A novel assay of biofilm antifungal activity reveals that amphotericin B and caspofungin lyse Candida albicans cells in biofilms

The ability of Candida albicans to form drug-resistant biofilms is an important factor in its contribution to human disease. Assays to identify and characterize molecules with activity against fungal biofilms are crucial for the development of drugs with improved anti-biofilm activity. Here we report the application of an adenylate kinase (AK)-based cytotoxicity assay of fungal cell lysis to the characterization of agents active against C. albicans biofilms. We have developed three protocols for the AK assay. The first measures AK activity in the supernatants of biofilms treated with antifungal drugs and can be performed in parallel with a standard 2,3-bis-(2-methoxy-4-nitro-5-sulphophenyl)-2H-tetrazolium-5-caboxanilide-based biofilm susceptibility assay; a second, more sensitive protocol measures the AK activity present within the biofilm matrix; and a third procedure allows the direct visualization of lytic activity toward biofilms formed on catheter material. Amphotericin B and caspofungin, the two most effective anti-biofilm drugs currently used to treat fungal infections, both directly lyse planktonic C. albicans cells in vitro, leading to the release of AK into the culture medium. These studies serve to validate the AK-based lysis assay as a useful addition to the methods for the characterization of antifungal agents active toward biofilms and provide insights into the mode of action of amphotericin B and caspofungin against C. albicans biofilms.     

Novel, nanoporous silica and titania layers fabricated by magnetron sputtering

Composite asymmetric membranes are fabricated through the deposition of submicrometer thick (100 nm) silica (SiO(2)) and titania (TiO(2)) films onto flat nanoporous silica and zirconia substrates by magnetron sputtering. The deposition conditions for both coating types were systematically altered to determine their influence on the deposited coating morphology and thickness. Ideal He/N(2) gas selectivity was measured for all of the membranes. The TiO(2) coatings, when deposited onto a ZrO(2) support layer with a pore size of 3 nm, formed a long columnar grain structure with average column diameter of 38 nm. A similar columnar structure was observed for TiO(2) coatings deposited onto a SiO(2) support layer with a pore size of 1 nm. Under the same conditions, SiO(2) coatings, deposited onto the same SiO(2) supports, formed a closely packed spherical grain structure whereas, when deposited onto ZrO(2) supports, the SiO(2) coatings formed an open grain structure. The average SiO(2) grain diameter was 36 nm in both cases. This preliminary investigation was aimed at studying the effect of sputtering parameters on the density and morphology of the deposited coatings. For the depositions carried out, the coating material was found to be very dense. However, the presence of grain boundaries resulted in poor ideal He/N(2) separation efficiencies.     

LTCC package for high temperature applications

There is a growing demand for sensors and electronics that can work in harsh environments and at high temperature. Applications include sensors and actuators for control in petroleum and geothermal industry, process monitoring and distributed control systems in the automotive and aerospace fields. Process development and packaging materials for electronic devices are closely connected to such packaging issues. In many cases the package is as important as the device itself in meeting the applications needs.Low temperature co-fired ceramics (LTCC) and thick-film technologies have the potential to incorporate multilayer structures, enabling fabrication of specialized packaging systems. LTCC technology enables easy electrical or optical connections within and between layers in addition to enabling use of integrated passive components, heaters, sensors, converters etc.This paper presents attempts to develop a reliable packaging technology for silicon carbide (SiC) based hydrogen sensors operating at temperatures up to 300 °C. Some simulations of thermal properties were carried out and package structures were made and investigated. The package protects the sensor against mechanical damage and makes possible easy electrical connections. Moreover, the heater and temperature sensors allow for proper temperature regulation of the element. The manufacturing process, basic electrical parameters of the integrated heater as well as real temperature distribution are presented.     

