The South African Football Association has confirmed the appointment of advocate Tebogo Motlanthe as new acting CEO.

Previous studies have shown that sphingosine kinase interacting protein (SKIP) inhibits sphingosine kinase (SK) function in fibroblasts. SK phosphorylates sphingosine producing the potent signaling molecule sphingosine-1-phosphate (S1P). SKIP gene (SPHKAP) expression is silenced by hypermethylation of its promoter in acute myeloid leukemia (AML). However, why SKIP activity is silenced in primary AML cells is unclear. Here, we investigated the consequences of SKIP down-regulation in AML primary cells and the effects of SKIP re-expression in leukemic cell lines. Using targeted ultra-HPLC-tandem MS (UPLC-MS/MS), we measured sphingolipids (including S1P and ceramides) in AML and control cells. Primary AML cells had significantly lower SK activity and intracellular S1P concentrations than control cells, and SKIP-transfected leukemia cell lines exhibited increased SK activity. These findings show that SKIP re-expression enhances SK activity in leukemia cells. Furthermore, other bioactive sphingolipids such as ceramide were also down-regulated in primary AML cells. Of note, SKIP re-expression in leukemia cells increased ceramide levels 2-fold, inactivated the key signaling protein extracellular signal-regulated kinase, and increased apoptosis following serum deprivation or chemotherapy. These results indicate that SKIP down-regulation in AML reduces SK activity and ceramide levels, an effect that ultimately inhibits apoptosis in leukemia cells. The findings of our study contrast with previous results indicating that SKIP inhibits SK function in fibroblasts and therefore challenge the notion that SKIP always inhibits SK activity.

Marilyn Goudreault
Jan 1, 2009; 8:157-171
Research

Invitation Only Research Event

Peggy Yarborough
Jan 1, 2003; 16:
Case Studies

Previous studies have shown that sphingosine kinase interacting protein (SKIP) inhibits sphingosine kinase (SK) function in fibroblasts. SK phosphorylates sphingosine producing the potent signaling molecule sphingosine-1-phosphate (S1P). SKIP gene (SPHKAP) expression is silenced by hypermethylation of its promoter in acute myeloid leukemia (AML). However, why SKIP activity is silenced in primary AML cells is unclear. Here, we investigated the consequences of SKIP down-regulation in AML primary cells and the effects of SKIP re-expression in leukemic cell lines. Using targeted ultra-HPLC-tandem MS (UPLC-MS/MS), we measured sphingolipids (including S1P and ceramides) in AML and control cells. Primary AML cells had significantly lower SK activity and intracellular S1P concentrations than control cells, and SKIP-transfected leukemia cell lines exhibited increased SK activity. These findings show that SKIP re-expression enhances SK activity in leukemia cells. Furthermore, other bioactive sphingolipids such as ceramide were also down-regulated in primary AML cells. Of note, SKIP re-expression in leukemia cells increased ceramide levels 2-fold, inactivated the key signaling protein extracellular signal-regulated kinase, and increased apoptosis following serum deprivation or chemotherapy. These results indicate that SKIP down-regulation in AML reduces SK activity and ceramide levels, an effect that ultimately inhibits apoptosis in leukemia cells. The findings of our study contrast with previous results indicating that SKIP inhibits SK function in fibroblasts and therefore challenge the notion that SKIP always inhibits SK activity.

Previous studies have shown that sphingosine kinase interacting protein (SKIP) inhibits sphingosine kinase (SK) function in fibroblasts. SK phosphorylates sphingosine producing the potent signaling molecule sphingosine-1-phosphate (S1P). SKIP gene (SPHKAP) expression is silenced by hypermethylation of its promoter in acute myeloid leukemia (AML). However, why SKIP activity is silenced in primary AML cells is unclear. Here, we investigated the consequences of SKIP down-regulation in AML primary cells and the effects of SKIP re-expression in leukemic cell lines. Using targeted ultra-HPLC-tandem MS (UPLC-MS/MS), we measured sphingolipids (including S1P and ceramides) in AML and control cells. Primary AML cells had significantly lower SK activity and intracellular S1P concentrations than control cells, and SKIP-transfected leukemia cell lines exhibited increased SK activity. These findings show that SKIP re-expression enhances SK activity in leukemia cells. Furthermore, other bioactive sphingolipids such as ceramide were also down-regulated in primary AML cells. Of note, SKIP re-expression in leukemia cells increased ceramide levels 2-fold, inactivated the key signaling protein extracellular signal-regulated kinase, and increased apoptosis following serum deprivation or chemotherapy. These results indicate that SKIP down-regulation in AML reduces SK activity and ceramide levels, an effect that ultimately inhibits apoptosis in leukemia cells. The findings of our study contrast with previous results indicating that SKIP inhibits SK function in fibroblasts and therefore challenge the notion that SKIP always inhibits SK activity.

