Voriconazole (VCZ), a triazole with a large spectrum of action is one of the most recommended antifungal agents as the first line therapy against several clinically important systemic fungal ...infections, including those by Candida albicans. This antifungal has moderate water solubility and exhibits a nonlinear pharmacokinetic (PK) profile. By entrapping VCZ into liposomes, it is possible to circumvent certain downsides of the currently available product such as a reduction in the rate of its metabolization into an inactive form, avoidance of the toxicity of the sulfobutyl ether-beta-cyclodextrin (SBECD), vehicle used to increase its solubility. PKs and biodistribution of VCZ modified by encapsulation into liposomes resulted in improved antifungal activity, due to increased specificity and tissue penetration. In this work, liposomal VCZ resulted in AUC
0-24
/MIC ratio of 53.51 ± 11.12, whereas VFEND
®
resulted in a 2.5-fold lower AUC
0-24
/MIC ratio (21.51 ± 2.88), indicating favorable antimicrobial systemic activity. VCZ accumulation in the liver and kidneys was significantly higher when the liposomal form was used. Protection of the drug from biological degradation and reduced rate of metabolism leads to a 30% reduction of AUC of the inactive metabolite voriconazole-N-oxide (VNO) when the liposomal drug was administered. Liposomal VCZ presents an alternative therapeutic platform, leading to a safe and effective treatment against systemic fungal infections.
Background
Currently, considerable efforts to standardize methods for accurate assessment of properties and safety aspects of nanomaterials are being made. However, immunomodulation effects upon skin ...exposure to nanomaterial have not been explored.
Objectives
To investigate the immunotoxicity of single‐wall carbon nanotubes, titanium dioxide, and fullerene using the current mechanistic understanding of skin sensitization by applying the concept of adverse outcome pathway (AOP).
Methods
Investigation of the ability of nanomaterials to interact with skin proteins using the micro‐direct peptide reactivity assay; the expression of CD86 cell surface marker using the U937 cell activation test (OECD No. 442E/2018); and the effects of nanomaterials on modulating inflammatory response through inflammatory cytokine release by U937 cells.
Results
The nanomaterials easily internalized into keratinocytes cells, interacted with skin proteins, and triggered activation of U937 cells by increasing CD86 expression and modulating inflammatory cytokine production. Consequently, these nanomaterials were classified as skin sensitizers in vitro.
Conclusions
Our study suggests the potential immunotoxicity of nanomaterials and highlights the importance of studying the immunotoxicity and skin sensitization potential of nanomaterials to anticipate possible human health risks using standardized mechanistic nonanimal methods with high predictive accuracy. Therefore, it contributes toward the applicability of existing OECD (Organisation for Economic Co‐operation and Development) testing guidelines for accurate assessment of nanomaterial skin sensitization potential.
(A) Control cells with nonspecific background illumination. CytoViva hyperspectral imaging of (B) single‐wall carbon nanotubes (SWCNs), (C) titanium dioxide (TiO2), and (D) fullerene (C60) internalized into human HaCaT keratinocytes after 2 hours of exposure. Scale bar: 3 μm.
In this paper, the authors review the field of parallax error (PE) minimization in positron emission tomography (PET) imaging systems by using depth of interaction (DOI) capable concepts. The review ...includes apparatus as well as an overview of various methods described in the literature. It also discusses potential advantages gained via these approaches, as discussed with reference to various metrics and tasks, particularly in the improvement of spatial resolution (SR) performance. Furthermore, the authors emphasize limitations encountered in the context of DOI decoding, which can be a considerable pitfall depending on the task of interest.
Probing anomalous Wtb couplings in top pair decays Aguilar-Saavedra, J.A.; Carvalho, J.; Castro, N. ...
The European physical journal. C, Particles and fields,
04/2007, Letnik:
50, Številka:
3
Journal Article
Recenzirano
Odprti dostop
We investigate several quantities, defined in the decays of top quark pairs, which can be used to explore non-standard Wtb interactions. Two new angular asymmetries are introduced in the leptonic ...decay of top (anti)quarks. Both are very sensitive to anomalous Wtb couplings, and their measurement allows for a precise determination of the W helicity fractions. We also examine other angular and energy asymmetries, the W helicity fractions and their ratios, as well as spin correlation asymmetries, analysing their dependence on anomalous Wtb couplings and identifing the quantities which are most sensitive to them. It is explicitly shown that spin correlation asymmetries are less sensitive to new interactions in the decay of the top quark; therefore, when combined with the measurement of other observables, they can be used to determine the tt̄ spin correlation even in the presence of anomalous Wtb couplings. We finally discuss some asymmetries which can be used to test CP violation in tt̄ production and complex phases in the effective Wtb vertex.
Laser spectroscopy of muonic deuterium Pohl, Randolf; Nez, François; Fernandes, Luis M. P. ...
