The Input Signal Step Function (ISSF), a Standard Method to Encode Input Signals in SBML Models with Software Support, Applied to Circadian Clock Models

LetterThis is the final version of the article. Available from SAGE Publications via the DOI in this record.Time-dependent light input is an important feature of computational models of the circadian clock. However, publicly available models encoded in standard representations such as the Systems Biology Markup Language (SBML) either do not encode this input or use different mechanisms to do so, which hinders reproducibility of published results as well as model reuse. The authors describe here a numerically continuous function suitable for use in SBML for models of circadian rhythms forced by periodic light-dark cycles. The Input Signal Step Function (ISSF) is broadly applicable to encoding experimental manipulations, such as drug treatments, temperature changes, or inducible transgene expression, which may be transient, periodic, or mixed. It is highly configurable and is able to reproduce a wide range of waveforms. The authors have implemented this function in SBML and demonstrated its ability to modify the behavior of publicly available models to accurately reproduce published results. The implementation of ISSF allows standard simulation software to reproduce specialized circadian protocols, such as the phase-response curve. To facilitate the reuse of this function in public models, the authors have developed software to configure its behavior without any specialist knowledge of SBML. A community-standard approach to represent the inputs that entrain circadian clock models could particularly facilitate research in chronobiology.K.S. was supported by the UK BBSRC grant BB/E015263/1. SynthSys Edinburgh is a Centre for Integrative Systems Biology (CISB) funded by BBSRC and EPSRC, reference BB/D019621/1

Interacting electrons in a 2D quantum dot

The exact numerical diagonalization of the Hamiltonian of a 2D circular quantum dot is performed for 2, 3, and 4 electrons.The results are compared with those of the perturbation theory.Our numerical results agree reasonably well for small values of the dimensionles coupling constant \lambda=a\over a_B where a is the dot radius and a_B is the effective Bohr radius.Exact diagonalization results are compared with the classical predictions, and they are found to be almost coincident for large \lambda values. PACS Numbers: 73.20.Dx, 73.61.-rComment: 12 pages, 5 postscript figure

Shock tunnel studies of scramjet phenomena, supplement 5

A series of reports are presented on SCRAMjet studies, shock tunnel studies, and expansion tube studies. The SCRAMjet studies include: (1) Investigation of a Supersonic Combustion Layer; (2) Wall Injected SCRAMjet Experiments; (3) Supersonic Combustion with Transvers, Circular, Wall Jets; (4) Dissociated Test Gas Effects on SCRAMjet Combustors; (5) Use of Silane as a Fuel Additive for Hypersonic Thrust Production, (6) Pressure-length Correlations in Supersonic Combustion; (7) Hot Hydrogen Injection Technique for Shock Tunnels; (8) Heat Release - Wave Interaction Phenomena in Hypersonic Flows; (9) A Study of the Wave Drag in Hypersonic SCRAMjets; (10) Parametric Study of Thrust Production in the Two Dimensional SCRAMjet; (11) The Design of a Mass Spectrometer for use in Hypersonic Impulse Facilities; and (12) Development of a Skin Friction Gauge for use in an Impulse Facility. The shock tunnel studies include: (1) Hypervelocity flow in Axisymmetric Nozzles; (2) Shock Tunnel Development; and (3) Real Gas Efects in Hypervelocity Flows over an Inclined Cone. The expansion tube studies include: (1) Investigation of Flow Characteristics in TQ Expansion Tube; and (2) Disturbances in the Driver Gas of a Shock Tube

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

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

Effect of seminal plasma on functional integrity of rabbit sperm membranes during storage at 4ºC or freezing

[EN] The effect of semen plasma removal either by simple centrifugation or by separation through a Percoll gradient on the integrity of plasma membranes of rabbit spermatozoa during storage at 4°C and freezing was evaluated in two successive experiments. A modifi ed hypo-osmotic swelling test procedure combined with supravital staining was employed to evaluate simultaneously membrane integrity of head and tail membranes of sperm cells. In the first experiment, the impact of semen plasma on membrane integrity of sperm cells was examined in Tris-citric acid-glucose extender at 4°C for 96 h. The percentage of sperm cells with disintegrated tail and head membranes increased in all groups in correlation with the length of storage. After storage for 96 h, removal of semen plasma, irrespective of the method of removal, resulted in signifi cant increase (P<0.01) in the percentage of sperm cells with disintegrated plasma membranes. The adverse effect of storage and removal of semen plasma was more prominent on the tail membranes, and especially during the fi rst 24 h of the storage period. In the second experiment, the impact of semen plasma on membrane integrity of sperm cells undergoing freezing was examined. A total of three groups were arranged as described in the fi rst experiment, and semen samples were frozen in straws using an extender including acetamide and methyl cellulose. Freezing of semen drastically reduced the percentage of sperm cells with intact plasma membranes in postthaw samples. However, removal of semen plasma, irrespective of the method of removal, did not affect the proportion of sperm cells with intact plasma membranes. In conclusion, the effect of semen plasma on plasma membranes varied signifi cantly relative to the preservation temperature of sperm cells. Although it exerted a protective infl uence during storage at 4°C, no protective impact was monitored during freezing.Aksoy, M.; Cankat Lehimcioglu, N.; Akman, O. (2010). Effect of seminal plasma on functional integrity of rabbit sperm membranes during storage at 4ºC or freezing. World Rabbit Science. 16(1). doi:10.4995/wrs.2008.64216

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

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

Functionalization of silicon nanowires with transition metal atoms

This paper investigates atomic structure, mechanical, electronic, and magnetic properties of silicon nanowires (SiNW) using first-principles plane-wave calculations within density-functional theory. We considered bare, hydrogen-terminated, and 3d -transition metal (TM) adsorbed SiNWs oriented along [001] direction. We also studied Cr interstitial impurity. Nanowires of different sizes are initially cut from the bulk Si crystal in rodlike forms, and subsequently their atomic structures are relaxed before and also after the termination of surface dangling bonds by hydrogen atoms. We first presented an extensive analysis of the atomic structure, stability, elastic, and electronic properties of bare and hydrogen-terminated SiNWs. The energetics of adsorption and resulting electronic and magnetic properties are examined for different levels of 3d -TM atom coverage. Adsorption of TM atoms generally results in magnetic ground state. The net magnetic moment increases with increasing coverage. While specific SiNWs acquire half-metallic behavior at low coverage, at high coverage ferromagnetic nanowires become metallic for both spin directions, and some of them have very high spin polarization at the Fermi level. Our results suggest that the electronic and spintronic devices with conducting interconnects between them can be fabricated on a single SiNW at a desired order. We believe that our study will initiate new research on spintronic applications of SiNWs. © 2008 The American Physical Society