Identifying dynamical modules from genetic regulatory systems: applications to the segment polarity network

BACKGROUND It is widely accepted that genetic regulatory systems are 'modular', in that the whole system is made up of smaller 'subsystems' corresponding to specific biological functions. Most attempts to identify modules in genetic regulatory systems have relied on the topology of the underlying network. However, it is the temporal activity (dynamics) of genes and proteins that corresponds to biological functions, and hence it is dynamics that we focus on here for identifying subsystems. RESULTS Using Boolean network models as an exemplar, we present a new technique to identify subsystems, based on their dynamical properties. The main part of the method depends only on the stable dynamics (attractors) of the system, thus requiring no prior knowledge of the underlying network. However, knowledge of the logical relationships between the network components can be used to describe how each subsystem is regulated. To demonstrate its applicability to genetic regulatory systems, we apply the method to a model of the Drosophila segment polarity network, providing a detailed breakdown of the system. CONCLUSION We have designed a technique for decomposing any set of discrete-state, discrete-time attractors into subsystems. Having a suitable mathematical model also allows us to describe how each subsystem is regulated and how robust each subsystem is against perturbations. However, since the subsystems are found directly from the attractors, a mathematical model or underlying network topology is not necessarily required to identify them, potentially allowing the method to be applied directly to experimental expression data

Electromagnetic Pulse Sounding for Surveying Underground Water

This project supported in part by the Office of Water Resources Research U. S. Department of the Interior Washington, D. C. under Project B-028-OHIOA number of approaches have been explored for measuring the water content of soil electrically. In contrast with traditional measurements, which utilize electric currents at DC or at specific frequencies, our techniques have been based on the transmission and reflection of sharp, regularly repeated pulses. Such pulse measurements can be shown to be equivalent to measuring the electrical properties at all frequencies in a very wide band, and therefore the possibility of extracting the desired information is much greater than with single-frequency measurements. Because the information content of the signal is great, data processing can be used to extract those features which relate most directly to moisture content and reject those which appear to depend more on soil inhomogenieties. For example, it was found that the attenuation in the frequency band of approximately 10 to 20 MHz had a much higher correlation with soil moisture than that in other frequency bands for the actual field conditions under which our measurements were made. This information content increase is obtained by means of sophisticated research equipment. The measurements reported herein were made and processed under real-time computer control. They include the signal scattered from known buried targets, transmission measurements through the ground, and the measurement of reflections in a coaxial test cell, all with pulses containing very wide frequency bands. The results are encouraging in that definite correlations with moisture were found. Unfortunately the one-year time limitation of this effort, much of it spent in instrumentation development, was insufficient to allow testing these correlations quantitatively over extended time periods or in a variety of locations. Thus the techniques must be evaluated at present as promising, but not fully proven. It should be noted that, while the research system to obtain this information is complex, field equipment based on these techniques need not be unduly complicated or expensive. Once the features relating to moisture content under the greatest variety of field conditions are identified, means for extracting this information more simply should be devised. This is proposed as the objective for continuation of this effort.Summary -- Introduction -- 1. The Measuring System -- 2. Data Processing -- 3. Underground Moisture Content Monitoring by Measurement of Buried Target Signatures -- 4. Sampled Moisture Conditions -- 5. Underground Propagation Experiment -- 6. Reflection Measurements on Soil Samples in a Vertical Coaxial Test Cell -- 7. Propagation Calculations -- Conclusions -- Recommendations -- References -- Appendix I - Transmission Measurements using a Buried Antenn

An epidemiologic study of early biologic effects of benzene in Chinese workers.

Benzene is a recognized hematotoxin and leukemogen, but its mechanisms of action in humans are still uncertain. To provide insight into these processes, we carried out a cross-sectional study of 44 healthy workers currently exposed to benzene (median 8-hr time-weighted average; 31 ppm), and unexposed controls in Shanghai, China. Here we provide an overview of the study results on peripheral blood cells levels and somatic cell mutation frequency measured by the glycophorin A (GPA) gene loss assay and report on peripheral cytokine levels. All peripheral blood cells levels (i.e., total white blood cells, absolute lymphocyte count, platelets, red blood cells, and hemoglobin) were decreased among exposed workers compared to controls, with the exception of the red blood cell mean corpuscular volume, which was higher among exposed subjects. In contrast, peripheral cytokine levels (interleukin-3, interleukin-6, erythropoietin, granulocyte colony-stimulating factor, tissue necrosis factor-alpha) in a subset of the most highly exposed workers (n = 11) were similar to values in controls (n = 11), suggesting that benzene does not affect these growth factor levels in peripheral blood. The GPA assay measures stem cell or precursor erythroid cell mutations expressed in peripheral red blood cells of MN heterozygous subjects, identifying NN variants, which result from loss of the GPA M allele and duplication of the N allele, and N phi variants, which arise from gene inactivation. The NN (but not N phi) GPA variant cell frequency was elevated in the exposed workers compared with controls (mean +/- SD, 13.9 +/- 8.4 mutants per million cells versus 7.4 +/- 5.2 per million cells, (respectively; p = 0.0002), suggesting that benzene produces gene-duplicating but not gene-inactivating mutations at the GPA locus in bone marrow cells of exposed humans. These findings, combined with ongoing analyses of benzene macromolecular adducts and chromosomal aberrations, will provide an opportunity to comprehensively evaluate a wide range of early biologic effects associated with benzene exposure in humans

