Skeletal muscle cells lacking the retinoblastoma protein display defects in muscle gene expression and accumulate in S and G2 phases of the cell cycle.

Viral oncoproteins that inactivate the retinoblastoma tumor suppressor protein (pRb) family both block skeletal muscle differentiation and promote cell cycle progression. To clarify the dependence of terminal differentiation on the presence of the different pRb-related proteins, we have studied myogenesis using isogenic primary fibroblasts derived from mouse embryos individually deficient for pRb, p107, or p130. When ectopically expressed in fibroblasts lacking pRb, MyoD induces an aberrant skeletal muscle differentiation program characterized by normal expression of early differentiation markers such as myogenin and p21, but attenuated expression of late differentiation markers such as myosin heavy chain (MHC). Similar defects in MHC expression were not observed in cells lacking either p107 or p130, indicating that the defect is specific to the loss of pRb. In contrast to wild-type, p107-deficient, or p130-deficient differentiated myocytes that are permanently withdrawn from the cell cycle, differentiated myocytes lacking pRb accumulate in S and G2 phases and express extremely high levels of cyclins A and B, cyclin-dependent kinase (Cdk2), and Cdc2, but fail to readily proceed to mitosis. Administration of caffeine, an agent that removes inhibitory phosphorylations on inactive Cdc2/cyclin B complexes, specifically induced mitotic catastrophe in pRb-deficient myocytes, consistent with the observation that the majority of pRb-deficient myocytes arrest in S and G2. Together, these findings indicate that pRb is required for the expression of late skeletal muscle differentiation markers and for the inhibition of DNA synthesis, but that a pRb-independent mechanism restricts entry of differentiated myocytes into mitosis

Spotify tailoring for promoting effectiveness in cross-functional autonomous squads

Organisations tend to tailor agile methods to scale employed practices to have cross-functional autonomous teams while promoting sustainable creative and productive development at a constant pace. Thus, it is important to investigate how organisations tailor agile practices to get the balance right between teams' autonomy and alignment. Spotify model is originally introduced to facilitate the development of music streaming services in a very large-scale project with a Business-to-Consumer (B2C) model. However, developing a large-scale mission-critical project with a Business-to-Business (B2B) model is not essentially supported by the Spotify model. Thus, embracing Spotify model for such projects should be concerned about the question of how Spotify practices are adjusted to promote the effectiveness of cross-functional autonomous squads in a mission-critical project with B2B model? In this paper, we conduct a longitudinal embedded case study, which lasted 21 months during which 14 semi-structured interviews were conducted. The Grounded Theory (GT) is adopted to analyse the collected data. As a result, we identify practices and processes that promote effectiveness in cross-functional autonomous squads, which have never been discussed in terms of Spotify model before. We also present Spotify Tailoring by highlighting modified and newly introduced practices by the organisation in which the case study was conducted

Factors and options for improved frequency regulation: Case study of utility scale solar in Nigeria

This paper presents the structure, tuning, and evaluation of a model for power system frequency response in Nigeria. We demonstrate that a 100MW utility scale solar farm is unlikely to degrade frequency performance, and we quantify the effect of several possible interventions to improve frequency regulation. The Nigerian system already experiences wide frequency variations due to steel mill loads and load rejection during storms, and this often necessitates manual intervention and load management. The model is one of several employed in grid-integration evaluations of proposed large utility-scale solar farms. The model is intended to support ongoing discussions on how grid code and market policies should specify ancillary services supplied by participants

Defense responses in tomato fruit induced by oligandrin against Botrytis cinerea

Oligandrin is known to induce resistance against a number of plant diseases. However, its effects on postharvest diseases are still unclear. The effects of oligandrin on the control of postharvest diseases in tomato fruit and its underlying mechanisms were investigated in this study. The treat01ent of tomato fruit with oligandrin (10 μg/ml) significantly reduced the incidence and severity of gray mould (caused by Botrytis cinerea). After 5, 7 and 9 days of artificial inoculation, the relative cure effect was 60.5, 52.1 and 48.5%, respectively. The results from bio-assay indicated that the treatment stimulated the activity of the defense related enzymes. Phenylalanine ammonia-lyase (PAL), polyphenol oxidase (PPO) and peroxidase (POD) activity in the oligandrin-treated fruit was about 39.2, 69.6 and 52.6% higher than that in control on the 3rd day, respectively. Furthermore, mRNA level of the genes encoding pathogenesis-related proteins (PRs), such as PR-2a (extracellular β-1, 3 -glucanase) and PR-3a (extracellular chitinase) in tomato fruit was about 2.7-fold and 4.6-fold above that of the control at the peak stage. The expression of LeERF2 and PR6, which confer an ethylene-dependent signaling pathway, were also significantly increased 6.6-fold and 3.6-fold by such treatment. These results indicate that oligandrin has the potential to control gray mould and it may play an important role in the induction of resistance to B. cinerea and the activation of the ethylene-dependent signaling pathway.Key words: Tomato, disease resistance, oligandrin, Botrytis cinerea

