Buffering...

Buffering… focuses on scenes from everyday life such as cooking breakfast or a day at the office which are presented in a half-rendered frozen form. The works are partially pixilated in certain areas to create a sense of perpetual buffering illustrating a never-ending frustration between advancement and expectation. This body of work is meant to create an opportunity for viewer to experience a sensation of tension while information perpetually buffers. This sensation reflects how society has been conditioned by its technological devices and their implied promises of instant gratification. This body of work aims to shed light on the frustration that happens when the promises are broken. This body of work uses visuals of modern technology to explore our culture of instant gratification. Technological speeds increase at the expense of human patience and tolerance for even the minutest delays this causes people to experience frustration after mere seconds of interruption while streaming a video or downloading a webpage. These few seconds of “buffering” contribute to the growing disconnect between advanced technology and the perception of the delays such devices eventually experience. It often seems that we are caught in a three-legged race where technological improvement and human expectation are attempting to run in tandem yet the two are never exactly in sync

Gut microbiome variation is associated to Multiple Sclerosis phenotypic subtypes

Objective Multiple sclerosis (MS) is a heterogenous, inflammatory disease of the central nervous system. Microbiota alterations in MS versus healthy controls (HC) are observed, but results are inconsistent. We studied diversity, enterotypes, and specific gut microbial taxa variation between MS and HC, and between MS subgroups. Methods Amplicon sequencing of the 16S ribosomal RNA V4 region (Illumina MiSeq) was used to evaluate alpha and beta diversity, enterotypes, and relative taxa abundances on stool samples. MS subgroups were based on phenotype, disease course modifiers, and treatment status. Results were controlled for recently identified confounders of microbiota composition. Results Ninety-eight MS patients and 120 HC were included. Microbial richness was lower in interferon-treated (RRMS_I, N = 24) and untreated relapsing-remitting MS during relapse (RRMS_R, N = 4) when compared to benign (BMS, N = 20; Z = -3.07, Pcorr = 0.032 and Z = -2.68, Pcorr = 0.055) and primary progressive MS (PPMS, N = 26; Z = -2.39, Pcorr = 0.062 and Z = -2.26, Pcorr = 0.071). HC (N = 120) and active untreated MS (RRMS_U, N = 24) showed intermediate microbial richness. Enterotypes were associated with clinical subgroups (N = 218, chi(2) = 36.10, P = 0.002), with Bacteroides 2 enterotype being more prevalent in RRMS_I. Butyricicoccus abundance was lower in PPMS than in RRMS_U (Z = -3.00, Pcorr = 0.014) and BMS (Z = -2.56, Pcorr = 0.031), lower in RRMS_I than in BMS (Z = -2.50, Pcorr = 0.034) and RRMS_U (Z = -2.91, Pcorr = 0.013), and inversely correlated with self-reported physical symptoms (rho = -0.400, Pcorr = 0.001) and disease severity (rho = -0.223, P = 0.027). Interpretation These results emphasize the importance of phenotypic subcategorization in MS-microbiome research, possibly explaining previous result heterogeneity, while showing the potential for specific microbiome-based biomarkers for disease activity and severity

Embalmed|Unembalmed: the problems of the lived event within media studies 2.0

Media Studies 2.0 seeks to rewire the discipline of media studies from prevailing notions of aggregate third-person, top-down or imposed identities (as found within the domain of industrial mass communications media) toward what it sees as the communication of new bottom-up, first-person or singular reflexive identities favored within the post-fordist, post-industrial spaces of the internet, social networking sites, second life-like domains and computer game spaces. This article will point toward many of the hidden, though still important, intersections between these two supposedly separate conceptions through the use of a case study that throws notions of clean “communication” into question. From this it will go on to argue for a recognition of such new media spaces as better conceptualized through Batailleʼs notion of ʻGeneral Economyʼ and Derridaʼs notion of ʻUndecidabilityʼ, as dually taken forward in the work of Arkady Plotnitsky. The conclusion? Far from modern teletechnologies offering a new sense of micro-community or as channels of individual self-expression (a new Rousseauian or McLuhanesque global village of intimate contact), these emergent teletechnologies serve to further displace or undecide the locus of any signature context of communication, which this article takes as a cause for celebration

Artificial restoration of the linkage between laminin and dystroglycan ameliorates the disease progression of MDC1A muscular dystrophy at all stages

