Periodic pattern formation in reaction-diffusion systems -an introduction for numerical simulation

The aim of the present review is to provide a comprehensive explanation of Turing reaction–diffusion systems in sufficient detail to allow readers to perform numerical calculations themselves. The reaction–diffusion model is widely studied in the field of mathematical biology, serves as a powerful paradigm model for self-organization and is beginning to be applied to actual experimental systems in developmental biology. Despite the increase in current interest, the model is not well understood among experimental biologists, partly because appropriate introductory texts are lacking. In the present review, we provide a detailed description of the definition of the Turing reaction–diffusion model that is comprehensible without a special mathematical background, then illustrate a method for reproducing numerical calculations with Microsoft Excel. We then show some examples of the patterns generated by the model. Finally, we discuss future prospects for the interdisciplinary field of research involving mathematical approaches in developmental biology

The dynamic mosaic phenotypes of flowering plants

Ecological interaction and adaptation both depend on phenotypic characteristics. In contrast with the common conception of the ‘adult’ phenotype, plant bodies develop continuously during their lives. Furthermore, the different units (metamers) that comprise plant bodies are not identical copies, but vary extensively within individuals. These characteristics foster recognition of plant phenotypes as dynamic mosaics. We elaborate this conception based largely on a wide‐ranging review of developmental, ecological and evolutionary studies of plant reproduction, and identify its utility in the analysis of plant form, function and diversification. An expanded phenotypic conception is warranted because dynamic mosaic features affect plant performance and evolve. Evidence demonstrates that dynamic mosaic phenotypes enable functional ontogeny, division of labour, resource and mating efficiency. In addition, dynamic mosaic features differ between individuals and experience phenotypic selection. Investigation of the characteristics and roles of dynamic and mosaic features of plant phenotypes benefits from considering within‐individual variation as a function‐valued trait that can be analysed with functional data methods. Phenotypic dynamics and within‐individual variation arise despite an individual's genetic uniformity, and develop largely by heterogeneous gene expression and associated hormonal control. These characteristics can be heritable, so that dynamic mosaic phenotypes can evolve and diversify by natural selection.Fil: Harder, Lawrence. University of Calgary; CanadáFil: Strelin, Marina Micaela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Patagonia Norte. Instituto de Investigaciones en Biodiversidad y Medioambiente. Universidad Nacional del Comahue. Centro Regional Universidad Bariloche. Instituto de Investigaciones en Biodiversidad y Medioambiente; Argentina. Universidad Nacional Autónoma de México. Departamento de Ecología Evolutiva. Instituto de Ecología; MéxicoFil: Clocher, Ilona C.. University of Calgary; CanadáFil: Kulbaba, Mason. University of Calgary; CanadáFil: Aizen, Marcelo Adrian. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Patagonia Norte. Instituto de Investigaciones en Biodiversidad y Medioambiente. Universidad Nacional del Comahue. Centro Regional Universidad Bariloche. Instituto de Investigaciones en Biodiversidad y Medioambiente; Argentin

Increased variability in Greenland Ice Sheet runoff from satellite observations

Runoff from the Greenland Ice Sheet has increased over recent decades affecting global sea level, regional ocean circulation, and coastal marine ecosystems, and it now accounts for most of the contemporary mass imbalance. Estimates of runoff are typically derived from regional climate models because satellite records have been limited to assessments of melting extent. Here, we use CryoSat-2 satellite altimetry to produce direct measurements of Greenland's runoff variability, based on seasonal changes in the ice sheet's surface elevation. Between 2011 and 2020, Greenland's ablation zone thinned on average by 1.4 ± 0.4 m each summer and thickened by 0.9 ± 0.4 m each winter. By adjusting for the steady-state divergence of ice, we estimate that runoff was 357 ± 58 Gt/yr on average - in close agreement with regional climate model simulations (root mean square difference of 47 to 60 Gt/yr). As well as being 21 % higher between 2011 and 2020 than over the preceding three decades, runoff is now also 60 % more variable from year-to-year as a consequence of large-scale fluctuations in atmospheric circulation. Because this variability is not captured in global climate model simulations, our satellite record of runoff should help to refine them and improve confidence in their projections

Ecological Determinants of Highly Pathogenic Avian Influenza (H5N1) Outbreaks in Bangladesh

