Emergent structure in unstructured epidemic multicast

In epidemic or gossip-based multicast protocols, each node simply relays each message to some random neighbors, such that all destinations receive it at least once with high proba- bility. In sharp contrast, structured multicast protocols explicitly build and use a spanning tree to take advantage of efficient paths, and aim at having each message received exactly once. Unfortunately, when failures occur, the tree must be rebuilt. Gossiping thus provides simplicity and resilience at the expense of performance and resource efficiency. In this paper we propose a novel technique that exploits knowledge about the environment to schedule payload transmission when gossiping. The resulting protocol retains the desirable qualities of gossip, but approximates the performance of structured multicast. In some sense, instead of imposing structure by construction, we let it emerge from the operation of the gossip protocol. Experimental evaluation shows that this approach is effective even when knowledge about the environment is only approximate.(undefined

Reputation Failure: The Limits of Market Discipline in Consumer Markets

Many believe that consumersourced reputational information about products would increasingly replace topdown regulation Instead of protecting consumers through coercive laws reputational information gleaned from the wisdom of the crowd would guide consumer decision making There is now a growing pressure to deregulate in diverse fields such as contracts products liability consumer protection and occupational licensingbrbrThis Article presents a common failure mode of systems of reputation Reputation Failure By spotlighting the publicgood nature of reviews rankings and even gossip this Article shows the mismatch between the private incentives consumers have to create reputational information and its social value As a result of this divergence reputational information is beset by participation selection and social desirability biases that systematically distort it The Article argues that these distortions are inherent to most systems of reputation and that they make reputation far less reliable than traditionally understoodbrbrThe limits of reputation highlight the centrality of the law to the future of the marketplace Proper legal institutions can deal not only with the symptoms of reputation failure ” consumer mistakes ” but improve the flow and quality of reputational information thus correcting reputation failures before they arise The Article offers a general framework and explores a number of strategies A more robust system of reputation can preserve consumer autonomy without sacrificing consumer welfar

Website Proprietorship and Online Harassment

Although harassment and bullying have always existed, when such behavior is conducted online, the consequences can be uniquely devastating. The anonymity of harassers, the ease of widespread digital dissemination, and the inability to contain and/or eliminate online information can aggravate the nature of harassment on the Internet. Furthermore, section 230 of the Communications Decency Act provides Web site sponsors with immunity for content posted by others and no incentive to remove offending content. Given the unique nature of online harassment, ex post punitive measures are inadequate to redress grievances. In this Article, I propose the imposition of proprietorship liability upon Web site sponsors who fail to adopt reasonable measures to prevent foreseeable harm, such as online harassment. I also introduce several proposals to deter online harassment that would qualify as reasonable measures. These proposals incorporate contractual and architectural restraints, limits on anonymity, and restrictions on posting certain types of digital images

Website Proprietorship and Online Harassment

Although harassment and bullying have always existed, when such behavior is conducted online, the consequences can be uniquely devastating. The anonymity of harassers, the ease of widespread digital dissemination, and the inability to contain and/or eliminate online information can aggravate the nature of harassment on the Internet. Furthermore, section 230 of the Communications Decency Act provides Web site sponsors with immunity for content posted by others and no incentive to remove offending content. Given the unique nature of online harassment, ex post punitive measures are inadequate to redress grievances. In this Article, I propose the imposition of proprietorship liability upon Web site sponsors who fail to adopt reasonable measures to prevent foreseeable harm, such as online harassment. I also introduce several proposals to deter online harassment that would qualify as reasonable measures. These proposals incorporate contractual and architectural restraints, limits on anonymity, and restrictions on posting certain types of digital images

Bioinformatics

This book is divided into different research areas relevant in Bioinformatics such as biological networks, next generation sequencing, high performance computing, molecular modeling, structural bioinformatics, molecular modeling and intelligent data analysis. Each book section introduces the basic concepts and then explains its application to problems of great relevance, so both novice and expert readers can benefit from the information and research works presented here

