Abstract Pathogenic microorganisms have to face hostile environments while colonizing and infecting their hosts. Unfortunately, they can cope with it and have evolved a number of complex secretion ...systems, which direct virulence factors either at the bacterial cell surface into the environmental extracellular milieu or into the host cell cytosol. Six different classes of secretion systems have been described so far, currently identified as type I secretion system (T1SS) up to type VI secretion system (T6SS). The Gram-negative opportunistic human pathogen Pseudomonas aeruginosa possesses a broad panel of secretion systems. Five of the six secretion machines characterized in Gram-negative bacteria are at P. aeruginosa disposal, sometimes in several copies. All these machines are dedicated to the specific secretion of exoproteins, which display various activities useful for bacterial adaptation to the environment or for bacterial pathogenicity. This review will summarize the functional organization of these different secretion systems, which could constitute potential targets for therapeutic treatment of patients infected by one of the most potent nosocomial pathogens identified nowadays.
The development of efficient solid-state sources of single photons is a major challenge in the context of quantum communication, optical quantum information processing and metrology. Such a source ...must enable the implementation of a stable, single-photon emitter, like a colour centre in diamond or a semiconductor quantum dot. Achieving a high extraction efficiency has long been recognized as a major issue, and both classical solutions and cavity quantum electrodynamics effects have been applied. We adopt a different approach, based on an InAs quantum dot embedded in a GaAs photonic nanowire with carefully tailored ends. Under optical pumping, we demonstrate a record source efficiency of 0.72, combined with pure single-photon emission. This non-resonant approach also provides broadband spontaneous emission control, thus offering appealing novel opportunities for the development of single-photon sources based on spectrally broad emitters, wavelength-tunable sources or efficient sources of entangled photon pairs.
Purpose Blinatumomab is a bispecific T-cell engager antibody construct targeting CD19 on B-cell lymphoblasts. We evaluated the safety, pharmacokinetics, recommended dosage, and potential for efficacy ...of blinatumomab in children with relapsed/refractory B-cell precursor acute lymphoblastic leukemia (BCP-ALL). Methods This open-label study enrolled children < 18 years old with relapsed/refractory BCP-ALL in a phase I dosage-escalation part and a phase II part, using 6-week treatment cycles. Primary end points were maximum-tolerated dosage (phase I) and complete remission rate within the first two cycles (phase II). Results We treated 49 patients in phase I and 44 patients in phase II. Four patients had dose-limiting toxicities in cycle 1 (phase I). Three experienced grade 4 cytokine-release syndrome (one attributed to grade 5 cardiac failure); one had fatal respiratory failure. The maximum-tolerated dosage was 15 µg/m
/d. Blinatumomab pharmacokinetics was linear across dosage levels and consistent among age groups. On the basis of the phase I data, the recommended blinatumomab dosage for children with relapsed/refractory ALL was 5 µg/m
/d for the first 7 days, followed by 15 µg/m
/d thereafter. Among the 70 patients who received the recommended dosage, 27 (39%; 95% CI, 27% to 51%) achieved complete remission within the first two cycles, 14 (52%) of whom achieved complete minimal residual disease response. The most frequent grade ≥ 3 adverse events were anemia (36%), thrombocytopenia (21%), and hypokalemia (17%). Three patients (4%) and one patient (1%) had cytokine-release syndrome of grade 3 and 4, respectively. Two patients (3%) interrupted treatment after grade 2 seizures. Conclusion This trial, which to the best of our knowledge was the first such trial in pediatrics, demonstrated antileukemic activity of single-agent blinatumomab with complete minimal residual disease response in children with relapsed/refractory BCP-ALL. Blinatumomab may represent an important new treatment option in this setting, requiring further investigation in curative indications.
Innate lymphoid cells (ILCs) have potent immunological functions in experimental conditions in mice, but their contributions to immunity in natural conditions in humans have remained unclear. We ...investigated the presence of ILCs in a cohort of patients with severe combined immunodeficiency (SCID). All ILC subsets were absent in patients with SCID who had mutation of the gene encoding the common γ-chain cytokine receptor subunit IL-2Rγ or the gene encoding the tyrosine kinase JAK3. T cell reconstitution was observed in patients with SCID after hematopoietic stem cell transplantation (HSCT), but the patients still had considerably fewer ILCs in the absence of myeloablation than did healthy control subjects, with the exception of rare cases of reconstitution of the ILC1 subset of ILCs. Notably, the ILC deficiencies observed were not associated with any particular susceptibility to disease, with follow-up extending from 7 years to 39 years after HSCT. We thus report here selective ILC deficiency in humans and show that ILCs might be dispensable in natural conditions, if T cells are present and B cell function is preserved.
We introduce the photonic trumpet, a dielectric structure which ensures a nearly perfect coupling between an embedded quantum light source and a Gaussian free-space beam. A photonic trumpet exploits ...both the broadband spontaneous emission control provided by a single-mode photonic wire and the expansion of this mode within a conical taper. Numerical simulations highlight the performance and robustness of this concept. As a first application in the field of quantum optics, we report the realization of an ultrabright single-photon source. The device, a high aspect ratio GaAs photonic trumpet containing a few InAs quantum dots, demonstrates a first-lens external efficiency of 0.75±0.1 and an external coupling efficiency to a Gaussian beam as high as 0.58±0.08.
We experimentally investigate the spontaneous emission (SE) rates of single InAs quantum dots embedded in GaAs photonic nanowires. For a diameter leading to the optimal confinement of the fundamental ...guided mode HE11, the coupling to HE11 dominates the SE process and an increase of the SE rate by a factor of 1.5 is achieved. When the diameter is decreased, the coupling to this mode vanishes rapidly, thus allowing the coupling to the other radiation modes to be probed. In these conditions, a SE inhibition factor of 16, equivalent to the one obtained in state-of-the-art photonic crystals, is measured. These results, which are supported by fully vectorial calculations, confirm the potential of photonic nanowires for a nearly perfect, broadband SE control.
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