Introduction to the special section on dependable network computing

Dependable network computing is becoming a key part of our daily economic and social life. Every day, millions of users and businesses are utilizing the Internet infrastructure for real-time electronic commerce transactions, scheduling important events, and building relationships. While network traffic and the number of users are rapidly growing, the mean-time between failures (MTTF) is surprisingly short; according to recent studies, in the majority of Internet backbone paths, the MTTF is 28 days. This leads to a strong requirement for highly dependable networks, servers, and software systems. The challenge is to build interconnected systems, based on available technology, that are inexpensive, accessible, scalable, and dependable. This special section provides insights into a number of these exciting challenges

Novel Approaches for Preventing Lipid Oxidation in Emulsion-Based Food Systems

Consumer interest in “clean” labels has continued to be a key driver of consumer behavior and purchasing habits over the past decade. Food manufacturers are therefore eager to replace synthetic antioxidants such as ethylenediaminetetraacetic acid (EDTA) with natural alternatives, however alternative chelators that will bind iron at low pH remain elusive. Coupled with the current oil shortages and supply chain challenges that have arisen recently, there is an urgent need for innovative solutions to increase the oxidative stability of edible oils. One available strategy is diluting oils high in unsaturated fatty acids into more stable, more saturated oils, thus delaying lipid oxidation by decreasing free-radical propagation reactions between oxidized fatty acids and unsaturated lipids. The effect of diluting fish oil into medium-chain triglycerides (MCTs) on oxidative stability was investigated using lipid hydroperoxides and gas chromatography headspace analysis. Dilutions up to 1 in 20 of fish oil in MCT extended propanal formation from 1 to 6 days in Tween-80-stabilized oil-in-water emulsions. This protective effect was not observed in emulsions wherein the two oils were in separate droplets. Fish oil blended with high oleic sunflower oil (HOSO) also demonstrated a protective effect when the oils were in the same emulsion droplets but not in separate emulsion droplets. The present study indicates that dilution can be used to increase the oxidative stability of polyunsaturated fatty acids in oil-in-water emulsions. Another potential strategy relies on oxidized α-tocopherol being regenerated by phosphatidylethanolamine (PE). Although current commercial sources of PE are too expensive for use as a food additive, the present study aims to determine the optimal reaction conditions for generating high PE lecithin (MHPEL) enzymatically and to validate the MHPEL’s synergism with tocopherol in delaying lipid oxidation in an oil-in-water emulsion systems at pH 7, and 4, and in bulk oil. Under optimal conditions of pH 9.0, 37°C and 4h, a MHPEL with ~71.6% PE was obtained from 96% phosphatidylcholine lecithin using phospholipase D from Streptomyces chromofuscus. Compared to mixed tocopherols alone, the addition of MHPEL synergistically increased the both the hydroperoxide and hexanal lag phase of lipid oxidation in oil-in-water emulsions by 3 days in o/w emulsions at pH 7 and 3 and 2 days, respectively, at pH 4. In combination with 50 µmol/kg oil of α-tocopherol, the addition of 1000 µmol/kg oil MHPEL synergistically increased the lag phases by 5 and 4 days in bulk oil compared to tocopherol alone. The novel approaches contained herein represent potential clean-label strategies for increasing the oxidative stability of food systems and have strong potential for commercial applications to decrease food waste

Expand+Functional selection and systematic analysis of intronic splicing elements identify active sequence motifs and associated splicing factors

Despite the critical role of pre-mRNA splicing in generating proteomic diversity and regulating gene expression, the sequence composition and function of intronic splicing regulatory elements (ISREs) have not been well elucidated. Here, we employed a high-throughput in vivo Screening PLatform for Intronic Control Elements (SPLICE) to identify 125 unique ISRE sequences from a random nucleotide library in human cells. Bioinformatic analyses reveal consensus motifs that resemble splicing regulatory elements and binding sites for characterized splicing factors and that are enriched in the introns of naturally occurring spliced genes, supporting their biological relevance. In vivo characterization, including an RNAi silencing study, demonstrate that ISRE sequences can exhibit combinatorial regulatory activity and that multiple trans-acting factors are involved in the regulatory effect of a single ISRE. Our work provides an initial examination into the sequence characteristics and function of ISREs, providing an important contribution to the splicing code

