Receptor for advanced glycation end-products: Biological significance and imaging applications.

The receptor for advanced glycation end-products (RAGE or AGER) is a transmembrane, immunoglobulin-like receptor that, due to its multiple isoform structures, binds to a diverse range of endo- and exogenous ligands. RAGE activation caused by the ligand binding initiates a cascade of complex pathways associated with producing free radicals, such as reactive nitric oxide and oxygen species, cell proliferation, and immunoinflammatory processes. The involvement of RAGE in the pathogenesis of disorders such as diabetes, inflammation, tumor progression, and endothelial dysfunction is dictated by the accumulation of advanced glycation end-products (AGEs) at pathologic states leading to sustained RAGE upregulation. The involvement of RAGE and its ligands in numerous pathologies and diseases makes RAGE an interesting target for therapy focused on the modulation of both RAGE expression or activation and the production or exogenous administration of AGEs. Despite the known role that the RAGE/AGE axis plays in multiple disease states, there remains an urgent need to develop noninvasive, molecular imaging approaches that can accurately quantify RAGE levels in vivo that will aid in the validation of RAGE and its ligands as biomarkers and therapeutic targets. This article is categorized under: Diagnostic Tools > In Vivo Nanodiagnostics and Imaging Diagnostic Tools > Biosensing.

In Vitro and In Vivo Imaging-Based Evaluation of Doxorubicin Anticancer Treatment in Combination with the Herbal Medicine Black Cohosh.

As a substitution for hormone replacement therapy, many breast cancer patients use black cohosh (BC) extracts in combination with doxorubicin (DOX)-based chemotherapy. In this study, we evaluated the viability and survival of BC- and DOX-treated MCF-7 cells. A preclinical model of MCF-7 xenografts was used to determine the influence of BC and DOX administration on tumor growth and metabolism. The number of apoptotic cells after incubation with both DOX and BC was significantly increased (~100%) compared to the control. Treatment with DOX altered the potential of MCF-7 cells to form colonies; however, coincubation with BC did not affect this process. In vivo, PET-CT imaging showed that combined treatment of DOX and BC induced a significant reduction in both metabolic activity (29%) and angiogenesis (32%). Both DOX and BC treatments inhibited tumor growth by 20% and 12%, respectively, and combined by 57%, vs. control. We successfully demonstrated that BC increases cytotoxic effects of DOX, resulting in a significant reduction in tumor size. Further studies regarding drug transport and tumor growth biomarkers are necessary to establish the underlying mechanism and potential clinical use of BC in breast cancer patients.

Lithium Transport Studies on Chloride-Doped Argyrodites as Electrolytes for Solid-State Batteries.

In this study, the activation energy and ionic conductivity of the Li6PS5Cl material for all-solid-state batteries were investigated using solid-state nuclear magnetic resonance (NMR) spectroscopy and electrochemical impedance spectroscopy (EIS). The results show that the activation energy values estimated from nuclear relaxation rates are significantly lower than those obtained from impedance measurements. The total ionic conductivities for long-range lithium diffusion in Li6PS5Cl calculated from EIS studies depend on the crystal size and unit cell parameter. The study also presents a new sample preparation method for measuring activation energy using temperature-dependent EIS and compares the results with the solid-state NMR data. The activation energy for a thin-film sample is equivalent to the long-range lithium dynamics estimated from NMR measurements, indicating the presence of additional limiting processes in thick pellets. Additionally, a theoretical model of Li-ion hopping based on results obtained using density-functional theory methods in comparison with experimental findings was discussed. Overall, the study emphasizes the importance of sample preparation methods in determining accurate activation energy and ionic conductivity values for solid-state lithium batteries and the significance of solid-state electrolyte thickness in new solid-state battery design for faster Li-ion diffusion.

The Effect of the Iridium Alloying and Hydrogen Sorption on the Physicochemical and Electrochemical Properties of Palladium.

Thin layers (up to 1 µm) of Pd-Ir alloys were electrodeposited from aqueous, galvanic baths of PdCl2 and IrCl3 mixtures. The morphology of the electrodeposits was examined by means of scanning electron microscopy. The composition of alloys was determined with the use of energy-dispersive spectroscopy, atomic absorption spectrometry, X-ray photoelectron spectroscopy, and Auger electron spectroscopy. For the studies of the electrochemical properties of alloys, cyclic voltammetry, chronoamperometry, and chronopotentiometry were used. It was found that Pd-Ir alloy electrodes were surface-enriched with Pd. Pd-Ir alloys subjected to different electrochemical treatment involving hydrogen sorption changed their surface state. The continuous hydrogen sorption enhanced the Ir ions' dissolution. The values of thermodynamic functions of hydrogen sorption in strong alkaline electrolytes were comparable with those in acidic electrolytes, whereas the kinetics of the process in alkaline medium was hindered. The miscibility gap in the Pd-Ir-H system vanished for the electrode containing ca. 93.7 at.% Pd.

