Effects of electromagnetic waves on the electrical properties of contacts between grains

A DC electrical current is injected through a chain of metallic beads. The electrical resistances of each bead-bead contacts are measured. At low current, the distribution of these resistances is large and log-normal. At high enough current, the resistance distribution becomes sharp and Gaussian due to the creation of microweldings between some beads. The action of nearby electromagnetic waves (sparks) on the electrical conductivity of the chain is also studied. The spark effect is to lower the resistance values of the more resistive contacts, the best conductive ones remaining unaffected by the spark production. The spark is able to induce through the chain a current enough to create microweldings between some beads. This explains why the electrical resistance of a granular medium is so sensitive to the electromagnetic waves produced in its vicinity.Comment: 4 pages, 5 figure

Some aspects of electrical conduction in granular systems of various dimensions

We report on measurements of the electrical conductivity in both a 2D triangular lattice of metallic beads and in a chain of beads. The voltage/current characteristics are qualitatively similar in both experiments. At low applied current, the voltage is found to increase logarithmically in a good agreement with a model of widely distributed resistances in series. At high enough current, the voltage saturates due to the local welding of microcontacts between beads. The frequency dependence of the saturation voltage gives an estimate of the size of these welded microcontacts. The DC value of the saturation voltage (~ 0.4 V per contact) gives an indirect measure of the number of welded contact carrying the current within the 2D lattice. Also, a new measurement technique provides a map of the current paths within the 2D lattice of beads. For an isotropic compression of the 2D granular medium, the current paths are localized in few discrete linear paths. This quasi-onedimensional nature of the electrical conductivity thus explains the similarity between the characteristics in the 1D and 2D systems.Comment: To be published in The European Physical Journal

Recent Progress in the Use of Glucagon and Glucagon Receptor Antagonists in the Treatment of Diabetes Mellitus

Glucagon is an important pancreatic hormone, released into blood circulation by alpha cells of the islet of Langerhans. Glucagon induces gluconeogenesis and glycogenolysis in hepatocytes, leading to an increase in hepatic glucose production and subsequently hyperglycemia in susceptible individuals. Hyperglucagonemia is a constant feature in patients with T2DM. A number of bioactive agents that can block glucagon receptor have been identified. These glucagon receptor antagonists can reduce the hyperglycemia associated with exogenous glucagon administration in normal as well as diabetic subjects. Glucagon receptor antagonists include isoserine and beta-alanine derivatives, bicyclic 19-residue peptide BI-32169, Des-His1-[Glu9] glucagon amide and related compounds, 5-hydroxyalkyl-4-phenylpyridines, N-[3-cano-6- (1,1 dimethylpropyl)-4,5,6,7-tetrahydro-1-benzothien-2-yl]-2-ethylbutamide, Skyrin and NNC 250926. The absorption, dosage, catabolism, excretion and medicinal chemistry of these agents are the subject of this review. It emphasizes the role of glucagon in glucose homeostasis and how it could be applied as a novel tool for the management of diabetes mellitus by blocking its receptors with either monoclonal antibodies, peptide and non-peptide antagonists or gene knockout techniques

Expert opinion on pituitary complications in immunotherapy

Hypophysitis is a frequent toxic endocrine side-effect of immunotherapy. Prevalence is higher with anti-CTLA-4 antibodies (4-20%) or in association with PD-1 inhibitors (8%). Diagnosis is presumptive, based on poorly specific clinical symptoms (usually, headache and asthenia) and/or hyponatremia and/or at least one pituitary deficit and/or abnormal imaging. Visual disorder or polyuropolydipsic syndrome are exceptional. In decreasing order of frequency, deficits are thyrotropic (86-100%), gonadotropic (85-100%) or corticotropic (50-73%); somatotropin deficit or abnormal prolactin level are rarer. Pituitary MRI in acute phase shows variable moderate increase in pituitary volume, ruling out differential diagnoses, especially pituitary metastasis. Treatment of corticotropin deficiency requires systematic emergency replacement therapy, with the usual modalities, while treatment of other deficits depends on clinical status and progression. Thyrotropin and gonadotropin deficits usually recover, but corticotropin deficiency persists over the long term, requiring education and specialized endocrinologic follow-up. Onset of hypophysitis does not contraindicate continuation of immunotherapy and does not usually require high dose synthetic glucocorticoids

Recombinant forms of Leishmania amazonensis excreted/secreted promastigote surface antigen (PSA) induce protective immune responses in dogs

International audiencePreventive vaccination is a highly promising strategy for interrupting leishmaniasis transmission that can, additionally, contribute to elimination. A vaccine formulation based on naturally excreted secreted (ES) antigens was prepared from L. infantum promastigote culture supernatant. This vaccine achieved successful results in Phase III trials and was licensed and marketed as CaniLeish. We recently showed that newly identified ES promastigote surface antigen (PSA), from both viable promastigotes and axenically-grown amastigotes, represented the major constituent and the highly immunogenic antigen of L. infantum and L. amazonensis ES products. We report here that three immunizations with either the recombi-nant ES LaPSA-38S (rPSA) or its carboxy terminal part LaPSA-12S (Cter-rPSA), combined with QA-21 as adjuvant, confer high levels of protection in naive L. infantum-infected Beagle dogs, as checked by bone marrow parasite absence in respectively 78.8% and 80% of vaccinated dogs at 6 months post-challenge. The parasite burden in infected vaccinated dogs was significantly reduced compared to placebo group, as measured by q-PCR. Moreover, our results reveal humoral and cellular immune response clear-cut differences between vaccinated and control dogs. An early increase in specific IgG2 antibodies was observed in rPSA/QA-21-and Cter-rPSA/QA-21-immunized dogs only. They were found functionally active in vitro and were highly correlated with vaccine protection. In vaccinated protected dogs, IFN-γ and NO productions, as well as anti-leishmanial macrophage activity, were increased. These data strongly suggest that ES PSA or its carboxy-terminal part, in recom-binant forms, induce protection in a canine model of zoonotic visceral leishmaniasis by inducing a Th1-dominant immune response and an appropriate specific antibody response. These data suggest that they could be considered as important active components in vaccine candidates

