A coupled drug kinetics-cell cycle model to analyse the response of human cells to intervention by topotecan

A model describing the response of the growth of single human cells in the absence and presence of the anti-cancer agent topotecan (TPT) is presented. The model includes a novel coupling of both the kinetics of TPT and cell cycle responses to the agent. By linking the models in this way, rather than using separate (disjoint) approaches, it is possible to illustrate how the drug perturbs the cell cycle. The model is compared to experimental in vitro cell cycle response data (comprising single cell descriptors for molecular and behavioural events), showing good qualitative agreement for a range of TPT dose levels

Parallel window decoding enables scalable fault tolerant quantum computation

Quantum Error Correction (QEC) continuously generates a stream of syndrome data that contains information about the errors in the system. Useful fault-tolerant quantum computation requires online decoders that are capable of processing this syndrome data at the rate it is received. Otherwise, a data backlog is created that grows exponentially with the $T$-gate depth of the computation. Superconducting quantum devices can perform QEC rounds in sub-1 $\mu$s time, setting a stringent requirement on the speed of the decoders. All current decoder proposals have a maximum code size beyond which the processing of syndromes becomes too slow to keep up with the data acquisition, thereby making the fault-tolerant computation not scalable. Here, we will present a methodology that parallelizes the decoding problem and achieves almost arbitrary syndrome processing speed. Our parallelization requires some classical feedback decisions to be delayed, leading to a slow-down of the logical clock speed. However, the slow-down is now polynomial in code size and so an exponential backlog is averted. Furthermore, using known auto-teleportation gadgets the slow-down can be eliminated altogether in exchange for increased qubit overhead, all polynomially scaling. We demonstrate our parallelization speed-up using a Python implementation, combining it with both union-find and minimum weight perfect matching. Furthermore, we show that the algorithm imposes no noticeable reduction in logical fidelity compared to the original global decoder. Finally, we discuss how the same methodology can be implemented in online hardware decoders.Comment: 12 pages, 7 figure

Establishment and operation of a Good Manufacturing Practice-compliant allogeneic Epstein-Barr virus (EBV)-specific cytotoxic cell bank for the treatment of EBV-associated lymphoproliferative disease

Funded by Wellcome Trust Translational Award SNBTSPeer reviewedPublisher PD

Derivation of screening benchmarks for dietary methylmercury exposure for the common loon ( Gavia immer ): Rationale for use in ecological risk assessment

The current understanding of methylmercury (MeHg) toxicity to avian species has improved considerably in recent years and indicates that exposure to environmentally relevant concentrations of MeHg through the diet can adversely affect various aspects of avian health, reproduction, and survival. Because fish‐eating birds are at particular risk for elevated MeHg exposure, the authors surveyed the available primary and secondary literature to summarize the effects of dietary MeHg on the common loon ( Gavia immer ) and to derive ecologically relevant toxic thresholds for dietary exposure to MeHg in fish prey. After considering the available data, the authors propose three screening benchmarks of 0.1, 0.18, and 0.4 µg g −1 wet weight MeHg in prey fish. The lowest benchmark (0.1 µg g −1 wet wt) is the threshold for adverse behavioral impacts in adult loons and is close to the empirically determined no observed adverse effects level for subclinical effects observed in captive loon chicks. The remaining benchmarks (0.18 and 0.4 µg g −1 wet wt) correspond to MeHg levels in prey fish associated with significant reproductive impairment and reproductive failure in wild adult loons. Overall, these benchmarks incorporate recent findings and reviews of MeHg toxicity in aquatic fish‐eating birds and provide the basis for a national ecological risk assessment for Hg and loons in Canada. Environ. Toxicol. Chem. 2012; 31: 2399–2407. © 2012 SETACPeer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/93756/1/1971_ftp.pd

Physical and photophysical properties of a linear copper(I) complex of a bulky acenapthene-based NHC ligand

CFRM and EZ-C wish to thank the Engineering and Physical Sciences Research Council (EP/M02105X/1 and EP/R035164/1) for financial support. We would like to thank the Engineering and Physical Sciences Research Council and CRITICAT Centre for Doctoral Training for financial support (Ph.D. studentship to B. H.; EP/L016419/1).We report the first example of a charge-neutral linear 2-coordinate copper(I) complex bearing a sterically demanding acenaphthoimidazolylidene-based N-heterocyclic carbene ligand. The identity and geometry of the complex was confirmed by single-crystal XRD (X-Ray Diffraction) analysis. The complex is poorly emissive at room temperature, showing either ligand-centered (LC) emission at around 340 nm when excited at 300 nm or ligand-to-ligand charge-transfer (LLCT) emission at around 540 nm when excited at 420 nm; in chloroform, dual emission is observed upon photoexcitation at 300 nm. Nanosecond emission lifetimes were recorded for these processes. This is the first example of emissive linear copper(I) complexes containing this bulky NHC ligand.PostprintPeer reviewe

Apparent bypass of negative selection in CD8+ tumours in CD2-myc transgenic mice.

A role for antigen stimulation in lymphoid neoplasia has been postulated and is supported by indirect evidence that suggests that the interaction of antigen with both T cells and B cells may constitute an epigenetic event that can contribute to tumour induction or tumour progression. Using myc-bearing transgenic mice that develop mainly clonal T-cell lymphomas we have investigated the possibility that endogenous antigen-mediated clonal deletion might be overridden in tumorigenesis. CD2-myc transgenic mice were backcrossed on to a CBA/Ca background to ensure Mtv-mediated deletion of V beta 11-expressing T cells in the resultant offspring. Lymphomas arising from these mice were subsequently screened for V beta 11 expression. There was a clear correlation between the age at which mice developed neoplasia and the tumour phenotype. Mice with CD4- CD8+ tumours succumbed to thymic lymphoma at a significantly younger age than mice developing CD4+ CD8+ tumours. A small number of tumours consisted of the 'forbidden' V beta 11 phenotype, showing that cells vulnerable to transformation could escape negative selection. The majority of the V beta 11-positive tumours were CD4- CD8+ and were only observed in mice showing clinical evidence of tumour development at a relatively young age. The phenotype of these cells and the age at which tumours arose suggests that T cells escaping tolerance may be susceptible to transformation

Fertilisers for wine grapes : an information package to promote efficient fertiliser practices

https://researchlibrary.agric.wa.gov.au/bulletins/1278/thumbnail.jp