A novel approach to pulsed laser deposition of platinum catalyst on carbon particles for use in polymer electrolyte membrane fuel cells.

The research undertaken aimed to develop an efficient Pt-based catalyst for polymer electrolyte membrane fuel cells (PEMFCs) by using a cost-effective and efficient physical method to deposit platinum nanoparticles (PtNPs) on carbon supports directly from the platinum target. The method developed avoids the chemical functionalization of the carbon substrate and the chemical synthesis of PtNPs during catalyst fabrication. Platinum was deposited on carbon particles at room temperature using a pulsed laser deposition (PLD) system equipped with an ArF excimer laser (λ = 193 nm). The uniform deposition of PtNPs on carbon supports was achieved thanks to a specially designed electromechanical system that mixed the carbon support particles during platinum deposition. In the studies, Vulcan XC-72R carbon black powder, a popular material used as support in the anodes and cathodes of PEMFCs, and a porous carbon material with a high degree of graphitization were used as carbon supports. The best electrochemical measurement results were obtained for Pt deposited on Vulcan XC-72R. The peak power density measured for this material in a membrane electrode assembly (MEA) of a PEMFC (fed with H2/Air) was 0.41 W/cm2, which is a good result compared to 0.57 W/cm2 obtained for commercial 20% Pt Vulcan XC-72R. This result was achieved with three times less Pt catalyst on the carbon support compared to the commercial catalyst, which means that a higher catalyst utilization factor was achieved.

The Electrochemical Behavior of Unmodified and Pd-NPs Modified AB5 Hydrogen Storage Alloy in Selected Protic and Aprotic Ionic Liquids (ILs): Towards ILs-Based Electrolytes for Ni-MH Batteries.

The objective of this work was to study the electrochemical behavior of AB5 alloy and its composite with Pd nanoparticles in selected ionic liquids. The protic ionic liquid (diethylmethylammonium triflate) and the mixture of aprotic ionic liquid (1-ethyl-3-methylimidazolium methanesulfonate) with parent superacid were used as electrolytes in the process of hydrogen electrosorption in AB5 alloy electrodes. The impact of the surface modification of AB5 electrode with Pd nanoparticles has been checked. The studies revealed that the highest hydrogen absorption capacity can be obtained in Pd-NPs-AB5 electrode in DEMA-TFO. It was found that the surface modification with Pd-NPs facilitates the activation of the electrode and results in stabilization of the plateau potential of discharging. The studies show that more effort should be put into the synthesis of less corrosive tailored ionic liquids suitable to be used as electrolytes in hydride batteries.

Effect of the Alloying Metal on the Corrosion Resistance of Pd-Rich Binary Alloys with Pt, Rh, and Ru in Sulfuric Acid.

The paper presents the study of the corrosion resistance of electrodeposited Pd and its binary alloys with Pt, Rh, and Ru on a polycrystalline Au substrate. The corrosion resistance was tested in 0.5 M sulfuric acid at room temperature using potentiodynamic polarization and electrochemical impedance spectroscopy techniques. The morphology/composition and work function values were determined by scanning electron microscopy/energy-dispersive X-ray spectroscopy and scanning Kelvin probe, respectively. The obtained results revealed that the Pd electrode is the most resistant to corrosion, whereas the Pd-Ru electrode is the most susceptible to dissolution. It was found that the corrosion resistance of Pd-binary alloys decrease in the following order: Pd > Pd-Pt > Pd-Rh > Pd-Ru. This effect was assigned mainly to the difference in surface roughness factor of tested electrodes.

Sensitive Metal-Semiconductor Nanothermocouple Fabricated by FIB to Investigate Laser Beams with Nanometer Spatial Resolution.

The focused ion beam (FIB) technique was used to fabricate a nanothermocouple (with a 90 nm wide nanojunction) based on a metal-semiconductor (Pt-Si) structure, which showed a sensitivity up to 10 times larger (with Seebeck coefficient up to 140 µV/K) than typical metal-metal nanothermocouples. In contrast to the fabrication of nanothermocouples which requires a high-tech semiconductor manufacturing line with sophisticated fabrication techniques, environment, and advanced equipment, FIB systems are available in many research laboratories without the need for a high-tech environment, and the described processing is performed relatively quickly by a single operator. The linear response of the manufactured nanothermocouple enabled sensitive measurements even with small changes of temperature when heated with a stream of hot air. A nonlinear response of the nanothermocouple (up to 83.85 mV) was observed during the exposition to an argon-laser beam with a high optical power density (up to 17.4 Wcm-2), which was also used for the laser annealing of metal-semiconductor interfaces. The analysis of the results implies the application of such nanothermocouples, especially for the characterization of laser beams with nanometer spatial resolution. Improvements of the FIB processing should lead to an even higher Seebeck coefficient of the nanothermocouples; e.g., in case of the availability of other suitable metal sources (e.g., Cr).