Laminin-α2 deficient congenital muscular dystrophy, classified as MDC1A, is a severe progressive muscle-wasting disease that leads to death in early childhood. MDC1A is caused by mutations in lama2, the gene encoding the laminin-α2 chain being part of laminin-2, the main laminin isoform present in the extracellular matrix of muscles and peripheral nerves. Via selfpolymerization, laminin-2 forms the primary laminin scaffold and binds with high affinity to α- dystroglycan on the cell surface, providing a connection to the cytoskeleton via the transmembranous protein β-dystroglycan. Deficiency in laminin-α2 leads to absence of laminin-2 and to upregulation of laminin-8, a laminin isoform that cannot self-polymerize and does not bind to α-dystroglycan. Therefore, in laminin α2-deficient muscle the chain of proteins linking the intracellular contractile apparatus via the plasma membrane to the extracellular matrix is interrupted. Consequently, muscle fibers loose their stability and degenerate what finally leads to a progressive muscle wasting. In previous studies, we have shown that a miniaturized form of the extracellular matrix protein agrin, which is not related to the disease-causing lama2 gene and was designed to contain highaffinity binding sites for the laminins and for α-dystroglycan, was sufficient to markedly improve muscle function and overall health in the dyW-/- mouse model of MDC1A. In a follow-up study we provided additional evidence that mini-agrin, both increases the tolerance to mechanical load but also improves the regeneration capacity of the dystrophic muscle. We now report on our progress towards further testing the use of this approach for the treatment of MDC1A. To test whether mini-agrin application after onset of the disease would still ameliorate the dystrophic symptoms, we have established the inducible tetracycline-regulated “tet-off” expression system in dyW-/- mice to temporally control mini-agrin expression in skeletal muscles. We show that mini-agrin slows down the progression of the dystrophy when applied at birth or in advanced stages of the disease. However, the extent of the amelioration depends on the dystrophic condition of the muscle at the time of mini-agrin application. Thus, the earlier miniagrin is applied, the higher is the profit of its beneficial properties. In addition to gene therapeutical approaches, the increase of endogenous agrin expression levels in skeletal muscles by pharmacologically active compounds would be a safe and promising strategy for the treatment of MDC1A. To evaluate the potential and pave the way to further expand on the development of such a treatment, we determined whether full-length agrin ameliorates the dystrophic phenotype to a comparable extent as it was observed by application of mini-agrin. We provide evidence that constitutive overexpression of chick full-length agrin in dyW-/- muscle ameliorates the dystrophic phenotype, although not as pronounced as mini-agrin does. In conclusion, our results are conceptual proof that linkage of laminin to the muscle fiber membrane is a means to treat MDC1A at any stage of the disease. Our findings definitely encourage to further expanding on this therapeutic concept, especially in combination with treatment using functionally different approaches. Moreover, these experiments set the basis for further developing clinically feasible and relevant application methods such as gene therapy4 and/or the screening of small molecules able to upregulate production of agrin in muscle

Multi-touch For General-purpose Computing An Examination Of Text Entry

In recent years, multi-touch has been heralded as a revolution in humancomputer interaction. Multi-touch provides features such as gestural interaction, tangible interfaces, pen-based computing, and interface customization – features embraced by an increasingly tech-savvy public. However, multi-touch platforms have not been adopted as everyday computer interaction devices; that is, multi-touch has not been applied to general-purpose computing. The questions this thesis seeks to address are: Will the general public adopt these systems as their chief interaction paradigm? Can multi-touch provide such a compelling platform that it displaces the desktop mouse and keyboard? Is multi-touch truly the next revolution in human-computer interaction? As a first step toward answering these questions, we observe that generalpurpose computing relies on text input, and ask: Can multi-touch, without a text entry peripheral, provide a platform for efficient text entry? And, by extension, is such a platform viable for general-purpose computing? We investigate these questions through four user studies that collected objective and subjective data for text entry and word processing tasks. The first of these studies establishes a benchmark for text entry performance on a multi-touch platform, across a variety of input modes. The second study attempts to improve this performance by iv examining an alternate input technique. The third and fourth studies include mousestyle interaction for formatting rich-text on a multi-touch platform, in the context of a word processing task. These studies establish a foundation for future efforts in general-purpose computing on a multi-touch platform. Furthermore, this work details deficiencies in tactile feedback with modern multi-touch platforms, and describes an exploration of audible feedback. Finally, the thesis conveys a vision for a general-purpose multi-touch platform, its design and rationale