Barriers and enablers to implementation of the therapeutic engagement questionnaire in acute mental health inpatient wards in England: A qualitative study.

A strong association exists between the quality of nurse-service user therapeutic relationship and care outcomes on acute mental health inpatient wards. Despite evidence that service users desire improved therapeutic engagement, and registered mental health nurses recognize the benefits of therapeutic relationships, such interactions remain sub-optimal. There is a dearth of evidence on factors influencing implementation of interventions to support and encourage therapeutic engagement. This study aimed to understand the barriers and enablers to implementation of the Therapeutic Engagement Questionnaire (TEQ), across fifteen acute inpatient wards in seven English mental health organizations. Qualitative methods were used in which data were collected from ethnographic field notes and documentary review, coded, and analysed using thematic analysis. Theoretical framing supported data analysis and interpretation. Reporting adheres to the Standards for Reporting Qualitative Research. The TEQ as an evidence-based intervention co-produced with service users and nurses was valued and welcomed by many nurse directors, senior clinicians, and ward managers. However, a range of practical and perceptual factors impeded implementation. Furthermore, many existing contextual challenges for intervention implementation in acute inpatient wards were magnified by the COVID-19 pandemic. Suitable facilitation to address these barriers can help support implementation of the TEQ, with some transferability to implementation of other interventions in these settings. Our study suggests several facilitation methods, brought together in a conceptual model, including encouragement of reflective, facilitative discussion meetings among stakeholders and researchers, effort put into winning nurse 'buy-in' and identifying and supporting ward-level agents of change

Inhomogeneous magnetism in single crystalline Sr3_3CuIrO6+δ_{6+\delta}: Implications to phase-separation concepts

The single crystalline form of an insulator, Sr$_3$CuIrO$_{6+\delta}$, is shown to exhibit unexpectedly more than one magnetic transition (at 5 and 19 K) with spin-glass-like magnetic susceptibility behaviour. On the basis of this finding, viz., inhomogeneous magnetism in a chemically homogeneous material, we propose that the idea of "phase- separation" described for manganites [1] is more widespread in different ways. The observed experimental features enable us to make a comparison with the predictions of a recent toy model [2] on {\it magnetic} phase separation in an insulating environment.Comment: 4 pages, 4 figure

A systematic review on the effects of group singing on persistent pain in people with long‐term health conditions

Singing can have a range of health benefits; this paper reviews the evidence of the effects of group singing for chronic pain in people with long‐term health conditions. We searched for published peer‐reviewed singing studies reporting pain measures (intensity, interference and depression) using major electronic databases (last search date 31 July 2018). After screening 123 full texts, 13 studies met the inclusion criteria: five randomized controlled trials (RCTs), seven non‐RCTs and one qualitative study. Included studies were appraised using Downs and Black and the Critical Appraisals Skills Programme quality assessments. Included studies reported differences in the type of singing intervention, long‐term condition and pain measures. Due to the high heterogeneity, we conducted a narrative review. Singing interventions were found to reduce pain intensity in most studies, but there was more equivocal support for reducing pain interference and depression. Additionally, qualitative data synthesis identified three key linked and complementary themes: physical, psychological and social benefits. Group singing appears to have the potential to reduce pain intensity, pain interference and depression; however, we conclude that there is only partial support for singing on some pain outcomes based on the limited available evidence of varied quality. Given the positive findings of qualitative studies, this review recommends that practitioners are encouraged to continue this work. More studies of better quality are needed. Future studies should adopt more robust methodology and report their singing intervention in details. Group singing may be an effective and safe approach for reducing persistent pain and depression in people with long‐term health conditions.Health and Social Care Research Centr

