Modeling oscillatory Microtubule--Polymerization

Polymerization of microtubules is ubiquitous in biological cells and under certain conditions it becomes oscillatory in time. Here simple reaction models are analyzed that capture such oscillations as well as the length distribution of microtubules. We assume reaction conditions that are stationary over many oscillation periods, and it is a Hopf bifurcation that leads to a persistent oscillatory microtubule polymerization in these models. Analytical expressions are derived for the threshold of the bifurcation and the oscillation frequency in terms of reaction rates as well as typical trends of their parameter dependence are presented. Both, a catastrophe rate that depends on the density of {\it guanosine triphosphate} (GTP) liganded tubulin dimers and a delay reaction, such as the depolymerization of shrinking microtubules or the decay of oligomers, support oscillations. For a tubulin dimer concentration below the threshold oscillatory microtubule polymerization occurs transiently on the route to a stationary state, as shown by numerical solutions of the model equations. Close to threshold a so--called amplitude equation is derived and it is shown that the bifurcation to microtubule oscillations is supercritical.Comment: 21 pages and 12 figure

A first principle (3+1) dimensional model for microtubule polymerization

In this paper we propose a microscopic model to study the polymerization of microtubules (MTs). Starting from fundamental reactions during MT's assembly and disassembly processes, we systematically derive a nonlinear system of equations that determines the dynamics of microtubules in 3D. %coexistence with tubulin dimers in a solution. We found that the dynamics of a MT is mathematically expressed via a cubic-quintic nonlinear Schrodinger (NLS) equation. Interestingly, the generic 3D solution of the NLS equation exhibits linear growing and shortening in time as well as temporal fluctuations about a mean value which are qualitatively similar to the dynamic instability of MTs observed experimentally. By solving equations numerically, we have found spatio-temporal patterns consistent with experimental observations.Comment: 12 pages, 2 figures. Accepted in Physics Letters

Радиационный контроль в современных процессах нефтедобычи

Рассмотрены вопросы радиоэкологического контроля на нефтедобывающих предприятиях. Показана возможность использования программных продуктов для обеспечения комплексной оценки радиационной обстановки на объектах и территориях нефтедобывающих предприятий. Освещены основные аспекты взаимодействия научно-исследовательских лабораторий с Центрами экологической безопасности предприятий и их значение для эффективного ресурсосбережения в современных процессах нефтедобычи

Relationship between gene expression and observed intensities in DNA microarrays—a modeling study

A theoretical study of the physical properties which determine the variation in signal strength from probe to probe on a microarray is presented. A model which incorporates probe-target hybridization, as well as the subsequent dissociation which occurs during stringent washing of the microarray, is introduced and shown to reasonably describe publicly available spike-in experiments carried out at Affymetrix. In particular, this model suggests that probe-target dissociation during the stringent wash plays a critical role in determining the observed hybridization intensities. In addition, it is demonstrated that non-specific hybridization introduces uncertainties which significantly limit the ability of any model to accurately quantify absolute gene expression levels while, in contrast, target folding appears to have little effect on these results. Finally, for data from target spike-in experiments, our model is shown to compare favorably with an existing statistical model in determining target concentration levels

Insulin Sensitivity Measured With Euglycemic Clamp Is Independently Associated With Glomerular Filtration Rate in a Community-Based Cohort

OBJECTIVE—To investigate the association between insulin sensitivity and glomerular filtration rate (GFR) in the community, with prespecified subgroup analyses in normoglycemic individuals with normal GFR

Microfludic Device for Creating Ionic Strength Gradients over DNA Microarrays for Efficient DNA Melting Studies and Assay Development

The development of DNA microarray assays is hampered by two important aspects: processing of the microarrays is done under a single stringency condition, and characteristics such as melting temperature are difficult to predict for immobilized probes. A technical solution to these limitations is to use a thermal gradient and information from melting curves, for instance to score genotypes. However, application of temperature gradients normally requires complicated equipment, and the size of the arrays that can be investigated is restricted due to heat dissipation. Here we present a simple microfluidic device that creates a gradient comprising zones of defined ionic strength over a glass slide, in which each zone corresponds to a subarray. Using this device, we demonstrated that ionic strength gradients function in a similar fashion as corresponding thermal gradients in assay development. More specifically, we noted that (i) the two stringency modulators generated melting curves that could be compared, (ii) both led to increased assay robustness, and (iii) both were associated with difficulties in genotyping the same mutation. These findings demonstrate that ionic strength stringency buffers can be used instead of thermal gradients. Given the flexibility of design of ionic gradients, these can be created over all types of arrays, and encompass an attractive alternative to temperature gradients, avoiding curtailment of the size or spacing of subarrays on slides associated with temperature gradients