Dynamic spatial weight matrix and localised STARIMA for network modelling

Various statistical model specifications for describing spatiotemporal processes have been proposed over the years, including the space–time autoregressive integrated moving average (STARIMA) and its various extensions. These model specifications assume that the correlation in data can be adequately described by parameters that are globally fixed spatially and/or temporally. They are inadequate for cases in which the correlations among data are dynamic and heterogeneous, such as network data. The aim of this article is to describe autocorrelation in network data with a dynamic spatial weight matrix and a localized STARIMA model that captures the autocorrelation locally (heterogeneity) and dynamically (nonstationarity). The specification is tested with traffic data collected for central London. The result shows that the performance of estimation and prediction is improved compared with standard STARIMA models that are widely used for space–time modeling. En los últimos años, se han propuesto diversas especificaciones de modelado estadístico para describir procesos espacio-temporales. Esto incluye el modelo espacio-temporal autorregresivo integrado de media móvil (STARIMA) y sus varios derivados. Estas especificaciones de modelo asumen que la correlación de los datos puede ser adecuadamente descrita por parámetros que se fijan a nivel global en el espacio y/o tiempo. Dichos parámetros son inadecuados para los casos en los que las correlaciones entre los datos son dinámicas y heterogéneas, como en el contexto de los datos de la red. El objetivo de este artículo es describir la autocorrelación en los datos de red con una matriz de ponderación espacial dinámica y un modelo STARIMA localizado (LSTARIMA) que captura la autocorrelación local (heterogeneidad) de forma dinámica (no estacionariedad). La especificación del modelo es evaluada con datos de tráfico recolectados en el centro de Londres. Los resultados demuestran que los rendimientos de estimación y predicción mejoran con el método propuesto en comparación con los modelos STARIMA estándar que son ampliamente utilizados para el modelado de espacio-temporal

Parents’ experiences of health visiting for children with Down syndrome

© MA Healthcare Limited.Children with Down syndrome have an increased likelihoodof experiencing serious health conditions. Health visitors canhave an important role in monitoring and promoting healthand development for young children with Down syndrome.This study aimed to explore parents’ experiences of healthvisiting services for children with Down syndrome. Twentyfour parents of children with Down syndrome aged 0–5 yearscompleted a brief questionnaire about the number and natureof visits from health visitors in the previous 12 months andtheir support needs. Some parents commented that otherprofessionals met the needs of their child, whereas others saidthat they would like more advice and support from healthvisitors. A further exploration of broader health serviceprovision, including health visiting, for young children withDown syndrome is needed.Peer reviewedFinal Accepted Versio

Enhancement of defense responses by oligandrin against Botrytis cinerea

Oligandrin is an elicitin-like protein with a molecular mass of ∼10 kDa secreted by Pythium oligandrum. Here, the effect of oligandrin on defense response against Botrytis cinerea in tomato leaves is reported. Tomato seedlings were pretreated with 5 ml oligandrin (10 g/ml) by root submerging and then inoculated with B. cinerea. Disease severity was subsequently evaluated and compared with the control. Results indicate that oligandrin pretreatment reduced disease index by 78.6% on day 7 after inoculation. On day 3 after inoculation, oligandrin pretreatment caused up-regulation of peroxidases (POD), polyphenol oxidase (PPO) and phenylalanine ammonia lyase (PAL) in leaves by 20.0, 5.56 and 32.88%, compared with inoculation without oligandrin pretreatment, respectively. On day 5 after inoculation, POD, PPO and PAL were up-regulated by 46.24, 32.61 and 57.14%, respectively. 24 h after the treatment with oligandrin, the expression of pathogenesis-related protein (PRs) genes, PR-2a (extracellular β-1,3-glucanase) and PR-3a (extracellular chitinase), were up-regulated by 7.75 fold and 4.56 fold in tomato leaves, compared with the control, respectively. The expression of LeERF2, a member of ethylene-dependent signaling pathway, was also significantly elevated by 7.41 fold. At the same time, the expression of ethylene receptor homologue PR-6 protein was also induced. These results indicate that oligandrin can induce resistance to B. cinerea in tomatoes, and the induction of resistance involves the activation of the ethylene-dependent signaling pathway. Oligandrin is potentially useful for gray mould prevention in tomato crop.Key words: Botrytis cinerea, induced resistance, oligandrin, resistance related enzymes