Chemical analysis and aqueous solution properties of Charged Amphiphilic Block Copolymers PBA-b-PAA synthesized by MADIX

We have linked the structural and dynamic properties in aqueous solution of amphiphilic charged diblock copolymers poly(butyl acrylate)-b-poly(acrylic acid), PBA-b-PAA, synthesized by controlled radical polymerization, with the physico-chemical characteristics of the samples. Despite product imperfections, the samples self-assemble in melt and aqueous solutions as predicted by monodisperse microphase separation theory. However, the PBA core are abnormally large; the swelling of PBA cores is not due to AA (the Flory parameter chiPBA/PAA, determined at 0.25, means strong segregation), but to h-PBA homopolymers (content determined by Liquid Chromatography at the Point of Exclusion and Adsorption Transition LC-PEAT). Beside the dominant population of micelles detected by scattering experiments, capillary electrophoresis CE analysis permitted detection of two other populations, one of h-PAA, and the other of free PBA-b-PAA chains, that have very short PBA blocks and never self-assemble. Despite the presence of these free unimers, the self-assembly in solution was found out of equilibrium: the aggregation state is history dependant and no unimer exchange between micelles occurs over months (time-evolution SANS). The high PBA/water interfacial tension, measured at 20 mN/m, prohibits unimer exchange between micelles. PBA-b-PAA solution systems are neither at thermal equilibrium nor completely frozen systems: internal fractionation of individual aggregates can occur.Comment: 32 pages, 16 figures and 4 tables submitted to Journal of Interface and Colloidal Scienc

Update on the ICUD-SIU consultation on multi-parametric magnetic resonance imaging in localised prostate cancer

Introduction: Prostate cancer (PCa) imaging is a rapidly evolving field. Dramatic improvements in prostate MRI during the last decade will probably change the accuracy of diagnosis. This chapter reviews recent current evidence about MRI diagnostic performance and impact on PCa management. Materials and methods: The International Consultation on Urological Diseases nominated a committee to review the literature on prostate MRI. A search of the PubMed database was conducted to identify articles focussed on MP-MRI detection and staging protocols, reporting and scoring systems, the role of MP-MRI in diagnosing PCa prior to biopsy, in active surveillance, in focal therapy and in detecting local recurrence after treatment. Results: Differences in opinion were reported in the use of the strength of magnets [1.5 Tesla (T) vs. 3T] and coils. More agreement was found regarding the choice of pulse sequences; diffusion-weighted MRI (DW-MRI), dynamic contrast-enhanced MRI (DCE MRI), and/or MR spectroscopy imaging (MRSI) are recommended in addition to conventional T2-weighted anatomical sequences. In 2015, the Prostate Imaging Reporting and Data System (PI-RADS version 2) was described to standardize image acquisition and interpretation. MP-MRI improves detection of clinically significant PCa (csPCa) in the repeat biopsy setting or before the confirmatory biopsy in patients considering active surveillance. It is useful to guide focal treatment and to detect local recurrences after treatment. Its role in biopsy-naive patients or during the course of active surveillance remains debated. Conclusion: MP-MRI is increasingly used to improve detection of csPCa and for the selection of a suitable therapeutic approach

Tyrosine Kinase Syk Non-Enzymatic Inhibitors and Potential Anti-Allergic Drug-Like Compounds Discovered by Virtual and In Vitro Screening

In the past decade, the spleen tyrosine kinase (Syk) has shown a high potential for the discovery of new treatments for inflammatory and autoimmune disorders. Pharmacological inhibitors of Syk catalytic site bearing therapeutic potential have been developed, with however limited specificity towards Syk. To address this topic, we opted for the design of drug-like compounds that could impede the interaction of Syk with its cellular partners while maintaining an active kinase protein. To achieve this challenging task, we used the powerful potential of intracellular antibodies for the modulation of cellular functions in vivo, combined to structure-based in silico screening. In our previous studies, we reported the anti-allergic properties of the intracellular antibody G4G11. With the aim of finding functional mimics of G4G11, we developed an Antibody Displacement Assay and we isolated the drug-like compound C-13, with promising in vivo anti-allergic activity. The likely binding cavity of this compound is located at the close vicinity of G4G11 epitope, far away from the catalytic site of Syk. Here we report the virtual screen of a collection of 500,000 molecules against this new cavity, which led to the isolation of 1000 compounds subsequently evaluated for their in vitro inhibitory effects using the Antibody Displacement Assay. Eighty five compounds were selected and evaluated for their ability to inhibit the liberation of allergic mediators from mast cells. Among them, 10 compounds inhibited degranulation with IC50 values ≤10 µM. The most bioactive compounds combine biological activity, significant inhibition of antibody binding and strong affinity for Syk. Moreover, these molecules show a good potential for oral bioavailability and are not kinase catalytic site inhibitors. These bioactive compounds could be used as starting points for the development of new classes of non-enzymatic inhibitors of Syk and for drug discovery endeavour in the field of inflammation related disorders

