Trends and risk factors for human Q fever in Australia, 1991-2014.

Australian abattoir workers, farmers, veterinarians and people handling animal birthing products or slaughtering animals continue to be at high risk of Q fever despite an effective vaccine being available. National Notifiable Diseases Surveillance System data were analysed for the period 1991-2014, along with enhanced risk factor data from notified cases in the states of New South Wales and Queensland, to examine changes in the epidemiology of Q fever in Australia. The national Q fever notification rate reduced by 20% [incident rate ratio (IRR) 0·82] following the end of the National Q fever Management Program in 2006, and has increased since 2009 (IRR 1·01-1·34). Highest rates were in males aged 40-59 years (5·9/100 000) and 87% of Q fever cases occurred in New South Wales and Queensland. The age of Q fever cases and proportion of females increased over the study period. Based on the enhanced risk factor data, the most frequently listed occupation for Q fever cases involved contact with livestock, followed by 'no known risk' occupations. More complete and comparable enhanced risk factor data, at the State/Territory and national levels, would aid in further understanding of the epidemiology of Q fever.

Robust identification of large genetic networks.

Temporal and spatial gene expression, together with the concentration of proteins and metabolites, is tightly controlled in the cell. This is possible thanks to complex regulatory networks between these different elements. The identification of these networks would be extremely valuable. We developed a novel algorithm to identify a large genetic network, as a set of linear differential equations, starting from measurements of gene expression at steady state following transcriptional perturbations. Experimentally, it is possible to overexpress each of the genes in the network using an episomal expression plasmid and measure the change in mRNA concentration of all the genes, following the perturbation. Computationally, we reduced the identification problem to a multiple linear regression, assuming that the network is sparse. We implemented a heuristic search method in order to apply the algorithm to large networks. The algorithm can correctly identify the network, even in the presence of large noise in the data, and can be used to predict the genes that directly mediate the action of a compound. Our novel approach is experimentally feasible and it is readily applicable to large genetic networks.

Construction of a genetic toggle switch in Escherichia coli.

It has been proposed' that gene-regulatory circuits with virtually any desired property can be constructed from networks of simple regulatory elements. These properties, which include multistability and oscillations, have been found in specialized gene circuits such as the bacteriophage lambda switch and the Cyanobacteria circadian oscillator. However, these behaviours have not been demonstrated in networks of non-specialized regulatory components. Here we present the construction of a genetic toggle switch-a synthetic, bistable gene-regulatory network-in Escherichia coli and provide a simple theory that predicts the conditions necessary for bistability. The toggle is constructed from any two repressible promoters arranged in a mutually inhibitory network. It is flipped between stable states using transient chemical or thermal induction and exhibits a nearly ideal switching threshold. As a practical device, the toggle switch forms a synthetic, addressable cellular memory unit and has implications for biotechnology, biocomputing and gene therapy.

A theory for controlling cell cycle dynamics using a reversibly binding inhibitor.

We demonstrate, by using mathematical modeling of cell division cycle (CDC) dynamics, a potential mechanism for precisely controlling the frequency of cell division and regulating the size of a dividing cell. Control of the cell cycle is achieved by artificially expressing a protein that reversibly binds and inactivates any one of the CDC proteins. In the simplest case, such as the checkpoint-free situation encountered in early amphibian embryos, the frequency of CDC oscillations can be increased or decreased by regulating the rate of synthesis, the binding rate, or the equilibrium constant of the binding protein. In a more complex model of cell division, where size-control checkpoints are included, we show that the same reversible binding reaction can alter the mean cell mass in a continuously dividing cell. Because this control scheme is general and requires only the expression of a single protein, it provides a practical means for tuning the characteristics of the cell cycle in vivo.

Problem of track offset in optical disk systems.

In an optical disk drive, it is well known that a tilt of the disk causes an offset in the tracking-error signal (TES). One effect of disk tilt is the introduction of a dc component to the TES, which can be largely corrected by operation of the tracking system at the midpoint between the maximum and the minimum values of the open-loop TES. However, this method of correcting for the dc shift in the TES does not correct for the effect of coma in the focused spot, which leads to track offset. The track offset of a system is defined as the distance between the peak irradiance in the focused spot and the center of the groove when the tracking system is operating at the midpoint between the maximum and the minimum values of the open-loop TES in the presence of disk tilt. Calculations are performed that show the dependence of track offset on various system parameters, including track pitch, wavelength, and numerical aperture and rim intensity of the objective lens, and on the regions of the beam used to generate the TES. The track offsets for several beam-segmentation schemes are calculated for a digital versatile disk that uses push-pull and differential phase tracking. It is shown that for differential phase tracking the value of track offset depends on the mark length.