Tina Vilsbøll
Jun 1, 2007; 30:1608-1610
BR Emerging Treatments and Technologies

Alan J. Garber
May 1, 2011; 34:S279-S284
Diabetes Treatments

OBJECTIVE

To evaluate the efficacy and safety of fast-acting insulin aspart (faster aspart) compared with insulin aspart (IAsp), both with insulin degludec with or without metformin, in adults with type 2 diabetes not optimally controlled with a basal-bolus regimen.

The coronavirus pandemic put India's population of 1.3 billion into an extreme and sudden lockdown. Social entrepreneur Gayathri Vasudevan explains how the situation is impacting the country's migrant workers, who are stuck far from home with limited access to food and shelter, and calls for an overhaul of India's social infrastructure in order to get people the essentials they need right now. (This virtual conversation is part of the TED Connects series, hosted by current affairs curator Whitney Pennington Rodgers. Recorded April 9, 2020)

Lester coached at Maryland from 1969-71. He was 96.

Rockville, Maryland : National Institute on Drug Abuse, 1976.

Jere Koskela, Paul A. Jenkins, Adam M. Johansen, Dario Spanò.

Source: The Annals of Statistics, Volume 48, Number 1, 560--583.

Abstract:
We study weighted particle systems in which new generations are resampled from current particles with probabilities proportional to their weights. This covers a broad class of sequential Monte Carlo (SMC) methods, widely-used in applied statistics and cognate disciplines. We consider the genealogical tree embedded into such particle systems, and identify conditions, as well as an appropriate time-scaling, under which they converge to the Kingman $n$-coalescent in the infinite system size limit in the sense of finite-dimensional distributions. Thus, the tractable $n$-coalescent can be used to predict the shape and size of SMC genealogies, as we illustrate by characterising the limiting mean and variance of the tree height. SMC genealogies are known to be connected to algorithm performance, so that our results are likely to have applications in the design of new methods as well. Our conditions for convergence are strong, but we show by simulation that they do not appear to be necessary.

Giacomo Aletti, Irene Crimaldi, Andrea Ghiglietti.

Source: Bernoulli, Volume 26, Number 2, 1098--1138.

Abstract:
This work deals with a system of interacting reinforced stochastic processes , where each process $X^{j}=(X_{n,j})_{n}$ is located at a vertex $j$ of a finite weighted directed graph, and it can be interpreted as the sequence of “actions” adopted by an agent $j$ of the network. The interaction among the dynamics of these processes depends on the weighted adjacency matrix $W$ associated to the underlying graph: indeed, the probability that an agent $j$ chooses a certain action depends on its personal “inclination” $Z_{n,j}$ and on the inclinations $Z_{n,h}$, with $h eq j$, of the other agents according to the entries of $W$. The best known example of reinforced stochastic process is the Pólya urn. The present paper focuses on the weighted empirical means $N_{n,j}=sum_{k=1}^{n}q_{n,k}X_{k,j}$, since, for example, the current experience is more important than the past one in reinforced learning. Their almost sure synchronization and some central limit theorems in the sense of stable convergence are proven. The new approach with weighted means highlights the key points in proving some recent results for the personal inclinations $Z^{j}=(Z_{n,j})_{n}$ and for the empirical means $overline{X}^{j}=(sum_{k=1}^{n}X_{k,j}/n)_{n}$ given in recent papers (e.g. Aletti, Crimaldi and Ghiglietti (2019), Ann. Appl. Probab. 27 (2017) 3787–3844, Crimaldi et al. Stochastic Process. Appl. 129 (2019) 70–101). In fact, with a more sophisticated decomposition of the considered processes, we can understand how the different convergence rates of the involved stochastic processes combine. From an application point of view, we provide confidence intervals for the common limit inclination of the agents and a test statistics to make inference on the matrix $W$, based on the weighted empirical means. In particular, we answer a research question posed in Aletti, Crimaldi and Ghiglietti (2019).

