Differential expression of chemokine and matrix re-modelling genes is associated with contrasting schistosome-induced hepatopathology in murine models

The pathological outcomes of schistosomiasis are largely dependent on the molecular and cellular mechanisms of the host immune response. In this study, we investigated the contribution of variations in host gene expression to the contrasting hepatic pathology observed between two inbred mouse strains following Schistosoma japonicum infection. Whole genome microarray analysis was employed in conjunction with histological and immunohistochemical analysis to define and compare the hepatic gene expression profiles and cellular composition associated with the hepatopathology observed in S. japonicum-infected BALB/c and CBA mice. We show that the transcriptional profiles differ significantly between the two mouse strains with high statistical confidence. We identified specific genes correlating with the more severe pathology associated with CBA mice, as well as genes which may confer the milder degree of pathology associated with BALB/c mice. In BALB/c mice, neutrophil genes exhibited striking increases in expression, which coincided with the significantly greater accumulation of neutrophils at granulomatous regions seen in histological sections of hepatic tissue. In contrast, up-regulated expression of the eosinophil chemokine CCL24 in CBA mice paralleled the cellular influx of eosinophils to the hepatic granulomas. Additionally, there was greater down-regulation of genes involved in metabolic processes in CBA mice, reflecting the more pronounced hepatic damage in these mice. Profibrotic genes showed similar levels of expression in both mouse strains, as did genes associated with Th1 and Th2 responses. However, imbalances in expression of matrix metalloproteinases (e.g. MMP12, MMP13) and tissue inhibitors of metalloproteinases (TIMP1) may contribute to the contrasting pathology observed in the two strains. Overall, these results provide a more complete picture of the molecular and cellular mechanisms which govern the pathological outcome of hepatic schistosomiasis. This improved understanding of the immunopathogenesis in the murine model schistosomiasis provides the basis for a better appreciation of the complexities associated with chronic human schistosomiasis.

Pedigree-free animal models : the relatedness matrix reloaded

Animal models typically require a known genetic pedigree to estimate quantitative genetic parameters. Here we test whether animal models can alternatively be based on estimates of relatedness derived entirely from molecular marker data. Our case study is the morphology of a wild bird population, for which we report estimates of the genetic variance-covariance matrices (G) of six morphological traits using three methods: the traditional animal model; a molecular marker-based approach to estimate heritability based on Ritland's pairwise regression method; and a new approach using a molecular genealogy arranged in a relatedness matrix (R) to replace the pedigree in an animal model. Using the traditional animal model, we found significant genetic variance for all six traits and positive genetic covariance among traits. The pairwise regression method did not return reliable estimates of quantitative genetic parameters in this population, with estimates of genetic variance and covariance typically being very small or negative. In contrast, we found mixed evidence for the use of the pedigree-free animal model. Similar to the pairwise regression method, the pedigree-free approach performed poorly when the full-rank R matrix based on the molecular genealogy was employed. However, performance improved substantially when we reduced the dimensionality of the R matrix in order to maximize the signal to noise ratio. Using reduced-rank R matrices generated estimates of genetic variance that were much closer to those from the traditional model. Nevertheless, this method was less reliable at estimating covariances, which were often estimated to be negative. Taken together, these results suggest that pedigree-free animal models can recover quantitative genetic information, although the signal remains relatively weak. It remains to be determined whether this problem can be overcome by the use of a more powerful battery of molecular markers and improved methods for reconstructing genealogies.

A dual-scale modelling approach for drying hygroscopic porous media

A new dualscale modelling approach is presented for simulating the drying of a wet hygroscopic porous material that couples the porous medium (macroscale) with the underlying pore structure (microscale). The proposed model is applied to the convective drying of wood at low temperatures and is valid in the so-called hygroscopic range, where hygroscopically held liquid water is present in the solid phase and water exits only as vapour in the pores. Coupling between scales is achieved by imposing the macroscopic gradients of moisture content and temperature on the microscopic field using suitably-defined periodic boundary conditions, which allows the macroscopic mass and thermal fluxes to be defined as averages of the microscopic fluxes over the unit cell. This novel formulation accounts for the intricate coupling of heat and mass transfer at the microscopic scale but reduces to a classical homogenisation approach if a linear relationship is assumed between the microscopic gradient and flux. Simulation results for a sample of spruce wood highlight the potential and flexibility of the new dual-scale approach. In particular, for a given unit cell configuration it is not necessary to propose the form of the macroscopic fluxes prior to the simulations because these are determined as a direct result of the dual-scale formulation.

