Metallization system as a part of thermal memory.

This study aims to substantiate the potential of using "classical" metallization systems as microelectronic thermal memory cells. An experimental simulation is used to demonstrate that thermal information can be stored in memory for a certain time and then read without distortion. The possibility of using thin metal films on single-crystal silicon wafers as thermal memory cells is discussed. An experimental parametric study of "recording" thermal pulses and the temperature dynamics after their interruption is performed. This study uses rectangular current pulses with an amplitude of (1 … 6) × 1010 A/m2 and a duration of up to 1 ms. The temperature dynamics of a "thermal cell" are oscillographically studied up to the critical conditions when the contact area and metal film start degrading. The conditions of interconnections overheating up to the circuit break are considered.

Electrical and Recombination Properties of Polar Orthorhombic κ-Ga2O3 Films Prepared by Halide Vapor Phase Epitaxy.

In this study, the structural and electrical properties of orthorhombic κ-Ga2O3 films prepared using Halide Vapor Phase Epitaxy (HVPE) on AlN/Si and GaN/sapphire templates were studied. For κ-Ga2O3/AlN/Si structures, the formation of two-dimensional hole layers in the Ga2O3 was studied and, based on theoretical calculations, was explained by the impact of the difference in the spontaneous polarizations of κ-Ga2O3 and AlN. Structural studies indicated that in the thickest κ-Ga2O3/GaN/sapphire layer used, the formation of rotational nanodomains was suppressed. For thick (23 µm and 86 µm) κ-Ga2O3 films grown on GaN/sapphire, the good rectifying characteristics of Ni Schottky diodes were observed. In addition, deep trap spectra and electron beam-induced current measurements were performed for the first time in this polytype. These experiments show that the uppermost 2 µm layer of the grown films contains a high density of rather deep electron traps near Ec - 0.3 eV and Ec - 0.7 eV, whose presence results in the relatively high series resistance of the structures. The diffusion length of the excess charge carriers was measured for the first time in κ-Ga2O3. The film with the greatest thickness of 86 µm was irradiated with protons and the carrier removal rate was about 10 cm-1, which is considerably lower than that for ß-Ga2O3.

Genome sequence of the pattern-forming social bacterium Paenibacillus dendritiformis C454 chiral morphotype.

Paenibacillus dendritiformis is a Gram-positive, soil-dwelling, spore-forming social microorganism. An intriguing collective faculty of this strain is manifested by its ability to switch between different morphotypes, such as the branching (T) and the chiral (C) morphotypes. Here we report the 6.3-Mb draft genome sequence of the P. dendritiformis C454 chiral morphotype.

Structure and biological activity of particles produced from highly activated carbon adsorbent.

Over the recent years, carbon particles have gained relevance in the field of biomedical application to diminish the level of endo-/exogenous intoxication and oxidative stress products, which occur at different pathological states. However, it is very important that such carbon particles, specially developed for parenteral administration or per oral usage, possess a high adsorption potential and can remove hazard toxic substances of the hydrophilic, hydrophobic and amphiphilic nature usually accumulated in the blood due to the disease, and be absolutely safe for normal living cells and tissues of organism. In this work, the stable monodisperse suspension containing very small-sized (Dhydro = 1125.3 ± 243.8 nm) and highly pure carbon particles with an excellent accepting ability were obtained. UV-spectra, fluorescence quenching constant and binding association constant were provided by the information about conformational alterations in an albumin molecule in presence of carbon particles, about the dynamic type of quenching process and low binding affinity between carbon and protein. The later was confirmed by DSC method. In vitro cell culture experiments showed that carbon particles did not possess any cytotoxic effect towards all testing the normal cell lines of different histogenesis, did not show genotoxic effects and were absolutely safe for experimental animals during and after their parenteral administration. These observations may provide more information about how to develop a safe preparation of carbon particles for different biomedical applications, in particular, as a mean for intracorporeal therapy of various heavy diseases accompanied by the increased endogenous intoxication and the level of oxidative stress.

Cerium dioxide nanoparticles synthesized via precipitation at constant pH: Synthesis, physical-chemical and antioxidant properties.