Impact of Copper-Doped Mesoporous Bioactive Glass Nanospheres on the Polymerisation Kinetics and Shrinkage Stress of Dental Resin Composites

We embedded copper-doped mesoporous bioactive glass nanospheres (Cu-MBGN) with antibacterial and ion-releasing properties into experimental dental composites and investigated the effect of Cu-MBGN on the polymerisation properties. We prepared seven composites with a BisGMA/TEGDMA (60/40) matrix and 65 wt.% total filler content, added Cu-MBGN or a combination of Cu-MBGN and silanised silica to the silanised barium glass base, and examined nine parameters: light transmittance, degree of conversion (DC), maximum polymerisation rate (R_max), time to reach R_max, linear shrinkage, shrinkage stress (PSS), maximum PSS rate, time to reach maximum PSS rate, and depth of cure. Cu-MBGN without silica accelerated polymerisation, reduced light transmission, and had the highest DC (58.8 ± 0.9%) and R_max (9.8 ± 0.2%/s), but lower shrinkage (3 ± 0.05%) and similar PSS (0.89 ± 0.07 MPa) versus the inert reference (0.83 ± 0.13 MPa). Combined Cu-MBGN and silica slowed the R_max and achieved a similar DC but resulted in higher shrinkage. However, using a combined 5 wt.% Cu-MBGN and silica, the PSS resembled that of the inert reference. The synergistic action of 5 wt.% Cu-MBGN and silanised silica in combination with silanised barium glass resulted in a material with the highest likelihood for dental applications in future.     

CAST3M/ARCTURUS: A coupled heat transfer CFD code for thermal–hydraulic analyzes of gas cooled reactors

The safety of gas cooled reactors (High Temperature Reactors (HTR), Very High Temperature Reactors (VHTR) or Gas Cooled Fast Reactors (GFR)) must be ensured by systems (active or passive) which maintain loads on component (fuel) and structures (vessel, containment) within acceptable limits under accidental conditions. To achieve this objective, thermal–hydraulics computer codes are necessary tools to design, enhance the performance and ensure a high safety level of the different reactors. Some key safety questions are related to the evaluation of decay heat removal and containment pressure and thermal loads. This requires accurate simulations of conduction, convection, thermal radiation transfers and energy storage. Coupling with neutronics is also an important modeling aspect for the determination of representative parameters such as neutronics coefficient (Doppler coefficient, Moderator coeffcient, …), critical position of control rods, reactivity insertion aspects, …. For GFR, the high power density of the core and its necessary reduced dimension cannot rely only on passive systems for decay heat removal. Therefore, forced convection using active safety systems (gas blowers, heat exchangers, …) are highly recommended. Nevertheless, in case of station black-out, the safety demonstration of the concept should be guaranteed by natural circulation heat removal. This could be performed by keeping a relatively high back-up pressure for pure helium convection and also by heavy gas injection. So, it is also necessary to model mixing of different gases, the on-set of natural convection and the pressure and thermal loads onto the proximate or guard containment. In this paper, we report on the developments of the CAST3M/ARCTURUS thermal–hydraulics (Lumped Parameter and CFD) code developed at CEA, including its coupling to the neutronics code CRONOS2 and the system code CATHARE. Elementary validation cases are detailed, as well as application of the code to benchmark problems such as the HTR-10 thermal–hydraulic exercise. Examples of containment thermal–hydraulics calculations for fast reactor design (GFR) are also detailed.     

Inclusion Body Myositis and Neoplasia: A Narrative Review

Inclusion body myositis (IBM) is an acquired, late-onset inflammatory myopathy, with both inflammatory and degenerative pathogenesis. Although idiopathic inflammatory myopathies may be associated with malignancies, IBM is generally not considered paraneoplastic. Many studies of malignancy in inflammatory myopathies did not include IBM patients. Indeed, IBM is often diagnosed only after around 5 years from onset, while paraneoplastic myositis is generally defined as the co-occurrence of malignancy and myopathy within 1 to 3 years of each other. Nevertheless, a significant association with large granular lymphocyte leukemia has been recently described in IBM, and there are reports of cancer-associated IBM. We review the pathogenic mechanisms supposed to be involved in IBM and outline the common mechanisms in IBM and malignancy, as well as the therapeutic perspectives. The terminally differentiated, CD8+ highly cytotoxic T cells expressing NK features are central in the pathogenesis of IBM and, paradoxically, play a role in some cancers as well. Interferon gamma plays a central role, mostly during the early stages of the disease. The secondary mitochondrial dysfunction, the autophagy and cell cycle dysregulation, and the crosstalk between metabolic and mitogenic pathways could be shared by IBM and cancer. There are intermingled subcellular mechanisms in IBM and neoplasia, and probably their co-existence is underestimated. The link between IBM and cancers deserves further interest, in order to search for efficient therapies in IBM and to improve muscle function, life quality, and survival in both diseases.     

