Macroscopic limit of time-dependent density-functional theory for adiabatic local approximations of the exchange-correlation kernel

Time-dependent density-functional theory is a rather accurate and efficient way to compute electronic excitations for finite systems. However, in the macroscopic limit (systems of increasing size), for the usual adiabatic random-phase, local-density, or generalized-gradient approximations, one recovers the Kohn-Sham independent-particle picture, and thus the incorrect band gap. To clarify this trend, we investigate the macroscopic limit of the exchange-correlation kernel in such approximations by means of an algebraical analysis complemented with numerical studies of a one-dimensional tight-binding model. We link the failure to shift the Kohn-Sham spectrum of these approximate kernels to the fact that the corresponding operators in the transition space act only on a finite subspace.

Programmable motion and separation of single magnetic particles on patterned magnetic surfaces

Motion of single micrometer-sized magnetic particles on patterned magnetic surfaces is controlled by a rotating magnetic field (see Figure and cover). Patterns of thin-film magnetic elements are tailored to form transport lines. Individual particles are separated by adding junctions to the transport lines. The method can improve existing applications in biotechnology and generate new ones in life sciences.

Dressing Plasmons in Particle-in-Cavity Architectures

Placing metallic nanoparticles inside cavities, rather than in dimers, greatly improves their plasmonic response. Such particle-in-cavity (PIC) hybrid architectures are shown to produce extremely strong field enhancement at the particle cavity junctions, arising from the cascaded focusing of large optical cross sections into small gaps. These simply constructed PIC structures produce the strongest field enhancement for coupled nanoparticles, up to 90% stronger than for a dimer. The coupling is found to follow a universal power law with particle surface separation, both for field enhancements and resonant wavelength shifts. Significantly enhanced Raman signals are experimentally observed for molecules adsorbed in such PIC structures, in quantitive agreement with theoretical calculations. PIC architectures may have important implications in many applications, such as reliable single molecule sensing and light harvesting in plasmonic photovoltaic devices.

Robust food supply supply chains:An integrated framework for vulnerability assessment and disturbance management

