The rare C9 P167S risk variant for age-related macular degeneration increases polymerization of the terminal component of the complement cascade

Age-related macular degeneration (AMD) is a complex neurodegenerative eye disease with behavioral and genetic etiology and is the leading cause of irreversible vision loss among elderly Caucasians. Functionally significant genetic variants in the alternative pathway of complement have been strongly linked to disease. More recently, a rare variant in the terminal pathway of complement has been associated with increased risk, Complement component 9 (C9) P167S. To assess the functional consequence of this variant, C9 levels were measured in two independent cohorts of AMD patients. In both cohorts, it was demonstrated that the P167S variant was associated with low C9 plasma levels. Further analysis showed that patients with advanced AMD had elevated sC5b-9 compared to those with non-advanced AMD, although this was not associated with the P167S polymorphism. Electron microscopy of membrane attack complexes (MACs) generated using recombinantly produced wild type or P167S C9 demonstrated identical MAC ring structures. In functional assays, the P167S variant displayed a higher propensity to polymerize and a small increase in its ability to induce hemolysis of sheep erythrocytes when added to C9-depleted serum. The demonstration that this C9 P167S AMD risk polymorphism displays increased polymerization and functional activity provides a rationale for the gene therapy trials of sCD59 to inhibit the terminal pathway of complement in AMD that are underway

Clinicopathologic Implications of Complement Genetic Variants in Kidney Transplantation

Genetic testing has uncovered rare variants in complement proteins associated with thrombotic microangiopathy (TMA) and C3 glomerulopathy (C3G). Approximately 50% are classified as variants of uncertain significance (VUS). Clinical risk assessment of patients carrying a VUS remains challenging primarily due to a lack of functional information, especially in the context of multiple confounding factors in the setting of kidney transplantation. Our objective was to evaluate the clinicopathologic significance of genetic variants in TMA and C3G in a kidney transplant cohort. We used whole exome next-generation sequencing to analyze complement genes in 76 patients, comprising 60 patients with a TMA and 16 with C3G. Ten variants in complement factor H (CFH) were identified; of these, four were known to be pathogenic, one was likely benign and five were classified as a VUS (I372V, I453L, G918E, T956M, L1207I). Each VUS was subjected to a structural analysis and was recombinantly produced; if expressed, its function was then characterized relative to the wild-type (WT) protein. Our data indicate that I372V, I453L, and G918E were deleterious while T956M and L1207I demonstrated normal functional activity. Four common polymorphisms in CFH (E936D, N1050Y, I1059T, Q1143E) were also characterized. We also assessed a family with a pathogenic variant in membrane cofactor protein (MCP) in addition to CFH with a unique clinical presentation featuring valvular dysfunction. Our analyses helped to determine disease etiology and defined the recurrence risk after kidney transplant, thereby facilitating clinical decision making for our patients. This work further illustrates the limitations of the prediction models and highlights the importance of conducting functional analysis of genetic variants particularly in a complex clinicopathologic scenario such as kidney transplantation

A Java Based Network Security on Wireless Network communication

Now a day a Wireless networking provides many advantages, but it also integrated with new security threats and alters the organizations overall information security risk profile. Security of data and privacy issu es are important to individuals and organizations especially where exchange of data is done through computer networks. Organizations invest time and resources to reduce the threat and occurrence of data insecurity. Encryption is one of the many methods adopted because of its adaptability to electronic communication channels we are encrypting and decrypting a message from a server to a client, in which the message is encrypted on the server side and decrypt on the client side for some security purposes. Th ough there are many methods to handle such situations like data security encryption plays a vital role. We all see how DES works for countering those threats, when a data is transfer from server to client

Validation of Dunbar's number in Twitter conversations

Modern society's increasing dependency on online tools for both work and recreation opens up unique opportunities for the study of social interactions. A large survey of online exchanges or conversations on Twitter, collected across six months involving 1.7 million individuals is presented here. We test the theoretical cognitive limit on the number of stable social relationships known as Dunbar's number. We find that users can entertain a maximum of 100-200 stable relationships in support for Dunbar's prediction. The "economy of attention" is limited in the online world by cognitive and biological constraints as predicted by Dunbar's theory. Inspired by this empirical evidence we propose a simple dynamical mechanism, based on finite priority queuing and time resources, that reproduces the observed social behavior.Comment: 8 pages, 6 figure

On the expressiveness and trade-offs of large scale tuple stores

Proceedings of On the Move to Meaningful Internet Systems (OTM)Massive-scale distributed computing is a challenge at our doorstep. The current exponential growth of data calls for massive-scale capabilities of storage and processing. This is being acknowledged by several major Internet players embracing the cloud computing model and offering first generation distributed tuple stores. Having all started from similar requirements, these systems ended up providing a similar service: A simple tuple store interface, that allows applications to insert, query, and remove individual elements. Further- more, while availability is commonly assumed to be sustained by the massive scale itself, data consistency and freshness is usually severely hindered. By doing so, these services focus on a specific narrow trade-off between consistency, availability, performance, scale, and migration cost, that is much less attractive to common business needs. In this paper we introduce DataDroplets, a novel tuple store that shifts the current trade-off towards the needs of common business users, pro- viding additional consistency guarantees and higher level data process- ing primitives smoothing the migration path for existing applications. We present a detailed comparison between DataDroplets and existing systems regarding their data model, architecture and trade-offs. Prelim- inary results of the system's performance under a realistic workload are also presented

