Quantitative analysis of regulatory flexibility under changing environmental conditions

The circadian clock controls 24-h rhythms in many biological processes, allowing appropriate timing of biological rhythms relative to dawn and dusk. Known clock circuits include multiple, interlocked feedback loops. Theory suggested that multiple loops contribute the flexibility for molecular rhythms to track multiple phases of the external cycle. Clear dawn- and dusk-tracking rhythms illustrate the flexibility of timing in Ipomoea nil. Molecular clock components in Arabidopsis thaliana showed complex, photoperiod-dependent regulation, which was analysed by comparison with three contrasting models. A simple, quantitative measure, Dusk Sensitivity, was introduced to compare the behaviour of clock models with varying loop complexity. Evening-expressed clock genes showed photoperiod-dependent dusk sensitivity, as predicted by the three-loop model, whereas the one- and two-loop models tracked dawn and dusk, respectively. Output genes for starch degradation achieved dusk-tracking expression through light regulation, rather than a dusk-tracking rhythm. Model analysis predicted which biochemical processes could be manipulated to extend dusk tracking. Our results reveal how an operating principle of biological regulators applies specifically to the plant circadian clock

The DEAH-box RNA helicase RHAU binds an intramolecular RNA G‐quadruplex in TERC and associates with telomerase holoenzyme

Guanine-quadruplexes (G4) consist of non-canonical four-stranded helical arrangements of guanine-rich nucleic acid sequences. The bulky and thermodynamically stable features of G4 structures have been shown in many respects to affect normal nucleic acid metabolism. In vivo conversion of G4 structures to single-stranded nucleic acid requires specialized proteins with G4 destabilizing/unwinding activity. RHAU is a human DEAH-box RNA helicase that exhibits G4-RNA binding and resolving activity. In this study, we employed RIP-chip analysis to identify en masse RNAs associated with RHAU in vivo. Approximately 100 RNAs were found to be associated with RHAU and bioinformatics analysis revealed that the majority contained potential G4-forming sequences. Among the most abundant RNAs selectively enriched with RHAU, we identified the human telomerase RNA template TERC as a true target of RHAU. Remarkably, binding of RHAU to TERC depended on the presence of a stable G4 structure in the 5′-region of TERC, both in vivo and in vitro. RHAU was further found to associate with the telomerase holoenzyme via the 5′-region of TERC. Collectively, these results provide the first evidence that intramolecular G4-RNAs serve as physiologically relevant targets for RHAU. Furthermore, our results suggest the existence of alternatively folded forms of TERC in the fully assembled telomerase holoenyzm

Non-Commutative Batalin-Vilkovisky Algebras, Homotopy Lie Algebras and the Courant Bracket

We consider two different constructions of higher brackets. First, based on a Grassmann-odd, nilpotent \Delta operator, we define a non-commutative generalization of the higher Koszul brackets, which are used in a generalized Batalin-Vilkovisky algebra, and we show that they form a homotopy Lie algebra. Secondly, we investigate higher, so-called derived brackets built from symmetrized, nested Lie brackets with a fixed nilpotent Lie algebra element Q. We find the most general Jacobi-like identity that such a hierarchy satisfies. The numerical coefficients in front of each term in these generalized Jacobi identities are related to the Bernoulli numbers. We suggest that the definition of a homotopy Lie algebra should be enlarged to accommodate this important case. Finally, we consider the Courant bracket as an example of a derived bracket. We extend it to the "big bracket" of exterior forms and multi-vectors, and give closed formulas for the higher Courant brackets.Comment: 42 pages, LaTeX. v2: Added remarks in Section 5. v3: Added further explanation. v4: Minor adjustments. v5: Section 5 completely rewritten to include covariant construction. v6: Minor adjustments. v7: Added references and explanation to Section

First generation immigrant judgements of offence seriousness: evidence from the crime survey for England and Wales

This exploratory paper delves into differences and similarities in the rated seriousness of offences suffered by victims of different national origin. The issue is important because a mismatch between police and victim assessments of seriousness is likely to fuel discord. It was found that first generation immigrants did not differ in their rating of the seriousness of offences against the person from either the indigenous population or according to region of birth. However those of Asian origin rated vehicle and property crime they had suffered as more serious than did other groups about crimes they suffered. The anticipated higher seriousness rating of offences reported to the police r was observed for all groups. People of Asian origin reported to the police a smaller proportion of offences they rated trivial than did people in other groups. Analysis of seriousness judgements in victimization surveys represents a much-underused resource for understanding the nexus between public perceptions and criminal justice responses

