5,710 research outputs found
Orally active antischistosomal early leads identified from the open access malaria box.
BACKGROUND: Worldwide hundreds of millions of schistosomiasis patients rely on treatment with a single drug, praziquantel. Therapeutic limitations and the threat of praziquantel resistance underline the need to discover and develop next generation drugs. METHODOLOGY: We studied the antischistosomal properties of the Medicines for Malaria Venture (MMV) malaria box containing 200 diverse drug-like and 200 probe-like compounds with confirmed in vitro activity against Plasmodium falciparum. Compounds were tested against schistosomula and adult Schistosoma mansoni in vitro. Based on in vitro performance, available pharmacokinetic profiles and toxicity data, selected compounds were investigated in vivo. PRINCIPAL FINDINGS: Promising antischistosomal activity (IC50: 1.4-9.5 µM) was observed for 34 compounds against schistosomula. Three compounds presented IC50 values between 0.8 and 1.3 µM against adult S. mansoni. Two promising early leads were identified, namely a N,N'-diarylurea and a 2,3-dianilinoquinoxaline. Treatment of S. mansoni infected mice with a single oral 400 mg/kg dose of these drugs resulted in significant worm burden reductions of 52.5% and 40.8%, respectively. CONCLUSIONS/SIGNIFICANCE: The two candidates identified by investigating the MMV malaria box are characterized by good pharmacokinetic profiles, low cytotoxic potential and easy chemistry and therefore offer an excellent starting point for antischistosomal drug discovery and development
When Things Matter: A Data-Centric View of the Internet of Things
With the recent advances in radio-frequency identification (RFID), low-cost
wireless sensor devices, and Web technologies, the Internet of Things (IoT)
approach has gained momentum in connecting everyday objects to the Internet and
facilitating machine-to-human and machine-to-machine communication with the
physical world. While IoT offers the capability to connect and integrate both
digital and physical entities, enabling a whole new class of applications and
services, several significant challenges need to be addressed before these
applications and services can be fully realized. A fundamental challenge
centers around managing IoT data, typically produced in dynamic and volatile
environments, which is not only extremely large in scale and volume, but also
noisy, and continuous. This article surveys the main techniques and
state-of-the-art research efforts in IoT from data-centric perspectives,
including data stream processing, data storage models, complex event
processing, and searching in IoT. Open research issues for IoT data management
are also discussed
Robust Algorithms for Detecting Hidden Structure in Biological Data
Biological data, such as molecular abundance measurements and protein
sequences, harbor complex hidden structure that reflects its underlying
biological mechanisms. For example, high-throughput abundance measurements
provide a snapshot the global state of a living cell, while homologous
protein sequences encode the residue-level logic of the proteins\u27 function
and provide a snapshot of the evolutionary trajectory of the protein family.
In this work I describe algorithmic approaches and analysis software I
developed for uncovering hidden structure in both kinds of data.
Clustering is an unsurpervised machine learning technique commonly used
to map the structure of data collected in high-throughput experiments,
such as quantification of gene expression by DNA microarrays or
short-read sequencing. Clustering algorithms always yield a partitioning
of the data, but relying on a single partitioning solution can lead to
spurious conclusions. In particular, noise in the data can cause objects
to fall into the same cluster by chance rather than due to meaningful
association. In the first part of this thesis I demonstrate approaches to
clustering data robustly in the presence of noise and apply robust clustering
to analyze the transcriptional response to injury in a neuron cell.
