Grooved Laminated Waveguide devices for U-, V-, W-and G-band applications

International audienceThis paper reports on the results of the design and manufacturing of straight sections, tees, bends and loads in a Grooved Laminated Waveguide (GLWG) topology. These devices, intended for the U-, V-, W- and G-band, are fabricated in Low Temperature Co-fired Ceramics (LTCC) technology using the low relative permittivity tape, ESL41110, from ElectroScience Laboratory. Measurements ranging from 40 to 170 GHz prove the concept of grooved laminated waveguides

Grooved Laminated Waveguides in LTCC for mm-wave packaging

International audienceThe Laminated Waveguide (LWG) has earned lots of attention recently in its one-layer form referred to as Substrate Integrated Waveguide (SIW). This paper reports on the fabrication and measurement results of a type of LWG, the Grooved Laminated Waveguide (GLWG) which is implemented in Low Temperature Co-fired Ceramics (LTCC). Results are given on the fabrication issues and measurements for GLWG devices realized in one and four LTCC layers, working in four distinct frequency bands; U, V, W and G, i.e. from 40 to 220 GHz

Selective Expression of the Vβ14 T Cell Receptor on Leishmania guyanensis-Specific CD8+ T Cells during Human Infection

Peripheral blood mononuclear cells from subjects never exposed to Leishmania were stimulated with Leishmania guyanensis. We demonstrated that L. guyanensis-stimulated CD8+ T cells produced interferon (IFN)-γ and preferentially expressed the Vb14 T cell receptor (TCR) gene family. In addition, these cells expressed cutaneous lymphocyte antigen and CCR4 surface molecules, suggesting that they could migrate to the skin. Results obtained from the lesions of patients with localized cutaneous leishmaniaisis (LCL) showed that Vβ14 TCR expression was increased in most lesions (63.5%) and that expression of only a small number of Vb gene families (Vβ1, Vβ6, Vβ9, Vβ14, and Vβ24) was increased. The presence of Vβ14 T cells in tissue confirmed the migration of these cells to the lesion site. Thus, we propose the following sequence of events during infection with L. guyanensis. After initial exposure to L. guyanensis, CD8+ T cells preferentially expressing the Vb14 TCR and secreting IFN-γ develop and circulate in the periphery. During the infection, these cells migrate to the skin at the site of the parasitic infection. The role of these Vβ14 CD8+ T cells in resistance to infection remains to be determined conclusivel

T Cell Reactivity against Mycolyl Transferase Antigen 85 of M. tuberculosis in HIV-TB Coinfected Subjects and in AIDS Patients Suffering from Tuberculosis and Nontuberculous Mycobacterial Infections

The mycolyl transferase antigen 85 complex is a major secreted protein family from mycobacterial culture filtrate, demonstrating powerful T cell stimulatory properties in most HIV-negative, tuberculin-positive volunteers with latent M.tuberculosis infection and only weak responses in HIV-negative tuberculosis patients. Here, we have analyzed T cell reactivity against PPD and Ag85 in HIV-infected individuals, without or with clinical symptoms of tuberculosis, and in AIDS patients with disease caused by nontuberculous mycobacteria. Whereas responses to PPD were not significantly different in HIV-negative and HIV-positive tuberculin-positive volunteers, responses to Ag85 were significantly decreased in the HIV-positive (CDC-A and CDC-B) group. Tuberculosis patients demonstrated low T cell reactivity against Ag85, irrespective of HIV infection, and finally AIDS patients suffering from NTM infections were completely nonreactive to Ag85. A one-year follow-up of twelve HIV-positive tuberculin-positive individuals indicated a decreased reactivity against Ag85 in patients developing clinical tuberculosis, highlighting the protective potential of this antigen

Le développement de la technologie LTCC dans le LabSticc pour une intégration mixte RF et optoélectronique

National audienceLa technologie Low Temperature Co-fired Ceramics (LTCC) ou céramique cocuite à basse température, fait désormais partie de la filière technologie que propose le LabSticc. Nous apportons ici des précisions sur l'avancement de la mise en place de cette technologie, sur nos projets actuels et sur les pistes de développement que nous suivrons à l'avenir proche

In Leishmaniasis due to Leishmania guyanensis infection, distinct intralesional interleukin-10 and foxp3 mRNA expression are associated with unresponsiveness to treatment

The presence of intralesional natural regulatory T cells, characterized by the expression of Foxp3 mRNA, was analyzed in patients with localized leishmaniasis due to Leishmania guyanensis infection that was unresponsive to treatment with pentamidine isethionate. Foxp3 mRNA levels were associated with unresponsiveness to treatment among patients with a lesion duration of ⩾1 month, but this association was not observed among patients with a lesion duration of <1 month. In conclusion, high intralesional expression of Foxp3 might be an indicator of poor response to treatment, depending on the duration of lesion

Leishmaniavirus-dependent metastatic leishmaniasis is prevented by blocking IL-17A

