Sequential Wnt Agonist then Antagonist Treatment Accelerates Tissue Repair and Minimizes Fibrosis

Tissue fibrosis compromises organ function and occurs as a potential long-term outcome in response to acute tissue injuries. Currently, lack of mechanistic understanding prevents effective prevention and treatment of the progression from acute injury to fibrosis. Here, we combined quantitative experimental studies with a mouse kidney injury model and a computational approach to determine how the physiological consequences are determined by the severity of ischemia injury, and to identify how to manipulate Wnt signaling to accelerate repair of ischemic tissue damage while minimizing fibrosis. The study reveals that Wnt-mediated memory of prior injury contributes to fibrosis progression, and ischemic preconditioning reduces the risk of death but increases the risk of fibrosis. Furthermore, we validated the prediction that sequential combination therapy of initial treatment with a Wnt agonist followed by treatment with a Wnt antagonist can reduce both the risk of death and fibrosis in response to acute injuries

Master of Science

thesisThe induced polarization (IP) effect, in general, is related to the complex resistivity of rocks. Modeling IP phenomena is important for developing effective methods for remote sensing of subsurface geology. The Generalized Effective Medium Theory of Induced Polarization (GEMTIP) has been derived based on the effective medium approach to the characterization of heterogeneous, multiphase, polarized medium typical in rock formations. It describes the relationships between petrophysical and structural properties of rock and the parameters of the corresponding resistivity relaxation model (Zhdanov, 2008). The parameters of the GEMTIP model are determined by the intrinsic petrophysical and geometrical characteristics of the medium: the mineralization, the matrix composition, porosity, anisotropy, and polarizability of the formations. In this paper, two igneous rock samples and three shale samples were tested by the randomly oriented ellipsoidal GEMTIP model, both two-phases and three-phases models were used in the study. Inversion routines were developed and tested using synthetic data to recover the three variables: volume fraction (f), relaxation parameters (C), and time constant (τ). Both Regularized Conjugate Gradient (RCG) method and extensive search method were implemented in the study. Complex resistivity were calculated from recorded EM data from 0.005 Hz to 10000 Hz at 33 different frequencies, detailed geologic analysis using Quantitative Evaluation of Materials using Scanning Electron Microscope (QEMSCAN) and X-ray is conducted to determine GEMTIP model parameters and help better understand the inversion results. The application of shale samples shows that the shale samples are characterized by a significant IP response, and the GEMTIP model can be applied to hydrocarbon bearing shale rocks. The results of our study show that the ellipsoidal GEMTIP model can successfully interpret the IP effect of the mineral rocks and shale samples. By comparing the two-phases with three-phases inversion results, the mineral rock samples study shows that the three-phases model can separate the different mineral sizes and different mineral types from the same sample, the shale samples show the three- phases GEMTIP model can separate the membrane polarization caused by the internal structure of the shale samples from electrode polarization caused by disseminated pyrite. The GEMTIP parameter time constant increases with increases of the grain size. Successful GEMTIP model of the rock samples provided insight into controlling factors of the IP effect

Mechanisms controlling the infection of Culicoides biting midges with bluetongue virus

The mechanisms controlling the transmission of bluetongue virus (DTV) by vector Clilicoides species were studied using immunohistochemistry, virus titration assays, in vitro transmission tests, viral binding protein analyses and transmission electron microscopy. After infection with BTV by intrathoracic (IT) inoculation, 100% of C. variipennis individuals from a susceptible colony developed a fully disseminated infection and transmitted the virus through their saliva. However only 35.4% of midges were . persistently infected after ingestion of an infectious blood meal, while only 12.1 % of persistently infected midges transmitted the virus through their saliva. The titres of BTV were about 10,·oTCIDsJmidge [Standard error of means (SEM) of log-transformed data=0.15, n=1400] in IT inoculated midges and varied from 0.32 to lQs.oTCIDsJmidge in orally infected individuals. Only those midges containing ~1 03.oTCIDso of BTV could transmit the virus through their saliva. The following patterns were observed in orally (persistently) infected individuals: 1) virus was restricted to the anterior and posterior midgut, and the foregut-midgut junction; 2) virus replicated in the gut cells, disseminated into the haemocoel but could only be detected in a few sporadic fat body cells beyond the gut; 3) virus escaped from the gut cells into the haemocoel and replicated in some secondary organs/tissues but at low levels; 4) a fully disseminated infection was observed and virus replicated in the haemocoel and secondary organs/tissues, including the salivary glands, at high levels. The infection of the gut can be divided into two main types: 1) virus replication in gut cells ranging from very low to higher levels but with virus spread throughout the cytoplasm of the infected cells; 2) virus positive reaction restricted to endosome-like structures in the cytoplasm of some gut cells. BTV was detected in the anterior and posterior midgut, foregut-midgut junction, fat body, ganglia, salivary glands and ommatidia of the compound eyes of some infected midges. No virus was ever found in the hindgut cells, muscles, Malpighian tubes and oocytes/nurse cells of the ovaries. BTV infection of the salivary glands of C. l'ariipcnnis was shown to follow a typical pattern. Virus entered the acinar cells from the haemococl passing through the basement membrane, then localised and replicated in virus inclusion bodies (VIBs) in the cytoplasm of acinar cells. Mature progeny virus particles were released into acini, then transported through intermediate ducts and accumulated in crystalline arrays in the lumen of the major secretory ducts. No virus was released back into the haemocoel through the basement membrane; nor was virus released back into acinar cells from the acini. Nervous tissue of C. l'ariipennis is one of the most susceptible tissues to BTV. Ultrastructural observation showed characteristics ofBTV replication, including formation of VIBs, large amounts of progeny virus particles and tubules, in infected thoracic ganglia. A 60-kD viral protein adhered to both BHK-21 (mammalian) cells and a Culicoides cell line, KC cells. A 44-kD BTV viral protein, co-migrating with non structural protein NS2, adsorbed to BHK-21 cells but not to KC cells, while a 39.6 kD viral protein, co-migrating with major inner capsid protein VP7, adhered only to KC cells but not to BHK-21 cells