Reducing Communication Overhead for Average Consensus

International audienceAn average consensus protocol is an iterative distributed algorithm to calculate the average of local values stored at the nodes of a network. Each node maintains a local estimate of the average and, at every iteration, it sends its estimate to all its neighbors and then updates the estimate by performing a weighted average of the estimates received. The average consensus protocol is guaranteed to converge only asymptotically and implementing a termination algorithm is challenging when nodes are not aware of some global information (e.g. the diameter of the network or the total number of nodes). In this paper, we are interested in decreasing the rate of the messages sent in the network as nodes estimates become closer to the average. We propose a totally distributed algorithm for average consensus where nodes send more messages when they have large differences in their estimates, and reduce their message sending rate when the consensus is almost reached. The convergence of the system is guaranteed to be within a predefined margin. Tuning the parameter provides a trade-off between the precision of consensus and communication overhead of the protocol. The proposed algorithm is robust against nodes changing their initial values and can also be applied in dynamic networks with faulty links

Approaches to address the immunogenicity and immunosuppressive features of Isocitrate Dehydrogenase 1 mutated gliomas

The discovery of exploitable tumor-specific targets is central to the development of clinically relevant immunotherapeutic strategies for cancer. Mutations in isocitrate dehydrogenase 1 (IDH1), frequent in diffuse gliomas is one such target. The mutation IDH1R132H (mIDH1) is immunogenic, presented on human MHC-II molecules and induces CD4 T-cell responses in MHC-humanized A2DR1 tumor models as well as IDH1-mutated glioma patients when vaccinated with mIDH1-specific peptide vaccine. mIDH1, however plays the role of a double-edged knife. Its immunogenicity is compensated by the strong immunosuppressive environment orchestrated by the production of oncometabolite 2-HG that is imported by T-cells and leads to a suppression of their activation and proliferation. Inhibition of mIDH1 using small molecule inhibitors (IDH1i) has shown benefit in pre-clinical studies as therapy and has been associated with disease control in early clinical trials. Preclinical studies have also shown the ability of IDH1i to alleviate immunosuppression in the tumor microenvironment (TME). The impact of this inhibition on tumor infiltrating T-cells, however, has not been sufficiently evaluated. The first part of this work, therefore, aimed at deciphering the effect of IDH1i on tumor-infiltrating T-cell activity and fate in the tumor microenvironment using single-cell RNA and VDJ sequencing of tumor infiltrating immune cells. The lack of suitable murine glioma models where mIDH1 is presented in its native immunogenic capacity on human MHC-II molecules prompted the development of a novel syngeneic mIDH1 glioma model in MHC-humanized A2DR1 mice. Single-cell transcriptomic and T-cell receptor analysis of tumor infiltrating immune cells in IDH1i treated mice revealed an accumulation of infiltrating T-cells potentiated by IDH1i with an increased abundance of CD4 T-cells with a tumor reactive phenotype and a reduction in frequency regulatory T-cells as well as restoration of functional intercellular T-cell communication. Combination treatment of IDH1i and ICB provided a synergistic therapeutic benefit for mIDH1 A2DR1 gliomas. These findings suggest that reduction of 2-HG levels is necessary for enabling a functional anti-tumor immune response which is then exploitable by immune checkpoint blockade and warrants for clinical trials testing the efficacy of IDH1 inhibitors in combination with adjuvant immunotherapies such as vaccines or immune checkpoint inhibitors in patients with mIDH1 gliomas. The second part of this work focused on developing a setup for the identification and validation of mIDH1-reactive T-cell receptors (TCR) from IDH1RH-specific vaccinated A2DR1 mice and from the resected lesion of a glioma patient part of the NOA16 mIDH1 peptide vaccine trial. The latter revealed a unique transcriptional signature of mIDH1 reactive CD4 T-cells in the tumor microenvironment characterized by CXCL13 expression. The proof of principle identification of mIDH1 reactive TCRs demonstrates the feasibility of exploiting immune responses against CD4-restricted neo-epitopes as a first step in developing an adoptive TCR-transgenic T-cell therapy for glioma patient

What is normal anyway? Exploring the Effect of Social Norms on Grief Expectations, Expressions, and Social Support

Social support is a significant predictor of psychosocial outcomes following bereavement. Focused on advancing the community’s capacity to support, this thesis presents a mixed methods investigation of the nature and scope of grief-related norms and their influence on experiences of grief and being supported. This research offers a valuable contribution to the literature through advancing the research field, informing clinical practice with bereaved people, and directing best practice grief education for the general public