A Universal Model of Global Civil Unrest

Civil unrest is a powerful form of collective human dynamics, which has led to major transitions of societies in modern history. The study of collective human dynamics, including collective aggression, has been the focus of much discussion in the context of modeling and identification of universal patterns of behavior. In contrast, the possibility that civil unrest activities, across countries and over long time periods, are governed by universal mechanisms has not been explored. Here, we analyze records of civil unrest of 170 countries during the period 1919-2008. We demonstrate that the distributions of the number of unrest events per year are robustly reproduced by a nonlinear, spatially extended dynamical model, which reflects the spread of civil disorder between geographic regions connected through social and communication networks. The results also expose the similarity between global social instability and the dynamics of natural hazards and epidemics.Comment: 8 pages, 3 figure

Hydrostatic pressure does not cause detectable changes to survival of human retinal ganglion

Purpose: Elevated intraocular pressure (IOP) is a major risk factor for glaucoma. One consequence of raised IOP is that ocular tissues are subjected to increased hydrostatic pressure (HP). The effect of raised HP on stress pathway signaling and retinal ganglion cell (RGC) survival in the human retina was investigated. Methods: A chamber was designed to expose cells to increased HP (constant and fluctuating). Accurate pressure control (10-100mmHg) was achieved using mass flow controllers. Human organotypic retinal cultures (HORCs) from donor eyes (<24h post mortem) were cultured in serum-free DMEM/HamF12. Increased HP was compared to simulated ischemia (oxygen glucose deprivation, OGD). Cell death and apoptosis were measured by LDH and TUNEL assays, RGC marker expression by qRT-PCR (THY-1) and RGC number by immunohistochemistry (NeuN). Activated p38 and JNK were detected by Western blot. Results: Exposure of HORCs to constant (60mmHg) or fluctuating (10-100mmHg; 1 cycle/min) pressure for 24 or 48h caused no loss of structural integrity, LDH release, decrease in RGC marker expression (THY-1) or loss of RGCs compared with controls. In addition, there was no increase in TUNEL-positive NeuN-labelled cells at either time-point indicating no increase in apoptosis of RGCs. OGD increased apoptosis, reduced RGC marker expression and RGC number and caused elevated LDH release at 24h. p38 and JNK phosphorylation remained unchanged in HORCs exposed to fluctuating pressure (10-100mmHg; 1 cycle/min) for 15, 30, 60 and 90min durations, whereas OGD (3h) increased activation of p38 and JNK, remaining elevated for 90min post-OGD. Conclusions: Directly applied HP had no detectable impact on RGC survival and stress-signalling in HORCs. Simulated ischemia, however, activated stress pathways and caused RGC death. These results show that direct HP does not cause degeneration of RGCs in the ex vivo human retina

Spin-orbit-driven band inversion in bilayer graphene by the van der Waals proximity effect.

Spin-orbit coupling (SOC) is the key to realizing time-reversal-invariant topological phases of matter1,2. SOC was predicted by Kane and Mele3 to stabilize a quantum spin Hall insulator; however, the weak intrinsic SOC in monolayer graphene4-7 has precluded experimental observation in this material. Here we exploit a layer-selective proximity effect-achieved via a van der Waals contact with a semiconducting transition-metal dichalcogenide8-21-to engineer Kane-Mele SOC in ultra clean bilayer graphene. Using high-resolution capacitance measurements to probe the bulk electronic compressibility, we find that SOC leads to the formation of a distinct, incompressible, gapped phase at charge neutrality. The experimental data agree quantitatively with a simple theoretical model in which the new phase results from SOC-driven band inversion. In contrast to Kane-Mele SOC in monolayer graphene, the inverted phase is not expected to be a time-reversal-invariant topological insulator, despite being separated from conventional band insulators by electric-field-tuned phase transitions where crystal symmetry mandates that the bulk gap must close22. Our electrical transport measurements reveal that the inverted phase has a conductivity of approximately e2/h (where e is the electron charge and h Planck's constant), which is suppressed by exceptionally small in-plane magnetic fields. The high conductivity and anomalous magnetoresistance are consistent with theoretical models that predict helical edge states within the inverted phase that are protected from backscattering by an emergent spin symmetry that remains robust even for large Rashba SOC. Our results pave the way for proximity engineering of strong topological insulators as well as correlated quantum phases in the strong spin-orbit regime in graphene heterostructures

