The chemical stage of the Monte Carlo track-structure simulation code Geant4-DNA has been revised and validated. The root-mean-square (RMS) empirical parameter that dictates the displacement of water molecules after an ionization and excitation event in Geant4-DNA has been shortened to better fit experimental data. The pre-defined dissociation channels and branching ratios were not modified, but the reaction rate coefficients for simulating the chemical stage of water radiolysis were updated. The evaluation of Geant4-DNA was accomplished with TOPAS-nBio. For that, we compared predicted time-dependentGvalues in pure liquid water for·OH, e-aq, and H2with published experimental data. For H2O2and H·, simulation of added scavengers at different concentrations resulted in better agreement with measurements. In addition, DNA geometry information was integrated with chemistry simulation in TOPAS-nBio to realize reactions between radiolytic chemical species and DNA. This was used in the estimation of the yield of single-strand breaks (SSB) induced by137Csγ-ray radiolysis of supercoiled pUC18 plasmids dissolved in aerated solutions containing DMSO. The efficiency of SSB induction by reaction between radiolytic species and DNA used in the simulation was chosen to provide the best agreement with published measurements. An RMS displacement of 1.24 nm provided agreement with measured data within experimental uncertainties for time-dependentGvalues and under the presence of scavengers. SSB efficiencies of 24% and 0.5% for·OH and H·, respectively, led to an overall agreement of TOPAS-nBio results within experimental uncertainties. The efficiencies obtained agreed with values obtained with published non-homogeneous kinetic model and step-by-step Monte Carlo simulations but disagreed by 12% with published direct measurements. Improvement of the spatial resolution of the DNA damage model might mitigate such disagreement. In conclusion, with these improvements, Geant4-DNA/TOPAS-nBio provides a fast, accurate, and user-friendly tool for simulating DNA damage under low linear energy transfer irradiation.

• MeSH
• Linear Energy Transfer MeSH
• Monte Carlo Method MeSH
• Computer Simulation MeSH
• DNA Damage * MeSH
• Water * MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Research Support, N.I.H., Extramural MeSH
• Validation Study MeSH

The presence of artificial implants complicates the delivery of proton therapy due to inaccurate characterization of both the implant and the surrounding tissues. In this work, we describe a method to characterize implant and human tissue mimicking materials in terms of relative stopping power (RSP) using a novel proton counting detector. Each proton is tracked by directly measuring the deposited energy along the proton track using a fast, pixelated spectral detector AdvaPIX-TPX3 (TPX3). We considered three scenarios to characterize the RSPs. First, in-air measurements were made in the presence of metal rods (Al, Ti and CoCr) and bone. Then, measurements of energy perturbations in the presence of metal implants and bone in an anthropomorphic phantom were performed. Finally, sampling of cumulative stopping power (CSP) of the phantom were made at different locations of the anthropomorphic phantom. CSP and RSP information were extracted from energy spectra at each beam path. To quantify the RSP of metal rods we used the shift in the most probable energy (MPE) of CSP from the reference CSP without a rod. Overall, the RSPs were determined as 1.48, 2.06, 3.08, and 5.53 from in-air measurements; 1.44, 1.97, 2.98, and 5.44 from in-phantom measurements, for bone, Al, Ti and CoCr, respectively. Additionally, we sampled CSP for multiple paths of the anthropomorphic phantom ranging from 18.63 to 25.23 cm deriving RSP of soft tissues and bones in agreement within 1.6% of TOPAS simulations. Using minimum error of these multiple CSP, optimal mass densities were derived for soft tissue and bone and they are within 1% of vendor-provided nominal densities. The preliminary data obtained indicates the proposed novel method can be used for the validation of material and density maps, required by proton Monte Carlo Dose calculation, provided by competing multi-energy computed tomography and metal artifact reduction techniques.

• MeSH
• Phantoms, Imaging * MeSH
• Humans MeSH
• Monte Carlo Method * MeSH
• Prostheses and Implants * MeSH
• Proton Therapy instrumentation   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH

Ucelená publikace o vývoji, výrobě a jednotlivých verzích obrněného transportéru OT-62. V jednotlivých kapitolách se čtenáři podrobně seznámí s vývojem nového transportéru od předběžného projektu přes výrobu prototypů až po sériové provedení a jeho použití u útvarů ČSLA.

