1,542 research outputs found
Phase transitions in contagion processes mediated by recurrent mobility patterns
Human mobility and activity patterns mediate contagion on many levels,
including the spatial spread of infectious diseases, diffusion of rumors, and
emergence of consensus. These patterns however are often dominated by specific
locations and recurrent flows and poorly modeled by the random diffusive
dynamics generally used to study them. Here we develop a theoretical framework
to analyze contagion within a network of locations where individuals recall
their geographic origins. We find a phase transition between a regime in which
the contagion affects a large fraction of the system and one in which only a
small fraction is affected. This transition cannot be uncovered by continuous
deterministic models due to the stochastic features of the contagion process
and defines an invasion threshold that depends on mobility parameters,
providing guidance for controlling contagion spread by constraining mobility
processes. We recover the threshold behavior by analyzing diffusion processes
mediated by real human commuting data.Comment: 20 pages of Main Text including 4 figures, 7 pages of Supplementary
Information; Nature Physics (2011
The influence of standards and clinical guidelines on prosthetic and orthotic service quality : a scoping review
OBJECTIVES: Standards and guidelines are an integral part of prosthetic and orthotic service delivery in the developed world underpinned by an assumption that they lead to improved services. Implementing them has a cost, however, and that cost needs to be justified, particularly in resource-limited environments. This scoping review thus asks the question, "What is the evidence of the impact of standards and guidelines on service delivery outcomes in prosthetics and orthotics?"
MATERIALS AND METHODS: A structured search of three electronic databases (Medline, Scopus and Web of Science) followed by manual searching of title, abstract and full text, yielded 29 articles.
RESULTS: Four categories of papers were identified: Descriptions and Commentaries (17 papers), Guideline Development (7), Guideline Testing (2) and Standards implementation (3). No articles were explicitly designed to assess the impact of standards and guidelines on service delivery outcomes in prosthetics and orthotics.
DISCUSSION AND CONCLUSION: Studies tended to be commentaries on or descriptions of guideline development, testing or implementation of standards. The literature is not sufficiently well developed to warrant the cost and effort of a systematic review. Future primary research should seek to demonstrate whether and how guidelines and standards improve the outcomes for people that require prostheses, orthoses and other assistive devices. Implications for Rehabilitation International Standards and Clinical Guidelines are now an integral part of clinical service provision in prosthetics and orthotics in the developed world. Complying with standards and guidelines has a cost and, particularly in resource-limited environments, it should be possible to justify this in terms of the resulting benefits. This scoping review concludes that there have been no previous studies designed to directly quantify the effects of implementing standards and guidelines on service delivery
Legal determinants of external finance revisited : the inverse relationship between investor protection and societal well-being
This paper investigates relationships between corporate governance traditions and quality of life as measured by a number of widely reported indicators. It provides an empirical analysis of indicators of societal health in developed economies using a classification based on legal traditions. Arguably the most widely cited work in the corporate governance literature has been the collection of papers by La Porta et al. which has shown, inter alia, statistically significant relationships between legal traditions and various proxies for investor protection. We show statistically significant relationships between legal traditions and various proxies for societal health. Our comparative evidence suggests that the interests of investors may not be congruent with the interests of wider society, and that the criteria for judging the effectiveness of approaches to corporate governance should not be restricted to financial metrics
Developmental seizures and mortality result from reducing GABAᴀ receptor α2-subunit interaction with collybistin
Fast inhibitory synaptic transmission is mediated by γ-aminobutyric acid type A receptors (GABAARs) that are enriched at functionally diverse synapses via mechanisms that remain unclear. Using isothermal titration calorimetry and complementary methods we demonstrate an exclusive low micromolar binding of collybistin to the α2-subunit of GABAARs. To explore the biological relevance of collybistin-α2-subunit selectivity, we generate mice with a mutation in the α2-subunit-collybistin binding region (Gabra2-1). The mutation results in loss of a distinct subset of inhibitory synapses and decreased amplitude of inhibitory synaptic currents. Gabra2–1 mice have a striking phenotype characterized by increased susceptibility to seizures and early mortality. Surviving Gabra2-1 mice show anxiety and elevations in electroencephalogram δ power, which are ameliorated by treatment with the α2/α3-selective positive modulator, AZD7325. Taken together, our results demonstrate an α2-subunit selective binding of collybistin, which plays a key role in patterned brain activity, particularly during development
Hydroxymethylglutaryl-CoA reductase inhibition with simvastatin in acute lung injury to reduce pulmonary dysfunction (HARP-2) trial : study protocol for a randomized controlled trial
Acute lung injury (ALI) is a common devastating clinical syndrome characterized by life-threatening respiratory failure requiring mechanical ventilation and multiple organ failure. There are in vitro, animal studies and pre-clinical data suggesting that statins may be beneficial in ALI. The Hydroxymethylglutaryl-CoA reductase inhibition with simvastatin in Acute lung injury to Reduce Pulmonary dysfunction (HARP-2) trial is a multicenter, prospective, randomized, allocation concealed, double-blind, placebo-controlled clinical trial which aims to test the hypothesis that treatment with simvastatin will improve clinical outcomes in patients with ALI
