Complex networks as an emerging property of hierarchical preferential attachment

Real complex systems are not rigidly structured; no clear rules or blueprints exist for their construction. Yet, amidst their apparent randomness, complex structural properties universally emerge. We propose that an important class of complex systems can be modeled as an organization of many embedded levels (potentially infinite in number), all of them following the same universal growth principle known as preferential attachment. We give examples of such hierarchy in real systems, for instance in the pyramid of production entities of the film industry. More importantly, we show how real complex networks can be interpreted as a projection of our model, from which their scale independence, their clustering, their hierarchy, their fractality and their navigability naturally emerge. Our results suggest that complex networks, viewed as growing systems, can be quite simple, and that the apparent complexity of their structure is largely a reflection of their unobserved hierarchical nature.Comment: 12 pages, 7 figure

Phase transition of the susceptible-infected-susceptible dynamics on time-varying configuration model networks

We present a degree-based theoretical framework to study the susceptible-infected-susceptible (SIS) dynamics on time-varying (rewired) configuration model networks. Using this framework, we provide a detailed analysis of the stationary state that covers, for a given structure, every dynamic regimes easily tuned by the rewiring rate. This analysis is suitable for the characterization of the phase transition and leads to three main contributions. (i) We obtain a self-consistent expression for the absorbing-state threshold, able to capture both collective and hub activation. (ii) We recover the predictions of a number of existing approaches as limiting cases of our analysis, providing thereby a unifying point of view for the SIS dynamics on random networks. (iii) We reinterpret the concept of hub-dominated phase transition. Within our framework, it appears as a heterogeneous critical phenomenon : observables for different degree classes have a different scaling with the infection rate. This leads to the successive activation of the degree classes beyond the epidemic threshold.Comment: 14 pages, 11 figure

A Guide to Structured Illumination TIRF Microscopy at High Speed with Multiple Colors.

Optical super-resolution imaging with structured illumination microscopy (SIM) is a key technology for the visualization of processes at the molecular level in the chemical and biomedical sciences. Although commercial SIM systems are available, systems that are custom designed in the laboratory can outperform commercial systems, the latter typically designed for ease of use and general purpose applications, both in terms of imaging fidelity and speed. This article presents an in-depth guide to building a SIM system that uses total internal reflection (TIR) illumination and is capable of imaging at up to 10 Hz in three colors at a resolution reaching 100 nm. Due to the combination of SIM and TIRF, the system provides better image contrast than rival technologies. To achieve these specifications, several optical elements are used to enable automated control over the polarization state and spatial structure of the illumination light for all available excitation wavelengths. Full details on hardware implementation and control are given to achieve synchronization between excitation light pattern generation, wavelength, polarization state, and camera control with an emphasis on achieving maximum acquisition frame rate. A step-by-step protocol for system alignment and calibration is presented and the achievable resolution improvement is validated on ideal test samples. The capability for video-rate super-resolution imaging is demonstrated with living cells.This work was supported by grants from the Leverhulme Trust, the Engineering and Physical Sciences Research Council [EP/H018301/1, EP/G037221/1]; Alzheimer Research UK [ARUK-EG2012A-1]; Wellcome Trust [089703/Z/09/Z] and Medical Research Council [MR/K015850/1, MR/K02292X/1]. We thank K. O’Holleran for assistance with the design of the microscope, and L. Shao and R. Heintzmann for useful discussions and suggestions

One hundred twenty-five concomitant endovascular and open procedures for lower extremity arterial disease

AbstractObjective: Although the results of staged endovascular and open surgical reconstructions have been well documented, the safety and efficacy of concomitant procedures in the operating room are less well defined. Suboptimal performance of endovascular procedures in an operative setting, or inappropriate reliance on endovascular techniques, might theoretically compromise graft patency. We questioned whether late graft thrombosis is frequently attributable to failure at the endovascularly treated site in this setting. Materials and Methods: Between May 1, 1993, and June 30, 2001, we performed 125 concomitant endovascular and open arterial reconstructions (73 primary reconstructions, 52 graft revisions) in 106 patients. Endovascular techniques were used to treat inflow lesions in 72 cases, outflow lesions in 14 cases, both in four cases, and the graft itself in 35 cases. Fifty-five iliac, 18 femoral, 13 popliteal, six tibial, and 35 graft lesions were treated. For primary bypasses, 33 were to the popliteal level (21 prosthetic, 12 autogenous), 19 were to the tibial or pedal arteries (16 autogenous, three prosthetic or composite), and 12 were to the femoral arteries (one autogenous, 11 prosthetic). Nine patch angioplasties (eight femoral, one popliteal) were performed. For graft revisions, endovascular intervention was for inflow in 13 cases, outflow in three cases, both in one case, and of the graft itself in 35 cases. Surgical revisions involved segmental grafts in 33 cases, patch angioplasty in 18 cases, and both in one case. Results: In the primary group, the initial technical success rate of the endovascular procedure was 93% (68/73), with five patients needing open conversion. The 30-day mortality rate was 1.4%, and the morbidity rate was 11.0%. Of the 19 grafts in the primary group that occluded during the follow-up period (mean, 11.9 months), five thromboses could possibly be attributed to failure at the endovascular site. In the revision group, the initial technical success rate of the endovascular procedure was 88% (46/52), with six patients undergoing conversion to open procedure. The 30-day mortality rate was 0%, and the morbidity rate was 15.4%. Of 22 late graft occlusions in the revision group, only three were attributed to failure at the endovascular site. Conclusion: This largest report to date of concomitant lower extremity endovascular and open revascularization procedures shows the approach to be safe. Few late graft occlusions were attributable to failure at the endovascularly treated site. The concomitant approach offers the efficiency and convenience of single stage therapy and allows immediate treatment for inadequate endovascular results or their complications and potential cost savings. (J Vasc Surg 2003;37:316-22.

