Predictions of ultra-harmonic oscillations in coupled arrays of limit cycle oscillators

Coupled distinct arrays of nonlinear oscillators have been shown to have a regime of high frequency, or ultra-harmonic, oscillations that are at multiples of the natural frequency of individual oscillators. The coupled array architectures generate an in-phase high-frequency state by coupling with an array in an anti-phase state. The underlying mechanism for the creation and stability of the ultra-harmonic oscillations is analyzed. A class of inter-array coupling is shown to create a stable, in-phase oscillation having frequency that increases linearly with the number of oscillators, but with an amplitude that stays fairly constant. The analysis of the theory is illustrated by numerical simulation of coupled arrays of Stuart-Landau limit cycle oscillators.Comment: 24 pages, 9 figures, accepted to Phys. Rev. E, in pres

Nuclear Factor-κB-Independent Anti-Inflammatory Action of Salicylate in Human Endothelial Cells

In contrast to aspirin, salicylate, its active metabolite, possesses profound anti-inflammatory properties without blocking cyclooxygenase. Inhibition of the transcription factor nuclear factor-κB (NF-κB) has been discussed to play a role in the anti-inflammatory profile of salicylate. However, NF-κB-independent effects of salicylate have been assumed but have up to now been poorly investigated. Therefore, the aim of the present study was to investigate NF-κB-independent anti-inflammatory mechanisms of salicylate in human umbilical vein endothelial cells using interleukin-4 (IL-4) as NF-κB-independent proinflammatory stimulus and P-selectin as inflammatory read-out parameter. Using quantitative real-time reverse transcriptionpolymerase chain reaction, we found that salicylate decreases IL-4-induced P-selectin expression. As judged by Western blot analysis, salicylate increased endothelial heme oxygenase-1 (HO-1) protein levels. Using both the HO-1 inhibitor tin(II) protoporphyrin IX and HO-1 antisense oligonucleotides, we causally linked the induction of HO-1 to the decrease of P-selectin. Moreover, we were interested in the signaling mechanisms leading to the up-regulation of HO-1 by salicylate. c-Jun NH2-terminal kinase (JNK) was found to be activated by salicylate, and we could causally link this activation to the induction of HO-1 by using the JNK inhibitor 1,9-pyrazoloanthrone. By applying activator protein-1 (AP-1) decoys, it was shown that the transcription factor AP-1 is crucially involved in the up-regulation of HO-1 downstream of JNK. In summary, our study introduces HO-1 as novel NF-κB-independent anti-inflammatory target of salicylate in human endothelial cells. Moreover, we elucidated the JNK/AP-1 pathway as crucial for the induction of HO-1 by salicylate

Emulsion formation and stabilization by biomolecules: the leading role of cellulose

Emulsion stabilization by native cellulose has been mainly hampered because of its insolubility in water. Chemical modification is normally needed to obtain water-soluble cellulose derivatives. These modified celluloses have been widely used for a range of applications by the food, cosmetic, pharmaceutic, paint and construction industries. In most cases, the modified celluloses are used as rheology modifiers (thickeners) or as emulsifying agents. In the last decade, the structural features of cellulose have been revisited, with particular focus on its structural anisotropy (amphiphilicity) and the molecular interactions leading to its resistance to dissolution. The amphiphilic behavior of native cellulose is evidenced by its capacity to adsorb at the interface between oil and aqueous solvent solutions, thus being capable of stabilizing emulsions. In this overview, the fundamentals of emulsion formation and stabilization by biomolecules are briefly revisited before different aspects around the emerging role of cellulose as emulsion stabilizer are addressed in detail. Particular focus is given to systems stabilized by native cellulose, either molecularly-dissolved or not (Pickering-like effect).Financially support by the Portuguese Foundation for Science and Technology, FCT, via the projects PTDC/AGR-TEC/4814/2014, PTDC/ASP-SIL/30619/2017 and researcher grant IF/01005/2014. RISE Research Institutes of Sweden AB and PERFORM, a competence platform in Formulation Science at RISE, are acknowledged for additional financing. This research has been supported by Treesearch.se.info:eu-repo/semantics/publishedVersio

Consumer preferences for scanning modality to diagnose focal liver lesions

Objectives: Differences in the process of using liver imaging technologies might be important to patients. This study aimed to investigate preferences for scanning modalities used in diagnosing focal liver lesions. Methods: A discrete choice experiment was administered to 504 adults aged 25 years. Respondents made repeated choices between two hypothetical scans, described according to waiting time for scan and results, procedure type, the chance of minor side-effects, and whether further scanning procedures were likely to be required. Choice data were analyzed using mixed-logit models with respondent characteristics used to explain preference heterogeneity. Results: Respondents preferred shorter waiting times, the procedure to be undertaken with a handheld scanner on a couch instead of within a body scanner, no side-effects, and no follow–up scans (p .01). The average respondent was willing to wait an additional 2 weeks for the scan if it resulted in avoiding side-effects, 1.5 weeks to avoid further procedures or to be told the results immediately, and 1 week to have the scan performed on a couch with a handheld scanner. However, substantial heterogeneity was observed in the strength of preference for desirable imaging characteristics. Conclusions: An average individual belonging to a general population sub–group most likely to require imaging to characterize focal liver lesions in the United Kingdom would prefer contrast–enhanced ultrasound over magnetic resonance imaging or computed tomography. Insights into the patient perspective around differential characteristics of imaging modalities have the potential to be used to guide recommendations around the use of these technologies