Mitochondrial carrier homolog 1 (Mtch1) antibodies in neuro-Behçet's disease

Cataloged from PDF version of article.Efforts for the identification of diagnostic autoantibodies for neuro-Behcet's disease (NBD) have failed. Screening of NBD patients' sera with protein macroarray identified mitochondrial carrier homolog 1 (Mtch1), an apoptosis-related protein, as a potential autoantigen. ELISA studies showed serum Mtch1 antibodies in 68 of 144 BD patients with or without neurological involvement and in 4 of 168 controls corresponding to a sensitivity of 47.2% and specificity of 97.6%. Mtch1 antibody positive NBD patients had more attacks, increased disability and lower serum nucleosome levels. Mtch1 antibody might be involved in pathogenic mechanisms of NBD rather than being a coincidental byproduct of autoinflammation. © 2013 Elsevier B.V

An Integrated Qualitative and Quantitative Biochemical Model Learning Framework Using Evolutionary Strategy and Simulated Annealing

The authors would like to thank the support on this research by the CRISP Project (Combinatorial Responses In Stress Pathways) funded by the BBSRC (BB/F00513X/1) under the Systems Approaches to Biological Research (SABR) Initiative.Peer reviewedPublisher PD

Current Approaches to Punctuation in Computational Linguistics

Some recent studies in computational linguistics have aimed to take advantage of various cues presented by punctuation marks. This short survey is intended to summarise these research efforts and additionally, to outline a current perspective for the usage and functions of punctuation marks. We conclude by presenting an information-based framework for punctuation, influenced by treatments of several related phenomena in computational linguistics. © 1997 Kluwer Academic Publishers

MIR10B (microRNA 10b)

Review on MIR10B (microRNA 10b), with data on DNA, on the protein encoded, and where the gene is implicated

Mathematical model of a telomerase transcriptional regulatory network developed by cell-based screening: analysis of inhibitor effects and telomerase expression mechanisms

Cancer cells depend on transcription of telomerase reverse transcriptase (TERT). Many transcription factors affect TERT, though regulation occurs in context of a broader network. Network effects on telomerase regulation have not been investigated, though deeper understanding of TERT transcription requires a systems view. However, control over individual interactions in complex networks is not easily achievable. Mathematical modelling provides an attractive approach for analysis of complex systems and some models may prove useful in systems pharmacology approaches to drug discovery. In this report, we used transfection screening to test interactions among 14 TERT regulatory transcription factors and their respective promoters in ovarian cancer cells. The results were used to generate a network model of TERT transcription and to implement a dynamic Boolean model whose steady states were analysed. Modelled effects of signal transduction inhibitors successfully predicted TERT repression by Src-family inhibitor SU6656 and lack of repression by ERK inhibitor FR180204, results confirmed by RT-QPCR analysis of endogenous TERT expression in treated cells. Modelled effects of GSK3 inhibitor 6-bromoindirubin-3′-oxime (BIO) predicted unstable TERT repression dependent on noise and expression of JUN, corresponding with observations from a previous study. MYC expression is critical in TERT activation in the model, consistent with its well known function in endogenous TERT regulation. Loss of MYC caused complete TERT suppression in our model, substantially rescued only by co-suppression of AR. Interestingly expression was easily rescued under modelled Ets-factor gain of function, as occurs in TERT promoter mutation. RNAi targeting AR, JUN, MXD1, SP3, or TP53, showed that AR suppression does rescue endogenous TERT expression following MYC knockdown in these cells and SP3 or TP53 siRNA also cause partial recovery. The model therefore successfully predicted several aspects of TERT regulation including previously unknown mechanisms. An extrapolation suggests that a dominant stimulatory system may programme TERT for transcriptional stability