Colistin is the last hope to treat extensively drug resistance (XDR) Acinetobacter baumannii (A. baumannii) infections, but resistance to colistin is currently reported in clinical centers all over the world. Here, we studied two colistin-resistant A. baumannii isolates with a difference in minimum inhibitory concentrations (MICs) that were isolated from a single burn patient during treatment in the hospitalization period. The international clonal (IC) lineage, multilocus sequence typing (MLST), and multiple loci variable number tandem repeat (VNTR) analysis (MLVA) typing were used to characterize the relatedness of A. baumannii isolates. Lipopolysaccharides (LPS) and PmrAB system analysis by PCR sequencing, polyacrylamide gel electrophoresis (PAGE), and real-time PCR were performed to determine the intactness and probable modifications of the LPS as the main resistance mechanisms to colistin. A combination of PCR, sequencing, and restriction fragment length polymorphism (RFLP) was used for A. baumannii resistance islands (AbaR) mapping as resistance-determinant reservoirs. Two isolates were identical at all MLST and VNTR marker loci that indicated the isolates were the same strain. In comparison to colistin-heteroresistant A. baumannii strain TEH267 (MIC = 1.5 mg/L), colistin-resistant A. baumannii strain TEH273 (MIC ≥256 mg/L) acquired two genomic regions including Tn6018-topA sequence and topA sequence-3' CS in its AbaR structure containing ispA and cadA genes which, it would appear, could be associated with eightfold increase in colistin MIC. Both isolates had new variants of AbaR-like structures which could be derivatives of the typical AbaR3. According to the results of this study, AbaRs could be associated with an increase in MIC to colistin.

• MeSH
• Acinetobacter baumannii classification   drug effects   genetics   isolation & purification   MeSH
• Anti-Bacterial Agents pharmacology   MeSH
• Genes, Bacterial MeSH
• Bacterial Proteins genetics   MeSH
• Electrophoresis, Polyacrylamide Gel MeSH
• Genotype MeSH
• Acinetobacter Infections microbiology   MeSH
• Colistin pharmacology   MeSH
• Humans MeSH
• Lipopolysaccharides analysis   MeSH
• Microbial Sensitivity Tests MeSH
• Minisatellite Repeats MeSH
• Multilocus Sequence Typing MeSH
• Polymerase Chain Reaction MeSH
• Burns complications   MeSH
• Transcription Factors genetics   MeSH
• DNA Transposable Elements * MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH

BACKGROUND: Pathogenic uncultivable treponemes comprise human and animal pathogens including agents of syphilis, yaws, bejel, pinta, and venereal spirochetosis in rabbits and hares. A set of 10 treponemal genome sequences including those of 4 Treponema pallidum ssp. pallidum (TPA) strains (Nichols, DAL-1, Mexico A, SS14), 4 T. p. ssp. pertenue (TPE) strains (CDC-2, Gauthier, Samoa D, Fribourg-Blanc), 1 T. p. ssp. endemicum (TEN) strain (Bosnia A) and one strain (Cuniculi A) of Treponema paraluisleporidarum ecovar Cuniculus (TPLC) were examined with respect to the presence of nucleotide intrastrain heterogeneous sites. METHODOLOGY/PRINCIPAL FINDINGS: The number of identified intrastrain heterogeneous sites in individual genomes ranged between 0 and 7. Altogether, 23 intrastrain heterogeneous sites (in 17 genes) were found in 5 out of 10 investigated treponemal genomes including TPA strains Nichols (n = 5), DAL-1 (n = 4), and SS14 (n = 7), TPE strain Samoa D (n = 1), and TEN strain Bosnia A (n = 5). Although only one heterogeneous site was identified among 4 tested TPE strains, 16 such sites were identified among 4 TPA strains. Heterogeneous sites were mostly strain-specific and were identified in four tpr genes (tprC, GI, I, K), in genes involved in bacterial motility and chemotaxis (fliI, cheC-fliY), in genes involved in cell structure (murC), translation (prfA), general and DNA metabolism (putative SAM dependent methyltransferase, topA), and in seven hypothetical genes. CONCLUSIONS/SIGNIFICANCE: Heterogeneous sites likely represent both the selection of adaptive changes during infection of the host as well as an ongoing diversifying evolutionary process.

