Identifying Genetic Risk Factors in Canine Autoimmune Disorders

Autoimmune diseases are more common in dogs than in humans and are already threatening the future of some highly predisposed dog breeds. Susceptibility to autoimmune diseases is controlled by environmental and genetic factors, especially the major histocompatibility complex (MHC) gene region. Dogs show a similar physiology, disease presentation and clinical response as humans, making them an excellent disease model for autoimmune diseases common to both species. The genetic background of canine autoimmune disorders is largely unknown, but recent annotation of the dog genome and subsequent development of new genomic tools offer a unique opportunity to map novel autoimmune genes in various breeds. Many autoimmune disorders show breed-specific enrichment, supporting a strong genetic background. Furthermore, the presence of hundreds of breeds as genetic isolates facilitates gene mapping in complex autoimmune disorders. Identification of novel predisposing genes establishes breeds as models and may reveal novel candidate genes for the corresponding human disorders. Genetic studies will eventually shed light on common biological functions and interactions between genes and the environment. This study aimed to identify genetic risk factors in various autoimmune disorders, including systemic lupus erythematosus (SLE)-related diseases, comprising immune-mediated rheumatic disease (IMRD) and steroid-responsive meningitis arteritis (SMRA) as well as Addison s disease (AD) in Nova Scotia Duck Tolling Retrievers (NSDTRs) and chronic superficial keratitis (CSK) in German Shepherd dogs (GSDs). We used two different approaches to identify genetic risk factors. Firstly, a candidate gene approach was applied to test the potential association of MHC class II, also known as a dog leukocyte antigen (DLA) in canine species. Secondly, a genome-wide association study (GWAS) was performed to identify novel risk loci for SLE-related disease and AD in NSDTRs. We identified DLA risk haplotypes for an IMRD subphenotype of SLE-related disease, AD and CSK, but not in SMRA, and show that the MHC class II gene region is a major genetic risk factor in canine autoimmune diseases. An elevated risk was found for IMRD in dogs that carried the DLA-DRB1*00601/DQA1*005011/DQB1*02001 haplotype (OR = 2.0, 99% CI = 1.03-3.95, p = 0.01) and for ANA-positive IMRD dogs (OR = 2.3, 99% CI = 1.07-5.04, p-value 0.007). We also found that DLA-DRB1*01502/DQA*00601/DQB1*02301 haplotype was significantly associated with AD in NSDTRs (OR = 2.1, CI = 1.0-4.4, P = 0.044) and the DLA-DRB1*01501/DQA1*00601/DQB1*00301 haplotype with the CSK in GSDs (OR=2.67, CI=1.17-6.44, p= 0.02). In addition, we found that homozygosity for the risk haplotype increases the risk for each disease phenotype and that an overall homozygosity for the DLA region predisposes to CSK and AD. Our results have enabled the development of genetic tests to improve breeding practices by avoiding the production of puppies homozygous for risk haplotypes. We also performed the first successful GWAS for a complex disease in dogs. With less than 100 cases and 100 controls, we identified five risk loci for SLE-related disease and AD and found strong candidate genes involved in a novel T-cell activation pathway. We show that an inbred dog population has fewer risk factors, but each of them has a stronger genetic risk. Ongoing studies aim to identify the causative mutations and bring new knowledge to help diagnostics, treatment and understanding of the aetiology of SLE-related diseases.

Cultural differences and postmerger problems: Misconceptions and cognitive simplifications.

Researchers and practitioners have increasingly explained post-merger organizational problems with cultural differences, especially in the context of cross-border mergers and acquisitions. It is suggested here that cultural differences have great explanatory power in the context of post-merger change processes. There are, however, problems with a number of superficial cultural conceptions that are common in research in this area and in managerial rhetoric. This critical article provocatively delineates misconceptions widely held by researchers and practitioners in this field, which not only disregard cultural differentiation, fragmentation, inconsistencies and ambiguities, but further, illustrate a lack of understanding of cultural permeability and embeddedness in the environment, an overemphasis on abstract values and lack of attention to organizational practices, an overemphasis on initial structural differences and lack of attention to the new cultural layer, a lack of recognition of the political dimensions and a failure to recognize cultural differences as sources of value and learning. In this article, the theoretical problems associated with these misconceptions are examined and new conceptual perspectives suggested. The risks at stake for decision makers are also discussed.