Surface Photochemical Corrosion as a Mechanism for Fast Degradation of InGaN UV Laser Diodes.

We studied degradation mechanisms of ultraviolet InGaN laser diodes emitting in the UVA range. Short wavelength nitride devices are subjected to much faster degradation, under the same packaging and testing conditions, than their longer wavelength counterparts. Transmission electron microscopy analysis of the degraded laser diodes showed pronounced damage to facets in the area of the active layer (waveguide, quantum wells, and electron blocking layer). Energy-dispersive X-ray spectroscopy showed that the active layers were heavily oxidized, forming a compound close in composition to Ga2O3 with proportional addition of Al in the respective area. The oxidation depth was roughly proportional to the intensity of the optical field. We propose UV-light-induced water splitting on a semiconductor surface as a mechanism of the oxidation and degradation of these devices.

UV-Cured Poly(Siloxane-Urethane)-Based Polymer Composite Materials for Lithium Ion Batteries-The Effect of Modification with Ionic Liquids.

The results of studies on the synthesis and characterization of conductive polymer composite materials designed as potential separators for lithium ion batteries are presented. The conductive polymer composites were prepared from UV-cured poly(siloxane-urethanes)s (PSURs) containing poly(ethylene oxide) (PEO) segments and modified with lithium salts and ionic liquids (ILs). The most encouraging results in terms of specific conductivity and mechanical properties of the composite were obtained when part of UV-curable PSUR prepolymer was replaced with a reactive UV-curable IL. Morphology of the composites modified with ILs or containing a standard ethylene carbonate/dimethyl carbonate mixture (EC/DMC) as solvent was compared. It was found that the composites showed a two-phase structure that did not change when non-reactive ILs were applied instead of EC/DMC but was much affected when reactive UV-curable ILs were used. The selected IL-modified UV-cured PSUR composite that did not contain flammable EC/DMC solvent was preliminarily tested as gel polymer electrolyte and separator for lithium ion batteries.

Surface Oxidation of Nano-Silicon as a Method for Cycle Life Enhancement of Li-ion Active Materials.

Among the many studied Li-ion active materials, silicon presents the highest specific capacity, however it suffers from a great volume change during lithiation. In this work, we present two methods for the chemical modification of silicon nanoparticles. Both methods change the materials' electrochemical characteristics. The combined XPS and SEM results show that the properties of the generated silicon oxide layer depend on the modification procedure employed. Electrochemical characterization reveals that the formed oxide layers show different susceptibility to electro-reduction during the first lithiation. The single step oxidation procedure resulted in a thin and very stable oxide that acts as an artificial SEI layer during electrode operation. The removal of the native oxide prior to further reactions resulted in a very thick oxide layer formation. The created oxide layers (both thin and thick) greatly suppress the effect of silicon volume changes, which significantly reduces electrode degradation during cycling. Both modification techniques are relatively straightforward and scalable to an industrial level. The proposed modified materials reveal great applicability prospects in next generation Li-ion batteries due to their high specific capacity and remarkable cycling stability.

Tuning of reflection spectrum of a monolithic high-contrast grating by variation of its spatial dimensions.

We report the first experimental parametric analysis of subwavelength monolithic high-contrast grating (MHCG) mirrors. To date, subwavelength grating mirrors have been fabricated by suspending a thin grating membrane in the air or placing it on a low refractive index material - a scheme that requires sophisticated processing and makes the gratings sensitive to mechanical stress, impeding current injection, and heat dissipation if used in active devices. Inherently MHCGs are well suited for optoelectronic devices because they can be fabricated in all possible material systems. Here we demonstrate above 90% optical power reflectance, strong polarization discrimination. Based on experimental analysis aided by numerical simulations, we demonstrate the possibility of tuning the spectral characteristics of MHCGs reflectance for more than 200 nm via modification of the duty cycle of the MHCG stripes. We show our MHCG tuning method is convenient to define the properties of MHCG devices during the device processing.

Preclinical Efficacy of a Lipooligosaccharide Peptide Mimic Candidate Gonococcal Vaccine.