The causal effect of red blood cell folate on genome-wide methylation in cord blood: a Mendelian randomization approach

Background: Investigation of the biological mechanism by which folate acts to affect fetal development can inform appraisal of expected benefits and risk management. This research is ethically imperative given the ubiquity of folic acid fortified products in the US. Considering that folate is an essential component in the one-carbon metabolism pathway that provides methyl groups for DNA methylation, epigenetic modifications provide a putative molecular mechanism mediating the effect of folic acid supplementation on neonatal and pediatric outcomes. Results: In this study we use a Mendelian Randomization Unnecessary approach to assess the effect of red blood cell (RBC) folate on genome-wide DNA methylation in cord blood. Site-specific CpG methylation within the proximal promoter regions of approximately 14,500 genes was analyzed using the Illumina Infinium Human Methylation27 Bead Chip for 50 infants from the Epigenetic Birth Cohort at Brigham and Women’s Hospital in Boston. Using methylenetetrahydrofolate reductase genotype as the instrument, the Mendelian Randomization approach identified 7 CpG loci with a significant (mostly positive) association between RBC folate and methylation level. Among the genes in closest proximity to this significant subset of CpG loci, several enriched biologic processes were involved in nucleic acid transport and metabolic processing. Compared to the standard ordinary least squares regression method, our estimates were demonstrated to be more robust to unmeasured confounding. Conclusions: To the authors’ knowledge, this is the largest genome-wide analysis of the effects of folate on methylation pattern, and the first to employ Mendelian Randomization to assess the effects of an exposure on epigenetic modifications. These results can help guide future analyses of the causal effects of periconceptional folate levels on candidate pathways

Genetic diversity, infection prevalence, and possible transmission routes of Bartonella spp. in vampire bats

Bartonella spp. are globally distributed bacteria that cause endocarditis in humans and domestic animals. Recent work has suggested bats as zoonotic reservoirs of some human Bartonella infections; however, the ecological and spatiotemporal patterns of infection in bats remain largely unknown. Here we studied the genetic diversity, prevalence of infection across seasons and years, individual risk factors, and possible transmission routes of Bartonella in populations of common vampire bats (Desmodus rotundus) in Peru and Belize, for which high infection prevalence has previously been reported. Phylogenetic analysis of the gltA gene for a subset of PCR-positive blood samples revealed sequences that were related to Bartonella described from vampire bats from Mexico, other Neotropical bat species, and streblid bat flies. Sequences associated with vampire bats clustered significantly by country but commonly spanned Central and South America, implying limited spatial structure. Stable and nonzero Bartonella prevalence between years supported endemic transmission in all sites. The odds of Bartonella infection for individual bats was unrelated to the intensity of bat flies ectoparasitism, but nearly all infected bats were infested, which precluded conclusive assessment of support for vector-borne transmission. While metagenomic sequencing found no strong evidence of Bartonella DNA in pooled bat saliva and fecal samples, we detected PCR positivity in individual saliva and feces, suggesting the potential for bacterial transmission through both direct contact (i.e., biting) and environmental (i.e., fecal) exposures. Further investigating the relative contributions of direct contact, environmental, and vector-borne transmission for bat Bartonella is an important next step to predict infection dynamics within bats and the risks of human and livestock exposures

Pyrosequencing Evaluation of Widely Available Bisulfite Conversion Methods: Considerations for Application

Introduction: Bisulfite treatment of DNA introduces methylation-dependent sequence changes through selective chemical conversion of nonmethylated cytosine to uracil and serves as pretreatment step for the majority of DNA methylation analysis methods. Methods: We have evaluated the conversion performance of five of the most commonly used bisulfite treatment kits [MethylDetector (Active Motif), Epitect+ (Qiagen), Zymo Methylation, Zymo Gold and Zymo Lightning (all from Zymo Research)] by pyrosequencing four different regions with variable methylation levels, including: a repetitive element (ALUSX), a gene with low levels of methylation (IL6ST), an imprinted gene expected to be approximately 50% methylated (IGF2), and a fully methylated gene (ST3GAL2). In addition, we have studied the influence of duration (3 vs. 16 h) and type (fixed temperature vs. cycling program) of incubation protocol on the conversion efficiency of each evaluated kit. Results: All kits produced similar conversion rates of ALUSX, IGF2 and ST3GAL2, while the conversion of the low methylated IL6ST gene was variable between kits. The Zymo kits were highly consistent in their performance even when different protocols of incubation were applied, generating full conversion at the low methylated gene IL6; this was not true for the MethylDetector and Epitect+ kits. However, long-cycling incubation could produce similar conversion rates for the same locus in combination with Active Motif and Qiagen kits. Conclusions: The selection of a long-cycling protocol during conversion permits standardization of protocols, improving the reproducibility of methylation estimates across laboratories for gene-specific, genome-wide and bisulfite-based sequencing analyses

Negative discrete moments of the derivative of the Riemann zeta-function

We obtain conditional upper bounds for negative discrete moments of the derivative of the Riemann zeta-function averaged over a subfamily of zeros of the zeta function which is expected to have full density inside the set of all zeros. For $k\leq 1/2$, our bounds for the $2k$-th moments are expected to be almost optimal. Assuming a conjecture about the maximum size of the argument of the zeta function on the critical line, we obtain upper bounds for these negative moments of the same strength while summing over a larger subfamily of zeta zeros.Comment: 19 page