In Vitro Evaluation of a Soluble Leishmania Promastigote Surface Antigen as a Potential Vaccine Candidate against Human Leishmaniasis

International audiencePSA (Promastigote Surface Antigen) belongs to a family of membrane-bound and secreted proteins present in severalLeishmania (L.) species. PSA is recognized by human Th1 cells and provides a high degree of protection in vaccinated mice.We evaluated humoral and cellular immune responses induced by a L. amazonensis PSA protein (LaPSA-38S) produced in aL. tarentolae expression system. This was done in individuals cured of cutaneous leishmaniasis due to L. major (CCLm) or L.braziliensis (CCLb) or visceral leishmaniasis due to L. donovani (CVLd) and in healthy individuals. Healthy individuals weresubdivided into immune (HHR-Lm and HHR-Li: Healthy High Responders living in an endemic area for L. major or L. infantuminfection) or non immune/naive individuals (HLR: Healthy Low Responders), depending on whether they produce high orlow levels of IFN-c in response to Leishmania soluble antigen. Low levels of total IgG antibodies to LaPSA-38S were detectedin sera from the studied groups. Interestingly, LaPSA-38S induced specific and significant levels of IFN-c, granzyme B and IL-10 in CCLm, HHR-Lm and HHR-Li groups, with HHR-Li group producing TNF-a in more. No significant cytokine response wasobserved in individuals immune to L. braziliensis or L. donovani infection. Phenotypic analysis showed a significant increasein CD4+ T cells producing IFN-c after LaPSA-38S stimulation, in CCLm. A high positive correlation was observed between thepercentage of IFN-c-producing CD4+ T cells and the released IFN-c. We showed that the LaPSA-38S protein was able toinduce a mixed Th1 and Th2/Treg cytokine response in individuals with immunity to L. major or L. infantum infectionindicating that it may be exploited as a vaccine candidate. We also showed, to our knowledge for the first time, the capacityof Leishmania PSA protein to induce granzyme B production in humans with immunity to L. major and L. infantum infectio

From mesoscale to nanoscale mechanics in single-wall carbon nanotubes

The experimental work was carried out in collaboration with W. Wenseleers and S. Cambré at the University of Antwerp, Belgium. The computational results presented have been achieved in part using the Vienna Scientific Cluster (VSC). DJD is grateful for support from the Region Rhône-Alpes through the programme “Accueil-PRO 2014” and from the iMUST Labex programme “Mobility in 2015”. ACTD, TFTC, WC, MALM, SB, DM and ASM acknowledge support from the French Agence Nationale de la Recherche through contract ANR-11-NANO-025 “TRI-CO”. ACTD acknowledges postdoctoral grant from Brazilian Ministry of Education (CAPES)

French Endocrine Society Guidance on endocrine side-effects of immunotherapy

The management of cancer patients has changed due to the considerably more frequent use of immune checkpoint inhibitors (ICPI). However, the use of ICPI has a risk of side-effects, particularly endocrine toxicity. Since the indications for ICPI are constantly expanding due to their efficacy, it is important that endocrinologists and oncologists know how to look for this type of toxicity and how to treat it when it arises. In view of this, the French Endocrine Society initiated the formulation of a consensus document on ICPI-related endocrine toxicity. In this paper, we will introduce data on the general pathophysiology of endocrine toxicity, we will then outline expert opinion focusing primarily on methods for screening, management and monitoring for endocrine side-effects in patients treated by ICPI. We will then look in turn at endocrinopathies that are induced by ICPI including dysthyroidism, hypophysitis, primary adrenal insufficiency and fulminant diabetes. In each chapter, expert opinion will be given on the diagnosis, management and monitoring for each complication. These expert opinions will also discuss the methodology for categorizing these side-effects in oncology using \u27Common terminology criteria for adverse events\u27 (CTCAE) and the difficulties in applying this to endocrine side-effects in the case of these anti-cancer therapies. This is shown in particular by certain recommendations that are used for other side-effects (high-dose corticosteroids, contra-indicated in ICPI for example), and that cannot be considered as appropriate in the management of endocrine toxicity, as it usually does not require ICPI withdrawal or high dose glucocorticoid intake

A collaboratively derived environmental research agenda for Galapagos

Galápagos is one of the most pristine archipelagos in the world and its conservation relies upon research and sensible management. In recent decades both the interest in, and the needs of, the islands have increased, yet the funds and capacity for necessary research have remained limited. It has become, therefore, increasingly important to identify areas of priority research to assist decision-making in Galápagos conservation. This study identified 50 questions considered priorities for future research and management. The exercise involved the collaboration of policy makers, practitioners and researchers from more than 30 different organisations. Initially, 360 people were consulted to generate 781 questions. An established process of preworkshop voting and three rounds to reduce and reword the questions, followed by a two-day workshop, was used to produce the final 50 questions. The most common issues raised by this list of questions were human population growth, climate change and the impact of invasive alien species. These results have already been used by a range of organisations and politicians and are expected to provide the basis for future research on the islands so that its sustainability may be enhanced. </jats:p