The unresolved struggles between project managers and functional managers in matrix organizations

Having personal that works in projects but belongs to a functional organization is the way that many companies organized their labor force today. Previous research shows that this implies management contradictions and ambiguities between functional manager and project manager; there are unresolved struggles between these two roles in terms of power, accountability, authority and legitimacy. With this paper we aim to analyze those struggles based on previous research and to generate working hypotheses. We first provide a review of the different matrix organizations focusing on the relation between the functional manager and the project manager. We then review the literature concerning temporary organizations and projects as temporary organizations. We conclude by integrating the findings of these perspectives and by identifying working hypotheses and areas for further research.

The financial services cultural orientation matrix

With saturation within domestic marketplaces and increased growth opportunities overseas, many financial service providers are investing in foreign markets. However, cultural attitudes towards money can present market entry challenges to financial service providers. The industry would therefore benefit from a strategic model that helps to align financial marketing mixes with the cultural dimensions of a foreign market. The Financial Services Cultural Orientation (FSCO) Matrix has therefore been designed, with three cultural dimensions identified which influence preference for financial products; preference for cash, aversion to debt and savings orientation. Based on a combination of these dimensions and their relative strength within a culture, eight different consumer segments for financial products are identified, and marketing strategies for each consumer segment are then proposed. Three cultural clusters from the GLOBE Project House et al. (2002) are used to highlight possible geographic markets for each of these consumer segments. In particular, this paper focuses on GLOBE’s Confucian Asia, Southern Asia and Anglo cultural clusters, as these clusters represent the most well established financial markets in the world and the fastest growing financial markets for the future. The FSCO Matrix provides the financial services industry with an innovative and practical tool for addressing cross-cultural challenges and developing successful marketing strategies for entry into foreign markets.

The rationale for using microscopic units of a donor matrix in cartilage defect repair

The efficacy of existing articular cartilage defect repair strategies are limited. Native cartilage tissue forms via a series of exquisitely orchestrated morphogenic events spanning through gestation into early childhood. However, defect repair must be achieved in a non-ideal microenvironment over an accelerated time-frame compatible with the normal life of an adult patient. Scaffolds formed from decellularized tissues are commonly utilized to enable the rapid and accurate repair of tissues such as skin, bladder and heart valves. The intact extracellular matrix remaining following the decellularization of these relatively low-matrix-density tissues is able to rapidly and accurately guide host cell repopulation. By contrast, the extraordinary density of cartilage matrix limits both the initial decellularization of donor material as well as its subsequent repopulation. Repopulation of donor cartilage matrix is generally limited to the periphery, with repopulation of lacunae deeper within the matrix mass being highly inefficient. Herein, we review the relevant literature and discuss the trend toward the use of decellularized donor cartilage matrix of microscopic dimensions. We show that 2-µm microparticles of donor matrix are rapidly integrate with articular chondrocytes, forming a robust cartilage-like composites with enhanced chondrogenic gene expression. Strategies for the clinical application of donor matrix microparticles in cartilage defect repair are discussed.

Electron petrography of fine-grained matrix in the Karoonda C4 carbonaceous chondrite

The study of matrices of rare Type 4 carbonaceous chondrites can reveal important information on parent body rnetamorp~ic processes and provide a comparison with processes on parent bodies of ordinary chc-idrites. Reflectance spectra (Tholen, 1984) from the two largest asteroids in the asteroid belt, Ceres and Pallas, suggest that they may be metamorphosed carbonaceous chondrites. These two asteroids constitute - onethird of the mass in the asteroid belt implying that type 4-6 carbonaceous chondrites are poorly represented in the meteorite collection and may be of considerable importance. The matrix of the C4 chondrite Karoonda has been investigated using a JEOL 2000FX analytical electron microscope (AEM) with an attached Tracor-Northem TN5500 energy dispersive spectrometer (EDS). In previous studies (Scott and Taylor, 1985; Fitzgerald, 1979; Van Schmus, 1969), the petrography of the Karoonda matrix has been described as consisting largely of coarse-grained (50-200 urn in size) olivine and plagioclase (20-100 um in size), associated with micrometer sized magnetite and rare sulphides. AEM observations on matrix show that in addition to these large grains, there is a significant fraction (10 vol%) of interstitial fine grained phases « 5 urn). The mineralogy of these fine-grained phases differs in some respects from that of the coarser-grained matrix identified by optical and SEM techniques (Scott and Taylor, 1985; Fitzgerald, 1979; Van Schmus, 1969). I~ particular crystals of two compositionally distinct pyroxenes « 2 urn in size) have been identified which have not been previously observed in Karoonda by other analytical techniques. Thin film microanalyses (Mackinnon et al., 1986) of these two pyroxenes indicate compositions consistent with augite and low-Ca pyroxene (- Fs27). Fine-grained anhedral olivine « 2 urn size) is the most abundant phase with composition -Fa29' This composition is essentially indistinguishable from that determined for coarser-grained matrix olivines using an electron microprobe (Scott and Taylor, 1985; Fitzgerald, 1979; Van Schmus, 1969). All olivines are associated with subhedral magnetites « 1 urn size) which contain significant Cr (- 2%) and Al (- 1%) as was also noted for larger sized Karoonda magnetites by Delaney et al. (1985). It has recently been suggested (Burgess et al., 1987) on the basis of sulphur release profiles for S-isotope analyses of Karoonda that CaS04 (anhydrite) may be present. However, no sulphate phase has, as yet, been identified in the matrix of Karoonda. Low magnification contrast images suggest that Karoonda may have a significant porosity within the fine-grained matrix fraction. Most crystals are anhedral and do not show evidence for significant compaction. Individual grains often show single point contact with other grains which result in abundant intergranular voids. These voids frequently contain epoxy which was used as part of the specimen preparation procedure due to the friable nature of the bulk sample.

