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Alzheimer's disease (AD) is a debilitating neurodegenerative disorder affecting over five million people globally and has no established cure. Current AD-related treatments only alleviate cognitive and behavioral symptoms and do not address disease onset or progression, underlining the unmet need to create an effective, innovative AD therapeutic. Extracellular vesicles (EVs) have emerged as a new class of nanotherapeutics. These secreted, lipid-bound cellular signaling carriers show promise for potential clinical applications for neurodegenerative diseases like AD. Additionally, analyzing contents and characteristics of patient-derived EVs may address the unmet need for earlier AD diagnostic techniques, informing physicians of altered genetic expression or cellular communications specific to healthy and diseased physiological states. There are numerous recent advances in regenerative medicine using EVs and include bioengineering perspectives to modify EVs, target glial cells in neurodegenerative diseases like AD, and potentially use EVs to diagnose and treat AD earlier. This article is categorized under: Neurological Diseases > Biomedical Engineering Neurological Diseases > Molecular and Cellular Physiology Neurological Diseases > Stem Cells and Development.

Sequence analysis frequently requires intuitive understanding and convenient representation of motifs. Typically, motifs are represented as position weight matrices (PWMs) and visualized using sequence logos. However, in many scenarios, representing motifs by wildcard-style consensus sequences is compact and sufficient for interpreting the motif information and search for motif match. Based on mutual information theory and Jenson-Shannon Divergence, we propose a mathematical framework to minimize the information loss in converting PWMs to consensus sequences. We name this representation as sequence Motto and have implemented an efficient algorithm with flexible options for converting motif PWMs into Motto from nucleotides, amino acids, and customized alphabets. Here we show that this representation provides a simple and efficient way to identify the binding sites of 1156 common TFs in the human genome. The effectiveness of the method was benchmarked by comparing sequence matches found by Motto with PWM scanning results found by FIMO. On average, our method achieves 0.81 area under the precision-recall curve, significantly (p-value < 0.01) outperforming all existing methods, including maximal positional weight, Douglas and minimal mean square error. We believe this representation provides a distilled summary of a motif, as well as the statistical justification.AVAILABILITYMotto is freely available at http://wanglab.ucsd.edu/star/motto.

Black hat search engine optimization (SEO), the practice of abusively manipulating search results, is an enticing method to acquire targeted user traffic. In turn, a range of interventions--from modifying search results to seizing domains--are used to combat this activity. In this paper, we examine the effectiveness of these interventions in the context of an understudied market niche, counterfeit luxury goods. Using eight months of empirical crawled data, we identify 52 distinct SEO campaigns, document how well they are able to place search results for sixteen luxury brands, how this capability impacts the dynamics of their order volumes and how well existing interventions undermine this business when employed.

Cloaking is a common 'bait-and-switch' technique used to hide the true nature of a Web site by delivering blatantly different semantic content to different user segments. It is often used in search engine optimization (SEO) to obtain user traffic illegitimately for scams. In this paper, we measure and characterize the prevalence of cloaking on different search engines, how this behavior changes for targeted versus untargeted advertising and ultimately the response to site cloaking by search engine providers. Using a custom crawler, called Dagger, we track both popular search terms (e.g., as identified by Google, Alexa and Twitter) and targeted keywords (focused on pharmaceutical products) for over five months, identifying when distinct results were provided to crawlers and browsers. We further track the lifetime of cloaked search results as well as the sites they point to, demonstrating that cloakers can expect to maintain their pages in search results for several days on popular search engines and maintain the pages themselves for longer still.

After a decade of research and evaluation, a number of contractors and major oil companies have deployed massively parallel computers for production seismic processing. These investments both in hardware and in software development have been made despite disagreement among vendors over the best parallel architecture, a sense within the computer science community that automatic parallelization remains an unsolved problem, a relative inattention to parallel I/O and mass storage issues important to seismic processing, and close management scrutiny of the value added by high-end processing algorithms. Most of the issues raised by the supercomputing community have proved to be irrelevant to seismic processing: processor topology, code portability, ease-of-use, and scalability do not significantly impact our use of high-performance computers. The turning point came when our industry realized that only a few relevant issues remained: applicability, stability, and the programming paradigm. These have now been addressed by business trends, product maturity, and hard work. The idiosyncrasies of our business (the need to recognize and manage risk and the tremendous leveraging that occurs between research and successful exploration) have placed us among the earliest adopters of parallel computing technology. These idiosyncrasies are unlikely to change and will therefore continue to distinguish our usemore » of advanced technology from the way in which it is adopted by other industries.« less

We have developed a method for the spherical divergence correction of seismic reflection data based on normal moveout and stacking of cylindrical slant stacks. The method is illustrated on some Gulf of Mexico data. The results show that our method yields essentially the same traveltime information as does conventional processing. Our amplitudes, however, are more interpretable in terms of reflectivity than are those obtained by using an empirical spherical divergence correction.