A novel plant toxin, persin, with in vivo activity in the mammary gland, induces Bim-dependent apoptosis in human breast cancer cells

Phytochemicals have provided an abundant and effective source of therapeutics for the treatment of cancer. Here we describe the characterization of a novel plant toxin, persin, with in vivo activity in the mammary gland and a p53-, estrogen receptor-, and Bcl-2-independent mode of action. Persin was previously identified from avocado leaves as the toxic principle responsible for mammary gland-specific necrosis and apoptosis in lactating livestock. Here we used a lactating mouse model to confirm that persin has a similar cytotoxicity for the lactating mammary epithelium. Further in vitro studies in a panel of human breast cancer cell lines show that persin selectively induces a G(2)-M cell cycle arrest and caspase-dependent apoptosis in sensitive cells. The latter is dependent on expression of the BH3-only protein Bim. Bim is a sensor of cytoskeletal integrity, and there is evidence that unique structure of the compound, persin could represent a novel class of microtubule-targeting agent with potential specificity for breast cancers.

Hepatitis B surface antigen vector delivers protective cytotoxic T-lymphocyte responses to disease-relevant foreign epitopes

Although hepatitis B surface antigen (HBsAg) per se is highly immunogenic, its use as a vector for the delivery of foreign cytotoxic T-lymphocyte (CTL) epitopes has met with little success because of constraints on HBsAg stability and secretion imposed by the insertion of foreign sequence into critical hydrophobic/amphipathic regions. Using a strategy entailing deletion of DNA encoding HBsAg-specific CTL epitopes and replacement with DNA encoding foreign CTL epitopes, we have derived chimeric HBsAg DNA immunogens which elicited effector and memory CTL responses in vitro, and pathogen- and tumor-protective responses in vivo, when the chimeric HBsAg DNAs were used to immunize mice. We further show that HBsAg DNA recombinant for both respiratory syncytial virus and human papillomavirus CTL epitopes elicited simultaneous responses to both pathogens. These data demonstrate the efficacy of HBsAg DNA as a vector for the delivery of disease-relevant protective CTL responses. They also suggest the applicability of the approach of deriving chimeric HBsAg DNA immunogens simultaneously encoding protective CTL epitopes for multiple diseases. The DNAs we tested formed chimeric HBsAg virus-like particles (VLPs). Thus, our results have implications for the development of vaccination strategies using either chimeric HBsAg DNA or VLP vaccines. HBsAg is the globally administered vaccine for hepatitis B virus infection, inviting its usage as a vector for the delivery of immunogens from other diseases.

Recent developments on a nearshore, terrigenous-influenced reef: Low Isles Reef, Australia

Low Isles Reef is the most southerly located of 46 coral reef platforms unique to the inner shelf of the northern Great Barrier Reef Province, Australia, which support both sea grass and mangrove growth. Such reefs develop in areas that are influenced by river flood plumes and where interreef sediments are dominated by terrigenous mud. Low Isles Reef has long been a popular tourist destination. Informal reports of decreasing visibility, a decline in scleractinian corals, and increases in soft coral and macroalgae have sparked speculation that agricultural activities in coastal catchments are affecting the reef. Comparison of the modern surface of Low Isles Reef with historical surveys and photographs dating back to 1928 allows quantification of modern sedimentary processes, rates of change, and factors influencing reef development. Results indicate that changes on Low Isles Reef are related to remobilization of coarse sediment during storm events and gradual shoreline retreat associated with rising sea level. Retreat of shingle ramparts and elongate ridges of coral debris toward the reef interior has led to the infilling of subtidal ponds on the reef top, which supported hard coral colonies in 1928. The gradual development of a composite shingle rampart along the windward margin has promoted an increase (;150%) in the area of the reef top covered by mangroves. On the leeward margin, a decrease in hard corals since 1950 may reflect a rising contribution of organic debris from the expanding mangrove swamp. Results suggest that recent changes on Low Isles Reef can be explained in the context of natural processes. Further study is needed before the effects of agricultural activities in coastal catchments on reef health can be confirmed.

Characterization of sugar cane waste biomass derived chars from pressurized gasification

There is interest in the use of sugar cane waste biomass for electricity cogeneration, by integrated gasification combined cycle (IGCC) processes. This paper describes one aspect of an overall investigation into the reactivity of cane wastes under pressurized IGGC conditions, for input into process design. There is currently a gap in understanding the morphological transformations experienced by cane waste biomass undergoing conversion to char during pressurized gasification, which is addressed by this work. Char residuals remaining after pressurized pyrolysis and carbon dioxide gasification were analysed by optical microscope, nitrogen (BET) adsorption analysis, SEM/EDS, TEM/EDS and XPS techniques. The amorphous cane plant silica structures were found to remain physically intact during entrained flow gasification, but chemically altered in the presence of other inorganic species. The resulting crystalline silicates were mesoporous (with surface areas of the order of 20 m(2) g(-1)) and contributed to much of the otherwise limited pore volume present in the residual chars. Coke deposition and intimate blending of the carbonaceous and inorganic species was identified. Progressive sintering of the silicates appeared to trap coke deposits in the pore network. As a result ash residuals showed significant organic contents, even after extensive additional oxidation in air. The implications of the findings are that full conversion of cane trash materials under pressurized IGCC conditions may be significantly hampered by the silica structures inherent in these biomass materials and that further research of the contributing phenomena is recommended.

