Oral mucositis caused by Candida glabrata biofilms: failure of the concomitant use of fluconazole and ascorbic acid

Objectives: Candida glabrata is becoming one of the most prevalent pathogenic yeasts in cases of oral diseases. Mucositis is an recurrent oral infection in immunocompromised patients, and the actual guidelines recommend the use of fluconazole (Flu) for many cases. However, the azole resistance by C. glabrata is renowned, causing a reduced therapeutic response, especially when it occurs in biofilms. In this study, we performed an in vitro evaluation of an alternative pharmacotherapy for C. glabrata biofilm infections, combining ascorbic acid (AA) with Flu. AA is recognized for degrading -glucans, an important compound of the biofilm matrices, which prevent drug diffusion. Materials and Methods: Thus, routine clinical 30 or 40mg/l doses of Flu were applied to C. glabrata biofilms simultaneously with 200 or 300mg/l of AA. Results: The results showed that this combination effectively promoted the degradation of the biofilm network, but unfortunately, also stimulated the growth of the yeasts population due to release of several glucose monomers during -glucans hydrolysis. Conclusions: As a result, it was proven that, contrary to what happens in treatment of bacterial infection, AA should not be used together with Flu in the treatment of oral mucositis caused by Candida.The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was supported by the Programa Operacional, Fatores de competitividade – COMPETE and by national funds through FCT – Fundação para a Ciência e a Tecnologia on the scope of the projects FCT PTDC/SAU-MIC/119069/2010, RECI/EBBEBI/0179/2012 and PEst-OE/EQB/LA0023/2013 and Célia F. Rodrigues’ SFRH/BD/93078/2013 PhD grant

Fabrication of comb-drive actuators for straining nanostructured suspended graphene

We report on the fabrication and characterization of an optimized comb-drive actuator design for strain-dependent transport measurements on suspended graphene. We fabricate devices from highly p-doped silicon using deep reactive ion etching with a chromium mask. Crucially, we implement a gold layer to reduce the device resistance from $\approx51.6$ k$\mathrm{\Omega}$ to $\approx236$ $\mathrm{\Omega}$ at room temperature in order to allow for strain-dependent transport measurements. The graphene is integrated by mechanically transferring it directly onto the actuator using a polymethylmethacrylate membrane. Importantly, the integrated graphene can be nanostructured afterwards to optimize device functionality. The minimum feature size of the structured suspended graphene is 30 nm, which allows for interesting device concepts such as mechanically-tunable nanoconstrictions. Finally, we characterize the fabricated devices by measuring the Raman spectrum as well as the a mechanical resonance frequency of an integrated graphene sheet for different strain values.Comment: 10 pages, 9 figure

Gas-phase study on uridine: Conformation and X-ray photofragmentation

Fragmentation of RNA nucleoside uridine, induced by carbon 1s core ionization, has been studied. The measurements by combined electron and ion spectroscopy have been performed in gas phase utilizing synchrotron radiation. As uridine is a combination of d-ribose and uracil, which have been studied earlier with the same method, this study also considers the effect of chemical environment and the relevant functional groups. Furthermore, since in core ionization the initial core hole is always highly localized, charge migration prior to fragmentation has been studied here. This study also demonstrates the destructive nature of core ionization as in most cases the C 1s ionization of uridine leads to concerted explosions producing only small fragments with masses ≤43 amu. In addition to fragmentation patterns, we found out that upon evaporation the sugar part of the uridine molecule attains hexagonal formFinancial support from the Academy of Finland, the European COST Action XLIC CM1204 and the EU Transnational Access to Research Infrastructures programme. Computational resources from the FGI project (Finland) are acknowledged. D.T.H. acknowledges the Finnish Cultural Foundation for funding and the MINECO Project No. FIS2013-42002- R. E.R. acknowledges funding from the Swedish Research Council (VR

Integrated impedance bridge for absolute capacitance measurements at cryogenic temperatures and finite magnetic fields

We developed an impedance bridge that operates at cryogenic temperatures (down to 60 mK) and in perpendicular magnetic fields up to at least 12 T. This is achieved by mounting a GaAs HEMT amplifier perpendicular to a printed circuit board containing the device under test and thereby parallel to the magnetic field. The measured amplitude and phase of the output signal allows for the separation of the total impedance into an absolute capacitance and a resistance. Through a detailed noise characterization, we find that the best resolution is obtained when operating the HEMT amplifier at the highest gain. We obtained a resolution in the absolute capacitance of 6.4~aF$/\sqrt{\textrm{Hz}}$ at 77 K on a comb-drive actuator, while maintaining a small excitation amplitude of 15~$k_\text{B} T/e$. We show the magnetic field functionality of our impedance bridge by measuring the quantum Hall plateaus of a top-gated hBN/graphene/hBN heterostructure at 60~mK with a probe signal of 12.8~$k_\text{B} T/e$.Comment: 7 pages, 5 figure

