Localization analysis of variationally based gradient plasticity model

The paper presents analytical or semi-analytical solutions for the formation and evolution of localized plastic zone in a uniaxially loaded bar with variable cross-sectional area. A variationally based formulation of explicit gradient plasticity with linear softening is used, and the ensuing jump conditions and boundary conditions are discussed. Three cases with different regularity of the stress distribution are considered, and the problem is converted to a dimensionless form. Relations linking the load level, size of the plastic zone, distribution of plastic strain and plastic elongation of the bar are derived and compared to another, previously analyzed gradient formulation.Comment: 42 pages, 11 figure

Fluorescence Lifetime Imaging Microscopy (FLIM) Data Analysis with TIMP

Fluorescence Lifetime Imaging Microscopy (FLIM) allows fluorescence lifetime images of biological objects to be collected at 250 nm spatial resolution and at (sub-)nanosecond temporal resolution. Often n_comp kinetic processes underlie the observed fluorescence at all locations, but the intensity of the fluorescence associated with each process varies per-location, i.e., per-pixel imaged. Then the statistical challenge is global analysis of the image: use of the fluorescence decay in time at all locations to estimate the n_comp lifetimes associated with the kinetic processes, as well as the amplitude of each kinetic process at each location. Given that typical FLIM images represent on the order of 10^2 timepoints and 10^3 locations, meeting this challenge is computationally intensive. Here the utility of the TIMP package for R to solve parameter estimation problems arising in FLIM image analysis is demonstrated. Case studies on simulated and real data evidence the applicability of the partitioned variable projection algorithm implemented in TIMP to the problem domain, and showcase options included in the package for the visual validation of models for FLIM data.

The isolation of plasmids containing DNA complementary to messenger RNA for variant surface glycoproteins of Trypanosoma brucei.

We have isolated poly(A)+ RNA from four antigenic variants (117, 118, 121, 221) of one clone of Trypanosoma brucei. Translation of these poly(A)+ RNAs in a rabbit reticulocyte lysate gave rise to proteins that could be precipitated with antisera against homologous variant surface glycoprotein, the protein responsible for antigenic variation in trypanosomes. From the electrophoretic mobility of these in vitro products in sodium dodecyl sulphate (SDS) gels we infer that variant surface glycoproteins (VSGs) are made as pre-proteins, which require trimming to yield mature VSGs. The total translation products from the four poly(A)+ RNAs produced a complex set of bands on SDS gels, which only differed in the region where the variant pre-glycoproteins migrated. The only detectable variation in the messenger RNA populations of these variants is, therefore, in the messenger RNA for variant pre-glycoproteins. We have made duplex DNA copies of these poly(A)+ RNAs, linked the complementary DNA to plasmid pBR322 by GC tailing and cloned this recombinant DNA in Escherichia coli. Colony hybridization with complementary DNA made on poly(A)+ RNA showed that 7--10% of the colonies contained DNA that hybridized only with the homologous probe. Plasmid DNA was isolated from ten such colonies (two or three of each variant complementary DNA), bound to diazobenzyloxymethyl-cellulose (DBM) paper and used to select complementary messenger RNA from total poly(A)+ RNA by hybridization. In eight cases the RNA recovered from the filter gave variant pre-glycoprotein as the predominant product of in vitro translation. Poly(A)+ RNA from each of the variants only hydridized to the homologous complementary DNA in filter hybridizations. Each trypanosome variant, therefore, contains no detectable messenger RNAs for the three heterologous variant-specific glycoproteins tested. We conclude from this lack of cross-hybridization that antigenic diversity in trypanosomes, unlike antibody diversity in mammals, does not involve the linkage of a repertoire of genes for the variable N-terminal half to a single gene for the C-termina

Task allocation in a multi-server system

We consider a slotted queueing system with $C$ servers (processors) that can handle tasks (jobs). Tasks arrive in batches of random size at the start of every slot. Any task can be executed by any server in one slot with success probability $alpha$. If a task execution fails, then the task must be handled in some later time slot until it has been completed successfully. Tasks may be processed by several servers simultaneously. In that case, the task is completed successfully if the task execution is successful on at least one of the servers. We determine the distribution of the number of tasks in the system for a broad class of task allocation strategies. Subsequently, we examine the impact of various allocation strategies on the mean number of tasks in the system and the mean response time of tasks. It is proven that both these performance measures are minimized by the strategy which always distributes the tasks over the servers as evenly as possible. Some numerical experiments are performed to illustrate the performance characteristics of the various strategies for a wide range of scenarios

Charged Polypeptide Tail Boosts the Salt Resistance of Enzyme-Containing Complex Coacervate Micelles

