Phase behavior of a phospholipid/fatty acid/water mixture studied in atomic detail

Molecular dynamics simulations have been used to study the phase behavior of a dipalmitoylphosphatidylcholine (DPPC)/palmitic acid (PA)/water 1:2:20 mixture in atomic detail. Starting from a random solution of DPPC and PA in water, the system adopts either a gel phase at temperatures below similar to 330 K or an inverted hexagonal phase above similar to 330 K in good agreement with experiment. It has also been possible to observe the direct transformation from a gel to an inverted hexagonal phase at elevated temperature (similar to 390 K). During this transformation, a metastable fluid lamellar intermediate is observed. Interlamellar connections or stalks form spontaneously on a nanosecond time scale and subsequently elongate, leading to the formation of an inverted hexagonal phase. This work opens the possibility of studying in detail how the formation of nonlamellar phases is affected by lipid composition and (fusion) peptides and, thus, is an important step toward understanding related biological processes, such as membrane fusion.

Mechanisms of Mycoplasma-induced inflammation and cellular transformation

There is a growing interest in “medical gasses” for their antibacterial and anti-inflammatory properties. Hydrogen sulfide (H2S), a member of the family of gasotransmitters, is in fact increasingly being recognized as an important signaling molecule, but its precise role in the regulation of the inflammatory response is still not clear. For this reason, the aim of the first part of this thesis was to investigate the effects of H2S on the expression of pro-inflammatory cytokines, such as MCP-1, by using an in vitro model composed by both primary monocytes-derived macrophages cultures and the human monocytic cell line U937 infected with Mycoplasma fermentans, a well-known pro-inflammatory agent. In our experiments, we observed a marked increase in the production of pro-inflammatory cytokines in infected cells. In particular, MCP-1 was induced both at the RNA and at the protein level. To test the effects of H2S on infected cells, we treated the cells with two different H2S donors (NaHS and GYY4137), showing that both H2S treatments had anti-inflammatory effects in Mycoplasma-infected cells: the levels of MCP-1, both mRNA expression and protein production, were reduced. Our subsequent studies aimed at understanding the molecular mechanisms responsible for these effects, focused on two specific molecular pathways, both involved in inflammation: the NF-κB and the Nrf2 pathway. After treatment with pharmacological inhibitors, we demonstrated that Mycoplasma fermentans induces MCP-1 expression through the TLR-NF-κB pathway with the nuclear translocation of its subunits, while treatment with H2S completely blocked the nuclear translocation of NF-κB heterodimer p65/p50. Then, once infected cells were treated with H2S donors, we observed an increased protective effect of Nrf2 and also a decrease in ROS production. These results highlight the importance of H2S in reducing the inflammatory process caused by Mycoplasma fermentans. To this regard, it should be noted that several projects are currently ongoing to develop H2S-releasing compounds as candidate drugs capable of alleviating cell deterioration and to reduce the rate of decline in organ function. In the second part of this study, we investigated the role of Mycoplasma infection in cellular transformation. Infectious agents are involved in the etiology of many different cancers and a number of studies are still investigating the role of microbiota in tumor development. Mycoplasma has been associated with some human cancers, such as prostate cancer and non-Hodgkin’s lymphoma in HIV-seropositive people, and its potential causative role and molecular mechanisms involved are being actively investigated. To this regard, in vitro studies demonstrated that, upon infection, Mycoplasma suppresses the transcriptional activity of p53, key protein in the cancer suppression. As a consequence, infected cells were less susceptible to apoptosis and proliferated more than the uninfected cells. The mechanism(s) responsible for the Mycoplasma-induced inhibitory effect on p53 were not determined. Aim of the second part of this thesis was to better understand the tumorigenic role of the microorganism, by investigating more in details the effect(s) of Mycoplasma on p53 activity in an adenocarcinoma HCT116 cell line. Treatment of Mycoplasma-infected cells with 5FU or with Nutlin, two molecules that induce p53 activity, resulted in cellular proliferation comparable to untreated controls. These results suggested that Mycoplasma infection inhibited p53 activity. Immunoprecipitation of p53 with specific antibodies, and subsequent Gas Chromatography and Mass Spectroscopy (GC-MS) assays, allowed us to identify several Mycoplasma-specific proteins interacting with p53, such as DnaK, a prokaryotic heat shock protein and stress inducible chaperones. In cells transfected with DnaK we observed i) reduced p53 protein levels; ii) reduced activity and expression of p21, Bax and PUMA, iii) a marked increase in cells leaving G1 phase. Taken together, these data show an interaction between the human p53 and the Mycoplasma protein DnaK, with the consequent decreased p53 activity and decreased capability to respond to DNA damage and prevent cell proliferation. Our data indicate that Mycoplasma could be involved in cancer formation and the mechanism(s) has the potential to be a target for cancer diagnosis and treatment(s).