The operation of supply chains (SCs) has for many years been focused on efficiency, leanness and responsiveness. This has resulted in reduced slack in operations, compressed cycle times, increased productivity and minimised inventory levels along the SC. Combined with tight tolerance settings for the realisation of logistics and production processes, this has led to SC performances that are frequently not robust. SCs are becoming increasingly vulnerable to disturbances, which can decrease the competitive power of the entire chain in the market. Moreover, in the case of food SCs non-robust performances may ultimately result in empty shelves in grocery stores and supermarkets.
The overall objective of this research is to contribute to Supply Chain Management (SCM) theory by developing a structured approach to assess SC vulnerability, so that robust performances of food SCs can be assured. We also aim to help companies in the food industry to evaluate their current state of vulnerability, and to improve their performance robustness through a better understanding of vulnerability issues. The following research questions (RQs) stem from these objectives:
RQ1: What are the main research challenges related to (food) SC robustness?
RQ2: What are the main elements that have to be considered in the design of robust SCs and what are the relationships between these elements?
RQ3: What is the relationship between the contextual factors of food SCs and the use of disturbance management principles?
RQ4: How to systematically assess the impact of disturbances in (food) SC processes on the robustness of (food) SC performances?
To answer these RQs we used different methodologies, both qualitative and quantitative. For each question, we conducted a literature survey to identify gaps in existing research and define the state of the art of knowledge on the related topics. For the second and third RQ, we conducted both exploration and testing on selected case studies. Finally, to obtain more detailed answers to the fourth question, we used simulation modelling and scenario analysis for vulnerability assessment.
Main findings are summarised as follows.
Based on an extensive literature review, we answered RQ1. The main research challenges were related to the need to define SC robustness more precisely, to identify and classify disturbances and their causes in the context of the specific characteristics of SCs and to make a systematic overview of (re)design strategies that may improve SC robustness. Also, we found that it is useful to be able to discriminate between varying degrees of SC vulnerability and to find a measure that quantifies the extent to which a company or SC shows robust performances when exposed to disturbances.
To address RQ2, we define SC robustness as the degree to which a SC shows an acceptable performance in (each of) its Key Performance Indicators (KPIs) during and after an unexpected event that caused a disturbance in one or more logistics processes. Based on the SCM literature we identified the main elements needed to achieve robust performances and structured them together to form a conceptual framework for the design of robust SCs. We then explained the logic of the framework and elaborate on each of its main elements: the SC scenario, SC disturbances, SC performance, sources of food SC vulnerability, and redesign principles and strategies.
Based on three case studies, we answered RQ3. Our major findings show that the contextual factors have a consistent relationship to Disturbance Management Principles (DMPs). The product and SC environment characteristics are contextual factors that are hard to change and these characteristics initiate the use of specific DMPs as well as constrain the use of potential response actions. The process and the SC network characteristics are contextual factors that are easier to change, and they are affected by the use of the DMPs. We also found a notable relationship between the type of DMP likely to be used and the particular combination of contextual factors present in the observed SC.
To address RQ4, we presented a new method for vulnerability assessments, the VULA method. The VULA method helps to identify how much a company is underperforming on a specific Key Performance Indicator (KPI) in the case of a disturbance, how often this would happen and how long it would last. It ultimately informs the decision maker about whether process redesign is needed and what kind of redesign strategies should be used in order to increase the SC’s robustness. The VULA method is demonstrated in the context of a meat SC using discrete-event simulation. The case findings show that performance robustness can be assessed for any KPI using the VULA method.
To sum-up the project, all findings were incorporated within an integrated framework for designing robust SCs. The integrated framework consists of the following steps: 1) Description of the SC scenario and identification of its specific contextual factors; 2) Identification of disturbances that may affect KPIs; 3) Definition of the relevant KPIs and identification of the main disturbances through assessment of the SC performance robustness (i.e. application of the VULA method); 4) Identification of the sources of vulnerability that may (strongly) affect the robustness of performances and eventually increase the vulnerability of the SC; 5) Identification of appropriate preventive or disturbance impact reductive redesign strategies; 6) Alteration of SC scenario elements as required by the selected redesign strategies and repeat VULA method for KPIs, as defined in Step 3.
Contributions of this research are listed as follows. First, we have identified emerging research areas - SC robustness, and its counterpart, vulnerability. Second, we have developed a definition of SC robustness, operationalized it, and identified and structured the relevant elements for the design of robust SCs in the form of a research framework. With this research framework, we contribute to a better understanding of the concepts of vulnerability and robustness and related issues in food SCs. Third, we identified the relationship between contextual factors of food SCs and specific DMPs used to maintain robust SC performances: characteristics of the product and the SC environment influence the selection and use of DMPs; processes and SC networks are influenced by DMPs. Fourth, we developed specific metrics for vulnerability assessments, which serve as a basis of a VULA method. The VULA method investigates different measures of the variability of both the duration of impacts from disturbances and the fluctuations in their magnitude.
With this project, we also hope to have delivered practical insights into food SC vulnerability. First, the integrated framework for the design of robust SCs can be used to guide food companies in successful disturbance management. Second, empirical findings from case studies lead to the identification of changeable characteristics of SCs that can serve as a basis for assessing where to focus efforts to manage disturbances. Third, the VULA method can help top management to get more reliable information about the “health” of the company.
The two most important research opportunities are: First, there is a need to extend and validate our findings related to the research framework and contextual factors through further case studies related to other types of (food) products and other types of SCs. Second, there is a need to further develop and test the VULA method, e.g.: to use other indicators and statistical measures for disturbance detection and SC improvement; to define the most appropriate KPI to represent the robustness of a complete SC. We hope this thesis invites other researchers to pick up these challenges and help us further improve the robustness of (food) SCs.

Distinctive Profile of IsomiR Expression and Novel MicroRNAs in Rat Heart Left Ventricle