From START to FINISH : the influence of osmotic stress on the cell cycle
Peer reviewedPublisher PD
Downregulation of Mcl-1 has anti-inflammatory pro-resolution effects and enhances bacterial clearance from the lung
Phagocytes not only coordinate acute inflammation and host defense at mucosal sites, but also contribute to tissue damage. Respiratory infection causes a globally significant disease burden and frequently progresses to acute respiratory distress syndrome, a devastating inflammatory condition characterized by neutrophil recruitment and accumulation of protein-rich edema fluid causing impaired lung function. We hypothesized that targeting the intracellular protein myeloid cell leukemia 1 (Mcl-1) by a cyclin-dependent kinase inhibitor (AT7519) or a flavone (wogonin) would accelerate neutrophil apoptosis and resolution of established inflammation, but without detriment to bacterial clearance. Mcl-1 loss induced human neutrophil apoptosis, but did not induce macrophage apoptosis nor impair phagocytosis of apoptotic neutrophils. Neutrophil-dominant inflammation was modelled in mice by either endotoxin or bacteria (Escherichia coli). Downregulating inflammatory cell Mcl-1 had anti-inflammatory, pro-resolution effects, shortening the resolution interval (R(i)) from 19 to 7 h and improved organ dysfunction with enhanced alveolar–capillary barrier integrity. Conversely, attenuating drug-induced Mcl-1 downregulation inhibited neutrophil apoptosis and delayed resolution of endotoxin-mediated lung inflammation. Importantly, manipulating lung inflammatory cell Mcl-1 also accelerated resolution of bacterial infection (R(i); 50 to 16 h) concurrent with enhanced bacterial clearance. Therefore, manipulating inflammatory cell Mcl-1 accelerates inflammation resolution without detriment to host defense against bacteria, and represents a target for treating infection-associated inflammation
Ribose 2′-O-methylation provides a molecular signature for the distinction of self and non-self mRNA dependent on the RNA sensor Mda5
The 5'-cap-structures of higher eukaryote mRNAs are ribose 2'-O-methylated. Likewise, a number of viruses replicating in the cytoplasm of eukayotes have evolved 2'-O-methyltransferases to modify autonomously their mRNAs. However, a defined biological role of mRNA 2'-O-methylation remains elusive. Here we show that viral mRNA 2'-O-methylation is critically involved in subversion of type-I-interferon (IFN-I) induction. We demonstrate that human and murine coronavirus 2'-O-methyltransferase mutants induce increased IFN-I expression, and are highly IFN-I sensitive. Importantly, IFN-I induction by 2'-O-methyltransferase-deficient viruses is dependent on the cytoplasmic RNA sensor melanoma differentiation-associated gene 5 (MDA5). This link between MDA5-mediated sensing of viral RNA and mRNA 2'-O-methylation suggests that RNA modifications, such as 2'-O-methylation, provide a molecular signature for the discrimination of self and non-self mRNA
Hierarchy measure for complex networks
Nature, technology and society are full of complexity arising from the
intricate web of the interactions among the units of the related systems (e.g.,
proteins, computers, people). Consequently, one of the most successful recent
approaches to capturing the fundamental features of the structure and dynamics
of complex systems has been the investigation of the networks associated with
the above units (nodes) together with their relations (edges). Most complex
systems have an inherently hierarchical organization and, correspondingly, the
networks behind them also exhibit hierarchical features. Indeed, several papers
have been devoted to describing this essential aspect of networks, however,
without resulting in a widely accepted, converging concept concerning the
quantitative characterization of the level of their hierarchy. Here we develop
an approach and propose a quantity (measure) which is simple enough to be
widely applicable, reveals a number of universal features of the organization
of real-world networks and, as we demonstrate, is capable of capturing the
essential features of the structure and the degree of hierarchy in a complex
network. The measure we introduce is based on a generalization of the m-reach
centrality, which we first extend to directed/partially directed graphs. Then,
we define the global reaching centrality (GRC), which is the difference between
the maximum and the average value of the generalized reach centralities over
the network. We investigate the behavior of the GRC considering both a
synthetic model with an adjustable level of hierarchy and real networks.
Results for real networks show that our hierarchy measure is related to the
controllability of the given system. We also propose a visualization procedure
for large complex networks that can be used to obtain an overall qualitative
picture about the nature of their hierarchical structure.Comment: 29 pages, 9 figures, 4 table
Proteomic Profile of Reversible Protein Oxidation Using PROP, Purification of Reversibly Oxidized Proteins
Signal transduction pathways that are modulated by thiol oxidation events are beginning to be uncovered, but these discoveries are limited by the availability of relatively few analytical methods to examine protein oxidation compared to other signaling events such as protein phosphorylation. We report here the coupling of PROP, a method to purify reversibly oxidized proteins, with the proteomic identification of the purified mixture using mass spectrometry. A gene ontology (GO), KEGG enrichment and Wikipathways analysis of the identified proteins indicated a significant enrichment in proteins associated with both translation and mRNA splicing. This methodology also enabled the identification of some of the specific cysteine residue targets within identified proteins that are reversibly oxidized by hydrogen peroxide treatment of intact cells. From these identifications, we determined a potential consensus sequence motif associated with oxidized cysteine residues. Furthermore, because we identified proteins and specific sites of oxidation from both abundant proteins and from far less abundant signaling proteins (e.g. hepatoma derived growth factor, prostaglandin E synthase 3), the results suggest that the PROP procedure was efficient. Thus, this PROP-proteomics methodology offers a sensitive means to identify biologically relevant redox signaling events that occur within intact cells
- …