Exact analytical solution of irreversible binary dynamics on networks

In binary cascade dynamics, the nodes of a graph are in one of two possible states (inactive, active), andnodes in the inactive state make an irreversible transition to the active state, as soon as their precursors satisfya predetermined condition. We introduce a set of recursive equations to compute the probability of reachingany final state, given an initial state, and a specification of the transition probability function of each node.Because the naive recursive approach for solving these equations takes factorial time in the number of nodes, wealso introduce an accelerated algorithm, built around a breath-first search procedure. This algorithm solves theequations as efficiently as possible in exponential time

Nanoscale click-reactive scaffolds from peptide self-assembly.

Background Due to their natural tendency to self-assemble, proteins and peptides are important components for organic nanotechnology. One particular class of peptides of recent interest is those that form amyloid fibrils, as this self-assembly results in extremely strong, stable quasi-one-dimensional structures which can be used to organise a wide range of cargo species including proteins and oligonucleotides. However, as the amyloid state is accessible to a large number of proteins via misfolding, assembly of peptides already conjugated to proteins is limited to certain cargo species. Therefore, a general method is needed to conjugate proteins and other molecules to amyloid fibrils after the fibrils have self-assembled. Results Here we have designed an amyloidogenic peptide based on the TTR105-115 fragment of transthyretin to form fibrils that display an alkyne functionality, important for bioorthogonal chemical reactions, on their surface. The fibrils were formed and reacted both with an azide-containing amino acid and with an azide-functionalised dye by the Huisgen azidoalkyne cycloaddition, one of the class of “click” reactions. Mass spectrometry and total internal reflection fluorescence optical microscopy were used to show that peptides incorporated into the fibrils reacted with the azide while maintaining the structure of the fibril. These click-functionalised amyloid fibrils have a variety of potential uses in materials and as scaffolds for bionanotechnology. Discussion Although previous studies have produced peptides that can both form amyloid fibrils and undergo “click”-type reactions, this is the first example of amyloid fibrils that can undergo such a reaction after they have been formed. Our approach has the advantage that self-assembly takes place before click functionalization rather than pre-functionalised building blocks self-assembling. Therefore, the molecules used to functionalise the fibril do not themselves have to be exposed to harsh, amyloid-forming conditions. This means that a wider range of proteins can be used as ligands in this process. For instance, the fibrils can be functionalised with a green fluorescent protein that retains its fluorescence after it is attached to the fibrils, whereas this protein loses its fluorescence if it is exposed to the conditions used for aggregation

Live-cell super-resolution microscopy reveals a primary role for diffusion in polyglutamine-driven aggresome assembly.

The mechanisms leading to self-assembly of misfolded proteins into amyloid aggregates have been studied extensively in the test tube under well-controlled conditions. However, to what extent these processes are representative of those in the cellular environment remains unclear. Using super-resolution imaging of live cells, we show here that an amyloidogenic polyglutamine-containing protein first forms small, amorphous aggregate clusters in the cytosol, chiefly by diffusion. Dynamic interactions among these clusters limited their elongation and led to structures with a branched morphology, differing from the predominantly linear fibrils observed in vitro Some of these clusters then assembled via active transport at the microtubule-organizing center and thereby initiated the formation of perinuclear aggresomes. Although it is widely believed that aggresome formation is entirely governed by active transport along microtubules, here we demonstrate, using a combined approach of advanced imaging and mathematical modeling, that diffusion is the principal mechanism driving aggresome expansion. We found that the increasing surface area of the expanding aggresome increases the rate of accretion caused by diffusion of cytosolic aggregates and that this pathway soon dominates aggresome assembly. Our findings lead to a different view of aggresome formation than that proposed previously. We also show that aggresomes mature over time, becoming more compacted as the structure grows. The presence of large perinuclear aggregates profoundly affects the behavior and health of the cell, and our super-resolution imaging results indicate that aggresome formation and development are governed by highly dynamic processes that could be important for the design of potential therapeutic strategies

Cavities and shocks in the galaxy group HCG 62 as revealed by Chandra, XMM and GMRT data