MicroRNAs (miRNAs) are single-stranded non-coding RNAs that negatively regulate target gene expression through mRNA cleavage or translational repression. There is mounting evidence that they play critical roles in heart disease. The expression of known miRNAs in the heart has been studied at length by microarray and quantitative PCR but it is becoming evident that microRNA isoforms (isomiRs) are potentially physiologically important. It is well known that left ventricular (patho)physiology is influenced by transmural heterogeneity of cardiomyocyte phenotype, and this likely reflects underlying heterogeneity of gene expression. Given the significant role of miRNAs in regulating gene expression, knowledge of how the miRNA profile varies across the ventricular wall will be crucial to better understand the mechanisms governing transmural physiological heterogeneity. To determinine miRNA/isomiR expression profiles in the rat heart we investigated tissue from different locations across the left ventricular wall using deep sequencing. We detected significant quantities of 145 known rat miRNAs and 68 potential novel orthologs of known miRNAs, in mature, mature* and isomiR formation. Many isomiRs were detected at a higher frequency than their canonical sequence in miRBase and have different predicted targets. The most common miR-133a isomiR was more effective at targeting a construct containing a sequence from the gelsolin gene than was canonical miR-133a, as determined by dual-fluorescence assay. We identified a novel rat miR-1 homolog from a second miR-1 gene; and a novel rat miRNA similar to miR-676. We also cloned and sequenced the rat miR-486 gene which is not in miRBase (v18). Signalling pathways predicted to be targeted by the most highly detected miRNAs include Ubiquitin-mediated Proteolysis, Mitogen-Activated Protein Kinase, Regulation of Actin Cytoskeleton, Wnt signalling, Calcium Signalling, Gap junctions and Arrhythmogenic Right Ventricular Cardiomyopathy. Most miRNAs are not expressed in a gradient across the ventricular wall, with exceptions including miR-10b, miR-21, miR-99b and miR-486.

Chronic IL9 and IL-13 Exposure Leads to an Altered Differentiation of Ciliated Cells in a Well-Differentiated Paediatric Bronchial Epithelial Cell Model

Asthma is a chronic inflammatory disease characterised by airways remodelling. In mouse models IL-9 and IL-13 have been implicated in airways remodelling including mucus hypersecretion and goblet cell hyperplasia. Their role, especially that of IL-9, has been much less studied in authentic human ex vivo models of the bronchial epithelium from normal and asthmatic children. We assessed the effects of IL-9, IL-13 and an IL-9/IL-13 combination, during differentiation of bronchial epithelial cells from normal (n?=?6) and asthmatic (n?=?8) children. Cultures were analysed for morphological markers and factors associated with altered differentiation (MUC5AC, SPDEF and MMP-7). IL-9, IL-9/IL-13 combination and IL-13 stimulated bronchial epithelial cells from normal children had fewer ciliated cells [14.8% (SD 8.9), p?=?0.048, 12.4 (SD 6.1), p?=?0.016 and 7.3% (SD 6.6), p?=?0.031] respectively compared with unstimulated [(21.4% (SD 9.6)]. IL-9 stimulation had no effect on goblet cell number in either group whereas IL-9/IL-13 combination and IL-13 significantly increased goblet cell number [24.8% (SD 8.8), p?=?0.02), 32.9% (SD 8.6), p?=?0.007] compared with unstimulated normal bronchial cells [(18.6% (SD 6.2)]. All stimulations increased MUC5AC mRNA in bronchial epithelial cells from normal children and increased MUC5AC mucin secretion. MMP-7 localisation was dysregulated in normal bronchial epithelium stimulated with Th2 cytokines which resembled the unstimulated bronchial epithelium of asthmatic children. All stimulations resulted in a significant reduction in transepithelial electrical resistance values over time suggesting a role in altered tight junction formation. We conclude that IL-9 does not increase goblet cell numbers in bronchial epithelial cell cultures from normal or asthmatic children. IL-9 and IL-13 alone and in combination, reduce ciliated cell numbers and transepithelial electrical resistance during differentiation of normal epithelium, which clinically could inhibit mucociliary clearance and drive an altered repair mechanism. This suggests an alternative role for IL-9 in airways remodelling and reaffirms IL-9 as a potential therapeutic target.© 2013 Parker et al.

A Superfamily of Actin-Binding Proteins at the Actin-Membrane Nexus of Higher Plants

Complex animals use a wide variety of adaptor proteins to produce specialized sites of interaction between actin and membranes. Plants do not have these protein families, yet actin-membrane interactions within plant cells are critical for the positioning of subcellular compartments, for coordinating intercellular communication, and for membrane deformation [1]. Novel factors are therefore likely to provide interfaces at actin-membrane contacts in plants, but their identity has remained obscure. Here we identify the plantspecific Networked (NET) superfamily of actin-binding proteins, members of which localize to the actin cytoskeleton and specify different membrane compartments. The founding member of the NET superfamily, NET1A, is anchored at the plasma membrane and predominates at cell junctions, the plasmodesmata. NET1A binds directly to actin filaments via a novel actin-binding domain that defines a superfamily of thirteen Arabidopsis proteins divided into four distinct phylogenetic clades. Members of other clades identify interactions at the tonoplast, nuclear membrane, and pollen tube plasma membrane, emphasizing the role of this superfamily in mediating actin-membrane interactions.