Genetic testing of children for adult-onset conditions: opinions of the British adult population and implications for clinical practice

This study set out to explore the attitudes of a representative sample of the British public towards genetic testing in children to predict disease in the future. We sought opinions about genetic testing for adult-onset conditions for which no prevention/treatment is available during childhood, and about genetic 'carrier' status to assess future reproductive risks. The study also examined participants' level of agreement with the reasons professional organisations give in favour of deferring such testing. Participants (n=2998) completed a specially designed questionnaire, distributed by email. Nearly half of the sample (47%) agreed that parents should be able to test their child for adult-onset conditions, even if there is no treatment or prevention at time of testing. This runs contrary to professional guidance about genetic testing in children. Testing for carrier status was supported by a larger proportion (60%). A child's future ability to decide for her/himself if and when to be tested was the least supported argument in favour of deferring testing.European Journal of Human Genetics advance online publication, 5 November 2014; doi:10.1038/ejhg.2014.221

Ischemia reperfusion dysfunction changes model-estimated kinetics of myofilament interaction due to inotropic drugs in isolated hearts

BACKGROUND: The phase-space relationship between simultaneously measured myoplasmic [Ca(2+)] and isovolumetric left ventricular pressure (LVP) in guinea pig intact hearts is altered by ischemic and inotropic interventions. Our objective was to mathematically model this phase-space relationship between [Ca(2+)] and LVP with a focus on the changes in cross-bridge kinetics and myofilament Ca(2+ )sensitivity responsible for alterations in Ca(2+)-contraction coupling due to inotropic drugs in the presence and absence of ischemia reperfusion (IR) injury. METHODS: We used a four state computational model to predict LVP using experimentally measured, averaged myoplasmic [Ca(2+)] transients from unpaced, isolated guinea pig hearts as the model input. Values of model parameters were estimated by minimizing the error between experimentally measured LVP and model-predicted LVP. RESULTS: We found that IR injury resulted in reduced myofilament Ca(2+ )sensitivity, and decreased cross-bridge association and dissociation rates. Dopamine (8 μM) reduced myofilament Ca(2+ )sensitivity before, but enhanced it after ischemia while improving cross-bridge kinetics before and after IR injury. Dobutamine (4 μM) reduced myofilament Ca(2+ )sensitivity while improving cross-bridge kinetics before and after ischemia. Digoxin (1 μM) increased myofilament Ca(2+ )sensitivity and cross-bridge kinetics after but not before ischemia. Levosimendan (1 μM) enhanced myofilament Ca(2+ )affinity and cross-bridge kinetics only after ischemia. CONCLUSION: Estimated model parameters reveal mechanistic changes in Ca(2+)-contraction coupling due to IR injury, specifically the inefficient utilization of Ca(2+ )for contractile function with diastolic contracture (increase in resting diastolic LVP). The model parameters also reveal drug-induced improvements in Ca(2+)-contraction coupling before and after IR injury

