A quantitative model of the initiation of DNA replication in Saccharomyces cerevisiae predicts the effects of system perturbations.

BackgroundEukaryotic cell proliferation involves DNA replication, a tightly regulated process mediated by a multitude of protein factors. In budding yeast, the initiation of replication is facilitated by the heterohexameric origin recognition complex (ORC). ORC binds to specific origins of replication and then serves as a scaffold for the recruitment of other factors such as Cdt1, Cdc6, the Mcm2-7 complex, Cdc45 and the Dbf4-Cdc7 kinase complex. While many of the mechanisms controlling these associations are well documented, mathematical models are needed to explore the network's dynamic behaviour. We have developed an ordinary differential equation-based model of the protein-protein interaction network describing replication initiation.ResultsThe model was validated against quantified levels of protein factors over a range of cell cycle timepoints. Using chromatin extracts from synchronized Saccharomyces cerevisiae cell cultures, we were able to monitor the in vivo fluctuations of several of the aforementioned proteins, with additional data obtained from the literature. The model behaviour conforms to perturbation trials previously reported in the literature, and accurately predicts the results of our own knockdown experiments. Furthermore, we successfully incorporated our replication initiation model into an established model of the entire yeast cell cycle, thus providing a comprehensive description of these processes.ConclusionsThis study establishes a robust model of the processes driving DNA replication initiation. The model was validated against observed cell concentrations of the driving factors, and characterizes the interactions between factors implicated in eukaryotic DNA replication. Finally, this model can serve as a guide in efforts to generate a comprehensive model of the mammalian cell cycle in order to explore cancer-related phenotypes

Formation energy and interaction of point defects in two-dimensional colloidal crystals

The manipulation of individual colloidal particles using optical tweezers has allowed vacancies to be created in two-dimensional (2d) colloidal crystals, with unprecedented possibility of real-time monitoring the dynamics of such defects (Nature {\bf 413}, 147 (2001)). In this Letter, we employ molecular dynamics (MD) simulations to calculate the formation energy of single defects and the binding energy between pairs of defects in a 2d colloidal crystal. In the light of our results, experimental observations of vacancies could be explained and then compared to simulation results for the interstitial defects. We see a remarkable similarity between our results for a 2d colloidal crystal and the 2d Wigner crystal (Phys. Rev. Lett. {\bf 86}, 492 (2001)). The results show that the formation energy to create a single interstitial is $12$ lower than that of the vacancy. Because the pair binding energies of the defects are strongly attractive for short distances, the ground state should correspond to bound pairs with the interstitial bound pairs being the most probable.Comment: 5 pages, 2 figure

Mandate-driven networking eco-system : a paradigm shift in end-to-end communications

The wireless industry is driven by key stakeholders that follow a holistic approach of "one-system-fits-all" that leads to moving network functionality of meeting stringent End-to-End (E2E) communication requirements towards the core and cloud infrastructures. This trend is limiting smaller and new players for bringing in new and novel solutions. For meeting these E2E requirements, tenants and end-users need to be active players for bringing their needs and innovations. Driving E2E communication not only in terms of quality of service (QoS) but also overall carbon footprint and spectrum efficiency from one specific community may lead to undesirable simplifications and a higher level of abstraction of other network segments may lead to sub-optimal operations. Based on this, the paper presents a paradigm shift that will enlarge the role of wireless innovation at academia, Small and Medium-sized Enterprises (SME)'s, industries and start-ups while taking into account decentralized mandate-driven intelligence in E2E communications

A unified radio control architecture for prototyping adaptive wireless protocols

Experimental optimization of wireless protocols and validation of novel solutions is often problematic, due to limited configuration space present in commercial wireless interfaces as well as complexity of monolithic driver implementation on SDR-based experimentation platforms. To overcome these limitations a novel software architecture is proposed, called WiSHFUL, devised to allow: i) maximal exploitation of radio functionalities available in current radio chips, and ii) clean separation between the logic for optimizing the radio protocols (i.e. radio control) and the definition of these protocols

Skin Temperature Analysis and Bias Correction in a Coupled Land-Atmosphere Data Assimilation System

