Minimum-action paths for wave-number selection in nonequilibrium systems

The problem of wave-number selections in nonequilibrium pattern-forming systems in the presence of noise is investigated. The minimum-action method is proposed to study the noise-induced transitions between the different spatiotemporal states by generalizing the traditional theory previously applied in low-dimensional dynamical systems. The scheme is shown as an example in the stabilized Kuramoto-Sivashinsky equation. The present method allows us to conveniently find the unique noise selected state, in contrast to previous work using direct simulations of the stochastic partial differential equation, where the constraints of the simulation only allow a narrow band to be determined

Path-Goal Theory-based Leadership Development Deployment Guidelines for the Middle Managers of an International University in China

This research aims to 1) determine the current and desired situation of the middle managers' leadership behavior and leadership performance based on path-goal theory, 2) identify the significant differences between current and desired middle managers' leadership behavior, 3) explore ideas of key managers on leadership behavior and effectiveness through interviews, and 4) develop the final leadership effectiveness development deployment strategies based on the quantitative and qualitative findings. Questionnaire surveys and focus group discussions were used to collect data to identify and determine the significant difference between leadership behaviors and leadership effectiveness. The participants in this study were 67 teachers from Heilongjiang International University in China. Data analysis used frequency, percentage, paired-sample T-test for quantitative data, and Content analysis for qualitative data. Through quantitative research, it is found that focus should be given to Directive Leadership as priority, then Supportive Leadership and Participative Leadership, Achievement Leadership, and Leadership Effectiveness. The results of qualitative data analysis shows that there are four strategies for the development of leadership behaviors and leadership effectiveness

Large domains of heterochromatin direct the formation of short mitotic chromosome loops

During mitosis chromosomes reorganise into highly compact, rod-shaped forms, thought to consist of consecutive chromatin loops around a central protein scaffold. Condensin complexes are involved in chromatin compaction, but the contribution of other chromatin proteins, DNA sequence and histone modifications is less understood. A large region of fission yeast DNA inserted into a mouse chromosome was previously observed to adopt a mitotic organisation distinct from that of surrounding mouse DNA. Here, we show that a similar distinct structure is common to a large subset of insertion events in both mouse and human cells and is coincident with the presence of high levels of heterochromatic H3 lysine nine trimethylation (H3K9me3). Hi-C and microscopy indicate that the heterochromatinised fission yeast DNA is organised into smaller chromatin loops than flanking euchromatic mouse chromatin. We conclude that heterochromatin alters chromatin loop size, thus contributing to the distinct appearance of heterochromatin on mitotic chromosomes

Hybrid Decay: A Transgenerational Epigenetic Decline in Vigor and Viability Triggered in Backcross Populations of Teosinte with Maize.

In the course of generating populations of maize with teosinte chromosomal introgressions, an unusual sickly plant phenotype was noted in individuals from crosses with two teosinte accessions collected near Valle de Bravo, Mexico. The plants of these Bravo teosinte accessions appear phenotypically normal themselves and the F1 plants appear similar to typical maize × teosinte F1s. However, upon backcrossing to maize, the BC1 and subsequent generations display a number of detrimental characteristics including shorter stature, reduced seed set, and abnormal floral structures. This phenomenon is observed in all BC individuals and there is no chromosomal segment linked to the sickly plant phenotype in advanced backcross generations. Once the sickly phenotype appears in a lineage, normal plants are never again recovered by continued backcrossing to the normal maize parent. Whole-genome shotgun sequencing reveals a small number of genomic sequences, some with homology to transposable elements, that have increased in copy number in the backcross populations. Transcriptome analysis of seedlings, which do not have striking phenotypic abnormalities, identified segments of 18 maize genes that exhibit increased expression in sickly plants. A de novo assembly of transcripts present in plants exhibiting the sickly phenotype identified a set of 59 upregulated novel transcripts. These transcripts include some examples with sequence similarity to transposable elements and other sequences present in the recurrent maize parent (W22) genome as well as novel sequences not present in the W22 genome. Genome-wide profiles of gene expression, DNA methylation, and small RNAs are similar between sickly plants and normal controls, although a few upregulated transcripts and transposable elements are associated with altered small RNA or methylation profiles. This study documents hybrid incompatibility and genome instability triggered by the backcrossing of Bravo teosinte with maize. We name this phenomenon "hybrid decay" and present ideas on the mechanism that may underlie it

