A dairy bacterium displays in vitro probiotic properties for the pharyngeal mucosa by antagonizing group A streptococci and modulating the immune response

The probiotic approach represents an alternative strategy in the prevention and treatment of infectious diseases, not only at the intestinal level but also at other sites of the body where the microbiota plays a role in the maintenance of physiological homeostasis. In this context, we evaluated in vitro the potential abilities of probiotic and dairy bacteria in controlling Streptococcus pyogenes infections at the pharyngeal level. Initially, we analyzed bacterial adhesion to FaDu hypopharyngeal carcinoma cells and the ability to antagonize S. pyogenes on FaDu cell layers and HaCat keratinocytes. Due to its promising adhesive and antagonistic features, we studied the dairy strain Lactobacillus helveticus MIMLh5, also through in vitro immunological experiments. First, we performed quantification of several cytokines and measurement of NF-\u3baB activation in FaDu cells. MIMLh5 efficiently reduced the induction of interleukin-6 (IL-6), IL-8, and tumor necrosis factor alpha (TNF-\u3b1), in a dose-dependent manner. After stimulation of cells with IL-1\u3b2, active NF-\u3baB was still markedly lowered. Nevertheless, we observed an increased secretion of IL-6, gamma interferon (IFN-\u3b3), and granulocyte-macrophage colony-stimulating factor (GM-CSF) under these conditions. These effects were associated with the ability of MIMLh5 to enhance the expression of the heat shock protein coding gene hsp70. In addition, MIMLh5 increased the GM-CSF/G-CSF ratio. This is compatible with a switch of the immune response toward a TH1 pathway, as supported by our observation that MIMLh5, once in contact with bone marrow-derived dendritic cells, triggered the secretion of TNF-\u3b1 and IL-2. In conclusion, we propose MIMLh5 as a potential probiotic bacterium for the human pharynx, with promising antagonistic and immunomodulatory properties

Buffer breakdown in GaN-on-Si HEMTs: A comprehensive study based on a sequential growth experiment

Abstract The aim of this work is to investigate the breakdown mechanisms of the layers constituting the vertical buffer of GaN-on-Si HEMTs; in addition, for the first time we demonstrate that the breakdown field of the AlN nucleation layer grown on a silicon substrate is equal to 3.2 MV/cm and evaluate its temperature dependence. To this aim, three samples, obtained by stopping the epitaxial growth of a GaN on Silicon stack at different steps, are studied and compared: Si/AlN, Si/AlN/AlGaN, full vertical stack up to the Carbon doped buffer layer. The current-voltage (IV) characterizations performed at both room temperature and high temperature show that: (i) the defectiveness of the AlN nucleation layer is the root cause of the leakage through an AlN/Silicon junction, and causes the vertical I-V characteristics to have a high device-to-device variability; (ii) the first AlGaN layer grown over the AlN, beside improving the breakdown voltage of the whole structure, causes the leakage current to be more stable and uniform across the sample area; (iii) a thick strain-relief stack and a carbon-doped GaN buffer enhance the breakdown voltage up to more than 750 V at 170 °C, and guarantee a remarkably low device-to-device variability. Furthermore, a set of constant voltage stress on the Si/AlN sample demonstrate that the aluminum nitride layer shows a time dependent breakdown, with Weibull-distributed failures and a shape factor greater than 1, in line with the percolation model

Design and Vertical Tests of SPS-series Double-Quarter Wave (DQW) Cavity Prototypes for the HL-LHC Crab Cavity System

Crab crossing is essential for high-luminosity colliders. The High Luminosity Large Hadron Collider (HL-LHC) will equip one of its Interaction Points (IP1) with Double-Quarter Wave (DQW) crab cavities. A DQW cavity is a new generation of deflecting RF cavities that stands out for its compactness and broad frequency separation between fundamental and first high-order modes. The deflecting kick is provided by its fundamental mode. Each HL-LHC DQW cavity shall provide a nominal deflecting voltage of 3.4 MV, although up to 5.0 MV may be required. A Proof-of-Principle (PoP) DQW cavity was limited by quench at 4.6 MV. This paper describes a new, highly optimized cavity, designated DQW SPS-series, which satisfies dimensional, cryogenic, manufacturing and impedance requirements for beam tests at SPS and operation in LHC. Two prototypes of this DQW SPS-series were fabricated by US industry and cold tested after following conventional SRF surface treatment. Both units outperformed the PoP cavity, reaching a deflecting voltage of 5.3-5.9 MV. This voltage - the highest reached by a DQW cavity - is well beyond the nominal voltage of 3.4 MV and may even operate at the ultimate voltage of 5.0MVwith sufficient margin. This paper covers fabrication, surface preparation and cryogenic RF test results and implications

