Mutual information in random Boolean models of regulatory networks

The amount of mutual information contained in time series of two elements gives a measure of how well their activities are coordinated. In a large, complex network of interacting elements, such as a genetic regulatory network within a cell, the average of the mutual information over all pairs is a global measure of how well the system can coordinate its internal dynamics. We study this average pairwise mutual information in random Boolean networks (RBNs) as a function of the distribution of Boolean rules implemented at each element, assuming that the links in the network are randomly placed. Efficient numerical methods for calculating show that as the number of network nodes N approaches infinity, the quantity N exhibits a discontinuity at parameter values corresponding to critical RBNs. For finite systems it peaks near the critical value, but slightly in the disordered regime for typical parameter variations. The source of high values of N is the indirect correlations between pairs of elements from different long chains with a common starting point. The contribution from pairs that are directly linked approaches zero for critical networks and peaks deep in the disordered regime.Comment: 11 pages, 6 figures; Minor revisions for clarity and figure format, one reference adde

A Complete Catalog of Swift GRB Spectra and Durations: Demise of a Physical Origin for Pre-Swift High-Energy Correlations

We calculate durations and spectral paramaters for 218 Swift bursts detected by the BAT instrument between and including GRBs 041220 and 070509, including 77 events with measured redshifts. Incorporating prior knowledge into the spectral fits, we are able to measure the characteristic $\nu F_{\nu}$ spectral peak energy $E_{\rm pk,obs}$ and the isotropic equivalent energy $E_{\rm iso}$ (1--$10^4$ keV) for all events. This complete and rather extensive catalog, analyzed with a unified methodology, allows us to address the persistence and origin of high-energy correlations suggested in pre-Swift observations. We find that the $E_{\rm pk,obs}$-$E_{\rm iso}$ correlation is present in the Swift sample; however, the best-fit powerlaw relation is inconsistent with the best-fit pre-Swift relation at >5 sigma significance. Moreover, it has a factor >~ 2 larger intrinsic scatter, after accounting for large errors on $E_{\rm pk,obs}$. A large fraction of the Swift events are hard and subluminous relative to (and inconsistent with) the pre-Swift relation, in agreement with indications from BATSE GRBs without redshift. Moreover, we determine an experimental threshold for the BAT detector and show how the $E_{\rm pk,obs}$--$E_{\rm iso}$ correlation arises artificially due to partial correlation with the threshold. We show that pre-Swift correlations found by Amati et al.(2002), Yonetoku et al. (2004), Firmani et al.(2006) (and independently by others) are likely unrelated to the physical properties of GRBs and are likely useless for tests of cosmology. Also, an explanation of these correlations in terms of a detector threshold provides a natural and quantitative explanation for why short-duration GRBs and events at low redshift tend to be outliers to the correlations.Comment: 25 pages, 9 figures, 2 tables, Accepted to Ap

Molecular Predictors of Anakinra Treatment Success in Heart Failure Patients with Reduced Ejection Fraction

Background. Kineret (Anakinra) is an interleukin-1 antagonist that is under investigation for its novel clinical application treating patients that have heart failure with reduced (\u3c50%) ejection fraction (HFrEF). A prior study from our group indicated that Anakinra may restore heart function by addressing dysregulations in HFrEF metabolic pathways. Herein, we attempt to elicit Anakinra’s effects on both metabolome and lipidome. Methods. Lipids and metabolites that had previously been quantified by mass spectrometry (MS) from patients (n=49) who had ≥2 mg/L of high-sensitivity C-reactive protein (hs-CRP) were mTIC normalized and transformed. We conducted a stepwise Linear Discriminant Analysis (r- LDA) to test Anakinra (2 and 12 weeks) vs placebo for separation from combined baseline. Metabolic pathway analysis was performed with Fisher’s exact test algorithm for detection of over-represented and enriched analytes. Univariate analysis (one tailed t-test p\u3c0.05) compared placebo and Anakinra after 12-weeks for effect(s). Metaboanalyst 4.0, JMP Pro 14.0, and a proprietary package in R (version 3.4.4) were the software for all analyses and data wrangling. Results. Analytes such as acylcarnitines C10:0 and C16:0 and hsCRP showed significant improvements after 12 weeks of Anakinra, leading to improved mitochondrial function, reduced inflammation, and overall better health outcomes. Statistically significant (p\u3c0.05) pathways including the citrate cycle, cysteine and methionine metabolism, galactose metabolism among others were associated with treatment. Conclusions. We were able to determine significant alterations to metabolomic and lipidomic concentrations after 12 weeks of Anakinra therapy. Our biochemical analyses verifies that Anakinra did improve heart function within our HFrEF pilot cohort.https://scholarscompass.vcu.edu/gradposters/1081/thumbnail.jp