Short report: Lack of sex effect on the pharmacokinetics of primaquine

The pharmacokinetics of primaquine have been well defined in male volunteers, but there is little data on the disposition of the drug in women. We compared the kinetics of primaquine in nine male and nine female healthy Australian volunteers after the administration of a single oral dose (30 mg base) of primaquine. No statistical differences were observed in the following kinetic parameters of primaquine between men and women, respectively: maximum plasma concentration (93 +/- 26 and 115 +/- 38 ng/mL; 95% confidence interval [CI] of the mean difference: -55 to 10 ng/mL; P = 0.16), area under the curve (1.1 +/- 0.5 and 1.2 +/- 0.4 mu g.h/mL; 95% CI: -0.6 to 0.3 mu g.h/mL; P = 0.54), and clearance (0.34 +/- 0.12 and 0.39 +/- 0.14 L/h/kg; 95% CI: -0.17 to 0.08 L/h/kg; P = 0.46). The clinical relevance of such findings would suggest that sex does not have to be taken into account as a factor when prescribing primaquine for radical cure or terminal prophylaxis of Plasmodium vivax malaria.

ANÁLISE DAS MUDANÇAS DOS FATORES DETERMINANTES DA ESTRUTURA DE CAPITAL EM FUNÇÃO DO CICLO DE VIDA DAS EMPRESAS BRASILEIRAS SÃO BERNARDO DO CAMPO

As várias teorias acerca da estrutura de capital despertam interesse motivando diversos estudos sobre o assunto sem, no entanto, ter um consenso. Outro tema aparentemente pouco explorado refere-se ao ciclo de vida das empresas e como ele pode influenciar a estrutura de capital. Este estudo teve como objetivo verificar quais determinantes possuem maior relevância no endividamento das empresas e se estes determinantes alteram-se dependendo do ciclo de vida da empresa apoiada pelas teorias Trade Off, Pecking Order e Teoria da Agência. Para alcançar o objetivo deste trabalho foi utilizado análise em painel de efeito fixo sendo a amostra composta por empresas brasileiras de capital aberto, com dados secundários disponíveis na Economática® no período de 2005 a 2013, utilizando-se os setores da BM&FBOVESPA. Como resultado principal destaca-se o mesmo comportamento entre a amostra geral, alto e baixo crescimento pelo endividamento contábil para o determinante Lucratividade apresentando uma relação negativa, e para os determinantes Oportunidade de Crescimento e Tamanho, estes com uma relação positiva. Para os grupos de alto e baixo crescimento alguns determinantes apresentaram resultados diferentes, como a singularidade que resultou significância nestes dois grupos, sendo positiva no baixo crescimento e negativa no alto crescimento, para o valor colateral dos ativos e benefício fiscal não dívida apresentaram significância apenas no grupo de baixo crescimento. Para o endividamento a valor de mercado foi observado significância para o Benefício fiscal não dívida e Singularidade. Este resultado reforça o argumento de que o ciclo de vida influência a estrutura de capital

Comparing neural correlates of configural processing in faces and objects:An ERP study of the thatcher illusion

In the Thatcher illusion, a face with inverted eyes and mouth looks abnormal when upright but not when inverted. Behavioral studies have shown that thatcherization of an upright face disrupts perceptual processing of the local configuration. We recorded high-density EEG from normal observers to study ERP correlates of the illusion during the perception of faces and nonface objects, to determine whether inversion and thatcherization affect similar neural mechanisms. Observers viewed faces and houses in four conditions (upright vs. inverted, and normal vs. thatcherized) while detecting an oddball category (chairs). Thatcherization delayed the N170 component over occipito-temporal cortex to faces, but not to houses. This modulation matched the illusion as it was larger for upright than inverted faces. The P1 over medial occipital regions was delayed by face inversion but unaffected by thatcherization. Finally, face thatcherization delayed P2 over occipito-temporal but not over parietal regions, while inversion affected P2 across categories. All effects involving thatcherization were face-specific. These results indicate that effects of face inversion and feature inversion (in thatcherized faces) can be distinguished on a functional as well as neural level, and that they affect configural processing of faces in different time windows. © 2006 Elsevier Inc.