In the second part of this thesis I describe identifying hidden specificity
determining residues (SDPs) from alignments of protein sequences descended
through gene duplication from a common ancestor (paralogs) and apply the
approach to identify numerous putative SDPs in bacterial transcription
factors in the LacI family. Finally, I describe and demonstrate a new
algorithm for reconstructing the history of duplications by which paralogs
descended from their common ancestor. This algorithm addresses the
complexity of such reconstruction due to indeterminate or erroneous
homology assignments made by sequence alignment algorithms and to the
vast prevalence of divergence through speciation over divergence through
gene duplication in protein evolution
Machine Learning and Law
Part I of this Article explains the basic concepts underlying machine learning. Part II will convey a more general principle: non-intelligent computer algorithms can sometimes produce intelligent results in complex tasks through the use of suitable proxies detected in data. Part III will explore how certain legal tasks might be amenable to partial automation under this principle by employing machine learning techniques. This Part will also emphasize the significant limitations of these automated methods as compared to the capabilities of similarly situated attorneys
Experiences of aiding autobiographical memory Using the SenseCam
Human memory is a dynamic system that makes accessible certain memories of events based on a hierarchy of information, arguably driven by personal significance. Not all events are remembered, but those that are tend to be more psychologically relevant. In contrast, lifelogging is the process of automatically recording aspects of one's life in digital form without loss of information. In this article we share our experiences in designing computer-based solutions to assist people review their visual lifelogs and address this contrast. The technical basis for our work is automatically segmenting visual lifelogs into events, allowing event similarity and event importance to be computed, ideas that are motivated by cognitive science considerations of how human memory works and can be assisted. Our work has been based on visual lifelogs gathered by dozens of people, some of them with collections spanning multiple years. In this review article we summarize a series of studies that have led to the development of a browser that is based on human memory systems and discuss the inherent tension in storing large amounts of data but making the most relevant material the most accessible
Experiences of aiding autobiographical memory using the sensecam
Human memory is a dynamic system that makes accessible certain memories of events based on a hierarchy of information, arguably driven by personal significance. Not all events are remembered, but those that are tend to be more psychologically relevant. In contrast, lifelogging is the process of automatically recording aspects of one's life in digital form without loss of information. In this article we share our experiences in designing computer-based solutions to assist people review their visual lifelogs and address this contrast. The technical basis for our work is automatically segmenting visual lifelogs into events, allowing event similarity and event importance to be computed, ideas that are motivated by cognitive science considerations of how human memory works and can be assisted. Our work has been based on visual lifelogs gathered by dozens of people, some of them with collections spanning multiple years. In this review article we summarize a series of studies that have led to the development of a browser that is based on human memory systems and discuss the inherent tension in storing large amounts of data but making the most relevant material the most accessible
The Family of MapReduce and Large Scale Data Processing Systems
In the last two decades, the continuous increase of computational power has
produced an overwhelming flow of data which has called for a paradigm shift in
the computing architecture and large scale data processing mechanisms.
MapReduce is a simple and powerful programming model that enables easy
development of scalable parallel applications to process vast amounts of data
on large clusters of commodity machines. It isolates the application from the
details of running a distributed program such as issues on data distribution,
scheduling and fault tolerance. However, the original implementation of the
MapReduce framework had some limitations that have been tackled by many
research efforts in several followup works after its introduction. This article
provides a comprehensive survey for a family of approaches and mechanisms of
large scale data processing mechanisms that have been implemented based on the
original idea of the MapReduce framework and are currently gaining a lot of
momentum in both research and industrial communities. We also cover a set of
introduced systems that have been implemented to provide declarative
programming interfaces on top of the MapReduce framework. In addition, we
review several large scale data processing systems that resemble some of the
ideas of the MapReduce framework for different purposes and application
scenarios. Finally, we discuss some of the future research directions for
implementing the next generation of MapReduce-like solutions.Comment: arXiv admin note: text overlap with arXiv:1105.4252 by other author
Lucene4IR: Developing information retrieval evaluation resources using Lucene
The workshop and hackathon on developing Information Retrieval Evaluation Resources using Lucene (L4IR) was held on the 8th and 9th of September, 2016 at the University of Strathclyde in Glasgow, UK and funded by the ESF Elias Network. The event featured three main elements: (i) a series of keynote and invited talks on industry, teaching and evaluation; (ii) planning, coding and hacking where a number of groups created modules and infrastructure to use Lucene to undertake TREC based evaluations; and (iii) a number of breakout groups discussing challenges, opportunities and problems in bridging the divide between academia and industry, and how we can use Lucene for teaching and learning Information Retrieval (IR). The event was composed of a mix and blend of academics, experts and students wanting to learn, share and create evaluation resources for the community. The hacking was intense and the discussions lively creating the basis of many useful tools but also raising numerous issues. It was clear that by adopting and contributing to most widely used and supported Open Source IR toolkit, there were many benefits for academics, students, researchers, developers and practitioners - providing a basis for stronger evaluation practices, increased reproducibility, more efficient knowledge transfer, greater collaboration between academia and industry, and shared teaching and training resources
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