Gut dysbiosis might underlie the pathogenesis of type 1 diabetes. In mice of the non-obese diabetic (NOD) strain, we found that key features of disease correlated inversely with blood and fecal concentrations of the microbial metabolites acetate and butyrate. We therefore fed NOD mice specialized diets designed to release large amounts of acetate or butyrate after bacterial fermentation in the colon. Each diet provided a high degree of protection from diabetes, even when administered after breakdown of immunotolerance. Feeding mice a combined acetate- and butyrate-yielding diet provided complete protection, which suggested that acetate and butyrate might operate through distinct mechanisms. Acetate markedly decreased the frequency of autoreactive T cells in lymphoid tissues, through effects on B cells and their ability to expand populations of autoreactive T cells. A diet containing butyrate boosted the number and function of regulatory T cells, whereas acetate- and butyrate-yielding diets enhanced gut integrity and decreased serum concentration of diabetogenic cytokines such as IL-21. Medicinal foods or metabolites might represent an effective and natural approach for countering the numerous immunological defects that contribute to T cell-dependent autoimmune diseases.

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Web 2.0 is a buzzword introduced in 2003-04 which is commonly used to encompass various novel phenomena on the World Wide Web. Although largely a marketing term, some of the key attributes associated with Web 2.0 include the growth of social networks, bi-directional communication, various 'glue' technologies, and significant diversity in content types. We are not aware of a technical comparison between Web 1.0 and 2.0. While most of Web 2.0 runs on the same substrate as 1.0, there are some key differences. We capture those differences and their implications for technical work in this paper. Our goal is to identify the primary differences leading to the properties of interest in 2.0 to be characterized. We identify novel challenges due to the different structures of Web 2.0 sites, richer methods of user interaction, new technologies, and fundamentally different philosophy. Although a significant amount of past work can be reapplied, some critical thinking is needed for the networking community to analyze the challenges of this new and rapidly evolving environment.

Web search is an integral part of our daily lives. Recently, there has been a trend of personalization in Web search, where di erent users receive di erent results for the same search query. The increasing level of personalization is leading to concerns about Filter Bubble e ects, where certain users are simply unable to access information that the search engines' algorithm decides is irrelevant. Despite these concerns, there has been little quanti cation of the extent of personalization in Web search today, or the user attributes that cause it.In light of this situation, we make three contributions. First, we develop a methodology for measuring personalization in Web search results. While conceptually simple, there are numerous details that our methodology must handle in order to accurately attribute di erences in search results to personalization. Second, we apply our methodology to 200 users on Google Web Search and 100 users on Bing. We nd that, on average, 11.7% of results show di erences due to personalization on Google, while 15.8% of results are personalized on Bing, but that this varies widely by search query and by result ranking. Third, we investigate the user features used to personalize on Google Web Search and Bing. Surprisingly, we only nd measurable personalization as a result of searching with a logged in account and the IP address of the searching user. Our results are a rst step towards understanding the extent and e ects of personalization on Web search engines today.

Type 1 diabetes (T1D) is characterized by immune responses against several autoantigens expressed in pancreatic β cells. T cells specific for proinsulin and islet-specific glucose-6-phosphatase catalytic subunit-related protein (IGRP) can induce T1D in NOD mice. However, whether immune responses to multiple autoantigens are caused by spreading from one to another or whether they develop independently of each other is unknown. As cytotoxic T cells specific for IGRP were not detected in transgenic NOD mice tolerant to proinsulin, we determined that immune responses against proinsulin are necessary for IGRP-specific T cells to develop. On the other hand, transgenic overexpression of IGRP resulted in loss of intra-islet IGRP-specific T cells but did not protect NOD mice from insulitis or T1D, providing direct evidence that the response against IGRP is downstream of the response to proinsulin. Our results suggest that pathogenic proinsulin-specific immunity in NOD mice subsequently spreads to other antigens such as IGRP.