Interrelations between Dry Eye Syndrome and Tear Fluid Phospholipid Transfer Protein

The simplified model of human tear fluid (TF) is a three-layered structure composed of a homogenous gel-like layer of hydrated mucins, an aqueous phase, and a lipid-rich outermost layer found in the tear-air interface. It is assumed that amphiphilic phospholipids are found adjacent to the aqueous-mucin layer and externally to this a layer composed of non-polar lipids face the tear-air interface. The lipid layer prevents evaporation of the TF and protects the eye, but excess accumulation of lipids may lead to drying of the corneal epithelium. Thus the lipid layer must be controlled and maintained by some molecular mechanisms. In the circulation, phospholipid transfer protein (PLTP) and cholesteryl ester transfer protein (CETP) mediate lipid transfers. The aim of this thesis was to investigate the presence and molecular mechanisms of lipid transfer proteins in human TF. The purpose was also to study the role of these proteins in the development of dry eye syndrome (DES). The presence of TF PLTP and CETP was studied by western blotting and mass spectrometry. The concentration of these proteins was determined by ELISA. The activities of the enzymes were determined by specific lipid transfer assays. To study the molecular mechanisms involved in PLTP mediated lipid transfer Langmuir monolayers and asymmetrical flow field-flow fractionation (AsFlFFF) was used. Ocular tissue samples were stained with monoclonal antibodies against PLTP to study the secretion route of PLTP. Heparin-Sepharose affinity chromatography was used for PLTP pull-down experiments and co-eluted proteins were identified with MALDI-TOF mass spectrometry or Western blot analysis. To study whether PLTP plays any functional role in TF PLTP-deficient mice were examined. The activity of PLTP was also studied in dry eye patients. PLTP is a component of normal human TF, whereas CETP is not. TF PLTP concentration was about 2-fold higher than that in human plasma. Inactivation of PLTP by heat treatment or immunoinhibition abolished the phospholipid transfer activity in tear fluid. PLTP was found to be secreted from lacrimal glands. PLTP seems to be surface active and is capable of accepting lipid molecules without the presence of lipid-protein complexes. The active movement of radioactively labeled lipids and high activity form of PLTP to acceptor particles suggested a shuttle model of PLTP-mediated lipid transfer. In this model, PLTP physically transports lipids between the donor and acceptor. Protein-protein interaction assays revealed ocular mucins as PLTP interaction partners in TF. In mice with a full deficiency of functional PLTP enhanced corneal epithelial damage, increased corneal permeability to carboxyfluorescein, and decreased corneal epithelial occludin expression was demonstrated. Increased tear fluid PLTP activity was observed among human DES patients. These results together suggest a scavenger property of TF PLTP: if the corneal epithelium is contaminated by hydrophobic material, PLTP could remove them and transport them to the superficial layer of the TF or, alternatively, transport them through the naso-lacrimal duct. Thus, PLTP might play an integral role in tear lipid trafficking and in the protection of the corneal epithelium. The increased PLTP activity in human DES patients suggests an ocular surface protective role for this lipid transfer protein.