Autogenous shrinkage properties of high performance cement based products

Yüksek performanslı ve yüksek dayanımlı betonların üretimiyle, otojen rötre kavramı büyük bir önem kazanmıştır. Çimento miktarı yüksek, su/çimento oranı çok düşük seviyelerde olan bu betonlarda yeterince su bulunmamasından dolayı otojen rötrenin salt kimyasal faktör dışında kendiliğinden kurumanın yol açtığı bir fiziksel etkiyle de arttığı gözlenmiştir. Otojen rötrenin yüksek performanslı betonlarda, kuruma rötresi mertebesine erişmesiyle konu ilgi çekmeye başlamış ve konu üzerindeki araştırmalar yoğunlaşmıştır. Çimentoların çeşitli bileşenlerinin, kimyasal ve mineral katkıların bu rötre üzerindeki etkilerinin araştırıldığı çok sayıda araştırma mevcuttur. Portland çimentolarının minör bileşenleri olan alkalilerin, çok düşük miktarlarına karşın betonların işlenebilme, dayanım, dürabilite ve rötre özeliklerini önemli ölçüde etkilediği bilinmektedir. Bu deneysel çalışmada yüksek performanslı betonların otojen rötreleri üzerinde çimento bileşenlerinin (özellikle çözünen alkali içeriğinin) ve süperakışkanlaştırıcı katkının etkileri araştırılmış, bu iki faktörün hidratasyon süreci üzerindeki etkileri üzerine yoğunlaşılmıştır. Çalışmada değişik kimyasal bileşenlere sahip çimentolar kullanılarak hamur numuneler üretilmiş, bu numunelerin otojen rötreleri belirlenmiştir. Bu çimentoların hidratasyon aşamaları da çeşitli yöntemlerle takip edilmiştir. Sonuç olarak çimento bileşenlerinin (özellikle çözünen alkali içeriğinin) ve süperakışkanlaştırıcı kullanımının otojen rötre üzerindeki etkileri belirlenmiştir. Elde edilen ana sonuç şöyle özetlenebilir; çimentolardaki çözünen alkali miktarları FKOR büyüklüğünü arttırma yönünde etkinlik taşımktadır. Bunun yanında C3A, C4AF, (SO3/çözünen alkali oranı) ve incelik parametreleri de FKOR’yi etkileyen etkenler arasında dikkate alınmalıdır. Anahtar Kelimeler: Yüksek performasnlı beton, otojen rötre, hidratasyon, çözünen alkali. Autogenous shrinkage concept has started to gain more importance since the high performance-high strength concretes were began to be utilized for structural purposes. These concretes are generally designed with high cementitious materials contents and low water to cementitious material ratios. It is observed that, due to lack of water in capillary pores in these concretes, autogenous shrinkage increases under the effects of not only the chemical factors but also the physical effects. Autogenous shrinkage has started to draw attention with having the same magnitude of drying shrinkage, and the research dealing with this concept has been intensified.  There are numbers of investigations focusing on the effects of various components of cements, chemical and mineral admixtures on this shrinkage. It is well known that, alkalis, which are the minor components of Portland cements, affect the workability, strength, durability, and shrinkage properties of concretes drastically despite their low percentage in cement. These components also affect the hydration process of Portland cement crucially. Therefore, it is inevitable that the soluble alkalis existing in cement will have an effect on the autogenous shrinkage which became more important due to its use in the production of high performance concretes (HPC). Superplasticizers are indispensable ingredients of HPCs. Besides reducing the water to cement ratio, these admixtures also affect the hydration rate and morphology of the hydration products. In this experimental study; effects of cement components (especially soluble alkali content) and superplasticizers on the autogenous shrinkage were investigated. The effects of these two factors on the hydration process were also focused on.  Moreover, discussions were done on the definition of autogenous shrinkage. "Physicochemical Autogenous Shrinkage" term was attributed as to define this shrinkage which is mainly caused by physicochemical effects. Cement paste specimens were produced using cements having different chemical compositions. Autogenous shrinkages of these specimens were obtained by means of volumetric measurement technique. Measurements of volumetric changes was taken in water by means of Archimet balance. Hydration degree of these paste specimens were obtained by non-evaporable water technique. Heat of hydration values were also measured by means of semi-adiabadic calorimeter. The rate of hydration reaction was determined. Capillary pore size distributions were also obtained with Mercury Intrusion Porosimeter (MIP) technique. As a result, the effects of cement components (especially soluble alkali content) and superplasticizers on the autogenous shrinkage of HPC's were determined. Moreover, critical time periods for physcochemical autogenous shrinkage were obtained and the characteristic behavior of this shrinkage were exlained by hydration kinetics. Relations between capillary pore ratio and physcochemical autogenous shrinkage were determined. The main results obtained from this experimental study can be drawn as following: 1) Physicochemical autogenous shrinkage has three main phases for the pastes with low water to cement ratios containing superplasticizer. Generally, these stages were not observed for the specimens which do not contain superplasticizer. However, as an exceptional case, some specimens which do not include superplasticizer could show similar steps as the specimens having superplasticizer. 2) Although, lower hydration heats and hydration degrees were obtained for the lower water to cement ratio specimens, higher values of physicochemical autogenous shrinkage were measured. It was determined that the most effective factor in gaining the physicochemical shrinkage was the released heat values which show the rate of hydration. Higher physicochemical autogenous shrinkage values are measured for the cement pastes which have the higher values of released heat. Microporosity test results have shown that the increasing ratio of capillary pores to total pores causes to increase in physicochemical autogenous shrinkage. Soluble alkali contents were also found to be effective on the. Cements having higher soluble alkali contents exhibited higher physicochemical autogenous shrinkage. It was also concluded that besides the soluble alkali contents in cement, C3A, C4AF contents and SO /soluble alkali ratio are effective parameters and they should be taken into consideration.  Keywords: High performance concrete, autogenous shrinkage, hydration, soluble alkali