Cerium oxide nanoparticles (CeO2 NPs) are well known for their application in various fields of industry, as well as in biology and medicine. Knowledge of synthesis schemes, physicochemical and morphological features of nanoscale CeO2 is important for assessing their antioxidant behavior and understanding the mechanism of oxidative stress and its consequences. The choice of the method of synthesis should be based on the possibility to choose the conditions and parameters for obtaining CeO2 with controlled dimensions and a ratio of Се3+/Се4+ on their surface. In this study, CeO2 NPs are synthesized by precipitation in mixed water-alcohol solutions at constant pH = 9. The properties of obtained NPs are studied using various methods of physical-chemical characterization such as X-ray diffraction, X-ray photoelectron spectroscopy, transmission electron microscopy, and dynamic light scattering. The size of CeO2 NPs varied from 14 to 4.2 nm with increasing alcohol concentration, while the effect of constant pH during synthesis on the morphology of the particles was insignificant. The synthesized nanoparticles form highly stable aqueous suspensions since their zeta-potential is higher than + 40 mV. It is found that the ability of CeO2 NPs to self-stabilize is associated with the presence of hydrated Ce4+ ions on their surface. In vitro biological studies have shown that, regardless of particle size, CeO2 NPs have antioxidant potential, but smaller NPs with a higher percentage of Ce3+ on the surface had a more effective antioxidant effect. In addition, the size-depended activity of CeO2 NPs to inhibit the amyloid formation of insulin is demonstrated.

Intraspecific phylogenetic analysis of Siberian woolly mammoths using complete mitochondrial genomes.

We report five new complete mitochondrial DNA (mtDNA) genomes of Siberian woolly mammoth (Mammuthus primigenius), sequenced with up to 73-fold coverage from DNA extracted from hair shaft material. Three of the sequences present the first complete mtDNA genomes of mammoth clade II. Analysis of these and 13 recently published mtDNA genomes demonstrates the existence of two apparently sympatric mtDNA clades that exhibit high interclade divergence. The analytical power afforded by the analysis of the complete mtDNA genomes reveals a surprisingly ancient coalescence age of the two clades, approximately 1-2 million years, depending on the calibration technique. Furthermore, statistical analysis of the temporal distribution of the (14)C ages of these and previously identified members of the two mammoth clades suggests that clade II went extinct before clade I. Modeling of protein structures failed to indicate any important functional difference between genomes belonging to the two clades, suggesting that the loss of clade II more likely is due to genetic drift than a selective sweep.

Tackling the acute radiation syndrome: Hemoperfusion with activated carbon revisited.

Almost three decades ago Dr. Nikolaev and co-authors reported a remarkable finding that a single-course low-volume hemoperfusion through uncoated spherical activated carbon led to a significant increase in survival of dogs acutely irradiated with X-rays of the dose of 5.25 Gy (Artif. Organs. 1993; 17: 362-8). In those studies, the adsorptive detoxification, which is characteristic for carbon adsorbents, was less likely to play a predominant role in radioprotection, thus prompting the authors to assume that some other, unknown, mechanisms were involved. This article is aimed to interpret the radioprotective effect of activated carbon, based on the mounting evidence that it is capable of reducing the oxidative stress and promoting the recovery in various tissues and organs (including hematopoietic) with an active involvement of relatively radioresistant tissue-resident macrophages.

Genome sequence of the pattern forming Paenibacillus vortex bacterium reveals potential for thriving in complex environments.