The global spread of multidrug-resistant strains of Neisseria gonorrhoeae constitutes a public health emergency. With limited antibiotic treatment options, there is an urgent need for development of a safe and effective vaccine against gonorrhea. Previously, we constructed a prototype vaccine candidate comprising a peptide mimic (mimitope) of a glycan epitope on gonococcal lipooligosaccharide (LOS), recognized by monoclonal antibody 2C7. The 2C7 epitope is (i) broadly expressed as a gonococcal antigenic target in human infection, (ii) a critical requirement for gonococcal colonization in the experimental setting, and (iii) a virulence determinant that is maintained and expressed by gonococci. Here, we have synthesized to >95% purity through a relatively facile and economical process a tetrapeptide derivative of the mimitope that was cyclized through a nonreducible thioether bond, thereby rendering the compound homogeneous and stable. This vaccine candidate, called TMCP2, when administered at 0, 3, and 6 weeks to BALB/c mice at either 50, 100 or 200 µg/dose in combination with glucopyranosyl lipid A-stable oil-in-water nanoemulsion (GLA-SE; a Toll-like receptor 4 and TH1-promoting adjuvant), elicited bactericidal IgG and reduced colonization levels of gonococci in experimentally infected mice while accelerating clearance by each of two different gonococcal strains. Similarly, a 3-dose biweekly schedule (50 µg TMCP2/dose) was also effective in mice. We have developed a gonococcal vaccine candidate that can be scaled up and produced economically to a high degree of purity. The candidate elicits bactericidal antibodies and is efficacious in a preclinical experimental infection model.IMPORTANCENeisseria gonorrhoeae has become resistant to most antibiotics. The incidence of gonorrhea is also sharply increasing. A safe and effective antigonococcal vaccine is urgently needed. Lipooligosaccharide (LOS), the most abundant outer membrane molecule, is indispensable for gonococcal pathogenesis. A glycan epitope on LOS that is recognized by monoclonal antibody (MAb) 2C7 (called the 2C7 epitope) is expressed almost universally by gonococci in vivo Previously, we identified a peptide mimic (mimitope) of the 2C7 epitope, which when configured as an octamer and used as an immunogen, attenuated colonization of mice by gonococci. Here, a homogenous, stable tetrameric derivative of the mimitope, when combined with a TH1-promoting adjuvant and used as an immunogen, also effectively attenuates gonococcal colonization of mice. This candidate peptide vaccine can be produced economically, an important consideration for gonorrhea, which affects socioeconomically underprivileged populations disproportionately, and represents an important advance in the development of a gonorrhea vaccine.

Low Temperature Characteristics of Hydrogen Storage Alloy LaMm-Ni4.1Al0.3Mn0.4Co0.45 for Ni-MH Batteries.

Nickel hydride batteries (Ni-MH) are known of their good performance and high reliability at temperatures below 0 °C, which is significantly dependent on electrolyte composition. Here we present the low temperature characteristics of pristine AB5-type alloy, LaMm-Ni4.1Al0.3Mn0.4Co0.45, determined in various alkali metal hydroxide solutions. We found that the combination of KOH with NaOH showed a significant effect of enhancement of low temperature performance of the electrode material and diffusion of hydrogen in the alloy. This 6M binary mixed NaOH/KOH electrolyte, comprising 4M KOH component and 2M NaOH component, made it possible to maintain 81.7% and 61.0% of maximum capacity at -20 °C and -30 °C, respectively, enhancing the hydrogen storage properties of the alloy after reheating to room temperature.

Corrosion of Hydrogen Storage Metal Alloy LaMm-Ni4.1Al0.3Mn0.4Co0.45 in the Aqueous Solutions of Alkali Metal Hydroxides.

Corrosion of pristine AB5-type metal alloy LaMm-Ni4.1Al0.3Mn0.4Co0.45 in the aqueous solutions of alkali metal hydroxides of diverse composition and concentration was tested. Correlation was observed between the alloy corrosion intensity in various hydroxide solutions, and its electrochemical capacity in these electrolytes. Mm(OH)3, CoO(OH), and nickel metal aggregates were detected among the products of selective oxidation of the alloy. High intensity corrosion of the alloy was observed in RbOH and CsOH solutions leading to formation of ternary oxides at the surface of the alloy. Presence of rubidium and cesium ions in the electrolyte were found to create an additional driving force for lanthanides (La and Ce) to leave the lattice of the alloy, thus, enhancing its corrosion. Corrosion, together with mechanical degradation, were found to be the main reasons of deactivation of LaMm-Ni4.1Al0.3Mn0.4Co0.45 alloy upon elongated electrochemical treatment.