We report on the results of an analysis of Chandra, XMM-Newton and new GMRT data of the X-ray bright compact group of galaxies HCG 62, which is one of the few groups known to possess clear, small X-ray cavities in the inner regions. This is part of an ongoing X-ray/low-frequency radio study of 18 groups, initially chosen for the availability of good-quality X-ray data and evidence for AGN/hot gas interaction. At higher frequency (1.4 GHz), the HCG 62 cavity system shows minimal if any radio emission, but the new GMRT observations at 235 MHz and 610 MHz clearly detect extended low-frequency emission from radio lobes corresponding to the cavities. By means of the synergy of X-ray and low-frequency radio observations, we compare and discuss the morphology, luminosity and pressure of the gas and of the radio source. We find that the radio source is radiatively inefficient, with a ratio of radio luminosity to mechanical cavity power of $\sim 10^{-4}$, and that the radio pressure of the lobes is about one order of magnitude lower than the X-ray pressure of the surrounding thermal gas. Thanks to the high spatial resolution of the Chandra surface brightness and temperature profiles, we also identify a shock front located at 36 kpc to the south-west of the group center, close to the southern radio lobe, with a Mach number $\sim 1.5$ and a total power which is about one order of magnitude higher than the cavity power. Such a shock may have heated the gas in the southern region, as indicated by the temperature map. The shock may also explain the arc-like region of enriched gas seen in the iron abundance map, as this may be produced by a non-Maxwellian electron distribution near its front.Comment: 14 pages, 8 figures, accepted for publication in ApJ. Revised version including minor comments and expanded discussion (version with full resolution figures available at http://hea-www.harvard.edu/~mgitti/hcg62-gitti.pdf

Understanding innovators' experiences of barriers and facilitators in implementation and diffusion of healthcare service innovations: A qualitative study

This article is made available through the Brunel Open Access Publishing Fund - Copyright @ 2011 Barnett et al.Background: Healthcare service innovations are considered to play a pivotal role in improving organisational efficiency and responding effectively to healthcare needs. Nevertheless, healthcare organisations encounter major difficulties in sustaining and diffusing innovations, especially those which concern the organisation and delivery of healthcare services. The purpose of the present study was to explore how healthcare innovators of process-based initiatives perceived and made sense of factors that either facilitated or obstructed the innovation implementation and diffusion. Methods: A qualitative study was designed. Fifteen primary and secondary healthcare organisations in the UK, which had received health service awards for successfully generating and implementing service innovations, were studied. In-depth, semi structured interviews were conducted with the organisational representatives who conceived and led the development process. The data were recorded, transcribed and thematically analysed. Results: Four main themes were identified in the analysis of the data: the role of evidence, the function of inter-organisational partnerships, the influence of human-based resources, and the impact of contextual factors. "Hard" evidence operated as a proof of effectiveness, a means of dissemination and a pre-requisite for the initiation of innovation. Inter-organisational partnerships and people-based resources, such as champions, were considered an integral part of the process of developing, establishing and diffusing the innovations. Finally, contextual influences, both intra-organisational and extra-organisational were seen as critical in either impeding or facilitating innovators' efforts. Conclusions: A range of factors of different combinations and co-occurrence were pointed out by the innovators as they were reflecting on their experiences of implementing, stabilising and diffusing novel service initiatives. Even though the innovations studied were of various contents and originated from diverse organisational contexts, innovators' accounts converged to the significant role of the evidential base of success, the inter-personal and inter-organisational networks, and the inner and outer context. The innovators, operating themselves as important champions and being often willing to lead constructive efforts of implementation to different contexts, can contribute to the promulgation and spread of the novelties significantly.This research was supported financially by the Multidisciplinary Assessment of Technology Centre for Healthcare (MATCH)

Allelic variants of a potato HEAT SHOCK COGNATE 70 gene confer improved tuber yield under a wide range of environmental conditions

Funding: This work was funded by the Scottish Government Rural and Environment Science and Analytical Services Division as part of the Strategic Research Programme 2016‐2022, by a GCRF Foundation Awards for Global Agricultural and Food Systems Research funded by the BBSRC project BB/P022553/1 (Quickgro) and EPSRC Reference: EP/T01525X/1, GCRF Global Research Translation Awards, Food Security and Health for East Africa, 2019‐2021, and the European Union’s Horizon 2020 research and innovation programme ADAPT (Accelerated Development of Multiple‐Stress Tolerant Potato), grant agreement No GA 2020 862‐858 and G2P‐SOL (Linking genetic resources, genomes and phenotypes of Solanaceous crops) grant agreement No 677379.Previously, we developed and applied a glasshouse screen for potato tuber yield under heat stress and identified a candidate gene (HSc70) for heat tolerance by genetic analysis of a diploid potato population. Specific allelic variants were expressed at high levels on exposure to moderately elevated temperature due to variations in gene promoter sequence. In this study, we aimed to confirm the results from the glasshouse screen in field trials conducted over several seasons and locations including those in Kenya, Malawi and the UK. We extend our understanding of the HSc70 gene and demonstrate that expression level of HSc70 correlates with tolerance to heat stress in a wide range of wild potato relatives. The physiological basis of the protective effect of HSc70 was explored and we show that genotypes carrying the highly expressed HSc70 A2 allele are protected against photooxidative damage to PSII induced by abiotic stresses. Overall, we show the potential of HSc70 alleles for breeding resilient potato genotypes for multiple environments.Publisher PDFPeer reviewe