Infarct-remodelled hearts with limited oxidative capacity boost fatty acid oxidation after conditioning against ischaemia/reperfusion injury

Aims Infarct-remodelled hearts are less amenable to protection against ischaemia/reperfusion. Understanding preservation of energy metabolism in diseased vs. healthy hearts may help to develop anti-ischaemic strategies effective also in jeopardized myocardium. Methods and results Isolated infarct-remodelled/sham Sprague-Dawley rat hearts were perfused in the working mode and subjected to 15 min of ischaemia and 30 min of reperfusion. Protection of post-ischaemic ventricular work was achieved by pharmacological conditioning with sevoflurane. Oxidative metabolism was measured by substrate flux in fatty acid and glucose oxidation using [3H]palmitate and [14C]glucose. Mitochondrial oxygen consumption was measured in saponin-permeabilized left ventricular muscle fibres. Activity assays of citric acid synthase, hydroxyacyl-CoA dehydrogenase, and pyruvate dehydrogenase and mass spectrometry for acylcarnitine profiling were also performed. Six weeks after coronary artery ligation, the hearts exhibited macroscopic and molecular signs of hypertrophy consistent with remodelling and limited respiratory chain and citric acid cycle capacity. Unprotected remodelled hearts showed a marked decline in palmitate oxidation and acetyl-CoA energy production after ischaemia/reperfusion, which normalized in sevoflurane-protected remodelled hearts. Protected remodelled hearts also showed higher β-oxidation flux as determined by increased oxygen consumption with palmitoylcarnitine/malate in isolated fibres and a lower ratio of C16:1+C16OH/C14 carnitine species, indicative of a higher long-chain hydroxyacyl-CoA dehydrogenase activity. Remodelled hearts exhibited higher PPARα-PGC-1α but defective HIF-1α signalling, and conditioning enabled them to mobilize fatty acids from endogenous triglyceride stores, which closely correlated with improved recovery. Conclusions Protected infarct-remodelled hearts secure post-ischaemic energy production by activation of β-oxidation and mobilization of fatty acids from endogenous triglyceride store

Low Concentrations of Silver Nanoparticles in Biosolids Cause Adverse Ecosystem Responses under Realistic Field Scenario

A large fraction of engineered nanomaterials in consumer and commercial products will reach natural ecosystems. To date, research on the biological impacts of environmental nanomaterial exposures has largely focused on high-concentration exposures in mechanistic lab studies with single strains of model organisms. These results are difficult to extrapolate to ecosystems, where exposures will likely be at low-concentrations and which are inhabited by a diversity of organisms. Here we show adverse responses of plants and microorganisms in a replicated long-term terrestrial mesocosm field experiment following a single low dose of silver nanoparticles (0.14 mg Ag kg−1 soil) applied via a likely route of exposure, sewage biosolid application. While total aboveground plant biomass did not differ between treatments receiving biosolids, one plant species, Microstegium vimeneum, had 32 % less biomass in the Slurry+AgNP treatment relative to the Slurry only treatment. Microorganisms were also affected by AgNP treatment, which gave a significantly different community composition of bacteria in the Slurry+AgNPs as opposed to the Slurry treatment one day after addition as analyzed by T-RFLP analysis of 16S-rRNA genes. After eight days, N2O flux was 4.5 fold higher in the Slurry+AgNPs treatment than the Slurry treatment. After fifty days, community composition and N2O flux of the Slurry+AgNPs treatment converged with the Slurry. However, the soil microbial extracellular enzymes leucine amino peptidase and phosphatase had 52 and 27% lower activities, respectively, while microbial biomass was 35% lower than the Slurry. We also show that the magnitude of these responses was in all cases as large as or larger than the positive control, AgNO3, added at 4-fold the Ag concentration of the silver nanoparticles