New Experimental Limits on Macroscopic Forces Below 100 Microns

Results of an experimental search for new macroscopic forces with Yukawa range between 5 and 500 microns are presented. The experiment uses 1 kHz mechanical oscillators as test masses with a stiff conducting shield between them to suppress backgrounds. No signal is observed above the instrumental thermal noise after 22 hours of integration time. These results provide the strongest limits to date between 10 and 100 microns, improve on previous limits by as much as three orders of magnitude, and rule out half of the remaining parameter space for predictions of string-inspired models with low-energy supersymmetry breaking. New forces of four times gravitational strength or greater are excluded at the 95% confidence level for interaction ranges between 200 and 500 microns.Comment: 25 Pages, 7 Figures: Minor Correction

Vegetable diversity, injurious falls, and fracture risk in older women: A prospective cohort study

The importance of vegetable diversity for the risk of falling and fractures is unclear. Our objective was to examine the relationship between vegetable diversity with injurious falling and fractures leading to hospitalization in a prospective cohort of older Australian women (n = 1429, ≥70 years). Vegetable diversity was quantified by assessing the number of different vegetables consumed daily. Vegetable intake (75 g servings/day) was estimated using a validated food frequency questionnaire at baseline (1998). Over 14.5 years, injurious falls (events = 568, 39.7%), and fractures (events = 404, 28.3%) were captured using linked health records. In multivariable-adjusted Cox regression models, women with greater vegetable diversity (per increase in one different vegetable/day) had lower relative hazards for falls (8%; p = 0.02) and fractures (9%; p = 0.03). A significant interaction between daily vegetable diversity (number/day) and total vegetable intake (75 g servings/day) was observed for falls (pinteraction = 0.03) and fractures (pinteraction \u3c 0.001). The largest benefit of higher vegetable diversity were observed in the one third of women with the lowest vegetable intake (\u3c2.2 servings/day; falls HR 0.83 95% CI (0.71–0.98); fractures HR 0.74 95% CI (0.62–0.89)). Increasing vegetable diversity especially in older women with low vegetable intake may be an effective way to reduce injurious fall and fracture risk

Using Empirical Phase Diagrams to Understand the Role of Intramolecular Dynamics in Immunoglobulin G Stability

Understanding the relationship between protein dynamics and stability is of paramount importance to the fields of biology and pharmaceutics. Clarifying this relationship is complicated by the large amount of experimental data that must be generated and analyzed if motions that exist over the wide range of timescales are to be included. To address this issue, we propose an approach that utilizes a multidimensional vector-based empirical phase diagram (EPD) to analyze a set of dynamic results acquired across a temperature-pH perturbation plane. This approach is applied to a humanized immunoglobulin G1 (IgG1), a protein of major biological and pharmaceutical importance whose dynamic nature is linked to its multiple biological roles. Static and dynamic measurements are used to characterize the IgG and to construct both static and dynamic empirical phase diagrams. Between pH 5 and 8, a single, pH-dependent transition is observed that corresponds to thermal unfolding of the IgG. Under more acidic conditions, evidence exists for the formation of a more compact, aggregation resistant state of the immunoglobulin, known as A-form. The dynamics-based EPD presents a considerably more detailed pattern of apparent phase transitions over the temperature-pH plane. The utility and potential applications of this approach are discussed

Effects of Co-ingesting Dietary Nitrate and Vitamin C on Nitric Oxide Bioavailability, Blood Pressure, and Cardiovascular Reactivity in Hispanic Females

High blood pressure is a hallmark of chronic disease and is disproportionately prevalent in ethnic minorities. Dietary nitrate has been shown to lower blood pressure via increased nitric oxide (NO), but few studies have examined if combining nitrate with vitamin C (VITC) could have beneficial synergistic effects on blood pressure by augmenting NO, and limited data exist in females. PURPOSE: To investigate if combining nitrate-rich beetroot juice (BR) with VITC could further augment NO bioavailability and improve blood pressure in Hispanic females compared to BR and VITC ingested alone. METHODS: Eight sedentary Hispanic females participated in four conditions to ingest: 1) BR and VITC (BR+VITC), 2) BR and crystal light (BR+CRY), 3) nitrate-depleted BR and VITC (PL+VITC), and 4) PL and CRY (PL+CRY). A blood draw and blood pressure were obtained at rest, followed by a cardiovascular reactivity test. RESULTS: Plasma nitrate was increased in BR+VITC and BR+CRY compared to PL+VITC and PL+CRY (P0.05). Plasma nitrite was increased in BR+VITC and BR+CRY compared to PL+VITC and PL+CRY (P0.05). CONCLUSION: Co-ingestion of dietary nitrate and VITC increased plasma nitrite compared to BR alone, which could indicate augmented NO bioavailability following BR+VITC; however, there was no impact of nitrate supplementation on markers of cardiovascular health