Surgical approaches for possible positions of an olfactory implant to stimulate the olfactory bulb

Introduction: Current scientific developments seem to allow for an "olfactory implant"in analogy to cochlear implants. However, the position and surgical approaches for electrical stimulation of the olfactory system are unclear. Methods: In a human anatomic cadaver study, we investigated different endoscopic approaches to electrically stimulate the olfactory bulb (OB) based on the following considerations: (1) the stimulating electrode should be close to the OB. (2) The surgical procedure should be as non-invasive and safe as possible and (3) as easy as possible for an experienced ENT surgeon. Results: In summary, the endoscopic intracranial positioning of the electrode via a widened ostium of the fila olfactoria or a frontal sinus surgery like a Draf IIb procedure is a good option in terms of patients' risk, degree of difficulty for ENT surgeons, and position to the OB. Endoscopic intranasal positioning appeared to be the best option in terms of patient risk and the degree of difficulty for ENT surgeons. Although a bigger approach to the OB using a drill and the combined intranasal endoscopic and external approach enabled a close placement of the electrode to the OB, they do not seem relevant in practice due to their higher invasiveness. Conclusion: The study suggested that an intranasal positioning of a stimulating electrode is possible, with placements beneath the cribriform plate, extra- or intracranially, applying elegant surgical techniques with low or medium risk to the patient and a close placement to OB

Endoscopic-assisted transorbital surgery: Where do we stand on the scott’s parabola? personal considerations after a 10-year experience

Transorbital approaches are genuinely versatile surgical routes which show interesting potentials in skull base surgery. Given their "new" trajectory, they can be a very useful adjunct to traditional routes, even being a valid alternative to them in some cases, and add valuable opportunities in selected patients. Indications are constantly expanding, and currently include selected intraorbital, skull base and even intra-axial lesions, both benign and malignant. Given their relatively recent development and thus unfamiliarity among the skull base community, achieving adequate proficiency needs not only a personalized training and knowledge but also, above all, an adequate case volume and a dedicated setting. Current, but mostly future, applications should be selected by genetic, omics and biological features and applied in the context of a truly multidisciplinary environment

Engineering Design and Prototype Fabrication of HOM Couplers for HL-LHC Crab Cavities

The High-Luminosity upgrade for the LHC relies on a set of RF Crab Cavities for reaching its goals. Two parallel concepts, the Double Quarter Wave (DQW) and the RF Dipole (RFD), are going through a comprehensive design process along with preparation of fabrication in view of extensive tests with beam in SPS. High Order Modes (HOM) couplers are critical in providing damping in RF cavities for operation in accelerators. HOM prototyping and fabrication have recently started at CERN. In this paper, an overview of the final shape is provided along with an insight in the mechanical and thermal analyses performed to validate the design of these critical components. Emphasis is also given to test campaigns, material selection, prototyping and initial fabrication that are aimed at fulfilling the highly demanding tolerances of the couplers

Identification of the safe(r) by design alternatives for nanosilver-enabled wound dressings

The use of silver nanoparticles (NPs) in medical devices is constantly increasing due to their excellent antimicrobial properties. In wound dressings, Ag NPs are commonly added in large excess to exert a long-term and constant antimicrobial effect, provoking an instantaneous release of Ag ions during their use or the persistence of unused NPs in the wound dressing that can cause a release of Ag during the end-of-life of the product. For this reason, a Safe-by-Design procedure has been developed to reduce potential environmental risks while optimizing functionality and costs of wound dressings containing Ag NPs. The SbD procedure is based on ad-hoc criteria (e.g., mechanical strength, antibacterial effect, leaching of Ag from the product immersed in environmental media) and permits to identify the best one among five pre-market alternatives. A ranking of the SbD alternatives was obtained and the safer solution was selected based on the selected SbD criteria. The SbD framework was also applied to commercial wound dressings to compare the SbD alternatives with products already on the market. The iterative procedure permitted to exclude one of the alternatives (based on its low mechanical strength) and proved to be an effective approach that can be replicated to support the ranking, prioritisation, and selection of the most promising options early in the innovation process of nano-enabled medical devices as well as to encourage the production of medical devices safer for the environment