Reaction dynamics under confinement: an exact path integral treatment of a two-stage model of stochastic gene expression

Gene expression in living systems is inherently stochastic, and tends to produce varying numbers of proteins over repeated cycles of transcription and translation. In this paper, an expression is derived for the steady-state protein number distribution starting from a two-stage kinetic model of the gene expression process involving p proteins and r mRNAs. The derivation is based on an exact path integral evaluation of the joint distribution, P(p, r, t), of p and r at time t, which can be expressed in terms of the coupled Langevin equations for p and r that represent the two-stage model in continuum form. The steady-state distribution of p alone, P(p), is obtained from P(p, r, t) (a bivariate Gaussian) by integrating out the r degrees of freedom and taking the limit t -> infinity. P(p) is found to be proportional to the product of a Gaussian and a complementary error function. It provides a generally satisfactory fit to simulation data on the same two-stage process when the translational efficiency (a measure of intrinsic noise levels in the system) is relatively low; it is less successful as a model of the data when the translational efficiency (and noise levels) are high.

Supersolid in a one-dimensional model of hard-core bosons

We study a system of hard-core boson on a one-dimensional lattice with frustrated next-nearest-neighbor hopping and nearest-neighbor interaction. At half filling, for equal magnitude of nearest- and next-nearest-neighbor hopping, the ground state of this system exhibits a first-order phase transition from a bond-ordered solid to a charge-density-wave solid as a function of the nearest- neighbor interaction. Moving away from half filling we investigate the system at incommensurate densities, where we find a supersolid phase which has concurrent off-diagonal long-range order and density-wave order which is unusual in a system of hard-core bosons in one dimension. Using the finite-size density-matrix renormalization group method, we obtain the complete phase diagram for this model.

A DYNAMO MODEL OF MAGNETIC ACTIVITY IN SOLAR-LIKE STARS WITH DIFFERENT ROTATIONAL VELOCITIES

We attempt to provide a quantitative theoretical explanation for the observations that Ca II H/K emission and X-ray emission from solar-like stars increase with decreasing Rossby number (i.e., with faster rotation). Assuming that these emissions are caused by magnetic cycles similar to the sunspot cycle, we construct flux transport dynamo models of 1M(circle dot) stars rotating with different rotation periods. We first compute the differential rotation and the meridional circulation inside these stars from a mean-field hydrodynamics model. Then these are substituted in our dynamo code to produce periodic solutions. We find that the dimensionless amplitude f(m) of the toroidal flux through the star increases with decreasing rotation period. The observational data can be matched if we assume the emissions to go as the power 3-4 of f(m). Assuming that the Babcock-Leighton mechanism saturates with increasing rotation, we can provide an explanation for the observed saturation of emission at low Rossby numbers. The main failure of our model is that it predicts an increase of the magnetic cycle period with increasing rotation rate, which is the opposite of what is found observationally. Much of our calculations are based on the assumption that the magnetic buoyancy makes the magnetic flux tubes rise radially from the bottom of the convection zone. Taking into account the fact that the Coriolis force diverts the magnetic flux tubes to rise parallel to the rotation axis in rapidly rotating stars, the results do not change qualitatively.

Using formal reasoning on a model of tasks for FreeRTOS

FreeRTOS is an open-source real-time microkernel that has a wide community of users. We present the formal specification of the behaviour of the task part of FreeRTOS that deals with the creation, management, and scheduling of tasks using priority-based preemption. Our model is written in the Z notation, and we verify its consistency using the Z/Eves theorem prover. This includes a precise statement of the preconditions for all API commands. This task model forms the basis for three dimensions of further work: (a) the modelling of the rest of the behaviour of queues, time, mutex, and interrupts in FreeRTOS; (b) refinement of the models to code to produce a verified implementation; and (c) extension of the behaviour of FreeRTOS to multi-core architectures. We propose all three dimensions as benchmark challenge problems for Hoare's Verified Software Initiative.

A Statistical Model of Current Loops and Magnetic Monopoles

We formulate a natural model of loops and isolated vertices for arbitrary planar graphs, which we call the monopole-dimer model. We show that the partition function of this model can be expressed as a determinant. We then extend the method of Kasteleyn and Temperley-Fisher to calculate the partition function exactly in the case of rectangular grids. This partition function turns out to be a square of a polynomial with positive integer coefficients when the grid lengths are even. Finally, we analyse this formula in the infinite volume limit and show that the local monopole density, free energy and entropy can be expressed in terms of well-known elliptic functions. Our technique is a novel determinantal formula for the partition function of a model of isolated vertices and loops for arbitrary graphs.