Science (American Association for the Advancement of Science),
08/2016, Letnik:
353, Številka:
6300
Journal Article
Recenzirano
Odprti dostop
The deuteron is the simplest compound nucleus, composed of one proton and one neutron. Deuteron properties such as the root-mean-square charge radius rd and the polarizability serve as important ...benchmarks for understanding the nuclear forces and structure. Muonic deuterium μd is the exotic atom formed by a deuteron and a negative muon μ⁻. We measured three 2S-2P transitions in μd and obtain rd = 2.12562(78) fm, which is 2.7 times more accurate but 7.5σ smaller than the CODATA-2010 value rd = 2.1424(21) fm. The μd value is also 3.5σ smaller than the rd value from electronic deuterium spectroscopy. The smaller rd, when combined with the electronic isotope shift, yields a "small" proton radius rp, similar to the one from muonic hydrogen, amplifying the proton radius puzzle.
The use of ethanol as fuel in Brazil stimulated the competition between distribution companies and resellers, which aggravated the practice of adulteration of fuels, aiming for illicit gains and tax ...evasion. The most common practice of adulteration in fuel alcohol is the addition of water. The classic techniques for measuring the water content in ethanol offer good precision and good detailing as to the presence of water. However, they present disadvantages such as the need for sample collection, long analysis time, in addition to the need for specialized laboratory and labor. This work aims to propose digital signal processing techniques to analyze and quantify the presence of water in ethanol fuel using a combination of Principal Component Analysis (PCA), and Singular Spectrum Analysis (SSA) applied on ultrasonic signals. This method resulted in the proposal of a new score, which relates to the ethanol/water ratio information present in the mixture. The results were promising when relating the proposed score to the presence of moisture in ethanol to a greater or lesser degree. Experiments performed prove the technique's feasibility and pave the way for a new method for real-time monitoring.
The present study examined two sandstone deposits in the Aliaga outcrop as a reservoir analogue over a distance of 200-m-long and attempted to establish a correlation between sand facies and the ...petrophysical properties of the sandstones in order to investigate the reservoir heterogeneity. The Aliaga reservoir analogue represents the upper part of Camarillas Fm., deposited during the Barremian synrift phase of the Galve sub-basin (Iberian Basin, Spain). It is characterized by a transitional sedimentary interval from sandy-dominant deposits to carbonate-dominant deposits, which were deposited under the same palaeoenvironmental conditions (in relation to systems of back-barrier sedimentation).
The description of the Aliaga outcrop provided here consists of lithological descriptions of two sandstone deposits: a tsunami and a barrier island/inlet, at both mesoscopic (decimetres to tens of metres) and microscopic scales (millimetres to centimetres). Both deposits recognized at the basin scale were described in terms of sand grain size, sand sorting and cementation; further cores were drilled along outcrop to collect samples for porosity and permeability measurements.
Both sandstone reservoirs are the result of different sedimentary processes that determined facies characteristics, as the different petrophysical properties observed in these deposits. Consequently, the sedimentary process controls the heterogeneity of the sandstones facies and thus, the sand heterogeneity controls the distribution of the petrophysical properties. The classification of sand facies in terms of sand sorting seems to be more appropriate for describing sand heterogeneity; accordingly, petrophysical parameters in both deposits were also influenced by sand sorting.
The sand facies and petrophysics heterogeneity of the described deposits can be hierarchically ordered. First-order heterogeneity is related to the basin scale, second-order heterogeneity is related to genesis and the conditions of sediment deposition, and third-order heterogeneity is related to synsedimentary faults and/or post-sedimentation events.
•Facies classified by sand sorting described the petrophysics variability.•Sedimentary process controls the facies distribution, thus the petrophysics distribution.•Although tsunami deposit has great variation of sand grain size, the sand is well sorted.•B.i./Inlet deposit has heterogeneous distribution of facies and great variability of porosity.•Porosity and permeability are strongly correlated in both sandstone deposits.
The present study was aimed at evaluating the extent of dysfunction of the enteroendocrine and enteric nervous system, as indicated by changes in tissue levels of monoamines (dopamine, DA; ...norepinephrine, NE; 5-hydroxytryptamine, 5-HT) and their precursors and metabolites in the colonic mucosa of patients afflicted with ulcerative colitis (UC, N = 21) and Crohn's disease (CD, N = 22). In CD, but not in UC, NE tissue levels in both the noninflamed and inflamed colonic mucosa were markedly lower than in control subjects (N = 16). In the inflamed mucosa of CD and in UC patients levels of L-DOPA were twice those in controls. DA levels in the inflamed mucosa of CD and UC patients were markedly lower than in controls. This resulted in significant reductions in DA/L-DOPA tissue ratios, a rough measure of L-amino acid decarboxylase activity. 5-HT levels in the inflamed mucosa of CD and UC patients were markedly lower than in controls. In conclusion, intestinal cellular structures responsible for the synthesis and storage of DA, NE, and 5-HT may have been affected by the associated inflammatory process in both CD and UC.
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