BACKGROUND: The pattern-forming bacterium Paenibacillus vortex is notable for its advanced social behavior, which is reflected in development of colonies with highly intricate architectures. Prior to this study, only two other Paenibacillus species (Paenibacillus sp. JDR-2 and Paenibacillus larvae) have been sequenced. However, no genomic data is available on the Paenibacillus species with pattern-forming and complex social motility. Here we report the de novo genome sequence of this Gram-positive, soil-dwelling, sporulating bacterium. RESULTS: The complete P. vortex genome was sequenced by a hybrid approach using 454 Life Sciences and Illumina, achieving a total of 289× coverage, with 99.8% sequence identity between the two methods. The sequencing results were validated using a custom designed Agilent microarray expression chip which represented the coding and the non-coding regions. Analysis of the P. vortex genome revealed 6,437 open reading frames (ORFs) and 73 non-coding RNA genes. Comparative genomic analysis with 500 complete bacterial genomes revealed exceptionally high number of two-component system (TCS) genes, transcription factors (TFs), transport and defense related genes. Additionally, we have identified genes involved in the production of antimicrobial compounds and extracellular degrading enzymes. CONCLUSIONS: These findings suggest that P. vortex has advanced faculties to perceive and react to a wide range of signaling molecules and environmental conditions, which could be associated with its ability to reconfigure and replicate complex colony architectures. Additionally, P. vortex is likely to serve as a rich source of genes important for agricultural, medical and industrial applications and it has the potential to advance the study of social microbiology within Gram-positive bacteria.

Biological activity of cerium dioxide nanoparticles.

Cerium dioxide nanoparticles (CeO2 NPs) with a high value of ζ-potential (≥30 mV) have been synthesized in reverse microemulsions and they are able to form the high-stable aqueous suspension without any additional stabilizers. It has been shown that the interaction of such CeO2 NPs with transport proteins, such as BSA, affects their molecular conformation and biochemical activity. The observed changes in the UV-absorbance spectrum and intrinsic fluorescence quenching of BSA molecule are indicative of the occurrence of structural changes caused by binding with the surface of CeO2 NPs. Low affinity between BSA and CeO2 NPs has been confirmed by differential scanning calorimetry (DSC). Moreover, CeO2 NPs can act as regenerative free-radical scavengers, and their antioxidant activity depends on the concentration. The positive charge of CeO2 NPs can be attributed to their low toxicity toward human malignant lymphocytes MT-4 and breast cancer cells MCF-7 however, the morphofunctional features of MCF-7 cells interacting with CeO2 NPs are indicative of the decrease in oncogenicity.

The effect of two formulations of carbon enterosorbents on oxidative stress indexes and molecular conformation of serum albumin in experimental animals exposed to CCl4.

The liver failure means inability to perform its normal synthetic, biotransformation and excretory functions. The disturbance of metabolic processes leads to the development of "metabolic endogenous intoxication" resulting in oxidative stress. Oxidative stress initiates the processes of oxidation of amino acid residues of blood plasma proteins causing the changes in their structure and functions. The effect of administration of highly activated porous carbonic enterosorbents on oxidative stress manifestations and molecular conformation of serum albumin in blood of experimental animals with acute liver failure induced by carbon tetrachloride (CCl4) needs to be investigated. Two forms of activated carbonic enterosorbents such as AC1 (primary beads with the range of diameters of 125-250 µm) and AC2 (secondary granules prepared from micronized AC1 having the mean particle size of ~1 µm) derived from phenol-formaldehyde resin were used in rat model with CCl4 intoxication. The total level of reactive oxygen species (ROS) in blood plasma, the activity of catalase (CAT) in blood hemolysates; the content of reduced glutathione (GSH) in liver homogenates, and the level of oxidative modification of proteins (OMP) such as aldehyde-dinitrophenylhydrazone (A-DNPH) and ketone-dinitrophenylhydrazone (K-DNPH) derivatives in blood plasma and liver homogenates were determined. In addition, the level of pro/antioxidant ratio in blood hemolysates and the content of lipid peroxidation product - malondialdehyde (MDA), in blood plasma and liver were determined. Melting thermograms of blood plasma proteins (BPP) and molecular conformation changes of serum albumin were analyzed by biophysical methods (differential scanning microcalorimetry and spectrofluorimetry). The extent of CCl4-induced oxidative damage in blood and liver of experimental animals was shown to be less expressed for AC1 in comparison with AC2 enterosorbent. However, AC2 used in the form of secondary granules positively influenced some biophysical properties of albumin molecule (temperature of melting, shape of melting endotherm and intrinsic fluorescence) after rats exposure to CCl4. In general, administration of both AC1 and AC2 led to the reduction of oxidative stress manifestations and partial restoration of native molecular conformation of serum albumin. These observations are promising in terms of achieving recovery of detoxification potential of organism after severe liver injury.