Control of the AtMAP65-1 interaction with microtubules through the cell cycle

Cell division depends on the fine control of both microtubule dynamics and microtubule organisation. The microtubule bundling protein MAP65 is a 'midzone MAP' essential for the integrity of the anaphase spindle and cell division. Arabidopsis thaliana MAP65-1 (AtMAP65-1) binds and bundles microtubules by forming 25 nm cross-bridges. Moreover, as AtMAP65-1 bundles microtubules in interphase, anaphase and telophase but does not bind microtubules in prophase or metaphase, its activity through the cell cycle must be under tight control. Here we show that AtMAP65-1 is hyperphosphorylated during prometaphase and metaphase and that CDK and MAPK are involved in this phosphorylation. This phosphorylation inhibits AtMAP65-1 activity. Expression of nonphosphorylatable AtMAP65-1 has a negative effect on mitotic progression resulting in excessive accumulation of microtubules in the metaphase spindle midzone causing a delay in mitosis. We conclude that normal metaphase spindle organisation and the transition to anaphase is dependent on inactivation of AtMAP65-1.

Stacked multistage lumped element circulator

The novel concept and architecture of the vertically stacked multistage circulator with a single source of dc magnetic bias has been proposed. The distinctive features of the new arrangement are discussed and the main aspects of the circulator design, including the dc magnetic bias and concurrent thermal stabilization of multiple junctions, are presented. The experimental prototype of the VHF stacked double isolator exhibits low loss, high isolation, excellent thermal stability and the high power handling capability. The proposed class of multistage circulators can significantly increase dynamic range of the transceivers for the RF front-end of the emerging white space UHF/VHF applications. © 2012 IEEE.

Are there species smaller than 1 mm?

The rapid advance in genetic sequencing technologies has provided an unprecedented amount of data on the biodiversity of meiofauna. It was hoped that these data would allow the identification and counting of species, distinguished as tight clusters of similar genomes. Surprisingly, this appears not to be the case. Here, we begin a theoretical discussion of this phenomenon, drawing on an individual-based ecological model to inform our arguments. The determining factor in the emergence (or not) of distinguishable genetic clusters in the model is the product of population size with mutation rate—a measure of the adaptability of the population as a whole. This result suggests that indeed one should not expect to observe clearly distinguishable species groupings in data gathered from ultrasequencing of meiofauna.

What is the Role of the Bystander Response in Radionuclide Therapies?

Radionuclide therapy for cancer is undergoing a renaissance, with a wide range of radionuclide and clinical delivery systems currently under investigation. Dosimetry at the cellular and sub-cellular level is complex with inhomogeneity and incomplete targeting of all cells such that some tumor cells will receive little or no direct radiation energy. There is now sufficient preclinical evidence of a Bystander response which can modulate the biology of these un-irradiated cells with current research demonstrating both protective and inhibitory responses. Dependence upon fraction of irradiated cells has also been found and the presence of functional gap junctions appears to be import for several Bystander responses. The selection of either high or low LET radionuclides may be critical. While low LET radionuclides appear to have a Bystander response proportional to dose, the dose-response from high LET radionuclides are more complex. In media transfer experiments a "U" shaped response curve has been demonstrated for high LET treatments. However this "U" shaped response has not been seen with co-culture experiments and its relevance remains uncertain. For high LET treatments there is a suggestion that dose rate effects may also be important with inhibitory effects noted with 125I labelling study and a stimulatory seen with 123I labelling in one study.© 2013 Brady, O’Sullivan and Prise.