Cannabidiol and Nano-Selenium Increase Microvascularization and Reduce Degenerative Changes in Superficial Breast Muscle in C. perfringens-Infected Chickens

Here, we demonstrated the potential of Cannabis-derived cannabidiol (CBD) and nanosized selenium (nano-Se) for the modulation of microvascularization and muscle fiber lesions in superficial breast muscle in C. perfringens-challenged chickens. The administration of CBD resulted in a decreased number of atrophic fibers (3.13 vs. 1.13/1.5 mm²) compared with the control, whereas nano-Se or both substances resulted in a decreased split fiber number (4.13 vs. 1.55/1.5 mm²) and in a lower number of necrotic myofibers (2.38 vs. 0.69/1.5 mm²) in breast muscle than the positive control. There was a significantly higher number of capillary vessels in chickens in the CBD+Nano-Se group than in the control and positive control groups (1.31 vs. 0.97 and 0.98, respectively). Feeding birds experimental diets lowered the activity of DNA damage repair enzymes, including 3,N4-ethenodeoxycytosine (by 39.6%), 1,N6-ethenodeoxyadenosine (by 37.5%), 8-oxo-guanine (by 36.2%), formamidopyrimidine (fapy)-DNA glycosylase (by 56.2%) and human alkyl adenine DNA glycosylase (by 40.2%) in the ileal mucosa, but it did not compromise the blood mitochondrial oxygen consumption rate (−2.67 OD/min on average). These findings indicate a potential link between gut mucosa condition and histopathological changes in superficial pectoral muscle under induced inflammation and show the ameliorative effect of CBD and nano-Se in this cross-talk due to their protection from mucosal DNA damage.     

MK2 Promotes the Development and Progression of Pancreatic Neuroendocrine Tumors Mediated by Macrophages and Metabolomic Factors

Cases of pancreatic neuroendocrine tumors (PNETs) are growing in number, and new treatment options are needed in order to improve patient outcomes. The mitogen-activated protein kinase-activated protein kinase 2 (MK2) is a crucial regulator of cytokine/chemokine production. The significance of MK2 expression and signaling pathway mediated by MK2 in PNETs has not been investigated. To characterize the impact of MK2 on PNET growth, we used the RipTag2 transgenic murine model of PNETs, and we developed a primary PNET cell line for both in vitro and in vivo studies. In the transgenic murine model of PNETs, we found that MK2 inhibition improves survival of mice and prevents PNET progression. MK2 blockade abolished cytokine/chemokine production, which was related to macrophage function. A role for MK2 in the regulation of metabolic factor secretion in PNETs was identified, making this the first study to identify a potential role for the MK2 pathway in regulation of tumor metabolism. Moreover, using an in vitro approach and allograft model of PNETs, we were able to show that macrophages with MK2 depletion exhibit increased cytotoxicity against PNET cells and substantially decreased production of pro-inflammatory cytokines and chemokines, as well as metabolic factors. Taken together, our work identifies MK2 as a potent driver of immune response and metabolic effectors in PNETs, suggesting it is a potential therapeutic target for patients with PNETs.     

Sol–Gel Synthesis and Electrochemical Sensing Properties of Brownmillerite Calcium Ferrite–Ca2Fe2O5 Nanoparticles

Journal of Inorganic and Organometallic Polymers and Materials - Nanocrystalline brownmillerite Ca2Fe2O5 (CFO) has been prepared by sol–gel technique and the samples are presented as CFO1 and...     

Flow Field Simulation and Measurement in Packed Beds Based on 4D-X-Ray Computed Tomography

X-ray computed tomography (XCT) combined with computational fluid dynamics (CFD) simulations have proved to be a powerful and versatile tool to describe fluids flow through packed bed systems. In this contribution, two examples of the application of XCT experiments to track the fluid flow and fluid penetration in packed bed systems are shown. The first one shows how geometrical information extracted from XCT measurements can be coupled to CFD simulations to assess fluid flows reliably. Here the example of a packed bed of three-dimensional (3D) printed cylindrical-shaped particles is considered. Finally, a short case study on the monitoring of the progress of the water penetration front in a packed bed composed of glass spheres using four-dimensional (4D) XCT imaging data is presented.