Quantitative Analysis of High-Resolution Microendoscopic Images for Diagnosis of Esophageal Squamous Cell Carcinomaﾠ

Background & Aims: High-resolution microendoscopy is an optical imaging technique with the potential to improve the accuracy of endoscopic screening for esophageal squamous neoplasia. Although these microscopic images can be interpreted readily by trained personnel, quantitative image analysis software could facilitate the use of this technology in low-resource settings. In this study, we developed and evaluated quantitative image analysis criteria for the evaluation of neoplastic and non-neoplastic squamous esophageal mucosa. Methods: We performed an image analysis of 177 patients undergoing standard upper endoscopy for screening or surveillance of esophageal squamous neoplasia, using high-resolution microendoscopy, at 2 hospitals in China and at 1 hospital in the United States from May 2010 to October 2012. Biopsy specimens were collected from imaged sites (n = 375), and a consensus diagnosis was provided by 2 expert gastrointestinal pathologists and used as the standard. Results: Quantitative information from the high-resolution images was used to develop an algorithm to identify high-grade squamous dysplasia or invasive squamous cell cancer, based on histopathology findings. Optimal performance was obtained using the mean nuclear area as the basis for classification, resulting in sensitivities and specificities of 93% and 92% in the training set, 87% and 97% in the test set, and 84% and 95% in an independent validation set, respectively. Conclusions: High-resolution microendoscopy with quantitative image analysis can aid in the identification of esophageal squamous neoplasia. Use of software-based image guides may overcome issues of training and expertise in low-resource settings, allowing for widespread use of these optical biopsy technologies

Low-Cost High-Resolution Microendoscopy for the Detection of Esophageal Squamous Cell Neoplasia: An International Trial

Background & Aims: Esophageal squamous cell neoplasia has a high mortality rate as a result of late detection. In high-risk regions such as China, screening is performed by Lugol’s chromoendoscopy (LCE). LCE has low specificity, resulting in unnecessary tissue biopsy with a subsequent increase in procedure cost and risk. The purpose of this study was to evaluate the accuracy of a novel, low-cost, high-resolution microendoscope (HRME) as an adjunct to LCE. Methods: In this prospective trial, 147 consecutive high-risk patients were enrolled from 2 US and 2 Chinese tertiary centers. Three expert and 4 novice endoscopists performed white-light endoscopy followed by LCE and HRME. All optical images were compared with the gold standard of histopathology. Results: By using a per-biopsy analysis, the sensitivity of LCE vs LCE + HRME was 96% vs 91% (P = .0832), specificity was 48% vs 88% (P < .001), positive predictive value was 22% vs 45% (P < .0001), negative predictive value was 98% vs 98% (P = .3551), and overall accuracy was 57% vs 90% (P < .001), respectively. By using a per-patient analysis, the sensitivity of LCE vs LCE + HRME was 100% vs 95% (P = .16), specificity was 29% vs 79% (P < .001), positive predictive value was 32% vs 60%, 100% vs 98%, and accuracy was 47% vs 83% (P < .001). With the use of HRME, 136 biopsies (60%; 95% confidence interval, 53%–66%) could have been spared, and 55 patients (48%; 95% confidence interval, 38%–57%) could have been spared any biopsy. Conclusions: In this trial, HRME improved the accuracy of LCE for esophageal squamous cell neoplasia screening and surveillance. HRME may be a cost-effective optical biopsy adjunct to LCE, potentially reducing unnecessary biopsies and facilitating real-time decision making in globally underserved regions. ClinicalTrials.gov, NCT 01384708