Nonlinear signaling on biological networks: the role of stochasticity and spectral clustering

Signal transduction within biological cells is governed by networks of interacting proteins. Communication between these proteins is mediated by signaling molecules which bind to receptors and induce stochastic transitions between different conformational states. Signaling is typically a cooperative process which requires the occurrence of multiple binding events so that reaction rates have a nonlinear dependence on the amount of signaling molecule. It is this nonlinearity that endows biological signaling networks with robust switch-like properties which are critical to their biological function. In this study, we investigate how the properties of these signaling systems depend on the network architecture. Our main result is that these nonlinear networks exhibit bistability where the network activity can switch between states that correspond to a low and high activity level. We show that this bistable regime emerges at a critical coupling strength that is determined by the spectral structure of the network. In particular, the set of nodes that correspond to large components of the leading eigenvector of the adjacency matrix determines the onset of bistability. Above this transition, the eigenvectors of the adjacency matrix determine a hierarchy of clusters, defined by its spectral properties, which are activated sequentially with increasing network activity. We argue further that the onset of bistability occurs either continuously or discontinuously depending upon whether the leading eigenvector is localized or delocalized. Finally, we show that at low network coupling stochastic transitions to the active branch are also driven by the set of nodes that contribute more strongly to the leading eigenvector.Comment: 30 pages, 12 figure

Calcium spikes in activated macrophages during Fcγ receptor‐mediated phagocytosis

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/142318/1/jlb0677.pd

Navigating Emerging Adulthood: Exploring Current Challenges Experienced in the Community

Background: Despite experiencing challenges, many young people resist seeking formal mental health support services (McGorry & Mei, 2018). One possible reason for this underutilization is that outreach and current service frameworks might not meet the evolving needs of this group, especially among young people with marginalized identities (Robards et al., 2018). In collaboration with Hôtel-Dieu Grace Healthcare, a lead agency engaged with local community mental health services, this project seeks to contribute to initiatives specific to transitional-aged youth’s mental health, possible trauma symptoms, and help-seeking.Method: This study invites undergraduate students and transitional-aged youth (18–24 years old) residing in Windsor-Essex County, Ontario, to participate in a mixed-method project with two phases. The first phase is ongoing and consists of a quantitative online survey. The next phase of this project will involve adopting a narrative inquiry approach and interviewing a subsample of participants from community and university settings.Results: Preliminary analyses will be presented. Descriptive and correlational findings will reveal how local transitional-aged youth are coping with mental health challenges and engaging in help-seeking behaviours within the context of the COVID-19 pandemic and related restrictions and disruptions.Conclusion: The expected implications of this mixed-method study include gaining valuable insights into understanding the unique challenges experienced by a traditionally hard-to-reach population during the COVID-19 pandemic. The resulting insights may be leveraged to inform and refine existing support services. This project aims to accomplish these objectives by conceptualizing the problem at the local level from the youth perspective

Altered membrane trafficking in activated bone marrow‐derived macrophages

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/141402/1/jlb0487.pd

Supermodels for early LHC

We investigate what new physics signatures the LHC can discover in the 2009-2010 run, beyond the expected sensitivity of the Tevatron data by 2010. We construct "supermodels", for which the LHC sensitivity even with only 10 inverse picobarn is greater than that of the Tevatron with 10 inverse femtobarn. The simplest supermodels involve s-channel resonances in the quark-antiquark and especially in the quark-quark channels. We concentrate on easily visible final states with small standard model backgrounds, and find that there are simple searches, besides those for Z' states, which could discover new physics in early LHC data. Many of these are well-suited to test searches for "more conventional" models, often discussed for multi-inverse femtobarn data sets.Comment: 11 pages, 6 figures; v2, references adde

Syphilis in the Americas: a protocol for a systematic review of syphilis prevalence and incidence in four high-risk groups, 1980–2016

Background: Syphilis infection has recently resurfaced as a significant public health problem. Although there has been a tremendous amount of research on the epidemiology of syphilis, there has been limited work done to synthesize the extensive body of research and systematically estimate patterns of disease within high-risk groups in the Americas. The purpose of this systematic review and meta-analysis is to (1) summarize recent patterns of syphilis infection in North and South America among four high-risk groups (MSM, transgender women, sex workers, and incarcerated individuals) from 1980 to 2016, (2) identify and differentiate regional geographic epidemiologic characteristics, and (3) compare the epidemics of the economically developed countries of North America from the developing countries and public health systems of Latin America and the Caribbean. Methods/design: Primary studies reporting syphilis prevalence and/or incidence in at least one of the four high-risk groups will be identified from Medline/PubMed, Embase, Lilacs, SciELO, The Cochrane Library, Web of Science, Scopus, ProQuest, CINAHL, Clase, and Periódica, as well as "gray" literature sources (conference abstracts, country reports, etc.). Studies published from 1980 through 2016 will be included. Data will be extracted from studies meeting inclusion and exclusion criteria and a random effects meta-analysis of prevalence and incidence estimates will be conducted. Heterogeneity, risk of bias, and publication bias will be assessed. Pooled prevalence and incidence estimates will be calculated for comparisons based on geographic region, risk factors, and time period. Discussion: Our systematic review and meta-analysis aims to contribute to an improved understanding of global epidemiologic patterns of syphilis infection in most-at-risk populations. Through systematic classification of the existing literature, and comparison of disease patterns across regional, temporal and socio-behavioral differences, we hope to improve public health surveillance and improve efforts to control the spread of disease across the Americas. Systematic review registration: PROSPERO CRD42016047306.Revisión por pare