Understanding the campaign dynamics of the French presidential election

Now that the dust has settled on Emmanuel Macron’s victory in the French presidential election, what lessons can be derived from the campaign? Thomas Vitiello assesses both rounds of the election, highlighting the key campaign dynamics that ultimately shaped the result

Voters can be influenced by voter advice websites, but they do not follow the guidance blindly

Voter advice websites, where voters are matched with parties that share similar views to their own, have started to appear in the UK after becoming popular in the Netherlands and other countries. In this post Matt Wall, André Krouwel and Thomas Vitiello discuss a new site launched for the European Parliament elections and consider how influential these services can be on the choices voters make at the ballot box

Experts react: Macron and Le Pen advance to the run-off in the French presidential election

France held the first round of its presidential election on 23 April, with Emmanuel Macron and Marine Le Pen making it to the second round. The centrist Macron is projected to have won 23.8 percent of the vote, while the Front National’s leader Le Pen came second with 21.5 percent. For the first time since the 1970s, no candidate from either mainstream party has made it through to the run-off, pointing at the possibility of a radical realignment in French politics. Keep an eye on this page for more expert reactions coming in throughout the day. Marta Lorimer: “Macron is expected to win the election, but it is still unclear whether he will be able to govern” Thomas Vitiello: “The recomposition of the French left has started” David Lees: “It would be unwise to write off Le Pen just yet” Andrew Glencross: “Neither candidate would have made it this far if it was not for the confluence of short-term and long-term crises in French society” Nick Parsons: “The blurring of ideological divisions may make the run-off vote closer than expected

La République En Marche : anatomie d'un mouvement

Le paysage politique français a connu sa transformation la plus radicale depuis 1958, au terme d'une campagne sans exemple dans le passé à l'été 2017 où le clivage gauche-droite a éclaté pour donner naissance à un socle majoritaire agrégeant diverses composantes. Parmi les résultats les plus saillants de cette séquence, l'émergence d'une nouvelle formation politique désireuse de se démarquer des "partis traditionnels" : La République en Marche (ex-En Marche !). Qui sont les « marcheurs » ? D'où viennent-ils ? Comment se positionnent-ils sur l'échiquier politique ? Quelles sont leurs valeurs ? Le meilleur moyen de répondre à ces questions était d'aller à leur rencontre pour ausculter leur profil sociologique, leurs motivations, leurs pratiques, leurs croyances... C'est ce qu’a fait Terra Nova en réalisant une enquête indépendante de grande ampleur auprès des adhérents de La République en Marche. Inédite aussi bien par son objet que par son étendue, elle a permis de recueillir les réponses d’un échantillon représentatif de 8 815 marcheurs qui ont répondu à un questionnaire anonymisé de 112 questions. Les résultats que nous présentons font la lumière sur la sociologie des marcheurs, leur position sur l'échiquier politique, leur(s) culture(s) politique(s) et leurs pratiques militantes

Multi-spectral terahertz sensing: proposal for a coupled-cavity quantum cascade laser based optical feedback interferometer

We propose a laser feedback interferometer operating at multiple terahertz (THz) frequency bands by using a pulsed coupled-cavity THz quantum cascade laser (QCL) under optical feedback. A theoretical model that contains multi-mode reduced rate equations and thermal equations is presented, which captures the interplay between electro-optical, thermal, and feedback effects. By using the self-heating effect in both active and passive cavities, self-mixing signal responses at three different THz frequency bands are predicted. A multi-spectral laser feedback interferometry system based on such a coupled-cavity THz QCL will permit ultra-high-speed sensing and spectroscopic applications including material identification

Dual inhibition of TGFβ and AXL as a novel therapy for human colorectal adenocarcinoma with mesenchymal phenotype

A subset of colorectal cancer (CRC) with a mesenchymal phenotype (CMS4) displays an aggressive disease, with an increased risk of recurrence after surgery, reduced survival, and resistance to standard treatments. It has been shown that the AXL and TGFβ signaling pathways are involved in epithelial-to-mesenchymal transition, migration, metastatic spread, and unresponsiveness to targeted therapies. However, the prognostic role of the combination of these biomarkers and the anti-tumor effect of AXL and TGFβ inhibition in CRC still has to be assessed. To evaluate the role of AXL and TGFβ as negative biomarker in CRC, we conducted an in-depth in silico analysis of CRC samples derived from the Gene Expression Omnibus. We found that AXL and TGFβ receptors are upregulated in CMS4 tumors and are correlated with an increased risk of recurrence after surgery in stage II/III CRC and a reduced overall survival. Moreover, we showed that AXL receptor is differently expressed in human CRC cell lines. Dual treatment with the TGFβ galunisertib and the AXL inhibitor, bemcentinib, significantly reduced colony formation and migration capabilities of tumor cells and displayed a strong anti-tumor activity in 3D spheroid cultures derived from patients with advanced CRC. Our work shows that AXL and TGFβ receptors identify a subgroup of CRC with a mesenchymal phenotype and correlate with poor prognosis. Dual inhibition of AXL and TGFβ could represent a novel therapeutic strategy for patients with this aggressive disease

A longitudinal study on BIO14.6 hamsters with dilated cardiomyopathy: micro-echocardiographic evaluation