Many Faces of Mao Zedong

The main aim of this work was to explore the use of Mao Zedong s (毛泽东, 1893—1976) visual image in contemporary Chinese art during the years 1976—2006. Chairman Mao is the most visually reproduced person in the People's Republic of China (PRC), and the presence of his image is still unquestionable at many levels. Although several scholars have provided insightful observations on this topic, research focusing on Mao's visual image has been neglected. Employing the interdisciplinary approach of visual studies and using image as the main concept, this research combines different theoretical frameworks, deriving from art history, image studies and social sciences, for each chapter in order to explain the origins, intentions and major strategies of the contemporary Chinese artists. The focus of this research was to elucidate how Mao's visual image, deriving from the Maoist era, is re-created and negotiated in contemporary Chinese art works. The material reproductions - the visual images in contemporary art - are created to be juxtaposed with the immaterial mental images of Mao that were created during the Maoist era through the original visual images of Mao. This complex interaction between visual and mental images is further exemplified by art works that do not include Mao's visual image, but still imply his mental image. The methods used derive from both sinology and art history. The research is based on extensive fieldwork in China, which was crucial for gathering new information and materials from this vigorous art scene. The topic is approached through a Chinese cultural, political and historical perspective that is necessary for a further understanding of how the original visual images of Mao obtained their omnipotent status and what kind of iconography was created. Close structural analysis, taking into account the format, style, techniques, composition, colors, materials and space used in the art works, is employed to demonstrate the great variety of visual images created. The analysis is further placed in a continuous dialogue both with the contemporary art works of Mao and with the original visual images of Mao from the past. In this study it is shown that contemporary Chinese art relating to Chairman Mao is a more versatile and multilayered phenomenon than is generally assumed. Although some of the art works seem to fit into the definition of superficial art, the study demonstrates that this reading of the art works is not adequate. The author argues that employing Mao's visual images in contemporary Chinese art is based on three main strategies used by artists: to create a visual dialogue with a traumatizing past, to employ transcontextual parody, and to explore the importance of Tian'anmen through site-dependent art. These strategies are not exclusionary, but instead interdependent and many art works employ more than one of them. In addition, these three main strategies include versatile methods used by artists that make the use of Mao's visual images even more multifaceted.

Estimating national contributions of greenhouse gas emissions :The CSE-WRI controversy

Analysts have identified four related questions that need to be asked and answered before agreements to respond to global warming will be possible.1 Which countries bear responsibility for causing the problem? What quantities and mix of greenhouse gases should each country be allowed to emit? Which countries have the resources to do something about the problem? Where are the best opportunities for undertaking projects to respond to the problem? Failure to distinguish among these four questions, or willingness to accept superficial answers, promotes unnecessary controversy.

Phage Displayed Short Peptides against Cells of Candida albicans Demonstrate Presence of Species, Morphology and Region Specific Carbohydrate Epitopes

Candida albicans is a commensal opportunistic pathogen, which can cause superficial infections as well as systemic infections in immuocompromised hosts. Among nosocomial fungal infections, infections by C. albicans are associated with highest mortality rates even though incidence of infections by other related species is on the rise world over. Since C. albicans and other Candida species differ in their susceptibility to antifungal drug treatment, it is crucial to accurately identify the species for effective drug treatment. Most diagnostic tests that differentiate between C. albicans and other Candida species are time consuming, as they necessarily involve laboratory culturing. Others, which employ highly sensitive PCR based technologies often, yield false positives which is equally dangerous since that leads to unnecessary antifungal treatment. This is the first report of phage display technology based identification of short peptide sequences that can distinguish C. albicans from other closely related species. The peptides also show high degree of specificity towards its different morphological forms. Using fluorescence microscopy, we show that the peptides bind on the surface of these cells and obtained clones that could even specifically bind to only specific regions of cells indicating restricted distribution of the epitopes. What was peculiar and interesting was that the epitopes were carbohydrate in nature. This gives insight into the complexity of the carbohydrate composition of fungal cell walls. In an ELISA format these peptides allow specific detection of relatively small numbers of C. albicans cells. Hence, if used in combination, such a test could help accurate diagnosis and allow physicians to initiate appropriate drug therapy on time.

Image analysis using multifractals

The efficacy of the multifractal spectrum as a tool for characterizing images has been studied. This spectrum has been computed for digitized images of the nucleus of human cervical cancer cells and it was observed that the entire spectrum is almost fully reproduced for a normal cell while only the right half (q<0) of the spectrum is reproduced for a cancerous cell. Cells in stages in between the two extremes show a shortening of the left half of the spectrum proportional to their condition. The extent of this shortening has been found to be sufficient to permit a classification between three classes of cells at varying distances from a basal cancerous layer-the superficial cells, the intermediate cells and the parabasal cells. This technique may be used for automatic screening of the population while also indicating the stage of malignancy