Cutaneous leishmaniasis has various outcomes, ranging from self-healing reddened papules to extensive open ulcerations that metastasise to secondary sites and are often resistant to standard therapies. In the case of L. guyanensis (L.g), about 5-10% of all infections result in metastatic complications. We recently showed that a cytoplasmic virus within L.g parasites (LRV1) is able to act as a potent innate immunogen, worsening disease outcome in a murine model. In this study, we investigated the immunophenotype of human patients infected by L.g and found a significant association between the inflammatory cytokine IL-17A, the presence of LRV1 and disease chronicity. Further, IL-17A was inversely correlated to the protective cytokine IFN-γ. These findings were experimentally corroborated in our murine model, where IL-17A produced in LRV1+ L.g infection contributed to parasite virulence and dissemination in the absence of IFN-γ. Additionally, IL-17A inhibition in mice using digoxin or SR1001, showed therapeutic promise in limiting parasite virulence. Thus, this murine model of LRV1-dependent infectious metastasis validated markers of disease chronicity in humans and elucidated the immunologic mechanism for the dissemination of Leishmania parasites to secondary sites. Moreover, it confirms the prognostic value of LRV1 and IL-17A detection to prevent metastatic leishmaniasis in human patients

Autophagy protein 5 controls flow-dependent endothelial functions

Dysregulated autophagy is associated with cardiovascular and metabolic diseases, where impaired flow-mediated endothelial cell responses promote cardiovascular risk. The mechanism by which the autophagy machinery regulates endothelial functions is complex. We applied multi-omics approaches and in vitro and in vivo functional assays to decipher the diverse roles of autophagy in endothelial cells. We demonstrate that autophagy regulates VEGF-dependent VEGFR signaling and VEGFR-mediated and flow-mediated eNOS activation. Endothelial ATG5 deficiency in vivo results in selective loss of flow-induced vasodilation in mesenteric arteries and kidneys and increased cerebral and renal vascular resistance in vivo. We found a crucial pathophysiological role for autophagy in endothelial cells in flow-mediated outward arterial remodeling, prevention of neointima formation following wire injury, and recovery after myocardial infarction. Together, these findings unravel a fundamental role of autophagy in endothelial function, linking cell proteostasis to mechanosensing

Extracorporeal Membrane Oxygenation for Severe Acute Respiratory Distress Syndrome associated with COVID-19: An Emulated Target Trial Analysis.

RATIONALE: Whether COVID patients may benefit from extracorporeal membrane oxygenation (ECMO) compared with conventional invasive mechanical ventilation (IMV) remains unknown. OBJECTIVES: To estimate the effect of ECMO on 90-Day mortality vs IMV only Methods: Among 4,244 critically ill adult patients with COVID-19 included in a multicenter cohort study, we emulated a target trial comparing the treatment strategies of initiating ECMO vs. no ECMO within 7 days of IMV in patients with severe acute respiratory distress syndrome (PaO2/FiO2 <80 or PaCO2 ≥60 mmHg). We controlled for confounding using a multivariable Cox model based on predefined variables. MAIN RESULTS: 1,235 patients met the full eligibility criteria for the emulated trial, among whom 164 patients initiated ECMO. The ECMO strategy had a higher survival probability at Day-7 from the onset of eligibility criteria (87% vs 83%, risk difference: 4%, 95% CI 0;9%) which decreased during follow-up (survival at Day-90: 63% vs 65%, risk difference: -2%, 95% CI -10;5%). However, ECMO was associated with higher survival when performed in high-volume ECMO centers or in regions where a specific ECMO network organization was set up to handle high demand, and when initiated within the first 4 days of MV and in profoundly hypoxemic patients. CONCLUSIONS: In an emulated trial based on a nationwide COVID-19 cohort, we found differential survival over time of an ECMO compared with a no-ECMO strategy. However, ECMO was consistently associated with better outcomes when performed in high-volume centers and in regions with ECMO capacities specifically organized to handle high demand. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/)

Interleukin (IL)–13 Is the Predominant Th2 Cytokine in Localized Cutaneous Leishmaniasis Lesions and Renders Specific CD4 + T Cells Unresponsive to IL‐12

International audienceSemiquantitative reverse transcription-polymerase chain reaction analysis of leishmania lesion cytokine profile showed a Th2 cytokine expression pattern, as reflected by interleukin (IL)-4 and IL-13 mRNA expression. There was a predominance of IL-13 in most lesions from patients with American localized cutaneous leishmaniasis caused by Leishmania guyanensis. IL-13 production by peripheral blood mononuclear cells in response to specific leishmania antigens was confirmed in these patients. The absence of the second chain of the IL-12 receptor (IL-12Rbeta2) mRNA expression in lesions and the presence of specific IgE and IgG4 in some serum samples demonstrated the functional role of these Th2 cytokines. IL-13, unlike IL-4, rendered specific T cells unresponsive to IL-12 by inhibiting the expression of the IL-12Rbeta2 chain. These data establish the crucial role of IL-13 in human cutaneous leishmaniasis