Reprogramming Cellular Behavior with RNA Controllers Responsive to Endogenous Proteins

Synthetic genetic devices that interface with native cellular pathways can be used to change natural networks to implement new forms of control and behavior. The engineering of gene networks has been limited by an inability to interface with native components. We describe a class of RNA control devices that overcome these limitations by coupling increased abundance of particular proteins to targeted gene expression events through the regulation of alternative RNA splicing. We engineered RNA devices that detect signaling through the nuclear factor κB and Wnt signaling pathways in human cells and rewire these pathways to produce new behaviors, thereby linking disease markers to noninvasive sensing and reprogrammed cellular fates. Our work provides a genetic platform that can build programmable sensing-actuation devices enabling autonomous control over cellular behavior

The maximal tubes under the deformations of a class of 3-dimensional hyperbolic cone-manifolds

Recently, Hodgson and Kerckhoff found a small bound on Dehn surgered 3-manifolds from hyperbolic knots not admitting hyperbolic structures using deformations of hyperbolic cone-manifolds. They asked whether the area normalized meridian length squared of maximal tubular neighborhoods of the singular locus of the cone-manifold is decreasing and that summed with the cone angle squared is increasing as we deform the cone-angles. We confirm this near 0 cone-angles for an infinite family of hyperbolic cone-manifolds obtained by Dehn surgeries along the Whitehead link complements. The basic method is based on explicit holonomy computations using the A-polynomials and finding the maximal tubes. One of the key tool is the Taylor expression of a geometric component of the zero set of the A-polynomial in terms of the cone-angles. We also show a sequence of Taylor expressions for Dehn surgered manifolds converges to one for the limit hyperbolic manifold.Comment: 27 pages, 10 figure

Computing CMB Anisotropy in Compact Hyperbolic Spaces

The measurements of CMB anisotropy have opened up a window for probing the global topology of the universe on length scales comparable to and beyond the Hubble radius. For compact topologies, the two main effects on the CMB are: (1) the breaking of statistical isotropy in characteristic patterns determined by the photon geodesic structure of the manifold and (2) an infrared cutoff in the power spectrum of perturbations imposed by the finite spatial extent. We present a completely general scheme using the regularized method of images for calculating CMB anisotropy in models with nontrivial topology, and apply it to the computationally challenging compact hyperbolic topologies. This new technique eliminates the need for the difficult task of spatial eigenmode decomposition on these spaces. We estimate a Bayesian probability for a selection of models by confronting the theoretical pixel-pixel temperature correlation function with the COBE-DMR data. Our results demonstrate that strong constraints on compactness arise: if the universe is small compared to the `horizon' size, correlations appear in the maps that are irreconcilable with the observations. If the universe is of comparable size, the likelihood function is very dependent upon orientation of the manifold wrt the sky. While most orientations may be strongly ruled out, it sometimes happens that for a specific orientation the predicted correlation patterns are preferred over the conventional infinite models.Comment: 15 pages, LaTeX (IOP style included), 3 color figures (GIF) in separate files. Minor revision to match the version accepted in Class. Quantum Grav.: Proc. of Topology and Cosmology, Cleveland, 1997. The paper can be also downloaded from http://www.cita.utoronto.ca/~pogosyan/cwru_proc.ps.g

Noncyclic covers of knot complements

Hempel has shown that the fundamental groups of knot complements are residually finite. This implies that every nontrivial knot must have a finite-sheeted, noncyclic cover. We give an explicit bound, $\Phi (c)$, such that if $K$ is a nontrivial knot in the three-sphere with a diagram with $c$ crossings and a particularly simple JSJ decomposition then the complement of $K$ has a finite-sheeted, noncyclic cover with at most $\Phi (c)$ sheets.Comment: 29 pages, 8 figures, from Ph.D. thesis at Columbia University; Acknowledgments added; Content correcte

Dimension of the Torelli group for Out(F_n)

Let T_n be the kernel of the natural map from Out(F_n) to GL(n,Z). We use combinatorial Morse theory to prove that T_n has an Eilenberg-MacLane space which is (2n-4)-dimensional and that H_{2n-4}(T_n,Z) is not finitely generated (n at least 3). In particular, this recovers the result of Krstic-McCool that T_3 is not finitely presented. We also give a new proof of the fact, due to Magnus, that T_n is finitely generated.Comment: 27 pages, 9 figure