<p>Abstract</p> <p>Background</p> <p>In recent years, several new technologies for small-animal imaging have been developed. In particular, the use of ultrasound in animal imaging has focused on the investigation of accessible biological structures such as the heart, of which it provides a morphological and functional assessment. The purpose of this study was to investigate the role of micro-ultrasonography (μ-US) in a longitudinal study on BIO14.6 cardiomyopathic hamsters treated with gene therapy.</p> <p>Methods</p> <p>Thirty hamsters were divided into three groups (n = 10): Group I, untreated BIO 14.6 hamsters; Group II, BIO 14.6 hamsters treated with gene therapy; Group III, untreated wild type (WT) hamsters. All hamsters underwent serial μ-US sessions and were sacrificed at predetermined time points.</p> <p>Results</p> <p>μ-US revealed: in Group I, progressive dilation of the left ventricle with a change in heart morphology from an elliptical to a more spherical shape, altered configuration of the mitral valve and subvalvular apparatus, and severe reduction in ejection fraction; in Group II, mild decrease in contractile function and ejection fraction; in Group III, normal cardiac chamber morphology and function. There was a negative correlation between the percentage of fibrosis observed at histology and the ejection fraction obtained on μ-echocardiography (Spearman r: -0.839; p < 0.001).</p> <p>Conclusions</p> <p>Although histological examination remains indispensable for a conclusive diagnosis, high-frequency μ-echocardiography, thanks to the high spatial and contrast resolution, can be considered sufficient for monitoring therapeutic efficacy and/or the progression of dilated cardiomyopathy, providing an alternative tool for repeatable and noninvasive evaluation.</p

Calmodulin-dependent kinase IV links Toll-like receptor 4 signaling with survival pathway of activated dendritic cells.

Microbial products, including lipopolysaccharide (LPS), an agonist of Toll-like receptor 4 (TLR4), regulate the lifespan of dendritic cells (DCs) by largely undefined mechanisms. Here, we identify a role for calcium-calmodulin–dependent kinase IV (CaMKIV) in this survival program. The pharmacologic inhibition of CaMKs as well as ectopic expression of kinase-inactive CaMKIV decrease the viability of monocyte-derived DCs exposed to bacterial LPS. The defect in TLR4 signaling includes a failure to accumulate the phosphorylated form of the cAMP response element-binding protein (pCREB), Bcl-2, and Bcl-xL. CaMKIV null mice have a decreased number of DCs in lymphoid tissues and fail to accumulate mature DCs in spleen on in vivo exposure to LPS. Although isolated Camk4(−/−) DCs are able to acquire the phenotype typical of mature cells and release normal amounts of cytokines in response to LPS, they fail to accumulate pCREB, Bcl-2, and Bcl-xL and therefore do not survive. The transgenic expression of Bcl-2 in CaMKIV null mice results in full recovery of DC survival in response to LPS. These results reveal a novel link between TLR4 and a calcium-dependent signaling cascade comprising CaMKIV-CREB-Bcl-2 that is essential for DC survival

A model for a pulsed terahertz quantum cascade laser under optical feedback

Optical feedback effects in lasers may be useful or problematic, depending on the type of application. When semiconductor lasers are operated using pulsed-mode excitation, their behavior under optical feedback depends on the electronic and thermal characteristics of the laser, as well as the nature of the external cavity. Predicting the behavior of a laser under both optical feedback and pulsed operation therefore requires a detailed model that includes laser-specific thermal and electronic characteristics. In this paper we introduce such a model for an exemplar bound-to-continuum terahertz frequency quantum cascade laser (QCL), illustrating its use in a selection of pulsed operation scenarios. Our results demonstrate significant interplay between electro-optical, thermal, and feedback phenomena, and that this interplay is key to understanding QCL behavior in pulsed applications. Further, our results suggest that for many types of QCL in interferometric applications, thermal modulation via low duty cycle pulsed operation would be an alternative to commonly used adiabatic modulation

Dendritic Cells/Natural Killer Cross-Talk: A Novel Target for Human Immunodeficiency Virus Type-1 Protease Inhibitors

BACKGROUND: HIV-1 Protease Inhibitors, namely PIs, originally designed to inhibit HIV-1 aspartic protease, can modulate the immune response by mechanisms largely unknown, and independent from their activity on viral replication. Here, we analyzed the ability of PIs to interfere with differentiation program of monocytes toward dendritic cell (DCs) lineage, a key process in the inflammatory response. METHODOLOGY/PRINCIPAL FINDINGS: Monocytes from healthy donors were isolated and induced to differentiate in vitro in the presence or absence of saquinavir, ritonavir, nelfinavir, indinavir or amprenavir (sqv, rtv, nlfv, idv, apv, respectively). These drugs demonstrated a differential ability to sustain the generation of immature DCs (iDCs) with an altered phenotype, including low levels of CD1a, CD86, CD36 and CD209. DCs generated in the presence of rtv also failed to acquire the typical phenotype of mature DCs (mDCs), and secreted lower amounts of IL-12 and IL-15. Accordingly, these aberrant mDCs failed to support activation of autologous Natural Killer (NK) cells, and resulted highly susceptible to NK cell-mediated cytotoxicity. CONCLUSIONS/SIGNIFICANCE: Our findings uncover novel functional properties of PIs within the DC-NK cell cross-talk, unveiling the heterogeneous ability of members of this class drugs to drive the generation of atypical monocyte-derived DCs (MDDCs) showing an aberrant phenotype, a failure to respond appropriately to bacterial endotoxin, a weak ability to prime autologous NK cells, and a high susceptibility to NK cell killing. These unexpected properties might contribute to limit inflammation and viral spreading in HIV-1 infected patients under PIs treatment, and open novel therapeutical perspectives for this class drugs as immunomodulators in autoimmunity and cancer