapter 7. At last, a short summary of the results is given in chapter 8.

Synthesis and in vitro characterization of radioiodinatable benzodiazepines selective for type 1 and type 2 cholecystokinin receptors

Radiolabeled antagonists of specific peptide receptors identify a higher number of receptor binding sites than agonists and may thus be preferable for in vivo tumor targeting. In this study, two novel radioiodinated 1,4-benzodiazepines, (S)-1-(3-iodophenyl)-3-(1-methyl-2-oxo-5-phenyl-2,3-dihydro-1H-benzo[e][1,4]diazepin-3-yl)urea (9) and (R)-1-(3-iodophenyl)-3-(1-methyl-2-oxo-5-phenyl-2,3-dihydro-1H-benzo[e][1,4]diazepin-3-yl)urea (7), were developed. They were characterized in vitro as high affinity selective antagonists at cholecystokinin types 1 and 2 (CCK(1) and CCK(2)) receptors using receptor binding, calcium mobilization, and internalization studies. Their binding to human tumor tissues was assessed with in vitro receptor autoradiography and compared with an established peptidic CCK agonist radioligand. The (125)I-labeled CCK(1) receptor-selective compound 9 often revealed a substantially higher amount of CCK(1) receptor binding sites in tumors than the agonist (125)I-CCK. Conversely, the radioiodinated CCK(2) receptor-selective compound 7 showed generally weaker tumor binding than (125)I-CCK. In conclusion, compound 9 is an excellent radioiodinated nonpeptidic antagonist ligand for direct and selective labeling of CCK(1) receptors in vitro. Moreover, it represents a suitable candidate to test antagonist binding to CCK(1) receptor-expressing tumors in vivo.