Susceptibility Of strength development by lime in gypsiferous soil-A micro mechanistic study

The role of gypsum on the strength of lime treated soils after a long period of interaction is not well understood yet. The present study is performed to scrutinize the physical and strength behavior of lime treated soil with varying gypsum content. Lime and gypsum contents varying from 0 to 6% are considered in the present study for curing periods up to 28 days. To understand the long-term effects, the work has been extended up to 365 days, particularly with the use of 6% lime content and varying gypsum contents. Atterberg's limits turned out to be marginally affected by cation exchange. Unconfined compressive strength behavior of lime treated soil varies considerably with gypsum content and curing period. However, trivial alteration in strength is observed in the soil treated with lower lime content (up to 4%) and gypsum content up to 6%. On the contrary, strength of soil-6% lime mixture with addition of varying gypsum content shows acceleration in early strength at 14 days curing period. However, the strength at 28 days of curing declines but regains afterwards for 90 days. The trend at longer curing period for 180 and 365 days is, however, not unique but varies with gypsum contents. An attempt has been made to explain these changes on the basis of the form of gypsum, formation and conversion of reacted compounds (CASHH, CASH, MI and Ettringite). The proposed explanations were supported by detailed characterization through thermal analysis, XRD, SEM and EDAX studies of soil-lime-gypsum mixtures. (C) 2015 Elsevier B.V. All rights reserved.

Effect of combined treatment with zoledronic acid and propranolol on mechanical strength in an rat model of disuse osteoporosis

Objectives: A model that uses right hind-limb unloading of rats is used to study the consequences of skeletal unloading during various conditions like space flights and prolonged bed rest in elderly. This study was aimed to investigate the additive effects of antiresorptive agent zoledronic acid (ZOL), alone and in combination with propranolol (PRO) in a rat model of disuse osteoporosis. Methods: In the present study, 3-month-old male Wistar rats had their right hind-limb immobilized (RHLI) for 10 weeks to induce osteopenia, then were randomized into four groups: 1-RHLI positive control, 2-RHLI plus ZOL (50 mu g/kg, i.v. single dose), 3-RHLI plus PRO (0.1 mg/kg, s.c. 5 days per week), 4-RHLI plus PRO (0.1 mg/kg, s.c. 5 days per week) plus ZOL (50 mu g/kg, i.v. single dose) for another 10 weeks. One group of non-immobilized rats was used as negative control. At the end of treatment, the femurs were removed and tested for bone porosity, bone mechanical properties, and bone dry and ash weight. Results: With respect to improvement in the mechanical strength of the femoral mid-shaft, the combination treatment with ZOL plus PRO was more effective than ZOL or PRO monotherapy. Moreover, combination therapy using ZOL plus PRO was more effective in improving dry bone weight and preserved the cortical bone porosity better than monotherapy using ZOL or PRO in right hind-limb immobilized rats. Conclusions: These data suggest that this combined treatment with ZOL plus PRO should be recommended for the treatment of disuse osteoporosis. (C) 2014 Elsevier Editora Ltda. All rights reserved.

SUPPORTING ENVIRONMENTALLY-BENIGN DESIGN ELUCIDATING ENVIRONMENTAL IMPACT PROPAGATION IN CONCEPTUAL DESIGN PHASE BY SAPPHIRE MODEL OF CAUSALITY

Conceptual Design Phase is the most critical for design decisions and their impact on the Environment. It is also a phase of many `unknowns' making it flexible and allowing exploration of many solutions. Thus, it is a challenge to determine the most Environmentally-benign Solution or Concept to be translated in to a `good' product. The SAPPhIRE Model captures the various levels of abstractions present in Conceptual Design by Outcomes and defines a Solution-variant as a set of verifiable and quantifiable Outcomes. The Causality explains the propagation of Environmental Impact across Outcomes at varying levels of abstraction, suggesting that the Environmental Impact of an Outcome at a certain level can be represented as a collation of Environmental Impact information of all the Outcomes at each of its subsequent lower levels of abstraction. Thus a ball-park impact value can be associated with the higher-levels of abstraction, thereby supporting design decisions taken earlier on in Conceptual Design directing towards Environmentally-benign Design.