BACKGROUND: The agro-ecology and poultry husbandry of the south Asian and south-east Asian countries share common features, however, with noticeable differences. Hence, the ecological determinants associated with risk of highly pathogenic avian influenza (HPAI-H5N1) outbreaks are expected to differ between Bangladesh and e.g., Thailand and Vietnam. The primary aim of the current study was to establish ecological determinants associated with the risk of HPAI-H5N1 outbreaks at subdistrict level in Bangladesh. The secondary aim was to explore the performance of two different statistical modeling approaches for unmeasured spatially correlated variation. METHODOLOGY/PRINCIPAL FINDINGS: An ecological study at subdistrict level in Bangladesh was performed with 138 subdistricts with HPAI-H5N1 outbreaks during 2007-2008, and 326 subdistricts with no outbreaks. The association between ecological determinants and HPAI-H5N1 outbreaks was examined using a generalized linear mixed model. Spatial clustering of the ecological data was modeled using 1) an intrinsic conditional autoregressive (ICAR) model at subdistrict level considering their first order neighbors, and 2) a multilevel (ML) model with subdistricts nested within districts. Ecological determinants significantly associated with risk of HPAI-H5N1 outbreaks at subdistrict level were migratory birds' staging areas, river network, household density, literacy rate, poultry density, live bird markets, and highway network. Predictive risk maps were derived based on the resulting models. The resulting models indicate that the ML model absorbed some of the covariate effect of the ICAR model because of the neighbor structure implied in the two different models. CONCLUSIONS/SIGNIFICANCE: The study identified a new set of ecological determinants related to river networks, migratory birds' staging areas and literacy rate in addition to already known risk factors, and clarified that the generalized concept of free grazing duck and duck-rice cultivation interacted ecology are not significant determinants for Bangladesh. These findings will refine current understanding of the HPAI-H5N1 epidemiology in Bangladesh

A Retrospective Interventional Cohort Study to Assess the Safety and Efficacy of Sandostatin LAR for Treatment of Recurrent and/or Refractory Meningiomas.

Background: Meningiomas are the most common adult primary intracranial tumors in the United States. Despite high recurrence rate of atypical and malignant subtypes, there is no approved drug indicated specifically for meningioma. Since the majority of meningiomas exhibit high density of somatostatin receptors subtypes, somatostatin analogs have been under close investigation. The aim of this study was to evaluate efficacy and safety of Sandostatin LAR (octreotide) in patients with progressive, and/or recurrent meningioma, and identify subset of patients who were more likely to benefit from this treatment. Methods: A total of 43 patients ≥ 18 years old were included in the retrospective chart review. The patients underwent treatment with Sandostatin LAR (octreotide) from 01.01.2010 to 06.01.2017 at the University of California, Irvine after confirmation of the diagnosis. Six months progression free survival (PFS6) was defined as a primary endpoint, and the overall survival (OS), safety, and toxicity were identified as secondary endpoints. Results: The OS for 6 months, 1, and 3 years for all WHO grades was 94.8, 88.1, and 67.0%, respectively. The PFS6 for WHO I, II, III, and all was 89.4, 89, 33.3, and 80% respectively. For patients with no prior surgeries, chemotherapy or radiation, the PFS6 was 88.9, 84.8, and 94.8%, respectively. Interestingly, the PFS6 was 90.5% for skull-based and 80% for 3-6 cm tumors. Patients with tumors in parasagittal location had PFS6 of 83.3% compared to PFS6 of 50.0% for patients with convexity tumors. Evaluation of PFS6 based on the effect of estrogen and progesterone on meningioma identified that ER-PR+ tumors had PFS6 of 87.8% while patients with ER-PR- meningiomas had PFS6 of 62.5%. Median TTP for WHO grade I, II, and III was 3.1, 2.40, and 0.26 years, respectively. Subgroup analysis showed that median TTP was 3.1 years for <3 cm tumors, 3.22 years for skull-based tumors, 2.37 years for patients with prior surgeries and 3.10 years for patients with no history of chemotherapy. History of radiation had no effect on median TTP. Sandostatin LAR (octreotide) was well-tolerated. Conclusions:This is one of the largest retrospective analysis of meningioma patients treated with Sandostatin LAR (octreotide) suggesting that this treatment has minimal to no adverse events and could prolong overall survival, and progression free survival especially for patients with ER-PR+ tumors who underwent surgeries for small skull-based tumors

Restrictions and extensions of semibounded operators

We study restriction and extension theory for semibounded Hermitian operators in the Hardy space of analytic functions on the disk D. Starting with the operator zd/dz, we show that, for every choice of a closed subset F in T=bd(D) of measure zero, there is a densely defined Hermitian restriction of zd/dz corresponding to boundary functions vanishing on F. For every such restriction operator, we classify all its selfadjoint extension, and for each we present a complete spectral picture. We prove that different sets F with the same cardinality can lead to quite different boundary-value problems, inequivalent selfadjoint extension operators, and quite different spectral configurations. As a tool in our analysis, we prove that the von Neumann deficiency spaces, for a fixed set F, have a natural presentation as reproducing kernel Hilbert spaces, with a Hurwitz zeta-function, restricted to FxF, as reproducing kernel.Comment: 63 pages, 11 figure

Mathematical modelling of polyamine metabolism in bloodstream-form trypanosoma brucei: An application to drug target identification