Design, modeling and construction of a novel ablative fast pyrolysis reactor and product collection system

The objective of this work was to design, construct and commission a new ablative pyrolysis reactor and a high efficiency product collection system. The reactor was to have a nominal throughput of 10 kg/11r of dry biomass and be inherently scalable up to an industrial scale application of 10 tones/hr. The whole process consists of a bladed ablative pyrolysis reactor, two high efficiency cyclones for char removal and a disk and doughnut quench column combined with a wet walled electrostatic precipitator, which is directly mounted on top, for liquids collection. In order to aid design and scale-up calculations, detailed mathematical modelling was undertaken of the reaction system enabling sizes, efficiencies and operating conditions to be determined. Specifically, a modular approach was taken due to the iterative nature of some of the design methodologies, with the output from one module being the input to the next. Separate modules were developed for the determination of the biomass ablation rate, specification of the reactor capacity, cyclone design, quench column design and electrostatic precipitator design. These models enabled a rigorous design protocol to be developed capable of specifying the required reactor and product collection system size for specified biomass throughputs, operating conditions and collection efficiencies. The reactor proved capable of generating an ablation rate of 0.63 mm/s for pine wood at a temperature of 525 'DC with a relative velocity between the heated surface and reacting biomass particle of 12.1 m/s. The reactor achieved a maximum throughput of 2.3 kg/hr, which was the maximum the biomass feeder could supply. The reactor is capable of being operated at a far higher throughput but this would require a new feeder and drive motor to be purchased. Modelling showed that the reactor is capable of achieving a reactor throughput of approximately 30 kg/hr. This is an area that should be considered for the future as the reactor is currently operating well below its theoretical maximum. Calculations show that the current product collection system could operate efficiently up to a maximum feed rate of 10 kg/Fir, provided the inert gas supply was adjusted accordingly to keep the vapour residence time in the electrostatic precipitator above one second. Operation above 10 kg/hr would require some modifications to the product collection system. Eight experimental runs were documented and considered successful, more were attempted but due to equipment failure had to be abandoned. This does not detract from the fact that the reactor and product collection system design was extremely efficient. The maximum total liquid yield was 64.9 % liquid yields on a dry wood fed basis. It is considered that the liquid yield would have been higher had there been sufficient development time to overcome certain operational difficulties and if longer operating runs had been attempted to offset product losses occurring due to the difficulties in collecting all available product from a large scale collection unit. The liquids collection system was highly efficient and modeling determined a liquid collection efficiency of above 99% on a mass basis. This was validated due to the fact that a dry ice/acetone condenser and a cotton wool filter downstream of the collection unit enabled mass measurements of the amount of condensable product exiting the product collection unit. This showed that the collection efficiency was in excess of 99% on a mass basis.

Ordered mixing of drugs with particulate excipients

A novel direct compression tableting excipient has been made by recrystallisation of lactose. The particles produced had high porosity, high specific surface area and high surface roughness. The resistance to segregation of ordered mixes formed between a model drug; potassium chloride and the excipients recrystallised lactose, spray crystallised maltose-dextrose (Emdexl and a direct compacting sugar (Dipac) was studied using a vibrational segregation model. The highly porous excipients, Emdex and recrystallised lactose formed ordered mixes which did not segregate even at high accelerations and low frequencies whereas the relatively smooth excipient, Dipac, displayed marked segregation in most vibration conditions. The vibrations were related to practical conditions measured in pharmaceutical process machinery. The time required to form an ordered mix was inversely related to the stability of the mix when subjected to vibration. An ultracentrifuge technique was developed to determine the interparticle adhesion forces holding drug and excipient particles together as ordered units. Excipient powders such as Emdex and recrystallised lactose, which formed non-segregating ordered mixes, had high interparticle adhesion forces. Other ordered mixes that segregated when subjected to different vibration conditions were found to have large quantities of weekly-bound drug particles; such mixes included those with Dipac as the carrier excipient as well as those containing a high concentration of drug. The electrostatic properties of different drug and excipient powders were studied using a Faraday well and an electrometer. Excipient powders such as Emdex and recrystallised lactose which formed stable ordered mixes also had a widely different surface charge in comparison with drug particles, whereas Dipac had a similar surface charge to the drug particles and formed unstable ordered mixes. A specially constructed triboelectric charging apparatus based on an air cyclone was developed to increase the affinity of drug particles for different excipient particles. Using triboelectrification to increase the interparticle adhesion forces, the segregation tendencies of unstable ordered mixes were greatly reduced. The stability of ordered mixes is shown to be related to both the surface physical characteristics and the surface electrical properties of the constituent carrier (excipientl particles.