Toward Quantitative Electrochemical Measurements on the Nanoscale by Scanning Probe Microscopy: Environmental and Current Spreading Effects

The application of electric bias across tip–surface junctions in scanning probe microscopy can readily induce surface and bulk electrochemical processes that can be further detected though changes in surface topography, Faradaic or conductive currents, or electromechanical strain responses. However, the basic factors controlling tip-induced electrochemical processes, including the relationship between applied tip bias and the thermodynamics of local processes, remains largely unexplored. Using the model Li-ion reduction reaction on the surface in Li-ion conducting glass ceramic, we explore the factors controlling Li-metal formation and find surprisingly strong effects of atmosphere and back electrode composition on the process. We find that reaction processes are highly dependent on the nature of the counter electrode and environmental conditions. Using a nondepleting Li counter electrode, Li particles could grow significantly larger and faster than a depleting counter electrode. Significant Li ion depletion leads to the inability for further Li reduction. Time studies suggest that Li diffusion replenishes the vacant sites after 12 h. These studies suggest the feasibility of SPM-based quantitative electrochemical studies under proper environmental controls, extending the concepts of ultramicroelectrodes to the single-digit nanometer scale.

On the Complexity of Universal Leader Election

Electing a leader is a fundamental task in distributed computing. In its implicit version, only the leader must know who is the elected leader. This paper focuses on studying the message and time complexity of randomized implicit leader election in synchronous distributed networks. Surprisingly, the most "obvious" complexity bounds have not been proven for randomized algorithms. The "obvious" lower bounds of O(m) messages (m is the number of edges in the network) and O(D) time (D is the network diameter) are non-trivial to show for randomized (Monte Carlo) algorithms. (Recent results that show that even O(n) (n is the number of nodes in the network) is not a lower bound on the messages in complete networks, make the above bounds somewhat less obvious). To the best of our knowledge, these basic lower bounds have not been established even for deterministic algorithms (except for the limited case of comparison algorithms, where it was also required that some nodes may not wake up spontaneously, and that D and n were not known).

We establish these fundamental lower bounds in this paper for the general case, even for randomized Monte Carlo algorithms. Our lower bounds are universal in the sense that they hold for all universal algorithms (such algorithms should work for all graphs), apply to every D, m, and n, and hold even if D, m, and n are known, all the nodes wake up simultaneously, and the algorithms can make anyuse of node's identities. To show that these bounds are tight, we present an O(m) messages algorithm. An O(D) time algorithm is known. A slight adaptation of our lower bound technique gives rise to an O(m) message lower bound for randomized broadcast algorithms.

An interesting fundamental problem is whether both upper bounds (messages and time) can be reached simultaneously in the randomized setting for all graphs. (The answer is known to be negative in the deterministic setting). We answer this problem partially by presenting a randomized algorithm that matches both complexities in some cases. This already separates (for some cases) randomized algorithms from deterministic ones. As first steps towards the general case, we present several universal leader election algorithms with bounds that trade-off messages versus time. We view our results as a step towards understanding the complexity of universal leader election in distributed networks.

Endocytosis in the retinal and choroidal microcirculation

The endocytosis of horseradish peroxidase (HRP) by the vascular cells of retinal and choroidal blood vessels was compared in immersion and perfusion fixed eyes from individual rats. The mechanisms of endocytosis of HRP appeared identical in both retinal and choroidal vessels. The bulk of internalised tracer occurred in macropinosomes 300-400 nm in diameter. Tracer was localised to a 20-30 nm layer on the internal aspect of the limiting membrane. This layer was coincident with the glycocalyx of the luminal plasma membrane as revealed by ruthenium redosmium tetroxide staining. Horseradish peroxidase was also internalised by a small scattered population of vesicles (100-130 nm in diameter). The size of these vesicles suggested that they may have arisen from clathrin coated regions of the plasma membrane. It is suggested that the endocytosis of HRP in retinal and choroidal vascular endothelium occurs as a function of plasma membrane recycling. Horseradish peroxidase may also be internalised as a 'contaminant' of the glycocalyx in coated pits involved in receptor mediated endocytosis. The smooth 80 nm plasmalemmal caveolae of the retinal and choroidal vascular endothelial cells did not appear to participate either in absorptive endocytosis or vesicular transport.

Does unidirectional vesicular transport occur in retinal vessels?

This paper challenges the hypothesis that the smooth 80 nm plasmalemmal caveolae found in abundance at the abluminal aspect of the endothelium in retinal blood vessels participate in a unidirectional vesicular transport mechanism. Evidence is presented which indicates that horseradish peroxidase, when introduced to the extracellular space of the retina via the vitreous body, may enter the intravascular compartment through junctional incompetence which occurs at or after enucleation of the eye. It is proposed that the plasmalemmal caveolae at the abluminal plasma membrane of endothelial cells in retinal blood vessels are static structures which facilitate the transport of small solutes and ions across the blood retinal barrier.