Outcome of Total Parathyroidectomy and Autotransplantation as Treatment of Secondary and Tertiary Hyperparathyroidism in Children and Adults

Contains fulltext : 89902.pdf (publisher's version ) (Closed access)BACKGROUND: Treatment safety and effectiveness of total parathyroidectomy and autotransplantation for secondary and tertiary hyperparathyroidism have been extensively proven in adults; the evidence for children, however, is scarce. Children and adolescents cannot simply be seen as young adults in the case of chronic kidney disease and hyperparathyroidism. The aim of this retrospective study was therefore, to evaluate whether parathyroidectomy with forearm autograft is as effective and safe in children and adolescents as in adults. METHODS: A group of 64 adults and 8 children and adolescents treated for secondary or tertiary hyperparathyroidism were retrieved from our database. The outcomes were compared on patient demographics, operation results, and blood parameters consisting of parathyroid hormone (PTH) and calcium levels. Our results were compared with all currently available articles on parathyroidectomy in children with secondary or tertiary hyperparathyroidism (n = 11). RESULTS: For adults, preoperative mean serum calcium was 2.67 +/- 0.29 mmol/l and mean parathyroid hormone (PTH) level was 120 +/- 86 pmol/l. For children, preoperative mean serum calcium was 2.62 +/- 0.20 mmol/l and mean parathyroid hormone (PTH) level was 80 +/- 38 pmol/l. Postoperative calcium and parathyroid hormone levels for adults dropped to 2.39 +/- 0.23 mmol/l and 30 +/- 53 pmol/l, respectively. Postoperative calcium and parathyroid hormone levels for children dropped to 2.41 +/- 0.16 mmol/l and 26 +/- 33 pmol/l, respectively. The effectiveness of parathyroidectomy with autotransplantation was 75% in children and 72% in adults. Thus, effectiveness did not differ significantly between children and adults. CONCLUSIONS: Combining the results of our own study with a literature review on pediatric parathyroidectomy, we conclude that parathyroidectomy and forearm autograft is as effective a treatment for secondary and tertiary hyperparathyroidism in children and adolescents as it is in adults.1 mei 201

Position dependent mismatch discrimination on DNA microarrays – experiments and model

<p>Abstract</p> <p>Background</p> <p>The propensity of oligonucleotide strands to form stable duplexes with complementary sequences is fundamental to a variety of biological and biotechnological processes as various as microRNA signalling, microarray hybridization and PCR. Yet our understanding of oligonucleotide hybridization, in particular in presence of surfaces, is rather limited. Here we use oligonucleotide microarrays made in-house by optically controlled DNA synthesis to produce probe sets comprising all possible single base mismatches and base bulges for each of 20 sequence motifs under study.</p> <p>Results</p> <p>We observe that mismatch discrimination is mostly determined by the defect position (relative to the duplex ends) as well as by the sequence context. We investigate the thermodynamics of the oligonucleotide duplexes on the basis of double-ended molecular zipper. Theoretical predictions of defect positional influence as well as long range sequence influence agree well with the experimental results.</p> <p>Conclusion</p> <p>Molecular zipping at thermodynamic equilibrium explains the binding affinity of mismatched DNA duplexes on microarrays well. The position dependent nearest neighbor model (PDNN) can be inferred from it. Quantitative understanding of microarray experiments from first principles is in reach.</p

Higher Education and behavior analysis in Europe::Creating a unified approach for the training of autism professionals

Training of behaviour analysts for autism services, has improved notably within a European higher education context. However, regional discrepancies associated with economic, health care, social services, and institutional policies magnify the importance of creating appropriate unified training and consumer protection. Although the European Association for Behaviour Analysis (EABA) has endorsed the Behavior Analyst Certification Board’s (BACB) designations, the absence of European and national regulations, recognition, and accreditation remain significant barriers to quality training and implementation. These challenges are  particularly pertinent in light of BACB decision to limit certification to residents in the USA and Canada after 2022. Advances, challenges, and future directions are discussed within the context of higher education in the United Kingdom, the Czech Republic, Greece, Iceland, Italy, Norway, and Sweden. The post-Bologna European agenda for higher education, globalization and opportunities for the training of behaviour analysts within European higher education are outlined