Heparin-cellulose-charcoal composites for drug detoxification prepared using room temperature ionic liquids.

We report novel heparin-cellulose-charcoal composites prepared using room temperature ionic liquids (RTILs) to enhance the biocompatibility and blood compatibility of activated charcoal beads while decreasing the size of their active pores.

Densitometry of the optically magnified dried residues representing carbon microparticles as a simple and affordable technique for determining their concentrations in aqueous suspensions.

In extracorporeal blood purification, such as hemoperfusion, activated carbon (activated charcoal) beads are commonly used as an adsorbent, but their judgment in terms of extent of microparticle release is of great importance since the microparticles may represent the risk of entering the bloodstream. To quantitatively assess the release of carbon microparticles (CMPs) in the samples of the aqueous perfusion medium, in which the beads have been perfused, the calibration procedure with different concentrations of CMPs is likely to be needed. For this purpose, carbon beads were mechanically crushed to a fine powder, whose microparticles (<10 µm) were then serially diluted in the aqueous medium within the wide range of concentrations (0.2-100 µg/ml). To test these concentrations of CMPs, the micro-aliquots of each dilution of suspended CMPs were dried on a surface of hydrophobic membrane and at the optical magnification of 20× the dry residues were than analyzed by measuring the sum of densities. This simple and affordable technique was shown to be considerably more sensitive than spectrophotometry of the aqueous suspensions of CMPs.

Effect of protein-bound uraemic toxins on the thermodynamic characteristics of human albumin.

The ability of albumin to bind drugs and other lipophilic organic acids is decreased in chronic renal failure by the accumulation of albumin-bound uraemic toxins such as hippuric acid, indoxyl sulphate and 3-carboxy-4-methyl-5-propyl-2-furanpropanoic acid (CMPF). This furan acid is the most highly bound and is not removed by haemodialysis. The inhibitory effects of these three uraemic toxins on the interaction of three marker ligands sodium octanoate (for medium chain fatty acids), salicylic acid and phenol red (bilirubin site/site I) with albumin have been investigated by differential scanning microcalorimetry and flow microcalorimetry. CMPF was the most potent inhibitor and its binding site coincided with that of bilirubin (site I). Indoxyl sulphate binds to the site for medium-chain fatty acids and tryptophan (site II) and hippuric acid, the weakest inhibitor, inhibited binding to the salicylic acid site.

Extraction of uraemic toxins with activated carbon restores the functional properties of albumin.

BACKGROUND: Previous work has demonstrated that a partial normalization of the conformation of albumin from uraemic plasma and a substantial restoration of its binding abilities can be achieved by extraction with activated charcoal. This is best achieved at pH 3, but exposure of whole plasma to this low pH leads to the loss of some essential components. METHODS: The melting curves and ligand-binding abilities of uraemic albumin have been investigated after extraction with a new generation of activated carbon at three pH values (7.2, 3.0 and 5.08). RESULTS: Albumin isolated from uraemic plasma had a characteristically increased melting temperature because of bound ligands. Extraction of uraemic plasma at pH 7.2, 5.08 and 3.0 induced low-temperature shifts of albumin thermo-adsorption maximum T1 of 1.4, 3.8, 2.4 degrees C and T2 of 0.8, 3.9 and 1.2 degrees C, respectively. Flow microcalorimetry data demonstrated a decrease in the ability of uraemic albumin to bind octanoate, phenol red, salicylic acid, warfarin and diazepam. Purification of uraemic plasma at pH 5.08 completely restored the binding affinity of albumin for all the marker ligands. CONCLUSIONS: Highly efficient activated carbons, with clinically feasible acidification of plasma, can remove strongly albumin-bound uraemic toxins. Investigation of the melting curve of the isolated albumin is a new biophysical way to monitor both its molecular condition and the extent of removal of protein-bound toxins by dialysis. The melting curve provides new qualitative and quantitative information about albumin in an analogous way to an electrocardiogram and the heart.