RNA-interference in rice against Rice tungro bacilliform virus results in its decreased accumulation in inoculated rice plants

Rice tungro is a viral disease seriously affecting rice production in South and Southeast Asia. Tungro is caused by the simultaneous infection in rice of Rice tungro bacilliform virus (RTBV), a double-stranded DNA virus and Rice tungro spherical virus (RTSV), a single-stranded RNA virus. To apply the concept of RNA-interference (RNAi) for the control of RTBV infection, transgenic rice plants expressing DNA encoding ORF IV of RTBV, both in sense as well as in anti-sense orientation, resulting in the formation of double-stranded (ds) RNA, were raised. RNA blot analysis of two representative lines indicated specific degradation of the transgene transcripts and the accumulation of small molecular weight RNA, a hallmark for RNA-interference. In the two transgenic lines expressing ds-RNA, different resistance responses were observed against RTBV. In one of the above lines (RTBV-O-Ds1), there was an initial rapid buildup of RTBV levels following inoculation, comparable to that of untransformed controls, followed by a sharp reduction, resulting in approximately 50-fold lower viral titers, whereas the untransformed controls maintained high levels of the virus till 40 days post-inoculation (dpi). In RTBV-O-Ds2, RTBV DNA levels gradually rose from an initial low to almost 60% levels of the control by 40 dpi. Line RTBV-O-Ds1 showed symptoms of tungro similar to the untransformed control lines, whereas line RTBV-O-Ds2 showed extremely mild symptoms

Cloud droplet number closure for tropical convective clouds during the ACRIDICON CHUVA campaign

The main objective of the ACRIDICON-CHUVA campaign in September 2014 was the investigation of aerosol-cloud-interactions in the Amazon Basin. Cloud properties near cloud base of growing convective cumuli were characterized by cloud droplet size distribution measurements using a cloud combination probe and a cloud and aerosol spectrometer. In the current study, an adiabatic parcel model was used to perform cloud droplet number closure studies for several flights in differently polluted air masses

ESUR prostate MR guidelines 2012

The aim was to develop clinical guidelines for multi-parametric MRI of the prostate by a group of prostate MRI experts from the European Society of Urogenital Radiology (ESUR), based on literature evidence and consensus expert opinion. True evidence-based guidelines could not be formulated, but a compromise, reflected by “minimal” and “optimal” requirements has been made. The scope of these ESUR guidelines is to promulgate high quality MRI in acquisition and evaluation with the correct indications for prostate cancer across the whole of Europe and eventually outside Europe. The guidelines for the optimal technique and three protocols for “detection”, “staging” and “node and bone” are presented. The use of endorectal coil vs. pelvic phased array coil and 1.5 vs. 3 T is discussed. Clinical indications and a PI-RADS classification for structured reporting are presented

Business models innovation in investment banks: A resilience perspective

© 2020, The Author(s). Firms frequently change their business models in order to respond to internal and external challenges. This study aims to explore how investments banks adjust their business models in response to internal and external challenges. Based on a qualitative data from ten major investment banks operating in the largest financial market in the Middle East, we show that investment banks can achieve resilience by adjusting their business models through continuous activity changes in response to internal and external challenges. Specifically, investment banks adjust their business models through deploying alternative combinations of activities from a broad repertoire of activities. Within the same bank, divisions that respond to external challenges tend to sustain their performance, whereas resilient divisions that respond to both internal and external challenges tend to bounce back or achieve substantial increase in performance levels. This study contributes to the literature by proposing resilience as an alternative approach to business model innovation and by providing insight into how firms adjust their business models by altering specific activities in response to both internal and external challenges