Differential proteomic and genomic profiling of mouse striatal cell model of Huntington's disease and control; probable implications to the disease biology

Huntington's disease (HD) is an autosomal dominant disorder of central nervous system caused by expansion of CAG repeats in exon1 of the huntingtin gene (Htt). Among various dysfunctions originated from the mutation in Htt gene, transcriptional deregulation has been considered to be one of the most important abnormalities. Large numbers of investigations identified altered expressions of genes in brains of HD patients and many models of HD. In this study we employed 2D SDS-PAGE/MALDI-MS coupled with 2D-DIGE and real-time PCR experiments of an array of genes focused to HD pathway to determine altered protein and gene expressions in STHdh(Q111)/Hdh(Q111) cells, a cell model of HD and compared with STHdh(Q7)/Hdh(Q7) cells, its wild type counterpart. We annotated 76 proteins from these cells and observed differential expressions of 31 proteins (by 2D-DIGE) involved in processes like unfolded protein binding, negative regulation of neuron apoptosis, response to superoxides etc. Our PCR array experiments identified altered expressions of 47 genes. Altogether significant alteration of 77 genes/proteins could be identified in this HD cell line with potential relevance to HD biology. Biological significance: In this study we intended to find out differential proteomic and genomic profiles in HD condition. We used the STHdh cells, a cellular model for HD and control. These are mouse striatal neuronal cell lines harboring 7 and 111 knock -in CAG repeats in their two alleles. The 111Q containing cell line (STHdh(Q111)/Hdh(Q111)) mimics diseased condition, whereas the 7Q containing ones (STHdh(Q7)/Hdh(Q7)), serves as the proper control cell line. Proteomic experiments were performed earlier to obtain differential expressions of proteins in R6/2 mice models, Hdh(Q) knock -in mice and in plasma and CSF from HD patients. However, no earlier report on proteomic alterations in these two HD cell lines and control was available in literature. It was, therefore, an important objective to find out differential expressions of proteins in these two cell lines. In this study, we annotated 76 proteins from STHdh(Q7)/Hdh(Q7) and STHdh(Q111)/Hdh(Q111) cells using 2D-gel/mass spectrometry. Next, by performing 2D-DIGE, we observed differential expressions of 31 proteins (16 upregulated and 15 downregulated) between these two cell lines. We also performed customized qRT-PCR array focused to HD pathway and found differential expressions of 47 genes (8 gene exptessions increased and 39 genes were decreased significantly). A total of 77 genes/proteins (Htt downregulated in both the studies) were found to be significantly altered from both the experimental paradigms. We validated the differential expressions of Vim, Hypk, Ran, Dstn, Hspa5 and Sod2 either by qRT-PCR or Western blot analysis or both. Out of these 77, similar trends in alteration of 19 out of 31 and 38 out of 47 proteins/genes were reported in earlier studies. Thus our study confirmed earlier observations on differential gene/protein expressions in HD and are really useful. Additionally, we observed differential expression of some novel genes/proteins. One of this was Hypk, a Htt-interacting chaperone protein with the ability to solubilize mHtt aggregated structures in cell lines. We propose that downregulation of Hypk in STHdh-Qm (Q111)/Hdh(Q111) has a causal effect towards HD pathogenesis. Thus the novel findings from our study need further research and might be helpful to understand the molecular mechanism behind HD pathogenesis. (C) 2015 Elsevier B.V. All rights reserved.

Physiological role of FolD (methylenetetrahydrofolate dehydrogenase), FchA (methenyltetrahydrofolate cyclohydrolase) and Fhs (formyltetrahydrofolate synthetase) from Clostridium perfringens in a heterologous model of Escherichia coli

Most organisms possess bifunctional FolD 5,10-methylenetetrahydrofolate (5,10-CH2-THF) dehydrogenase-cyclohydrolase] to generate NADPH and 10-formyltetrandrofolate (10-CHO-THF) required in various metabolic steps. In addition, some organisms including Clostridium perfringens possess another protein, Fhs (formyltetrahydrofolate synthetase), to synthesize 10-CHO-THF. Here, we show that unlike the bifunctional FolD of Escherichia coli (Eco FolD), and contrary to its annotated bifunctional nature, C. perfringens FolD (Cpe FoID) is a monofunctional 5,10-CH2-THF dehydrogenase. The dehydrogenase activity of Cpe FoID is about five times more efficient than that of Eco FolD. The 5,10-methenyltetrahydrofolate (5,10-CH+-THF) cyclohydrolase activity in C. perfringens is provided by another protein, FchA (5,10-CH+-THF cyclohydrolase), whose cyclohydrolase activity is similar to 10 times more efficient than that of Eco FolD. Kinetic parameters for Cpe Fhs were also determined for utilization of all of its substrates. Both Cpe FoID and Cpe FchA are required to substitute for the single bifunctional FolD in E. coli. The simultaneous presence of Cpe FoID and Cpe FchA is also necessary to rescue an E coli folD deletion strain (harbouring Cpe Fhs support) for its formate and glycine auxotrophies, and to alleviate its susceptibility to trimethoprim (an antifolate drug) or UV light. The presence of the three clostridial proteins (FolD, FchA and Fhs) is required to maintain folate homeostasis in the cell.