Analysis of medical use of carbon adsorbents in China and additional possibilities in this field achieved in Ukraine.

The review is devoted to analysis of the use of carbon sorbents for medicinal purposes in China and description of some innovative technologies in this field in Ukraine. The review underlines the presence of common roots of sorption therapy development in these two countries determined by pioneer works of Prof. T.M.S. Chang, created to the concept of artificial cells. High level of works of Chinese scientists on sorption purification of blood and combined extracorporeal methods has been mentioned. At the same time, by author's opinion, two other methods of sorption therapy, namely enterosorption and sorption therapy of wounds and burns, has not been properly developed in China. In the review, there are also described the essential results of Ukrainian scientists in the field of blood purification from protein-bound toxins and other harmful compounds what is important for treatment of many serious human pathologies, and also the important data on the use of oral sorbents and dressings from activated carbon materials, which could be considered as a useful addition to achievements of Chinese scientists in the field of the development and use of sorbents for medicinal purposes.

Whole-genome shotgun sequencing of mitochondria from ancient hair shafts.

Although the application of sequencing-by-synthesis techniques to DNA extracted from bones has revolutionized the study of ancient DNA, it has been plagued by large fractions of contaminating environmental DNA. The genetic analyses of hair shafts could be a solution: We present 10 previously unexamined Siberian mammoth (Mammuthus primigenius) mitochondrial genomes, sequenced with up to 48-fold coverage. The observed levels of damage-derived sequencing errors were lower than those observed in previously published frozen bone samples, even though one of the specimens was >50,000 14C years old and another had been stored for 200 years at room temperature. The method therefore sets the stage for molecular-genetic analysis of museum collections.

High-porosity activated carbon as a possible matrix for native DNA and dextran-sulfate immobilization.

In this study, specific and nonspecific activity of calf thymus DNA and Dextran-Sulfate (DS)-containing synthetic carbonic adsorbents (0.7-7mg of each ligands per 1 cm3 of activated carbonic beads, 0.3-0.6mm diameter, bulk density gamma=0.1-0.2g/cm3) have been compared in stir-bath and micro-column in vitro tests. DS coating as well as DNA coating does not demonstrate deep influence on the unspecific adsorptive activity of carbonic matrix toward creatinine, vitamin B12, and unconjugated bilirubin. No essential difference has been found in the specific activity of DNA and DS containing adsorbents toward anti-ds- and anti-ss-DNA-antibodies, as well as antibodies against DNA-protein complexes (anti-DNP-antibodies): in both cases the percentage of decrease of appropriate antibody concentration varied between 35 and 51% for single-pass microcolumn experiments with moderate enhancement of extraction efficacy (up to 60-75%) due to additional recirculation (2 h) or preliminary plasma dilution in 2-5 times. In the micro-column experiments with the proinflammatory cytokines DNA or DS-coating did not diminish TNF-alpha, IL-1beta, and IL-6 adsorption from 3% BSA solution, but even improves to some extent its removal compared with uncoated matrix.

Albumin, bilirubin, and activated carbon: new edges of an old triangle.

The problem of interaction of human serum albumin (HSA), unconjugated bilirubin (UB) and high porosity activated HSGD carbons is investigated in this study. The decrease of UB to HSA molecular ratio by more than 300 times was demonstrated while the batch experiments in HSA-UB admixtures after contact with HSGD. HSGD carbons express extremely high activity for the removal of UB from HSA containing solutions (more than 100 mg of UB per 1 g of activated carbon). Ex-tempore albumin-coating of carbon surface decreases adsorbent capacity by bilirubin on 21%. At the same time ex-tempore albumin-coating of HSGD carbon surface as well as blood citratization prevent platelet and leukocytes loss and clotting inside of the column. Pharmacopoeia solution of HSA containing acetyl-tryptophan or octanoate used for albumin-coating of HSGD adsorbents, becomes ligand-free and rather more active in complexing with protein-bound substances. Combination of albumin-coated HSGD carbon as haemosorbent with HSA ligand-free solution as a transfusion media seems a new prospective modality of the extracorporeal removal of protein-bound toxins.