Effective knowledge management in translational medicine

<p>Abstract</p> <p>Background</p> <p>The growing consensus that most valuable data source for biomedical discoveries is derived from human samples is clearly reflected in the growing number of translational medicine and translational sciences departments across pharma as well as academic and government supported initiatives such as Clinical and Translational Science Awards (CTSA) in the US and the Seventh Framework Programme (FP7) of EU with emphasis on translating research for human health.</p> <p>Methods</p> <p>The pharmaceutical companies of Johnson and Johnson have established translational and biomarker departments and implemented an effective knowledge management framework including building a data warehouse and the associated data mining applications. The implemented resource is built from open source systems such as i2b2 and GenePattern.</p> <p>Results</p> <p>The system has been deployed across multiple therapeutic areas within the pharmaceutical companies of Johnson and Johnsons and being used actively to integrate and mine internal and public data to support drug discovery and development decisions such as indication selection and trial design in a translational medicine setting. Our results show that the established system allows scientist to quickly re-validate hypotheses or generate new ones with the use of an intuitive graphical interface.</p> <p>Conclusions</p> <p>The implemented resource can serve as the basis of precompetitive sharing and mining of studies involving samples from human subjects thus enhancing our understanding of human biology and pathophysiology and ultimately leading to more effective treatment of diseases which represent unmet medical needs.</p

A Standardised Procedure for Evaluating Creative Systems: Computational Creativity Evaluation Based on What it is to be Creative

Computational creativity is a flourishing research area, with a variety of creative systems being produced and developed. Creativity evaluation has not kept pace with system development with an evident lack of systematic evaluation of the creativity of these systems in the literature. This is partially due to difficulties in defining what it means for a computer to be creative; indeed, there is no consensus on this for human creativity, let alone its computational equivalent. This paper proposes a Standardised Procedure for Evaluating Creative Systems (SPECS). SPECS is a three-step process: stating what it means for a particular computational system to be creative, deriving and performing tests based on these statements. To assist this process, the paper offers a collection of key components of creativity, identified empirically from discussions of human and computational creativity. Using this approach, the SPECS methodology is demonstrated through a comparative case study evaluating computational creativity systems that improvise music

A measure of individual role in collective dynamics

Identifying key players in collective dynamics remains a challenge in several research fields, from the efficient dissemination of ideas to drug target discovery in biomedical problems. The difficulty lies at several levels: how to single out the role of individual elements in such intermingled systems, or which is the best way to quantify their importance. Centrality measures describe a node's importance by its position in a network. The key issue obviated is that the contribution of a node to the collective behavior is not uniquely determined by the structure of the system but it is a result of the interplay between dynamics and network structure. We show that dynamical influence measures explicitly how strongly a node's dynamical state affects collective behavior. For critical spreading, dynamical influence targets nodes according to their spreading capabilities. For diffusive processes it quantifies how efficiently real systems may be controlled by manipulating a single node.Comment: accepted for publication in Scientific Report

A Genetic Association Study of Serum Acute-Phase C-Reactive Protein Levels in Rheumatoid Arthritis: Implications for Clinical Interpretation

A genetic association study by Timothy Vyse and colleagues suggests that there is a significant association between CRP variants and acute-phase serum CRP concentrations in patients with rheumatoid arthritis, including those with chronic inflammation

Tameness of pseudovariety joins involving R

2000 Mathematics Subject Classification: 20M07 (primary); 20M05, 20M35, 68Q70 (secondary).In this paper, we establish several decidability results for pseudovariety joins of the form VvW, where V is a subpseudovariety of J or the pseudovariety R. Here, J (resp. R) denotes the pseudovariety of all J-trivial (resp. R-trivial) semigroups. In particular, we show that the pseudovariety VvW is (completely) kappa-tame when V is a subpseudovariety of J with decidable kappa-word problem and W is (completely) kappa-tame. Moreover, if W is a kappa-tame pseudovariety which satisfies the pseudoidentity x_1...x_ry^{\omega+1}zt^\omega = x_1... x_ryzt^\omega, then we prove that RvW is also kappa-tame. In particular the joins RvAb, RvG, RvOCR, and RvCR are decidable.União Europeia (UE). Fundo Europeu de Desenvolvimento Regional (FEDER) - POCTI/32817/MAT/2000.International Association for the Promotion of Co-operation with Scientists from the New Independent States (NIS) of the Former Soviet Union (INTAS) - project 99-1224.Fundação para a Ciência e a Tecnologia (FCT)