Mineralogy of chondritic porous aggregates : current status

Chondritic porous aggregates (CPA's) belong to an important subset of small particles (usually between 5 and 50 micrometers) collected from the stratosphere by high flying aircraft. These aggregates are approximately chondritic in elemental abundance and are composed of many thousands of small­er, submicrometer particles. CPA particles have been the subject of intensive study during the past few years [1-3] and there is strong evidence that they are a new class of extraterrestrial material not represented in the meteorite collection [3,4]. However, CPA's may be related to carbonaceous chondrites and in fact, both may be part of a continuum of primitive extraterrestrial materials [5]. The importance of CPA's stems from suggestions that they are very primitive solar system material possibly derived from early formed proto­ planets, chondritic parent bodies, or comets [3, 6]. To better understand the origin and evolution of these particles, we have attempted to summarize all of the mineralogical data on identified CPA's published since about 1976.

A multi-stage history for carbonaceous material in extraterrestrial chondritic porous aggregate W7029*A and a new cosmothermometer

A new set of primitive extraterrestrial materials collected in the Earth's stratosphere include Chondritic Porous Aggregates (CPA's) [1]. CPAs have a complex and variable mineralogy [1-3] that include 'organic compounds' [4,5] and poorly graphitised carbon (PGC)[6]. This study presents a continuation of our detailed Analytical Electron Microscope study on carbon-rich CPA W7029*A from the JSC Cosmic Dust Collection. This CPA is an uncontaminated sample that survived atmospheric entry without appreciable alteration [7] and which contains ~44% carbonaceous material. The carbonaceous composition of selected particles was confirmed by Electron Energy Loss Spectroscopy and Selected Area Electron Diffraction (SAED). Possible carbonaceous contaminants introduced by specimen preparation techniques are easily recognised from indigenous CPA carbon particles [8] and do not bias our interpretations.

Conduction-radiation effect on natural convection flow in a fluid-saturated non-Darcy porous medium enclosed by non-isothermal walls

The effect of conduction-convection-radiation on natural convection flow of Newtonian optically thick gray fluid, confined in a non-Darcian porous media square cavity is numerically studied. For the gray fluid consideration is given to Rosseland diffusion approximation. Further assuming that (i) the temperature of the left vertical wall is varying linearly with height, (ii) cooled right vertical and top walls and (iii) the bottom wall is uniformly-heated. The governing equations are solved using the Alternate Direct Implicit method together with the Successive Over Relaxation technique. The investigation of the effect of governing parameters namely the Forschheimer resistance (Γ), the Planck constant (Rd), and the temperature difference (Δ), on flow pattern and heat transfer characteristics has been carried out. It was seen that the reduction of flow and heat transfer occurs as the Forschheimer resistance is increased. On the other hand both the strength of flow and heat transfer increases as the temperature ratio, Δ, is increased.

Titanium-oxide magneli phases in four chondritic porous interplanetary dust particles

Detailed analytical electron microscope analyses of four fine-grained chondritic porous interplanetary dust particles (IDPs)reveal the presence of titanium oxide Magneli phases, TinO2n-1 (n=4,5,6), and rare Ti-metal. The titanium minerals are indigenous to these chondritic IDPs. The association of Magneli phases, Ti-metal, and carbonaceous material in chondritic IDPs, along with the grain size distributions support in situ solid carbon gasification in these extraterrestrial particles. The active catalyst in this process is titanium metal that we infer may be of interstellar origin. This favorable catalysis uniquely leads to the formation of Magneli phases. As chondritic IDPs may be solid debris of short-period comets, our data indicate that nuclei of short-period comets may show distinctive chemical reactions that lead to Ti-mineral assemblages that typically include Magneli phases. The proposed model provides a plausible mechnism to explain the higher solid carbon content of chondritic IDPs relative to bulk carbon abundances typical for carbonaceous chondrite matrices that represent another type of more evolved, that is, metamorphosed, undifferentiated solar system bodies.