Effect of laser processing parameters on the structure of ductile iron

Laser processing of structure sensitive hypereutectic ductile iron, a cast alloy employed for dynamically loaded automative components, was experimentally investigated over a wide range of process parameters: from power (0.5-2.5 kW) and scan rate (7.5-25 mm s(-1)) leading to solid state transformation, all the way through to melting followed by rapid quenching. Superfine dendritic (at 10(5) degrees C s(-1)) or feathery (at 10(4) degrees C s(-1)) ledeburite of 0.2-0.25 mu m lamellar space, gamma-austenite and carbide in the laser melted and martensite in the transformed zone or heat-affected zone were observed, depending on the process parameters. Depth of geometric profiles of laser transformed or melt zone structures, parameters such as dendrile arm spacing, volume fraction of carbide and surface hardness bear a direct relationship with the energy intensity P/UDb2, (10-100 J mm(-3)). There is a minimum energy intensity threshold for solid state transformation hardening (0.2 J mm(-3)) and similarly for the initiation of superficial melting (9 J mm(-3)) and full melting (15 J mm(-3)) in the case of ductile iron. Simulation, modeling and thermal analysis of laser processing as a three-dimensional quasi-steady moving heat source problem by a finite difference method, considering temperature dependent energy absorptivity of the material to laser radiation, thermal and physical properties (kappa, rho, c(p)) and freezing under non-equilibrium conditions employing Scheil's equation to compute the proportion of the solid enabled determination of the thermal history of the laser treated zone. This includes assessment of the peak temperature attained at the surface, temperature gradients, the freezing time and rates as well as the geometric profile of the melted, transformed or heat-affected zone. Computed geometric profiles or depth are in close agreement with the experimental data, validating the numerical scheme.

A cold model study of raceway hysteresis

The effect of a gas flow field on the size of raceway has been studied experimentally using a two-dimensional (2-D) cold model. It is observed that as the blast velocity from the tuyere increases, raceway size increases, and when the blast velocity is decreased from its highest value, raceway size does not change much until the velocity reaches a critical velocity. Below the critical velocity, raceway size decreases with decreasing velocity but is always larger than that for the same velocity when the velocity increased. This phenomenon is called "raceway hysteresis." Raceway hysteresis has been studied in the presence of different gas flow rates and different particle densities. Raceway hysteresis has been observed in all the experiments. The effect of liquid flow, with various superficial velocities, on raceway hysteresis has also been studied. A study of raceway size hysteresis shows that interparticle and particle-wall friction have a very large effect on raceway size. A hypothesis has been proposed to describe the hysteresis phenomenon in the packed beds. The relevance of hysteresis to blast furnace raceways has been discussed. Existing literature correlations for raceway size ignore the frictional effects. Therefore, their applicability to the ironmaking blast furnace is questionable.

Universal flame propagation behavior in packed bed of biomass

This article aims at seeking the universal behavior of propagation rate variation with air superficial velocity (V-s) in a packed bed of a range of biomass particles in reverse downdraft mode while also resolving the differing and conflicting explanations in the literature. Toward this, measurements are made of exit gas composition, gas phase and condensed phase surface temperature (T-g and T-s), and reaction zone thickness for a number of biomass with a range of properties. Based on these data, two regimes are identified: gasificationvolatile oxidation accompanied by char reduction reactions up to 16 +/- 1cm/s of V-s and above this, and char oxidationsimultaneous char oxidation and gas phase combustion. In the gasification regime, the measured T-s is less than T-g; a surface heat balance incorporating a diffusion controlled model for flaming combustion gives and matches with the experimental results to within 5%. In the char oxidation regime, T-g and T-s are nearly equal and match with the equilibrium temperature at that equivalence ratio. Drawing from a recent study of the authors, the ash layer over the oxidizing char particle is shown to play a critical role in regulating the radiation heat transfer to fresh biomass in this regime and is shown to be crucial in explaining the observed propagation behavior. A simple model based on radiation-convection balance that tracks the temperature-time evolution of a fresh biomass particle is shown to support the universal behavior of the experimental data on reaction front propagation rate from earlier literature and the present work for biomass with ash content up to 10% and moisture fraction up to 10%. Upstream radiant heat transfer from the ash-laden hot char modulated by the air flow is shown to be the dominant feature of this model.

