Insights into the Evolution and Emergence of a Novel Infectious Disease

Many zoonotic, novel infectious diseases in humans appear as sporadic infections with spatially and temporally restricted outbreaks, as seen with influenza A(H5N1). Adaptation is often a key factor for successfully establishing sustained human-to-human transmission. Here we use simple mathematical models to describe different adaptation scenarios with particular reference to spatial heterogeneity within the human population. We present analytical expressions for the probability of emergence per introduction, as well as the waiting time to a successful emergence event. Furthermore, we derive general analytical results for the statistical properties of emergence events, including the probability distribution of outbreak sizes. We compare our analytical results with a stochastic model, which has previously been studied computationally. Our results suggest that, for typical connection strengths between communities, spatial heterogeneity has only a weak effect on outbreak size distributions, and on the risk of emergence per introduction. For example, if or larger, any village connected to a large city by just ten commuters a day is, effectively, just a part of the city when considering the chances of emergence and the outbreak size distribution. We present empirical data on commuting patterns and show that the vast majority of communities for which such data are available are at least this well interconnected. For plausible parameter ranges, the effects of spatial heterogeneity are likely to be dominated by the evolutionary biology of host adaptation. We conclude by discussing implications for surveillance and control of emerging infections

Concentration of atomic hydrogen diffused into silicon in the temperature range 900–1300 °C

Boron-doped Czochralski silicon samples with [B]~1017 cm−3 have been heated at various temperatures in the range 800–1300 °C in an atmosphere of hydrogen and then quenched. The concentration of [H-B] pairs was measured by infrared localized vibrational mode spectroscopy. It was concluded that the solubility of atomic hydrogen is greater than [Hs] = 5.6 × 1018 exp( − 0.95 eV/kT)cm−3 at the temperatures investigated

Spores of Clostridium engineered for clinical efficacy and safety cause regression and cure of tumors in vivo.

Spores of some species of the strictly anaerobic bacteria Clostridium naturally target and partially lyse the hypoxic cores of tumors, which tend to be refractory to conventional therapies. The anti-tumor effect can be augmented by engineering strains to convert a non-toxic prodrug into a cytotoxic drug specifically at the tumor site by expressing a prodrug-converting enzyme (PCE). Safe doses of the favored prodrug CB1954 lead to peak concentrations of 6.3 μM in patient sera, but at these concentration(s) known nitroreductase (NTR) PCEs for this prodrug show low activity. Furthermore, efficacious and safe Clostridium strains that stably express a PCE have not been reported. Here we identify a novel nitroreductase from Neisseria meningitidis, NmeNTR, which is able to activate CB1954 at clinically-achievable serum concentrations. An NmeNTR expression cassette, which does not contain an antibiotic resistance marker, was stably localized to the chromosome of Clostridium sporogenes using a new integration method, and the strain was disabled for safety and containment by making it a uracil auxotroph. The efficacy of Clostridium-Directed Enzyme Prodrug Therapy (CDEPT) using this system was demonstrated in a mouse xenograft model of human colon carcinoma. Substantial tumor suppression was achieved, and several animals were cured. These encouraging data suggest that the novel enzyme and strain engineering approach represent a promising platform for the clinical development of CDEPT

Growth studies on Si0.8Ge0.2 channel two-dimensional hole gases

We report a study of the influences of MBE conditions on the low-temperature mobilities of Si/Si0.8Ge0.2 2DHG structures. A significant dependence of 2DHG mobility on growth temperature is observed with the maximum mobility of 3640 cm2 V−1 s−1 at 5.4 K being achieved at the relatively high-growth temperature of 640 °C. This dependence is associated with a reduction in interface charge density. Studies on lower mobility samples show that Cu contamination can be reduced both by growth interruptions and by modifications to the Ge source; this reduction produces improvements in the low-temperature mobilities. We suggest that interface charge deriving from residual metal contamination is currently limiting the 4-K mobility