Interaction Design, user experience & Urban Creativity scientific journal : how can cities become better human habitat?

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La confiance mutuelle dans l'espace pénal européen/Mutual Trust in the European Criminal Area

L'ouvrage constitue une réflexion approfondie sur la problématique de la confiance mutuelle dans l'espace pénal européen, un thème d’une brûlante actualité dès lors que l'importance de la confiance mutuelle dans cet espace va croissant

Targeting acute myeloid leukemia by dual inhibition of PI3K signaling and Cdk9-mediated Mcl-1 transcription

Resistance to cell death is a hallmark of cancer and renders transformed cells resistant to multiple apoptotic triggers. The Bcl-2 family member, Mcl-1, is a key driver of cell survival in diverse cancers, including acute myeloid leukemia (AML). A screen for compounds that downregulate Mcl-1 identified the kinase inhibitor, PIK-75, which demonstrates marked proapoptotic activity against a panel of cytogenetically diverse primary human AML patient samples. We show that PIK-75 transiently blocks Cdk7/9, leading to transcriptional suppression of MCL-1, rapid loss of Mcl-1 protein, and alleviation of its inhibition of proapoptotic Bak. PIK-75 also targets the p110α isoform of PI3K, which leads to a loss of association between Bcl-xL and Bak. The simultaneous loss of Mcl-1 and Bcl-xL association with Bak leads to rapid apoptosis of AML cells. Concordantly, low Bak expression in AML confers resistance to PIK-75–mediated killing. On the other hand, the induction of apoptosis by PIK-75 did not require the expression of the BH3 proteins Bim, Bid, Bad, Noxa, or Puma. PIK-75 significantly reduced leukemia burden and increased the survival of mice engrafted with human AML without inducing overt toxicity. Future efforts to cotarget PI3K and Cdk9 with drugs such as PIK-75 in AML are warranted

La confiance mutuelle dans l'espace pénal européen/Mutual Trust in the European Criminal Area

L'ouvrage constitue une réflexion approfondie sur la problématique de la confiance mutuelle dans l'espace pénal européen, un thème d’une brûlante actualité dès lors que l'importance de la confiance mutuelle dans cet espace va croissant

In vivo mapping of human spinal cord microstructure at 300 mT/m

The ability to characterize white matter microstructure non-invasively has important applications for the diagnosis and follow-up of several neurological diseases. There exists a family of diffusion MRI techniques, such as AxCaliber, that provide indices of axon microstructure, such as axon diameter and density. However, to obtain accurate measurements of axons with small diameters (<5 μm), these techniques require strong gradients, i.e. an order of magnitude higher than the 40–80 mT/m currently available in clinical systems. In this study we acquired AxCaliber diffusion data at a variety of different q-values and diffusion times in the spinal cord of five healthy subjects using a 300 mT/m whole body gradient system. Acquisition and processing were optimized using state-of-the-art methods (e.g., 64-channel coil, template-based analysis). Results consistently show an average axon diameter of 4.5 +/− 1.1 μm in the spinal cord white matter. Diameters ranged from 3.0 μm (gracilis) to 5.9 μm (spinocerebellar tracts). Values were similar across laterality (left-right), but statistically different across spinal cord pathways (p<10(−5)). The observed trends are similar to those observed in animal histology. This study shows, for the first time, in vivo mapping of axon diameter in the spinal cord at 300 mT/m, thus creating opportunities for applications in spinal cord diseases

Illustrated State-of-the-Art Capsules of the ISTH 2019 Congress in Melbourne, Australia : Plasminogen in wound healing

The 27th Congress of the International Society of Thrombosis and Haemostasis (ISTH) is an international conference held July 6-10, 2019, in Melbourne, the capital of the state of Victoria, Australia. The ISTH congress has previously been held every other year, with the Scientific and Standardization Committee (SSC) meeting held annually, until 2019 when it became one combined annual meeting of the ISTH and SSC. The conference covers clinical and basic aspects of hemostasis and thrombosis, and this year includes 5 Plenary lectures and &gt;50 State of Art (SOA) lectures, presented by internationally recognized speakers, as well as numerous oral session and poster presentations selected from submitted abstracts, including many early career and reach the world support recipients. This SOA review article in RPTH contains concise Illustrated Review Articles or 'Capsules' consisting of short text, three references and a figure, with topics including stroke, cancer-associated thrombosis, hemophilia, coagulation, the interface between infection and inflammation, and in the experimental and discovery areas, megakaryocyte biology and platelet production, structure-function of key receptors and coagulation factors, and emerging new roles for thrombotic/hemostatic factors. Together, these articles highlight novel findings which will advance knowledge and with the potential to change clinical practice and improve outcomes. It is hoped that conference attendees and followers will enjoy utilizing the images for ongoing education and during the conference for live tweeting during sessions, to assist in the broadcasting and promotion of the science to those unable to attend, or who have chosen to attend a concurrent session. Use #IllustratedReview and #ISTH2019 on social media