© 2013 Gu et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are creditedThis article has been made available through the Brunel Open Access Publishing Fund.We present the first computational kinetic model of polyamine metabolism in bloodstream-form Trypanosoma brucei, the causative agent of human African trypanosomiasis. We systematically extracted the polyamine pathway from the complete metabolic network while still maintaining the predictive capability of the pathway. The kinetic model is constructed on the basis of information gleaned from the experimental biology literature and defined as a set of ordinary differential equations. We applied Michaelis-Menten kinetics featuring regulatory factors to describe enzymatic activities that are well defined. Uncharacterised enzyme kinetics were approximated and justified with available physiological properties of the system. Optimisation-based dynamic simulations were performed to train the model with experimental data and inconsistent predictions prompted an iterative procedure of model refinement. Good agreement between simulation results and measured data reported in various experimental conditions shows that the model has good applicability in spite of there being gaps in the required data. With this kinetic model, the relative importance of the individual pathway enzymes was assessed. We observed that, at low-to-moderate levels of inhibition, enzymes catalysing reactions of de novo AdoMet (MAT) and ornithine production (OrnPt) have more efficient inhibitory effect on total trypanothione content in comparison to other enzymes in the pathway. In our model, prozyme and TSHSyn (the production catalyst of total trypanothione) were also found to exhibit potent control on total trypanothione content but only when they were strongly inhibited. Different chemotherapeutic strategies against T. brucei were investigated using this model and interruption of polyamine synthesis via joint inhibition of MAT or OrnPt together with other polyamine enzymes was identified as an optimal therapeutic strategy.The work was carried out under a PhD programme partly funded by Prof. Ray Welland, School of Computing Science, University of Glasgo

Shedding light on the elusive role of endothelial cells in cytomegalovirus dissemination.

Cytomegalovirus (CMV) is frequently transmitted by solid organ transplantation and is associated with graft failure. By forming the boundary between circulation and organ parenchyma, endothelial cells (EC) are suited for bidirectional virus spread from and to the transplant. We applied Cre/loxP-mediated green-fluorescence-tagging of EC-derived murine CMV (MCMV) to quantify the role of infected EC in transplantation-associated CMV dissemination in the mouse model. Both EC- and non-EC-derived virus originating from infected Tie2-cre(+) heart and kidney transplants were readily transmitted to MCMV-naïve recipients by primary viremia. In contrast, when a Tie2-cre(+) transplant was infected by primary viremia in an infected recipient, the recombined EC-derived virus poorly spread to recipient tissues. Similarly, in reverse direction, EC-derived virus from infected Tie2-cre(+) recipient tissues poorly spread to the transplant. These data contradict any privileged role of EC in CMV dissemination and challenge an indiscriminate applicability of the primary and secondary viremia concept of virus dissemination

Spatio-Temporal Magnitude and Direction of Highly Pathogenic Avian Influenza (H5N1) Outbreaks in Bangladesh

BACKGROUND: The number of outbreaks of HPAI-H5N1 reported by Bangladesh from 2007 through 2011 placed the country among the highest reported numbers worldwide. However, so far, the understanding of the epidemic progression, direction, intensity, persistence and risk variation of HPAI-H5N1 outbreaks over space and time in Bangladesh remains limited. METHODOLOGY/PRINCIPAL FINDINGS: To determine the magnitude and spatial pattern of the highly pathogenic avian influenza A subtype H5N1 virus outbreaks over space and time in poultry from 2007 to 2009 in Bangladesh, we applied descriptive and analytical spatial statistics. Temporal distribution of the outbreaks revealed three independent waves of outbreaks that were clustered during winter and spring. The descriptive analyses revealed that the magnitude of the second wave was the highest as compared to the first and third waves. Exploratory mapping of the infected flocks revealed that the highest intensity and magnitude of the outbreaks was systematic and persistent in an oblique line that connects south-east to north-west through the central part of the country. The line follows the Brahmaputra-Meghna river system, the junction between Central Asian and East Asian flyways, and the major poultry trading route in Bangladesh. Moreover, several important migratory bird areas were identified along the line. Geostatistical analysis revealed significant latitudinal directions of outbreak progressions that have similarity to the detected line of intensity and magnitude. CONCLUSION/SIGNIFICANCE: The line of magnitude and direction indicate the necessity of mobilizing maximum resources on this line to strengthen the existing surveillance

Global prevalence of childhood cataract: a systematic review

Childhood cataract is an avoidable cause of visual disability worldwide and is a priority for VISION 2020: The Right to Sight. There is a paucity of information about the burden of cataract in children and the aim of this review is to assess the global prevalence of childhood cataract. The methodology for the review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We performed a literature search for studies reporting estimates of prevalence or incidence of cataract among children (aged<18 years) at any global location using the Cochrane Library, Medline and Embase up to January 2015. No restrictions were imposed based on language or year of publication. Study quality was assessed using a critical appraisal tool designed for systematic reviews of prevalence. Twenty prevalence and four incidence studies of childhood cataract from five different geographical regions were included. The overall prevalence of childhood cataract and congenital cataract was in the range from 0.32 to 22.9/10000 children (median=1.03) and 0.63 to 9.74/10000 (median=1.71), respectively. The incidence ranged from 1.8 to 3.6/10000 per year. The prevalence of childhood cataract in low-income economies was found to be 0.42 to 2.05 compared with 0.63 to 13.6/10000 in high-income economies. There was no difference in the prevalence based on laterality or gender. This review highlights substantial gaps in the epidemiological knowledge of childhood cataract worldwide, particularly from low and lower middle-income economies. More studies are needed using standard definitions and case ascertainment methods with large enough sample sizes