Partisan Asymmetries in Online Political Activity

We examine partisan differences in the behavior, communication patterns and social interactions of more than 18,000 politically-active Twitter users to produce evidence that points to changing levels of partisan engagement with the American online political landscape. Analysis of a network defined by the communication activity of these users in proximity to the 2010 midterm congressional elections reveals a highly segregated, well clustered partisan community structure. Using cluster membership as a high-fidelity (87% accuracy) proxy for political affiliation, we characterize a wide range of differences in the behavior, communication and social connectivity of left- and right-leaning Twitter users. We find that in contrast to the online political dynamics of the 2008 campaign, right-leaning Twitter users exhibit greater levels of political activity, a more tightly interconnected social structure, and a communication network topology that facilitates the rapid and broad dissemination of political information.Comment: 17 pages, 10 figures, 6 table

Reasoning About a Service-oriented Programming Paradigm

This paper is about a new way for programming distributed applications: the service-oriented one. It is a concept paper based upon our experience in developing a theory and a language for programming services. Both the theoretical formalization and the language interpreter showed us the evidence that a new programming paradigm exists. In this paper we illustrate the basic features it is characterized by

Disease Extent at Secondary Cytoreductive Surgery is Predictive of Progression-free and Overall Survival in Advanced Stage Ovarian Cancer: an NRG Oncology/Gynecologic Oncology Group study

Purpose GOG 152 was a randomized trial of secondary cytoreductive surgery (SCS) in patients with suboptimal residual disease (residual tumor nodule >1 cm in greatest diameter) following primary cytoreductive surgery for advanced stage ovarian cancer. The current analysis was undertaken to evaluate the impact of disease findings at SCS on progression-free survival (PFS) and overall survival (OS). Methods Among the 550 patients enrolled on GOG-152, two-hundred-sixteen patients were randomly assigned following 3 cycles of cisplatin and paclitaxel to receive SCS. In 15 patients (7%) surgery was declined or contraindicated. In the remaining 201 patients the operative and pathology reports were utilized to classify their disease status at the beginning of SCS as; no gross disease/microscopically negative N= 40 (19.9%), no gross disease/microscopically positive N= 8 (4.0%), and gross disease N=153 (76.1%). Results The median PFS for patients with no gross disease/microscopically negative was 16.1 months, no gross disease/microscopically positive was 13.5 months and for gross disease was 11.7 months, p=0.002. The median OS for patients with no gross disease/microscopically negative was 51.5 months, no gross disease/microscopically positive was 42.6 months and for gross disease was 34.9 months, p=0.018. Conclusion Although as previously reported SCS did not change PFS or OS, for those who underwent the procedure, their operative and pathologic findings were predictive of PFS and OS. Surgical/pathological residual disease is a biomarker of response to chemotherapy and predictive of PFS and OS

Good Friends, Bad News - Affect and Virality in Twitter

The link between affect, defined as the capacity for sentimental arousal on the part of a message, and virality, defined as the probability that it be sent along, is of significant theoretical and practical importance, e.g. for viral marketing. A quantitative study of emailing of articles from the NY Times finds a strong link between positive affect and virality, and, based on psychological theories it is concluded that this relation is universally valid. The conclusion appears to be in contrast with classic theory of diffusion in news media emphasizing negative affect as promoting propagation. In this paper we explore the apparent paradox in a quantitative analysis of information diffusion on Twitter. Twitter is interesting in this context as it has been shown to present both the characteristics social and news media. The basic measure of virality in Twitter is the probability of retweet. Twitter is different from email in that retweeting does not depend on pre-existing social relations, but often occur among strangers, thus in this respect Twitter may be more similar to traditional news media. We therefore hypothesize that negative news content is more likely to be retweeted, while for non-news tweets positive sentiments support virality. To test the hypothesis we analyze three corpora: A complete sample of tweets about the COP15 climate summit, a random sample of tweets, and a general text corpus including news. The latter allows us to train a classifier that can distinguish tweets that carry news and non-news information. We present evidence that negative sentiment enhances virality in the news segment, but not in the non-news segment. We conclude that the relation between affect and virality is more complex than expected based on the findings of Berger and Milkman (2010), in short 'if you want to be cited: Sweet talk your friends or serve bad news to the public'.Comment: 14 pages, 1 table. Submitted to The 2011 International Workshop on Social Computing, Network, and Services (SocialComNet 2011