14,190 research outputs found
Addressing current challenges in cancer immunotherapy with mathematical and computational modeling
The goal of cancer immunotherapy is to boost a patient's immune response to a
tumor. Yet, the design of an effective immunotherapy is complicated by various
factors, including a potentially immunosuppressive tumor microenvironment,
immune-modulating effects of conventional treatments, and therapy-related
toxicities. These complexities can be incorporated into mathematical and
computational models of cancer immunotherapy that can then be used to aid in
rational therapy design. In this review, we survey modeling approaches under
the umbrella of the major challenges facing immunotherapy development, which
encompass tumor classification, optimal treatment scheduling, and combination
therapy design. Although overlapping, each challenge has presented unique
opportunities for modelers to make contributions using analytical and numerical
analysis of model outcomes, as well as optimization algorithms. We discuss
several examples of models that have grown in complexity as more biological
information has become available, showcasing how model development is a dynamic
process interlinked with the rapid advances in tumor-immune biology. We
conclude the review with recommendations for modelers both with respect to
methodology and biological direction that might help keep modelers at the
forefront of cancer immunotherapy development.Comment: Accepted for publication in the Journal of the Royal Society
Interfac
An Immune Inspired Approach to Anomaly Detection
The immune system provides a rich metaphor for computer security: anomaly
detection that works in nature should work for machines. However, early
artificial immune system approaches for computer security had only limited
success. Arguably, this was due to these artificial systems being based on too
simplistic a view of the immune system. We present here a second generation
artificial immune system for process anomaly detection. It improves on earlier
systems by having different artificial cell types that process information.
Following detailed information about how to build such second generation
systems, we find that communication between cells types is key to performance.
Through realistic testing and validation we show that second generation
artificial immune systems are capable of anomaly detection beyond generic
system policies. The paper concludes with a discussion and outline of the next
steps in this exciting area of computer security.Comment: 19 pages, 4 tables, 2 figures, Handbook of Research on Information
Security and Assuranc
Molecular modelling of dendrimers for nanoscale applications
Dendrimers are well defined, highly branched macromolecules that radiate from a central core and are synthesized through a stepwise, repetitive reaction sequence that guarantees complete shells for each generation, leading to polymers that are monodisperse. The synthetic procedures developed for dendrimer preparation permit nearly complete control over the critical molecular design parameters, such as size, shape, surface/interior chemistry, flexibility, and topology. Recent results suggest that dendritic polymers may provide the key to developing a reliable and economical fabrication and manufacturing route to functional nanoscale materials that would have unique properties (electronic, optical, opto-electronic, magnetic, chemical, or biological). In turn, these could be used in designing new nanoscale devices. In this paper, we determine the 3D molecular structure of various dendrimers with continuous configurational Boltzmann biased direct Monte Carlo method and study their energetic and structural properties using molecular dynamics after annealing these molecular representations
From secretome analysis to immunology: chitosan induces major alterations in the activation of dendritic cells via a TLR4-dependent mechanism
Dendritic cells are known to be activated by a wide range of microbial
products, leading to cytokine production and increased levels of membrane
markers such as major histocompatibility complex class II molecules. Such
activated dendritic cells possess the capacity to activate na\"ive T cells. In
the present study we demonstrated that immature dendritic cells secrete both
the YM1 lectin and lipocalin-2. By testing the ligands of these two proteins,
chitosan and siderophores, respectively, we also demonstrated that chitosan, a
degradation product of various fungal and protozoal cell walls, induces an
activation of dendritic cells at the membrane level, as shown by the
up-regulation of membrane proteins such as class II molecules, CD80 and CD86
via a TLR4-dependent mechanism, but is not able to induce cytokine production.
This led to the production of activated dendritic cells unable to stimulate T
cells. However, costimulation with other microbial products overcame this
partial activation and restored the capacity of these activated dendritic cells
to stimulate T cells. In addition, successive stimulation with chitosan and
then by lipopolysaccharide induced a dose-dependent change in the cytokinic
IL-12/IL-10 balance produced by the dendritic cells
Modeling Brain Circuitry over a Wide Range of Scales
If we are ever to unravel the mysteries of brain function at its most
fundamental level, we will need a precise understanding of how its component
neurons connect to each other. Electron Microscopes (EM) can now provide the
nanometer resolution that is needed to image synapses, and therefore
connections, while Light Microscopes (LM) see at the micrometer resolution
required to model the 3D structure of the dendritic network. Since both the
topology and the connection strength are integral parts of the brain's wiring
diagram, being able to combine these two modalities is critically important.
In fact, these microscopes now routinely produce high-resolution imagery in
such large quantities that the bottleneck becomes automated processing and
interpretation, which is needed for such data to be exploited to its full
potential. In this paper, we briefly review the Computer Vision techniques we
have developed at EPFL to address this need. They include delineating dendritic
arbors from LM imagery, segmenting organelles from EM, and combining the two
into a consistent representation
Neuro-memristive Circuits for Edge Computing: A review
The volume, veracity, variability, and velocity of data produced from the
ever-increasing network of sensors connected to Internet pose challenges for
power management, scalability, and sustainability of cloud computing
infrastructure. Increasing the data processing capability of edge computing
devices at lower power requirements can reduce several overheads for cloud
computing solutions. This paper provides the review of neuromorphic
CMOS-memristive architectures that can be integrated into edge computing
devices. We discuss why the neuromorphic architectures are useful for edge
devices and show the advantages, drawbacks and open problems in the field of
neuro-memristive circuits for edge computing
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