Missed opportunities for negotiating cultural and personal meaning in language classroom : an ethnographic study of Chinese language classes.

There are hidden difficulties in teaching a foreign language in a classroom context that have not been examined. Using ethnographic research methods of participant observation, field notes, audio-taping of classroom conversational exchange, and interviews with participants of the interactions, the hidden issues were identified through data analysis focusing on the discourse between teachers and students of Chinese language. While many classroom interaction studies focus on teaching methods or content that should be taught, this research study examines language classroom interactions from a sociocultural perspective. It provides a description of the cultural and social factors that influence the communicative process in classroom interactions. The underlying assumption guiding this study is that effective foreign language teaching and learning is a communicative process that involves more than simply instruction about the formal features of language and cultural knowledge. The purpose of this process is to develop the individual learner\u27s communicative competence. This competence includes not only language competence and cultural competence but also the openness and readiness of the mind and the flexibility of cognition to function in cross-cultural contexts. The study reveals that a central cause of language classroom miscommunication is the difficulty participants have in creating contextual coherence and meaning. This problem is the direct result of the participants\u27 simplified assumptions of cultural and social stereotypes. The stereotyping of individual and power relationships in the classroom hinders the learning process and can lead to underdeveloped perspectives of cultural images and social roles of individuals. With stereotyped cultural images and the narrowly defined social roles of participants in the classroom, the teaching and learning process limits opportunities to actively develop the learners\u27 communicative competence. The practice of teaching and learning thus may reinforce inflexibility in communicative negotiation and in dealing with the cultural, social, and individual diversities in the cross-cultural interactions outside the classroom. Therefore, cross-cultural openness--the awareness of sociocultural and individual diversity in cross-cultural interactions--is significant in language teaching and learning. The significance of cross-cultural openness is that it not only influences the process of language teaching and learning, but also the content of language teaching and learning

Nonlinear Instability for a Volume-Filling Chemotaxis Model with Logistic Growth

This paper deals with a Neumann boundary value problem for a volume-filling chemotaxis model with logistic growth in a d-dimensional box Td=(0,π)d  (d=1,2,3). It is proved that given any general perturbation of magnitude δ, its nonlinear evolution is dominated by the corresponding linear dynamics along a finite number of fixed fastest growing modes, over a time period of the order ln⁡(1/δ). Each initial perturbation certainly can behave drastically different from another, which gives rise to the richness of patterns

RoNet: Rotation-oriented Continuous Image Translation

The generation of smooth and continuous images between domains has recently drawn much attention in image-to-image (I2I) translation. Linear relationship acts as the basic assumption in most existing approaches, while applied to different aspects including features, models or labels. However, the linear assumption is hard to conform with the element dimension increases and suffers from the limit that having to obtain both ends of the line. In this paper, we propose a novel rotation-oriented solution and model the continuous generation with an in-plane rotation over the style representation of an image, achieving a network named RoNet. A rotation module is implanted in the generation network to automatically learn the proper plane while disentangling the content and the style of an image. To encourage realistic texture, we also design a patch-based semantic style loss that learns the different styles of the similar object in different domains. We conduct experiments on forest scenes (where the complex texture makes the generation very challenging), faces, streetscapes and the iphone2dslr task. The results validate the superiority of our method in terms of visual quality and continuity.Comment: 14 page