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Participants from all over the world joined together in Ireland for two weeks of training and outreach in partnership with local churches.

A group of 80 teenagers from Chicago, US, bless the local community in Volcán, Panama.

Cate Devine

Ebola Virus (EBOV) is among the most devastating pathogens causing fatal hemorrhagic fever in humans. The 2013–2016 epidemics resulted in over 11000 deaths, while another outbreak is currently ongoing. Since there is no FDA-approved drug so far to fight EBOV infection, there is an urgent need to focus on drug discovery. Considering the tight correlation between the high EBOV virulence and its ability to suppress the type-I Interferon (IFN-I) system, identifying molecules targeting viral protein VP24, one of the main virulence determinants blocking IFN response, is a promising novel anti-EBOV therapy approach. Hence, in the effort of finding novel EBOV inhibitors, a screening of a small set of flavonoids was performed, showing that Quercetin and Wogonin can suppress the VP24 effect on IFN-I signaling inhibition. The mechanism of action of the most active compound, Quercetin, showing an IC₅₀ value of 7.4 μM, was characterized to significantly restore the IFN-I signaling cascade, blocked by VP24, by directly interfering with the VP24 binding to karyopherin-α and thus restoring P-STAT1 nuclear transport and IFN genes transcription. Quercetin significantly blocked viral infection, specifically targeting EBOV VP24 anti-IFN-I function. Overall, Quercetin is the first identified inhibitor of the EBOV VP24 anti-IFN function, representing a molecule interacting with a viral binding site that is very promising for further drug development aiming to block EBOV infection at the early steps.

Learning how to listen and act with empathy is radically different from assuming traditional roles of teachers as experts, John M. Holland writes.

It’s not that the world is suddenly and cruelly bereft of writers, but let’s be honest: there aren’t too many of them coming to advertising.

Hello, i managed to extract my S-param data into vcsv file,however i need a standart S2P file

i have this table displayed, as shown bellow.
is there a way to extract s2p file in cadence virtuoso?
Thanks.

Hi all,

I am using ADE assembler.

I ran transient simulation and swept the input frequency (Fin) of the circuit. And I use Spectrum Measurement to return a value of the fundamental tone magnitude (Sig_fund) for each sweep point. 

Previously, I use "plot across design points" to plot both "Fin" and "Sig_fund", and then use "Y vs Y" to get a waveform of Sig_fund vs Fin. Measure the 1dB Bandwidth with markers. 

Can I realized above measurement with an expression in "output setup" ? And how?

I know to set the "Eval type" to "sweep" to process the data across sweep points. But here, it has to return an interpolated value from "Fin" with a criteria "(value(calcVal("Sig_fund"  0) - 1)". I am not sure whether it can be done in ADE assembler.

Thanks and regards,

Yutao

Q2 of 2015 saw a large increase in the generation of electricity from solar PV in the UK, with the growth having a significant impact on electricity market prices and other supply factors.

Q2 of 2015 saw a large increase in the generation of electricity from solar PV in the UK, with the growth having a significant impact on electricity market prices and other supply factors.

In this webinar for education institutions we will consider: - contract principles - early questions to consider: • what is the purpose of collaboration? • what IP may be generated? • who owns background IP? ...

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The country loses a veteran of diplomatic affairs and adviser to several prime ministers with the coronavirus death of former Foreign Ministry official Yukio Okamoto.

The head of China’s cabinet-level office that oversees Hong Kong affairs has urged the city’s leader to examine possible ways of enacting a national security law and to ensure that elections for the legislature this year are conducted in a fair manner.The meeting between Xia Baolong, director of the Hong Kong and Macau Affairs Office (HKMAO), and Chief Executive Carrie Lam Cheng Yuet-ngor was held in Shenzhen at the end of last month, according to sources.Hong Kong is facing mounting pressure…

Two-minute silence held for father-of-four Augustine Agyei-Mensah, a highly regarded learning disabilities nurse

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Tributes have been paid to a learning disabilities nurse who died after testing positive for coronavirus.

Augustine Agyei-Mensah, known to his colleagues as Gus, was described as a “highly regarded team member” at Northamptonshire Healthcare NHS foundation trust (NHFT).