Regulation of cell behaviour and identity in a branching epithelium

Branching morphogenesis is critical for the development of many organs including the lung, pancreas, kidney, breast and prostate. In the developing kidney, the branching epithelium is called the ureteric bud; it is divided into tip regions, at its ends, and the stalk regions everywhere else. The tip regions are capable of inducing nephron formation, unlike the stalk regions. Tip regions are also the regions where most branching occurs. The cells of the tip regions of the ureteric bud have the ability to proliferate and differentiate into cells of the stalk region. Although differentiation and morphogenesis of the ureteric bud have been studied for many years, the mechanisms that control their overall pattern remain unknown. In this thesis, I have tested a specific set of hypotheses in which both differentiation and morphogenesis are controlled by a self-organization based on inhibitory interactions between tip and stalk cells.Using micro dissection and organ culture I show that;• The ureteric bud is composed of at least two distinct populations of cells, those that bind Dolichos biflorus agglutinin (DBA) and those that do not. These correspond to the stalk and tip regions respectively. DBA is a marker of regions of the ureteric bud in which branching morphogenesis is inactivated. When branching morphogenesis is inactivated a change in cell behaviour of the tip cells of the ureteric bud takes place. Tip regions change to a stalk-like behaviour as they loose the expression of tip-specific markers with a parallel increase in stalk markers.• Stalk cells are capable of giving rise to tip cells. Using DBA as a marker of stalk cells, I investigate the mechanisms controlling branching of the ureteric bud. Firstly, I tested the hypothesis that branches rarely arise from the stalks of the ureteric bud because they have lost the ability to branch; it seems that the stalk cells retain their ability to become tips when provided with an appropriate environment. Differentiation of ureteric bud cells is therefore surprisingly plastic.• I also tested the hypothesis that tips of the ureteric bud space out by sensing and responding to other tips in the vicinity. There are two components to this hypothesis;(i) that tips are separated within the epithelium by a lateral inhibition mechanism that prevents new tips forming close to existing ones, and(ii) that tips of extending epithelia are repelled by the presence of nearby tips, so that they spread out to fill space optimally.I have gained evidence against the first hypothesis and show that tips can form from stalk regions. I have investigated the second hypothesis by manipulating cultures so that the tips of separate ureteric bud are placed on a collision course. These clustered ureteric buds prematurely ceased branching and appeared to be compressed in the direction of the collision with the neighbouring clustered kidney. This supports the idea that the tips of the ureteric bud interact with each other to avoid colliding. I did not find convincing evidence to suggest that the tips at the periphery of the colliding ureteric buds were influencing the position of their nearest neighbour. In addition to this, I attempted to compare the closest distance between tips when kidneys are placed on a collision course or are cultured in isolation.The data presented in this thesis provide evidence both to partially support, and also to limit, the specific self-organization hypothesis tested

Regulation of Chondrogenesis in Human Mesenchymal Stem Cells by Cartilage Extracellular Matrix and Therapeutic Applications

Cartilage has limited intrinsic healing potential upon injury, due to the low cell density and the lack of blood supply. Degenerative disease of the cartilage, such as osteoarthritis (OA), is challenging to treat without clear mechanistic understandings of cartilage development. With over 90% of the cartilage tissue occupied by extracellular matrix (ECM), understanding the cellular and molecular effects of cartilage ECM on chondrogenesis and chondrocyte behavior is crucial for therapeutic development. The focus of this work is to study the regulation of chondrogenesis and hypertrophic maturation of human mesenchymal stem cells (MSCs) by cartilage ECM in the context of potential therapeutic applications. To study the cartilage ECM, we created a decellularized ECM digest from native porcine cartilage and examined its effects on MSCs. Since native cartilage ECM maintains chondrocyte homeostasis without progressing to hypertrophic degeneration, we hypothesized that the decellularized ECM would promote MSC chondrogenesis and inhibit hypertrophy. Indeed, we showed that ECM promoted MSC chondrogenesis and matrix production, and inhibited hypertrophy and endochondral ossification. The chondrogenic effect was shown to potentially involve the PI3K-Akt-Foxo1 and Hif1 pathways. By recapitulating the activated Hif1 pathway, roxadustat, a small molecule stabilizer of Hif, was able to reproduce the chondrogenic and anti-hypertrophic effects of the cartilage ECM. It also reduced the expression of matrix metalloproteases (MMPs) in MSCs, healthy chondrocytes, and OA chondrocytes, and alleviated matrix degradation in bovine cartilage explants. We also attempted to identify ECM components that display chondrogenic properties. Collagen XI, a minor component of articular cartilage, was shown to promote cartilage matrix formation in MSCs and healthy chondrocytes, and to reduce matrix degradation in bovine cartilage explants. Taken together, this study reveals the dual roles of cartilage ECM in promoting chondrogenesis and matrix production and inhibiting cartilage hypertrophy. Importantly, small molecule drugs that recapitulate the signaling pathways of ECM regulation, and collagen XI, a component of the ECM, may serve as leads for further therapeutic development for cartilage injury and degenerative disease