Calculating Biological Behaviors of Epigenetic States in Phage lambda Life Cycle

Gene regulatory network of lambda phage is one the best studied model systems in molecular biology. More 50 years of experimental study has provided a tremendous amount of data at all levels: physics, chemistry, DNA, protein, and function. However, its stability and robustness for both wild type and mutants has been a notorious theoretical/mathematical problem. In this paper we report our successful calculation on the properties of this gene regulatory network. We believe it is of its first kind. Our success is of course built upon numerous previous theoretical attempts, but following 3 features make our modeling uniqu: 1) A new modeling method particular suitable for stability and robustness study; 2) Paying a close attention to the well-known difference of in vivo and in vitro; 3) Allowing more important role for noise and stochastic effect to play. The last two points have been discussed by two of us (Ao and Yin, cond-mat/0307747), which we believe would be enough to make some of previous theoretical attempts successful, too. We hope the present work would stimulate a further interest in the emerging field of gene regulatory network.Comment: 16 pages, 3 figures, 1 tabl

Discriminating cool-water from warm-water carbonates and their diagenetic environments using element geochemistry: the Oligocene Tikorangi Formation (Taranaki Basin) and the dolomite effect

Fields portrayed within bivariate element plots have been used to distinguish between carbonates formed in warm- (tropical) water and cool- (temperate) water depositional settings. Here, element concentrations (Ca, Mg, Sr, Na, Fe, and Mn) have been determined for the carbonate fraction of bulk samples from the late Oligocene Tikorangi Formation, a subsurface, mixed dolomite-calcite, cool-water limestone sequence in Taranaki Basin, New Zealand. While the occurrence of dolomite is rare in New Zealand Cenozoic carbonates, and in cool-water carbonates more generally, the dolomite in the Tikorangi carbonates is shown to have a dramatic effect on the "traditional" positioning of cool-water limestone fields within bivariate element plots. Rare undolomitised, wholly calcitic carbonate samples in the Tikorangi Formation have the following average composition: Mg 2800 ppm; Ca 319 100 ppm; Na 800 ppm; Fe 6300 ppm; Sr 2400 ppm; and Mn 300 ppm. Tikorangi Formation dolomite-rich samples (>15% dolomite) have average values of: Mg 53 400 ppm; Ca 290 400 ppm; Na 4700 ppm; Fe 28 100 ppm; Sr 5400 ppm; and Mn 500 ppm. Element-element plots for dolomite-bearing samples show elevated Mg, Na, and Sr values compared with most other low-Mg calcite New Zealand Cenozoic limestones. The increased trace element contents are directly attributable to the trace element-enriched nature of the burial-derived dolomites, termed here the "dolomite effect". Fe levels in the Tikorangi Formation carbonates far exceed both modern and ancient cool-water and warm-water analogues, while Sr values are also higher than those in modern Tasmanian cool-water carbonates, and approach modern Bahaman warm-water carbonate values. Trace element data used in conjunction with more traditional petrographic data have aided in the diagenetic interpretation of the carbonate-dominated Tikorangi sequence. The geochemical results have been particularly useful for providing more definitive evidence for deep burial dolomitisation of the deposits under the influence of marine-modified pore fluids

Conditional evolution in single-atom cavity QED

We consider a typical setup of cavity QED consisting of a two-level atom interacting strongly with a single resonant electromagnetic field mode inside a cavity. The cavity is resonantly driven and the output undergoes continuous homodyne measurements. We derive an explicit expression for the state of the system conditional on a discrete photocount record. This expression takes a particularly simple form if the system is initially in the steady state. As a byproduct, we derive a general formula for the steady state that had been conjectured before in the strong driving limit.Comment: 15 pages, 1 postscript figure, added discussion of mode

Serotonin signaling through the 5-HT1B receptor and NADPH oxidase 1 in pulmonary arterial hypertension