Single Step, Electrochemical Preparation of Copper-Based Positive Electrode for Lithium Primary Cells.

Lithium primary cells are commonly used in applications where high energy density and low self-discharge are the most important factors. This include small coin cells for electronics, power backup batteries for complementary metal-oxide-semiconductor memory or as a long-term emergency power source. In our study we present a fast, electrochemical method of the positive electrode preparation for lithium primary cells. The influence of the current density and oxygen presence in a solution on the preparation of the electrode and thus its electrochemical behavior is examined. Electrode compositions were characterized by X-ray photoelectron spectroscopy (XPS). The prepared electrodes may be used in Li cells as competition to Zn-MnO2 primary batteries.

Comparative Physicochemical and Electrochemical Characterization of the Structure and Composition of Thin Pd Binary and Ternary Codeposits with Pt, Ru, and Rh.

Pd-Ru, Pd-Rh, Pd-Pt-Ru, and Pd-Rh-Ru electrodes were prepared as thin layers by potentiostatic codeposition or chemical co-precipitation of metals from baths containing mixtures of chloride salts. The formation of substitutional solid solutions, with lattice parameters smaller than that of pure Pd, was confirmed by X-ray diffraction (XRD). The compositions at various levels of sample volume and thickness were analyzed by inductively coupled plasma atomic emission spectroscopy (ICP-AES), energy-dispersive X-ray spectroscopy (EDS), X-ray photoelectron spectroscopy (XPS), Auger electron spectroscopy (AES), and also electrochemically by cyclic voltammetry (CV) in 0.5 M H2SO4. The differences between surface, subsurface, and bulk compositions were compared for various systems in a wide composition spectrum.

Evaluation of a dimeric-cRGD peptide for targeted PET-CT imaging of peripheral angiogenesis in diabetic mice.

The α V ß3 integrin plays an important role in many physiological functions and pathological disorders. α V ß3 is minimally expressed in normal quiescent endothelial cells, but significantly upregulated during neovascularization. In this study, we evaluated a 64Cu-labeled dimeric cRGD tracer targeted at α V ß3 integrin and report its applicability to assess peripheral angiogenesis in diabetes mellitus (DM). We established a murine model of type-1 DM characterized by elevated glucose, glycated serum protein (GSP), and glycated hemoglobin A1c (HbA1c). We demonstrated that our imaging probe is specific to α V ß3 integrin under both normo- and hyperglycemic conditions. We found that the analysis of in vivo PET-CT images correlated well with gamma well counting (GWC). Both GWC and PET-CT imaging demonstrated increased uptake of 64Cu-NOTA-PEG4-cRGD2 in the ischemic hindlimb in contrast to non-ischemic control. GWC of the distal ischemic tissue from DM mice showed significantly lower probe accumulation than in non-DM mice. The immunofluorescence staining of the ischemic tissues showed a 3-fold reduction in CD31 and 4-fold reduction in the α V ß3 expression in DM vs. non-DM animals. In conclusion, we successfully demonstrated that diabetes-associated reductions in peripheral angiogenesis can be non-invasively detected with PET-CT imaging using targeted dimeric-cRGD probe.

The effect of compressive stresses on a silicon electrode's cycle life in a Li-ion battery.

Lithium-ion cells are currently very promising electrochemical power sources. New high-capacity electrodes made from silicon are currently under intensive study. As well as its high capacity, silicon undergoes a significant volume increase (up to 300%) during lithiation. This leads to the generation of internal stresses and fast cell degradation due to active material pulverization and separation from the current collector. Stress formation and its effect on silicon lithiation has been theoretically investigated by many researchers. It has been shown that internal compressive stress can slow down or stop silicon lithiation. In our study we applied external stress to an electrode active layer and measured the cell electrochemical parameters: capacity, cycle life, and charge transfer resistance. In contrast with theoretical estimations we observed an increase in capacity and cycle life when high compressive stress was applied. We believe this behavior is related to stress-induced lithiation front slowdown, which entails a longer stress relaxation period and as a consequence improves the cell parameters.

Peptide therapeutics from venom: Current status and potential.

Peptides are recognized as being highly selective, potent and relatively safe as potential therapeutics. Peptides isolated from the venom of different animals satisfy most of these criteria with the possible exception of safety, but when isolated as single compounds and used at appropriate concentrations, venom-derived peptides can become useful drugs. Although the number of venom-derived peptides that have successfully progressed to the clinic is currently limited, the prospects for venom-derived peptides look very optimistic. As proteomic and transcriptomic approaches continue to identify new sequences, the potential of venom-derived peptides to find applications as therapeutics, cosmetics and insecticides grows accordingly.