An Agenda for Best Practice Research on Group Singing, Health, and Well-Being

Research on choirs and other forms of group singing has been conducted for several decades and there has been a recent focus on the potential health and well-being benefits, particularly in amateur singers. Experimental, quantitative, and qualitative studies show evidence of a range of biopsychosocial and well-being benefits to singers; however, there are many challenges to rigor and replicability. To support the advances of research into group singing, the authors met and discussed theoretical and methodological issues to be addressed in future studies. The authors are from five countries and represent the following disciplinary perspectives: music psychology, music therapy, community music, clinical psychology, educational and developmental psychology, evolutionary psychology, health psychology, social psychology, and public health. This article summarizes our collective thoughts in relation to the priority questions for future group singing research, theoretical frameworks, potential solutions for design and ethical challenges, quantitative measures, qualitative methods, and whether there is scope for a benchmarking set of measures across singing projects. With eight key recommendations, the article sets an agenda for best practice research on group singing

The Status of Glaucous Gulls Larus hyperboreus in the Circumpolar Arctic

The entire world population of the Glaucous Gull Larus hyperboreus breeds in the circumpolar Arctic. Some local populations appear to be declining significanty. In this paper, we summarize the current state of knowledge on Glaucous Gull populations and trends. The total Arctic population is estimated at approximately 171 000 breeding pairs (> 342 000 breeding individuals) distributed among at least 2700 colonies (many not documented). Population declines may be attributable to egg harvest, contaminants, or food shortages, but other factors operating outside the breeding season should not be excluded. We recommend collaborative conservation efforts that will include better population estimates in most countries, as well as standardized monitoring programs.Toute la population mondiale de goélands bourgmestres Larus hyperboreus se reproduit dans l’Arctique circumpolaire. Certaines populations locales semblent diminuer considérablement. Dans cette communication, nous résumons l’état actuel des connaissances sur les populations et les tendances concernant le goéland bourgmestre. La population arctique totale est estimée à environ 171 000 couples reproducteurs (> 342 000 individus reproducteurs) répartis dans au moins 2 700 colonies (dont grand nombre n’ont pas été consignées). Les déclins de population peuvent être attribuables à la récolte des œufs, aux contaminants ou aux pénuries de nourriture, bien qu’il ne faille pas exclure d’autres facteurs ne se rapportant pas à la saison de reproduction. Nous recommandons des efforts de conservation communs qui comprendront de meilleures estimations de population dans la plupart des pays de même que des programmes de surveillance normalisés

Magnetic anomalies in the spin chain system, Sr3_3Cu1−x_{1-x}Znx_xIrO6_6

We report the results of ac and dc magnetization (M) and heat-capacity (C) measurements on the solid solution, Sr$_3$Cu$_{1-x}$Zn$_x$IrO$_6$. While the Zn end member is known to form in a rhombohedral pseudo one-dimensional K$_4$CdCl$_6$ structure with an antiferromagnetic ordering temperature of (T$_N$ =) 19 K, the Cu end member has been reported to form in a monoclinically distorted form with a Curie temperature of (T$_C$ =) 19 K. The magnetism of the Zn compound is found to be robust to synthetic conditions and is broadly consistent with the behavior known in the literature. However, we find a lower magnetic ordering temperature (T$_o$) for our Cu compound (~ 13 K), thereby suggesting that T$_o$ is sensitive to synthetic conditions. The Cu sample appears to be in a spin-glass-like state at low temperatures, judged by a frequency dependence of ac magnetic susceptibility and a broadening of the C anomaly at the onset of magnetic ordering, in sharp contrast to earlier proposals. Small applications of magnetic field, however, drive this system to ferromagnetism as inferred from the M data. Small substitutions for Cu/Zn (x = 0.75 or 0.25) significantly depress magnetic ordering; in other words, T$_o$ varies non-monotonically with x (T$_o$ ~ 6, 3 and 4 K for x = 0.25, 0.5, and 0.67 respectively). The plot of inverse susceptibility versus temperature is non-linear in the paramagnetic state as if correlations within (or among) the magnetic chains continuously vary with temperature. The results establishComment: 7 pages, 7 figures, Revte

Modified spin-wave study of random antiferromagnetic-ferromagnetic spin chains

We study the thermodynamics of one-dimensional quantum spin-1/2 Heisenberg ferromagnetic system with random antiferromagnetic impurity bonds. In the dilute impurity limit, we generalize the modified spin-wave theory for random spin chains, where local chemical potentials for spin-waves in ferromagnetic spin segments are introduced to ensure zero magnetization at finite temperature. This approach successfully describes the crossover from behavior of pure one-dimensional ferromagnet at high temperatures to a distinct Curie behavior due to randomness at low temperatures. We discuss the effects of impurity bond strength and concentration on the crossover and low temperature behavior.Comment: 14 pages, 7 eps figure