The mechanical properties and formability of dual-phase steel

In recent years dual phase steels comprising of 5-20% martensite in a ferrite matrix have come into the limelight of high strength cold formable steels because of their potential for vehicle weight saving. They show the following features: no yield point; relatively low initial flow stress; high initial workhardening rate; well sustained work hardening. As a consequence of these characteristics, dual phase steels exhibit a better combination of strength and elongation than other HSLA steels. In this thesis, a broad view of the factors which influence their properties is presented. Mechanical properties and forming ability of a commercially available dual phase steel and an AL-Si killed steel processed to dual phase form are investigated to ascertain the effect of their microstructure on their properties. It is found that the yield phenomena are masked by the transformation induced stresses present during processing and so yield point could be recovered under suitable ageing treatment; that apart from giving the above properties dual phasing gives rise to very low strain-rate sensitivity and a low R value ~ 1; that the mechanical response under rolling conditions is not different from those under tension; that there is a danger of damage to tooling during forming operations of these steels if fracture should precede instability as a result of grain size dependent strength found for these steels. It is also found that very little deformation of the martensite islands took place during deformation except at high strains. The work-hardening and the strength levels can be controlled by either decreasing the grain size or increasing the martensite volume fraction, but it is found that increasing martensite has a detrimental effect on ductility and the ductility and fracture strength can be controlled better by refining the grain size. A remarkable effect found in the dual phase steel tested is that the compressive strength is higher than the tensile strength. The reason for this observation is not yet clear but it is suggested that it might be due to the introduction of emissary type dislocations into the ferrite lattice as a result of twins formed in the martensite during transformation from austenite. The twins are envisaged to be {111} <112> in character.

Valorisation of vietnamese rice straw waste:catalytic aqueous phase reforming of hydrolysate from steam explosion to platform chemicals

A family of tungstated zirconia solid acid catalysts were synthesised via wet impregnation and subsequent thermochemical processing for the transformation of glucose to 5-hydroxymethylfurfural (HMF). Acid strength increased with tungsten loading and calcination temperature, associated with stabilisation of tetragonal zirconia. High tungsten dispersions of between 2 and 7 W atoms·nm−2 were obtained in all cases, equating to sub-monolayer coverages. Glucose isomerisation and subsequent dehydration via fructose to HMF increased with W loading and calcination temperature up to 600 °C, indicating that glucose conversion to fructose was favoured over weak Lewis acid and/or base sites associated with the zirconia support, while fructose dehydration and HMF formation was favoured over Brönsted acidic WOx clusters. Aqueous phase reforming of steam exploded rice straw hydrolysate and condensate was explored heterogeneously for the first time over a 10 wt% WZ catalyst, resulting in excellent HMF yields as high as 15% under mild reaction conditions.

Eigen-Adaptation and Distributed Representation of 2-D Phase, Energy, Scale and Orientation in Spatial Vision

Distributed representations (DR) of cortical channels are pervasive in models of spatio-temporal vision. A central idea that underpins current innovations of DR stems from the extension of 1-D phase into 2-D images. Neurophysiological evidence, however, provides tenuous support for a quadrature representation in the visual cortex, since even phase visual units are associated with broader orientation tuning than odd phase visual units (J.Neurophys.,88,455–463, 2002). We demonstrate that the application of the steering theorems to a 2-D definition of phase afforded by the Riesz Transform (IEEE Trans. Sig. Proc., 49, 3136–3144), to include a Scale Transform, allows one to smoothly interpolate across 2-D phase and pass from circularly symmetric to orientation tuned visual units, and from more narrowly tuned odd symmetric units to even ones. Steering across 2-D phase and scale can be orthogonalized via a linearizing transformation. Using the tiltafter effect as an example, we argue that effects of visual adaptation can be better explained by via an orthogonal rather than channel specific representation of visual units. This is because of the ability to explicitly account for isotropic and cross-orientation adaptation effect from the orthogonal representation from which both direct and indirect tilt after-effects can be explained.

What cases on lean hospital transformation tell us?

The scientific knowledge about the lean transformation of hospital processes is at best in its “emerging” phase; neither related international, nor Hungarian literature offers a systematic, comprehensive description of the phenomenon (Brandao de Souza, 2009). In this paper empirical evidences concerning the lean transformation of hospital processes are researched and systemized. Thus it provides a new insight of existing knowledge in order to provide solid base for further researches and practical actions.

Condensed phase combustion travelling waves with sequential exothermic or endothermic reactions

The one-dimensional propagation of a combustion wave through a premixed solid fuel for two-stage kinetics is studied. We re-examine the analysis of a single reaction travelling-wave and extend it to the case of two-stage reactions. We derive an expression for the travelling wave speed in the limit of large activation energy for both reactions. The analysis shows that when both reactions are exothermic, the wave structure is similar to the single reaction case. However, when the second reaction is endothermic, the wave structure can be significantly different from single reaction case. In particular, as might be expected, a travelling wave does not necessarily exist in this case. We establish conditions in the limiting large activation energy limit for the non-existence, and for monotonicity of the temperature profile in the travelling wave.