Effect of potassium present in stratum corneum during non-invasive measurement of potassium in human subjects using reverse iontophoresis

Purpose: Reverse iontophoresis (RI) is one of the potential techniques used to monitor the concentration of various analytes in body fluids non -invasively. Transdermal extraction of potassium is investigated using RI. In the present work, the effect of potassium on stratum corneum (SC) during RI, feasibility of RI for continuous monitoring of potassium, and use of potassium as internal standard in RI, are investigated. Methods: Tape stripping experiment is carried out to find potassium concentration in SC. RI is carried out continuously for 180 min without passive diffusion and after passive diffusion for 60 min. Skin impedance measurements are done at 20 Hz and 20 kHz. Results: Potassium is found to be in the range 300-650 nmol/cm(2) on SC by tape stripping experiment. Correlation coefficient between blood potassium and extracted potassium through RI after passive diffusion (R-2 = 0.5870) is more than without passive diffusion (R-2 = 0.5117). The skin impedance measurement shows that RI has more effect on SC than superficial layer of SC during RI. Conclusion: The present investigations conclude that it is possible to monitor potassium continuously through RI and using potassium as internal standard in RI.

Novel Investigation on Principle of Similarity for Microgravity Two-Phase Flow

根据两流体同心环状流线性稳定性分析的结果 ,对微重力气 /液两相流地面模拟实验所应遵循的相似准则进行了探讨 ,得到了一个新的重力无关性准则 ,即Bond数和环形区流体相的毛细数之比的绝对值不大于 1 .此外 ,微重力气 /液两相流模拟实验还必须满足两个条件 ,即流量比和气相表观Weber数应与所模拟的流动中对应数值相等 . In the present paper, the principle of similarity for two phase flows at microgravity is studied based on the results of the linear stability analysis of the two fluid concentric annular flow configuration. A new criterion of gravity independence, namely the absolute value of the ratio between the Bond number and the capillary number of the phase flowing in the annulus is no more than one, is achieved. It is also pointed out that the flowrate ratio and the gas superficial Weber number must have the same ...

Experimental study on two-phase gas-liquid flow patterns at normal and reduced gravity conditions

Experimental studies have been performed for horizontal two-phase air-water flows at normal and reduced gravity conditions in a square cross-section channel. The experiments at reduced gravity are conducted on board the Russian IL-76 reduced gravity airplane. Four flow patterns, namely bubble, slug, slug-annular transition and annular flows, are observed depending on the liquid and gas superficial velocities at both conditions. Semi-theoretical Weber number model is developed to include the shape influence on the slug-annular transition. It is shown that its prediction is in reasonable agreement with the experimental slug-annular transition under both conditions. For the case of two-phase gas-liquid flow with large value of the Froude number, the drift-flux model can predict well the observed boundary between bubble and slug flows.

La erodabilidad de cuatro series de suelos determinada por el mini-simulador de lluvia y el nomograma de Wischmeier

Se realizó un estudio con el propósito de obtener información acerca de le Erodabilidad del suelo, así como distinguir un método confiable y sencillo pera la determinación de ésta. Se seleccionaron cuatro Series de suelos (San Ignacio, Nejapa, Esquipulas y Zambrano), ubicadas en le Cuenca Sur del Lago de Managua, en base a una recopilación de información existente (topografía, reconocimiento y caracterización del terreno), se procedió a obtener les pérdidas de suelo, escurrimiento superficial, concentración de sedimentos y el Índice de Erodabilidad de cada Serie de suelos, por medio de un Mini-simulador de lluvia de Erodabilidad por Kamphorst (1987). El factor de erodabilidad (K) se obtuvo a través de cuatro propiedades del suelo (textura, materia orgánica, estructura y permeabilidad), cuyos valores son introducidos en el Nomograma de Wischmeier (1971). Una vez obtenidos los Índices de erodabilidad (I.K.) y Factor de erodabilidad (K) se determinó que las cuatro Series muestran diferentes grados de susceptibilidad e le erosión. Además, las pérdidas de suelo, escurrimiento superficial, concentración de sedimentos, el índice de erodabilidad y el Factor de erodabilidad son influenciadas por la materia orgánica. Así también se comprobó que el comparar el Índice y el Factor de erodabilidad, tienen un alto valor de correlación. Se pudo observar que le textura no tiene una influencia directa sobre les pérdidas de suelo, escurrimiento superficial, Índice de erodabilidad y Factor de erodabilidad.