[Image: see text] Encapsulation of proteins can have advantages for their protection, stability, and delivery purposes. One of the options to encapsulate proteins is to incorporate them in complex coacervate core micelles (C3Ms). This can easily be achieved by mixing aqueous solutions of the protein and an oppositely charged neutral-hydrophilic diblock copolymer. However, protein-containing C3Ms often suffer from salt-inducible disintegration due to the low charge density of proteins. The aim of this study is to improve the salt stability of protein-containing C3Ms by increasing the net charge of the protein by tagging it with a charged polypeptide. As a model protein, we used CotA laccase and generated variants with 10, 20, 30, and 40 glutamic acids attached at the C-terminus of CotA using genetic engineering. Micelles were obtained by mixing the five CotA variants with poly(N-methyl-2-vinyl-pyridinium)-block-poly(ethylene oxide) (PM2VP(128)-b-PEO(477)) at pH 10.8. Hydrodynamic radii of the micelles of approximately 31, 27, and 23 nm for native CotA, CotA-E20, and CotA-E40, respectively, were determined using dynamic light scattering (DLS) and fluorescence correlation spectroscopy (FCS). The encapsulation efficiency was not affected using enzymes with a polyglutamic acid tail but resulted in more micelles with a smaller number of enzyme molecules per micelle. Furthermore, it was shown that the addition of a polyglutamic acid tail to CotA indeed resulted in improved salt stability of enzyme-containing C3Ms. Interestingly, the polyglutamic acid CotA variants showed an enhanced enzyme activity. This study demonstrates that increasing the net charge of enzymes through genetic engineering is a promising strategy to improve the practical applicability of C3Ms as enzyme delivery systems

Enhanced stability of complex coacervate core micelles following different core-crosslinking strategies

Complex coacervate core micelles (C3Ms) are formed by mixing aqueous solutions of a charged (bio)macromolecule with an oppositely charged-neutral hydrophilic diblock copolymer. The stability of these structures is dependent on the ionic strength of the solution; above a critical ionic strength, the micelles will completely disintegrate. This instability at high ionic strengths is the main drawback for their application in, e.g., drug delivery systems or protein protection. In addition, the stability of C3Ms composed of weak polyelectrolytes is pH-dependent as well. The aim of this study is to assess the effectiveness of covalent crosslinking of the complex coacervate core to improve the stability of C3Ms. We studied the formation of C3Ms using a quaternized and amine-functionalized cationic-neutral diblock copolymer, poly(2-vinylpyridine)-block-poly(ethylene oxide) (QP2VP-b-PEO), and an anionic homopolymer, poly(acrylic acid) (PAA). Two different core-crosslinking strategies were employed that resulted in crosslinks between both types of polyelectrolyte chains in the core (i.e., between QP2VP and PAA) or in crosslinks between polyelectrolyte chains of the same type only (i.e., QP2VP). For these two strategies we used the crosslinkers 1-ethyl-3-(3′-dimethylaminopropyl)carbodiimide hydrochloride (EDC) and dimethyl-3,3′-dithiopropionimidate dihydrochloride (DTBP), respectively. EDC provides permanent crosslinks, while DTBP crosslinks can be broken by a reducing agent. Dynamic light scattering showed that both approaches significantly improved the stability of C3Ms against salt and pH changes. Furthermore, reduction of the disulphide bridges in the DTBP core-crosslinked micelles largely restored the original salt-stability profile. Therefore, this feature provides an excellent starting point for the application of C3Ms in controlled release formulations

Markovian polling systems with an application to wireless random-access networks

Motivated by an application in wireless random-access networks, we study a class of polling systems with Markovian routing, in which the server visits the queues in an order governed by a discrete-time Markov chain. Assuming that the service disciplines at each of the queues fall in the class of branching-type service disciplines, we derive a functional equation for (the probability generating function of) the joint queue length distribution conditioned on a point in time when the server visits a certain queue. From this functional equation, expressions for the (cross-)moments of the queue lengths follow. We also derive a pseudo-conservation law for this class of polling systems. Using these results, we compute expressions for certain system parameters that minimise the total expected amount of work in systems that arise from the wireless random-access network setting. In addition, we derive approximations for those parameters that minimise a weighted sum of mean waiting times in these systems. Based on these expressions, we also present an adaptive control algorithm for finding the optimal parameter values in a distributed fashion, which is particularly relevant in the context of wireless random-access networks

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OBJECTIVE Our aim is to compare the effect of type 2 diabetes on recurrent major cardiovascular events (MCVE) for patients with symptomatic vascular disease at different locations. RESEARCH DESIGN AND METHODS A total of 6,841 patients from the single-center, prospective Second Manifestations of ARTerial disease (SMART) cohort study from Utrecht, the Netherlands, with clinically manifest vascular disease with (n = 1,155) and without (n = 5,686) type 2 diabetes were monitored between 1996 and 2013. The effect of type 2 diabetes on recurrent MCVE was analyzed with Cox proportional hazards models, stratified for disease location (cerebrovascular disease, peripheral artery disease, abdominal aortic aneurysm, coronary artery disease, or polyvascular disease, defined as >= 2 vascular locations). RESULTS Five-year risks for recurrent MCVE were 9% in cerebrovascular disease, 9% in peripheral artery disease, 20% in those with an abdominal aortic aneurysm, 7% in coronary artery disease, and 21% in polyvascular disease. Type 2 diabetes increased the risk of recurrent MCVE in coronary artery disease (hazard ratio [HR] 1.67; 95% CI 1.25-2.21) and seemed to increase the risk in cerebrovascular disease (HR 1.36; 95% CI 0.90-2.07), while being no risk factor in polyvascular disease (HR 1.12; 95% CI 0.83-1.50). Results for patients with peripheral artery disease (HR 1.42; 95% CI 0.79-2.56) or an abdominal aortic aneurysm (HR 0.93; 95% CI 0.23-3.68) were inconclusive. CONCLUSIONS Type 2 diabetes increased the risk of recurrent MCVE in patients with coronary artery disease, but there is no convincing evidence that it is a major risk factor for subsequent MCVE in all patients with symptomatic vascular disease