Objective: Serotonin can induce human pulmonary artery smooth muscle cell (hPASMC) proliferation through reactive oxygen species (ROS), influencing the development of pulmonary arterial hypertension (PAH). We hypothesise that in PASMCs, serotonin induces oxidative stress through NADPH-oxidase-derived ROS generation and reduced Nrf-2 anti-oxidant systems, promoting vascular injury. Approach and Results: HPASMCs from controls and PAH patients, and PASMCs from Nox1-/- mice, were stimulated with serotonin in the absence/presence of inhibitors of Src kinase, the 5-HT1B receptor and NADPH oxidase 1 (Nox1). Markers of fibrosis were also determined. The pathophysiological significance of our findings was examined in vivo in serotonin transporter overexpressing (SERT+) female mice, a model of pulmonary hypertension (PH). We confirmed serotonin increased superoxide and H2O2 production in these cells. For the first time, we show that serotonin increased oxidized protein tyrosine phosphatases and peroxiredoxin-SO3H and decreased Nrf-2 and catalase activity in hPASMCs. ROS generation was exaggerated, and dependent on c-Src, 5-HT1B receptor and the serotonin transporter in PAH-hPASMCs. Proliferation and extracellular matrix remodeling were exaggerated in PAH-hPASMCs and dependent on 5-HT1B receptor signaling and Nox1, confirmed in PASMCs from Nox1-/- mice. In SERT+ mice, SB216641, a 5-HT1B receptor antagonist, prevented development of PH in a ROS-dependent manner. Conclusions: Serotonin can induce c-Src-regulated Nox1-induced ROS and Nrf-2 dysregulation, contributing to increased post-translational oxidative modification of proteins, activation of redox-sensitive signaling pathways in hPASMCs; associated with mitogenic responses. 5-HT1B receptors contribute to experimental PH by inducing lung ROS production. Our results suggest 5-HT1B receptor-dependent c-Src-Nox1-pathways contribute to vascular remodeling in PAH

Isolation of Unknown Genes from Human Bone Marrow by Differental Screening and Single-Pass cDNA Sequences Determination

A cDNA sequencing project was initiated to characterize gene expression in human bone marrow and develop strategies to isolate novel genes. Forty-eight random cDNAs from total human bone marrow were subjected to single-pass DNA sequence analysis to determine a limited complexity of mRNAs expressed in the bone marrow. Overall, 8 cDNAs (17%) showed no similarity to known sequences. Information from DNA sequence analysis was used to develop a differential prescreen to subtract unwanted cDNAs and to enrich for unknown cDNAs. Forty-eight cDNAs that were negative with a complex probe were subject to single-pass DNA sequence determination. Of these prescreened cDNAs, the number of unknown sequences increased to 23 (48%). Unknown cDNAs were also characterized by RNA expression analysis using 25 different human leukemic cell lines. Of 13 unknown cDNAs tested, 10 were expressed in all cell types tested and 3 revealed a hematopoietic lineage-restricted expression pattern. Interestingly, while a total of only 96 bone marrow cDNAs were sequenced, 31 of these cDNAs represent sequences from unknown genes and 12 showed significant similarities to sequences in the data bases. One cDNA revealed a significant similarity to a serine/threonine-protein kinase at the amino acid level (56% identity for 123 amino acids) and may represent a previously unknown kinase. Differential screening techniques coupled with single-pass cDNA sequence analysis may prove to be a powerful and simple technique to examine developmental gene expression

A Nanoflare Distribution Generated by Repeated Relaxations Triggered by Kink Instability

Context: It is thought likely that vast numbers of nanoflares are responsible for the corona having a temperature of millions of degrees. Current observational technologies lack the resolving power to confirm the nanoflare hypothesis. An alternative approach is to construct a magnetohydrodynamic coronal loop model that has the ability to predict nanoflare energy distributions. Aims: This paper presents the initial results generated by such a model. It predicts heating events with a range of sizes, depending on where the instability threshold for linear kink modes is encountered. The aims are to calculate the distribution of event energies and to investigate whether kink instability can be predicted from a single parameter. Methods: The loop is represented as a straight line-tied cylinder. The twisting caused by random photospheric motions is captured by two parameters, representing the ratio of current density to field strength for specific regions of the loop. Dissipation of the loop's magnetic energy begins during the nonlinear stage of the instability, which develops as a consequence of current sheet reconnection. After flaring, the loop evolves to the state of lowest energy where, in accordance with relaxation theory, the ratio of current to field is constant throughout the loop and helicity is conserved. Results: The results suggest that instability cannot be predicted by any simple twist-derived property reaching a critical value. The model is applied such that the loop undergoes repeated episodes of instability followed by energy-releasing relaxation. Hence, an energy distribution of the nanoflares produced is collated. Conclusions: The final energy distribution features two nanoflare populations that follow different power laws. The power law index for the higher energy population is more than sufficient for coronal heating.Comment: 13 pages, 18 figure