Latrunculin A delays anaphase onset in fission yeast by disrupting an ase1-independent pathway controlling mitotic spindle stability

It has been proposed previously that latrunculin A, an inhibitor of actin polymerization, delays the onset of anaphase by causing spindle misorientation in fission yeast. However, we show that {Delta}mto1 cells, which are defective in nucleation of cytoplasmic microtubules, have profoundly misoriented spindles but are not delayed in the timing of sister chromatid separation, providing compelling evidence that fission yeast does not possess a spindle orientation checkpoint. Instead, we show that latrunculin A delays anaphase onset by disrupting interpolar microtubule stability. This effect is abolished in a latrunculin A-insensitive actin mutant and exacerbated in cells lacking Ase1, which cross-links antiparallel interpolar microtubules at the spindle midzone both before and after anaphase. These data indicate that both Ase1 and an intact actin cytoskeleton are required for preanaphase spindle stability. Finally, we show that loss of Ase1 activates a checkpoint that requires only the Mad3, Bub1, and Mph1, but not Mad1, Mad2, or Bub3 checkpoint proteins

Checkpoint proteins come under scrutiny

Details are emerging of the interactions between the kinetochore and various spindle checkpoint proteins that ensure that sister chromatids are equally divided between daughter cells during cell division

Accurate simulations of the interplay between process and statistical variability for nanoscale FinFET-based SRAM cell stability

In this paper we illustrate how by using advanced atomistic TCAD tools the interplay between long-range process variation and short-range statistical variability in FinFETs can be accurately modelled and simulated for the purposes of Design-Technology Co-Optimization (DTCO). The proposed statistical simulation and compact modelling methodology is demonstrated via a comprehensive evaluation of the impact of FinFET variability on SRAM cell stability

Data management of nanometre­ scale CMOS device simulations

In this paper we discuss the problems arising in managing and curating the data generated by simulations of nanometre scale CMOS (Complementary Metal–Oxide Semiconductor) transistors, circuits and systems and describe the software and operational techniques we have adopted to address them. Such simulations pose a number of challenges including, inter alia, multi­TByte data volumes, complex datasets with complex inter-relations between datasets, multi­-institutional collaborations including multiple specialisms and a mixture of academic and industrial partners, and demanding security requirements driven by commercial imperatives. This work was undertaken as part of the NanoCMOS project. However, the problems, solutions and experience seem likely to be of wider relevance, both within the CMOS design community and more generally in other disciplines

Inferring orthologous gene regulatory networks using interspecies data fusion

MOTIVATION: The ability to jointly learn gene regulatory networks (GRNs) in, or leverage GRNs between related species would allow the vast amount of legacy data obtained in model organisms to inform the GRNs of more complex, or economically or medically relevant counterparts. Examples include transferring information from Arabidopsis thaliana into related crop species for food security purposes, or from mice into humans for medical applications. Here we develop two related Bayesian approaches to network inference that allow GRNs to be jointly inferred in, or leveraged between, several related species: in one framework, network information is directly propagated between species; in the second hierarchical approach, network information is propagated via an unobserved 'hypernetwork'. In both frameworks, information about network similarity is captured via graph kernels, with the networks additionally informed by species-specific time series gene expression data, when available, using Gaussian processes to model the dynamics of gene expression. RESULTS: Results on in silico benchmarks demonstrate that joint inference, and leveraging of known networks between species, offers better accuracy than standalone inference. The direct propagation of network information via the non-hierarchical framework is more appropriate when there are relatively few species, while the hierarchical approach is better suited when there are many species. Both methods are robust to small amounts of mislabelling of orthologues. Finally, the use of Saccharomyces cerevisiae data and networks to inform inference of networks in the budding yeast Schizosaccharomyces pombe predicts a novel role in cell cycle regulation for Gas1 (SPAC19B12.02c), a 1,3-beta-glucanosyltransferase

From the pursuit of excellence to the quest for significance: Promotion of a Childsafe South Africa

Trauma represents a major burden of disease in South Africa. Children are disproportionately affected by trauma; rightly, childhood trauma can be referred to as ‘the neglected childhood killer disease’. Unlike the field of infectious diseases, where vaccinations and prevention are the norm, paediatric trauma is usually ignored and prevention strategies are scarce. In this article, we review paediatric trauma and its effect on our society in light of the development of more effective child safety promotion strategies

2D-TCAD Simulation on Retention Time of Z2FET for DRAM Application

Traditional memory devices are facing more challenges due to continuous down-scaling. 6T-SRAM suffers from variability [1-2] and reliability [3-4] issues, which introduce cell stability problems. DRAM cells with one transistor, one capacitor (1T1C) struggle to maintain refresh time [5-6]. Efforts have been made to find new memory solutions, such as one transistor (1T) solutions [7-9]. Floating body based memory structures are among the potential candidates, but impact ionization or band-to-band tunnelling (B2BT) limits their refresh time [10]. A recently proposed zero impact ionization and zero subthreshold swing device named Z2FET [9, 11-12] has been demonstrated and is a promising candidate for 1T DRAM memory cell due to technology advantages such as CMOS technology compatibility, novel capacitor-less structure and sharp switching characteristics. In the Z2FET memory operation, refresh frequency is determined by data retention time. Previous research [11-12] is lacking systematic simulation analysis and understanding on the underlying mechanisms. In this paper, we propose a new simulation methodology to accurately extract retention time in Z2FET devices and understand its dependency on applied biases, temperatures and relevant physical mechanisms. Since the stored ‘1’ state in Z2FET is an equilibrium state [9, 11-12] and there is no need to refresh, we will concentrate on state ‘0’ retention. Two types of ‘0’ retention time: HOLD ‘0’ and READ ‘0’ retention time will be discussed separately

Enhanced anti-tumour activity of carmustine (BCNU) with tumour necrosis factor in vitro and in vivo.

The effects on experimental melanoma of a combination of recombinant human tumour necrosis factor alpha (rhTNF alpha) and carmustine (BCNU) were studied in vitro and in vivo. In vitro, BCNU alone was cytotoxic to murine B16 melanoma cells, and at all concentrations of BCNU this toxicity was increased by the addition of TNF. In vivo, BCNU and TNF, when given separately, caused tumour growth delay of B16 melanoma and of human melanoma xenografts in immune-deprived mice. The combination of TNF at low dose 2.5 x 10(5) U kg-1 = 122 ng kg-1) with BCNU (35 mg kg-1) resulted in significant growth delay (compared with either drug alone) in B16 melanoma (P = 0.005). There was no significant increase in toxicity as assessed by weight loss and peripheral blood counts. Experiments with human melanoma xenografts yielded similar results (P = 0.001) but only at higher doses of TNF (1 x 10(6) U kg-1 = 489 ng kg-1). The enhancement of BCNU cytotoxicity by TNF may be important if it can be translated into patients with melanoma. A randomised study is now underway to investigate the clinical potential of this observation