In an initial investigation, remotely sensed surface temperature is assimilated into a coupled atmosphere/land global data assimilation system, with explicit accounting for biases in the model state. In this scheme, an incremental bias correction term is introduced in the model's surface energy budget. In its simplest form, the algorithm estimates and corrects a constant time mean bias for each gridpoint; additional benefits are attained with a refined version of the algorithm which allows for a correction of the mean diurnal cycle. The method is validated against the assimilated observations, as well as independent near-surface air temperature observations. In many regions, not accounting for the diurnal cycle of bias caused degradation of the diurnal amplitude of background model air temperature. Energy fluxes collected through the Coordinated Enhanced Observing Period (CEOP) are used to more closely inspect the surface energy budget. In general, sensible heat flux is improved with the surface temperature assimilation, and two stations show a reduction of bias by as much as 30 Wm(sup -2) Rondonia station in Amazonia, the Bowen ratio changes direction in an improvement related to the temperature assimilation. However, at many stations the monthly latent heat flux bias is slightly increased. These results show the impact of univariate assimilation of surface temperature observations on the surface energy budget, and suggest the need for multivariate land data assimilation. The results also show the need for independent validation data, especially flux stations in varied climate regimes

Decision Analysis of Dynamic Spectrum Access Rules

A current trend in spectrum regulation is to incorporate spectrum sharing through the design of spectrum access rules that support Dynamic Spectrum Access (DSA). This paper develops a decision-theoretic framework for regulators to assess the impacts of different decision rules on both primary and secondary operators. We analyze access rules based on sensing and exclusion areas, which in practice can be enforced through geolocation databases. Our results show that receiver-only sensing provides insufficient protection for primary and co-existing secondary users and overall low social welfare. On the other hand, using sensing information between the transmitter and receiver of a communication link, provides dramatic increases in system performance. The performance of using these link end points is relatively close to that of using many cooperative sensing nodes associated to the same access point and large link exclusion areas. These results are useful to regulators and network developers in understanding in developing rules for future DSA regulation

Impact of particle size, oxidation state and capping agent of different cerium dioxide nanoparticles on the phosphate-induced transformations at different pH and concentration

The potential hazard posed by nanomaterials can be significantly influenced by transformations which these materials undergo during their lifecycle, from manufacturing through to disposal. The transformations may depend on the nanomaterials’ own physicochemical properties as well as the environment they are exposed to. This study focuses on the mechanisms of transformation of cerium oxide nanoparticles (CeO$_{2}$ NPs) in laboratory experiments which simulate potential scenarios in which the NPs are exposed to phosphate-bearing media. We have experimented with the transformation of four different kinds of CeO$_{2}$ NPs, in order to investigate the effects of nanoparticle size, capping agent (three were uncapped and one was PVP capped) and oxidation state (two consisted mostly of Ce$^{4+}$ and two were a mix of Ce$^{3+}$/Ce$^{4+}$). They were exposed to a reaction solution containing KH$_{2}$PO$_{4}$, citric acid and ascorbic acid at pH values of 2.3, 5.5 and 12.3, and concentrations of 1mM and 5mM. The transformations were followed by UV-vis, zeta potential and XRD measurements, which were taken after 7 and 21 days, and by transmission electron microscopy after 21 days. X-ray photoelectron spectroscopy was measured at 5mM concentration after 21 days for some samples. Results show that for pH 5 and 5mM phosphate concentration, CePO$_{4}$ NPs were formed. Nanoparticles that were mostly Ce$^{4+}$ did not dissolve at 1mM reagent concentration, and did not produce CePO$_{4}$ NPs. When PVP was present as a capping agent it proved to be an extra reducing agent, and CePO$_{4}$ was found under all conditions used. This is the first paper where the transformation of CeO$_{2}$ NPs in the presence of phosphate has been studied for particles with different size, shapes and capping agents, in a range of different conditions and using many different characterisation methods

A combination of curcumin and ginger extract improves abrasion wound healing in corticosteroid-impaired hairless rat skin

Hairless rats were topically treated with a combination of 10% curcumin and 3% ginger extract (or with each agent alone) for a 21-day period. Following this, the rats were treated topically with Temovate (corticosteroid) for an additional 15 days. At the end of the treatment period, superficial abrasion wounds were induced in the treated skin. Abrasion wounds healed more slowly in the skin of Temovate-treated rats than in skin of control animals. Healing was more rapid in skin of rats that had been pretreated with either curcumin or ginger extract alone or with the combination of curcumin–ginger extract (along with Temovate) than in the skin of rats treated with Temovate and vehicle alone. Skin samples were obtained at the time of wound closure. Collagen production was increased and matrix metalloproteinase-9 production was decreased in the recently healed skin from rats treated with the botanical preparation relative to rats treated with Temovate plus vehicle. In none of the rats was there any indication of skin irritation during the treatment phase or during wounding and repair. Taken together, these data suggest that a combination of curcumin and ginger extract might provide a novel approach to improving structure and function in skin and, concomitantly, reducing formation of nonhealing wounds in “at-risk” skin.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/74673/1/j.1524-475X.2009.00483.x.pd