Determinación de la calidad fitosanitaria de la semilla de frijol común en Nicaragua y alternativas de manejo del grano

En Nicaragua el género Phaseolus, representa una fuente importante de nutrientes que la población incluye en su dieta diaria, además provee ingresos a los productores con los que subsanan una parte de sus necesidades, El 95% de la producción de frijol en el país descansa en pequeños y medianos productores que enfrentan problemas como: Falta de asistencia técnica, poca o ninguna disponibilidad de créditos, poseen terrenos no adecuados para este cultivo y el uso constante de semillas remanentes de un ciclo a otro; Esto ha incidido de forma directa en la disminución de los rendimientos y en el aumento de los niveles de inoculo en la semilla. Son muchas las enfermedades que atacan a esta leguminosa y algunas de estas llegan a infestar y/o infectar la semilla logrando así un eficiente mecanismo de dispersión. Con el objetivo de conocer sobre la calidad fitosanitaria de la semilla utilizada por los productores, evaluar algunas técnicas para la preservación de la misma, determinar el nivel de conocimiento de los productores con respecto a las enfermedades y discernir sobre la efectividad de las técnicas de almacenamiento de la semilla utilizadas por los productores, se realizó este trabajo involucrando 75 productores del país, logrando recolectar de sus manos un total de 15 variedades las que corresponden a los nombres de: DOR-364, RAB-310, Honduras-46, Estelí-150, Estelí-90A, Estelí-B, Negro, Blanco, Chiricano, Rojo criollo, DICTA-114, Balin tíco, Revolución-84 y dos variedades del Centro Nacional de Investigación Agropecuaria (CNIA), DOR-805 y DOR-576. El trabajo se dividió en dos fases: una de campo que consistió en la colecta de datos y muestras de semillas en las zonas de estudio en el mes de Marzo y una de laboratorio en la que se determinaron los diferentes tipos de microorganismos presente en las semillas a través de Observación de síntomas, pruebas de laboratorio y identificación de los microorganismos. Se hizo una prueba de almacenaje mediante el uso de botes plásticos con tapadera, los tratamientos utilizados para la preservación fueron• Cal, Ceniza y Ceniza+Cal en dosis de 80gr de producto por libra de semilla, más o menos 25 libras por quintal de grano y un testigo. Los resultados de las encuestas demuestran que los productores reconocen las enfem1edades como tales, pero no pueden diferenciarlas en su totalidad como causadas por hongos, bacterias o virus. Se identificaron los siguientes patógenos: Rhizoctonia sotaní, Thanatephoms cucumeris, Collectotrichum lindemuthianum, Fusarium solani, Fusarium poae, Fusarium tricinctum, l-i1sarium oxyspomm, Penicillium .;pp, Aspergillus ochraceus, Aspergillus ustus, Aspergillus glaucus (Emericella nidulans)(Eim>tium link), Aspergiilus niger, Aspergillus parasitim Aspergillus candidus, Aspergillus terreus, Rhizopus oryzae, Rhizopus stolonifer, Xanthomona;• campestris pv phaseoli, Pseudomonas spp, el virus del mosaico común no se detectó en este trabajo. Los mejores resultados se observaron en los tratamientos de cal y cal+ceniza, siendo cal+ceniza quién presentó alta significancia en la disminución de la infección por hongos, gorgojos (Bruchidae) y bacterias, pudiendo disminuir hasta un 57% las infecciones de hongos, un 68% de las infecciones por bacterias a nivel superficial y un l 00% la población de gorgojos, con respecto a las presentadas por el testigo de laboratorio. El tratamiento de cal+ceniza es más barato, eficaz y menos peligroso que el uso de cualquier químico.