Photodissociation dynamics of the iodide-uracil (I-U) complex

Photofragment action spectroscopy and femtosecond time-resolved photoelectron imaging are utilized to probe the dissociation channels in iodide-uracil (I− ⋅ U) binary clusters upon photoexcitation. The photofragment action spectra show strong I− and weak [U- H]− ion signal upon photoexcitation. The action spectra show two bands for I− and [U- H]− production peaking around 4.0 and 4.8 eV. Time-resolved experiments measured the rate of I− production resulting from excitation of the two bands. At 4.03 eV and 4.72 eV, the photoelectron signal from I− exhibits rise times of 86 ± 7 ps and 36 ± 3 ps, respectively. Electronic structure calculations indicate that the lower energy band, which encompasses the vertical detachment energy (4.11 eV) of I−U, corresponds to excitation of a dipole-bound state of the complex, while the higher energy band is primarily a π-π∗ excitation on the uracil moiety. Although the nature of the two excited states is very different, the long lifetimes for I− production suggest that this channel results from internal conversion to the I− ⋅ U ground state followed by evaporation of I−. This hypothesis was tested by comparing the dissociation rates to Rice-Ramsperger-Kassel-Marcus calculations

Application of Ozone-Assisted Membrane Cleaning for Natural Organic Matter Fouled Membranes

The popularity of membrane technology in water treatment has been rising for over last 50 years due to wide range of filtration processes and applications, cost effective production and installation as well as safe and efficient water production. However, the development and improvement of membranes is ongoing due to number of weaknesses. Membrane fouling is a major drawback of membrane application in water and waste water treatment. Mostly caused by natural organic matter (NOM), fouling forms a layer on top of the membrane and blocks pores reducing the water permeation and can be potentially destructive to the membrane structure. The issue of membrane fouling can be addressed during membrane manufacturing, maintenance and operation. In the current study, the graphene-based nanomaterials (GBN) were incorporated in polyvinylidene fluoride (PVDF) to manufacture membranes via the phase-inversion technique. The resulting membranes show significant improvement to the properties of the pure PVDF membranes and their antifouling ability. The addition of GBN enhanced the water permeation by over 79% as a result of increased membrane hydrophilicity. Although this enhancement is beneficial, membrane fouling remained an issue despite the observed improvement. In this study, ozone, which is an effective oxidant, was evaluated as a novel technique for the cleaning of humic acid-fouled membranes. When ozone cleaning was applied to the humic acid-fouled membranes, reestablishment of close to original flux values was observed after just 30 min of cleaning. This statement is supported by SEM images that give an insight into the fouling of the membrane surface after the application of the cleaning methods. The data indicate that ozone is an effective technique for membrane cleaning against NOM-induced fouling

Fingerprinting of hydroxyl radical-attacked polysaccharides by N-isopropyl-2-aminoacridone labelling

Hydroxyl radicals ((•)OH) cause non-enzymic scission of polysaccharides in diverse biological systems. Such reactions can be detrimental (e.g. causing rheumatic and arthritic diseases in mammals) or beneficial (e.g. promoting the softening of ripening fruit, and biomass saccharification). Here we present a method for documenting (•)OH action, based on fluorescent labelling of the oxo groups that are introduced as glycosulose residues when (•)OH attacks polysaccharides. The method was tested on several polysaccharides, especially pectin, after treatment with Fenton reagents. 2-Aminoacridone plus cyanoborohydride reductively aminated the oxo groups in treated polysaccharides; the product was then reacted with acetone plus cyanoborohydride, forming a stable tertiary amine with the carbohydrate linked to N-isopropyl-2-aminoacridone (pAMAC). Digestion of labelled pectin with ‘Driselase’ yielded several fluorescent products which on electrophoresis and HPLC provided a useful ‘fingerprint’ indicating (•)OH attack. The most diagnostic product was a disaccharide conjugate of the type pAMAC·UA-GalA (UA=unspecified uronic acid), whose UA-GalA bond was Driselase-resistant (product 2A). 2A was clearly distinguishable from GalA-GalA–pAMAC (disaccharide labelled at its reducing end), which was digestible to GalA–pAMAC. The methodology is applicable, with appropriate enzymes in place of Driselase, for detecting natural and artificial (•)OH attack in diverse plant, animal and microbial polysaccharides