• MeSH
• Genome, Bacterial MeSH
• Humans MeSH
• Bacterial Outer Membrane Proteins genetics   MeSH
• Retrospective Studies MeSH
• Treponema classification   genetics   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH

The catalytic reaction of copper amine oxidase proceeds through a ping-pong mechanism comprising two half-reactions. In the initial half-reaction, the substrate amine reduces the Tyr-derived cofactor, topa quinone (TPQ), to an aminoresorcinol form (TPQamr) that is in equilibrium with a semiquinone radical (TPQsq) via an intramolecular electron transfer to the active-site copper. We have analyzed this reductive half-reaction in crystals of the copper amine oxidase from Arthrobacter globiformis. Anerobic soaking of the crystals with an amine substrate shifted the equilibrium toward TPQsq in an "on-copper" conformation, in which the 4-OH group ligated axially to the copper center, which was probably reduced to Cu(I). When the crystals were soaked with substrate in the presence of halide ions, which act as uncompetitive and noncompetitive inhibitors with respect to the amine substrate and dioxygen, respectively, the equilibrium in the crystals shifted toward the "off-copper" conformation of TPQamr. The halide ion was bound to the axial position of the copper center, thereby preventing TPQamr from adopting the on-copper conformation. Furthermore, transient kinetic analyses in the presence of viscogen (glycerol) revealed that only the rate constant in the step of TPQamr/TPQsq interconversion is markedly affected by the viscogen, which probably perturbs the conformational change. These findings unequivocally demonstrate that TPQ undergoes large conformational changes during the reductive half-reaction.

• MeSH
• Arthrobacter enzymology   MeSH
• Bacterial Proteins chemistry   MeSH
• Amine Oxidase (Copper-Containing) chemistry   MeSH
• Crystallography, X-Ray MeSH
• Copper chemistry   MeSH
• Protein Structure, Tertiary MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH

Autor knihy Ochranné kameny Wolfgang Hahl, ví, o čem mluví. Už jako malý chlapec těžceonemocněl, což ho později donutilo vzít léčení do vlastních rukou a zvládnout hluboké zákonitosti života a smrti. Během let pobýval v buddhistických klášterech, u filipínských léčitelů či indiánských šamanů, učil se bojovým uměním u největších korejských mistrů, ale rovněž se školil v moderních duchovních a psychoterapeutických léčebných postupech, takže nakonec dokázal sám sebe zcela uzdravit. Kameny zajímají lidstvo už od pradávna. Dlouhá tisíciletí lidé používají krystaly nejen pro ozdobu, ale i k léčení a ochraně. Kdyby to nefungovalo, zřejmě by s tím už dávno přestali. Jenže je tomu naopak. Zájem o práci s drahými kameny poslední dobou spíš roste. A praxe ukazuje, že v nich opravdu máme mocné pomocníky netušené síly. Prospět nám mohou snad ve všech oblastech života, záleží jen na tom, co právě potřebujeme. Zda ochranu před agresí, napadením a násilím, prevenci před hrozící mrtvicí či infarktem, ochranu před škodlivým zářením z mobilů a monitorů nebo před magickým útokem. Stačí si vybrat.

• MeSH
• Complementary Therapies methods   MeSH
• Minerals therapeutic use   MeSH
• Spiritual Therapies MeSH
• Publication type
• Handbook MeSH

• Conspectus
• Fyzioterapie. Psychoterapie. Alternativní lékařství
• NML Fields
• alternativní lékařství
• okultní vědy

Michael Gienger získal svými příspěvky o léčbě kameny mezinárodní věhlas. Příroda je pro něj velká kniha, ve které se dají pozorným čtením odhalit četná tajemství života a objevit klíče k jejich porozumění. Jeho výzkumná činnost se zaměřuje na celou oblast přírodovědy a přírodního léčitelství. Výzkumu vody se věnuje více než dvacet let, aby vytvořil fundovaný základ pro nové odvětví léčby kameny.

• MeSH
• Chemical Phenomena MeSH
• Complementary Therapies methods   MeSH
• Minerals MeSH
• Water MeSH
• Publication type
• Popular Work MeSH

• Conspectus
• Fyzioterapie. Psychoterapie. Alternativní lékařství
• NML Fields
• alternativní lékařství

• Publication type
• Meeting Abstract MeSH

• Keywords
• slovníky odborné, slovník věcný, slovník synonymický,
• Publication type
• Dictionary MeSH

• Conspectus
• Čeština
• NML Fields
• lingvistika, lékařská terminologie