Freezing and melting transitions of liquids in mesopores with ink-bottle geometry

Freezing and melting behavior of nitrobenzene in mesoporous silicon with different pore size and with different porous structure have been studied using H-1 NMR cryoporometry. With the bulk phase surrounding the porous monoliths, in materials with uniform channel-like pores distinct pore-size-dependent freezing and melting transitions have been measured. These data were further used for the analysis of the fluid behavior in samples with modulated porous structure, namely linear pores with alternating cross-section. We have, in particular, considered two materials consisting of channel sections, which were separated by almost identical channel `necks' but notably differed in the respective channel diameters. In the smaller channel segments, the observed shift in the freezing temperature provides direct evidence of the relevance of a pore-blocking mechanism, i.e. of the retardation in the propagation of a solid front by the channel necks. In the channel segments with larger diameter, on the other hand, freezing is found to be initiated by homogeneous nucleation.DF

Movement of cadmium and lead in anthropogenically formed trophic chains of a pasture type

ABSTRACT: An investigation on the movement of Lead (Pb) and cadmium (Cd) in a trophic chain in 2 villages (industrial polluted and non polluted) has been conducted. The contents of the 2 heavy metals in the soil, food and in different organs of young kids, so as their transfer in the 3 trophic levels (using different static and dynamic methods of recalculation) have been established. The authors show, that it is expedient to determine quantitatively the chemical heterogeneity at the heterotrophic levels applying two criteria: along with the dynamic criterion “Clarc of concentration”(Cc), used up to know, to include also “Factor of bioaccumulation” (FB), which shows the real value of accumulation or dispersal of the chemical element according to its content in soil or at the trophic level of the autotrophic organisms. The increased Cc of lead /4,72/ and cadmium /49,14/ in soil is not the reason for the concentration in the nutrition chain at the level of the autotrophic organisms and at the level of the organisms phytophages /kids/. The studies of the FB show that the technogenically high Clarc of lead and cadmium in the ecotope is the reason for some changes in the metabolism, enabling the dispersal of lead along the trophic chain, the values falling down to 0,05 – 0,02 compared to its content in the ecotope, and, of cadmium – down to 0,03 – 0,15 in the tested organs and tissues. РЕЗЮМЕ: Проведено е изследване за движението на олово (Pb) и кадмий (Cd) в трофична верига в две села(промишлено замърсено и незамърсено). Установено е съдържанието на двата тежки метала в почвата, храната и различните органи на млади ярета и трансферът им в трите трофични нива, използвайки различни статични и динамични методи на изчисление. Авторите доказват, че е възможно количественото определяне на химичната хетерогенност на хетеротрофните нива, използвайки два критерия: наред с динамичния критерий “Кларк на концентрация” (Сс), използван досега, се включва и “Фактор на биоакумулация” (FB), който показва реалната стойност на натрупване или разсейване на химичния елемент според съдържанието му в почвата или на трофично ниво в автотрофния организъм. Повишеният Сс на олово /4,72/ и кадмий /49,14/ в почвата не е причина за концентрацията им в хранителната верига на нивото на автотрофните организми и на нивото на организмите-фитофаги /ярета/. Изследванията на FB показват, че техногенно високият кларк на олово и кадмий в екотопа е причина за някои промени в метаболизма, способстващи за разпръскване на оловото по трофичната верига и спада на стойностите до 0,05 – 0,02 в сравнение със съдържанието му в екотопа, и на кадмия – до 0,03 – 0,15 в изследваните органи и тъкани

Проучване на химичната нееднородност на кадмий и олово в трофична верига: автотрофни организми - дребни преживни животни в антропогенни екосистеми с повишен техногенен кларк

Our study discuss the movement of lead and cadmium in the anthropogenic ecosystem with increased technogenic klarck, investigating the changes in autotrophic organisms and secondary biological production from kids and lambs. We offer a new measure for estimation of chemical heterogeneity and it was found the topographic difference of species in the bioaccumulation of these toxic elements

Direct and Auger Electron-Induced, Single- and Double-Strand Breaks on Plasmid DNA Caused by 99mTc-Labeled Pyrene Derivatives and the Effect of Bonding Distance.

It is evident that 99mTc causes radical-mediated DNA damage due to Auger electrons, which were emitted simultaneously with the known γ-emission of 99mTc. We have synthesized a series of new 99mTc-labeled pyrene derivatives with varied distances between the pyrene moiety and the radionuclide. The pyrene motif is a common DNA intercalator and allowed us to test the influence of the radionuclide distance on damages of the DNA helix. In general, pUC 19 plasmid DNA enables the investigation of the unprotected interactions between the radiotracers and DNA that results in single-strand breaks (SSB) or double-strand breaks (DSB). The resulting DNA fragments were separated by gel electrophoresis and quantified by fluorescent staining. Direct DNA damage and radical-induced indirect DNA damage by radiolysis products of water were evaluated in the presence or absence of the radical scavenger DMSO. We demonstrated that Auger electrons directly induced both SSB and DSB in high efficiency when 99mTc was tightly bound to the plasmid DNA and this damage could not be completely prevented by DMSO, a free radical scavenger. For the first time, we were able to minimize this effect by increasing the carbon chain lengths between the pyrene moiety and the 99mTc nuclide. However, a critical distance between the 99mTc atom and the DNA helix could not be determined due to the significantly lowered DSB generation resulting from the interaction which is dependent on the type of the 99mTc binding motif. The effect of variable DNA damage caused by the different chain length between the pyrene residue and the Tc-core as well as the possible conformations of the applied Tc-complexes was supplemented with molecular dynamics (MD) calculations. The effectiveness of the DNA-binding 99mTc-labeled pyrene derivatives was demonstrated by comparison to non-DNA-binding 99mTcO4-, since nearly all DNA damage caused by 99mTcO4- was prevented by incubating with DMSO

F-18-Labeled phosphopeptide-cell-penetrating peptide dimers with enhanced cell uptake properties in human cancer cells

Introduction: Phosphopeptides represent interesting compounds to study and elucidate cellular protein phosphorylation/dephosphorylation processes underlying various signal transduction pathways. However, studies of phosphopeptide action in cells are severely constrained by the negatively charged phosphate moiety of the phosphopeptide resulting in poor transport through the cell membrane. The following study describes the synthesis and radiopharmacological evaluation of two F-18-labeled phosphopeptide-cell-penetrating peptide dimers. The polo-like kinase-1-binding hexaphosphopeptide H-Met-Gln-Ser-pThr-ProLeu-OH was coupled to cell-penetrating peptides (CPPs), either sC18, a cathelicidin-derived peptide, or the human calcitonin derivative hCT(18-32)-k7. Methods: Radiolabeling was accomplished with the prosthetic group N-succinimidyl 4-[F-18]fluorobenzoate ([F-18]SFB) using both, conventional and microfluidic-based bioconjugation of [F-18]SEB to N-terminal end of phosphopeptide part of the peptide dimers. Cellular uptake studies in human cancer cell lines HT-29 and FaDu cells at 4 T and 37 T and small animal PET in BALB/c mice were utilized for radiopharmacological characterization. Results: Isolated radiochemical yields ranged from 2% to 4% for conventional bioconjugation with [F-18]SFB. Significantly improved isolated radiochemical yields of up to 26% were achieved using microfluidic technology. Cellular uptake studies of radiolabeled phosphopeptide and phosphopeptide-CPP dimers indicate enhanced internalization of 50% ID/mg protein after 2 h for both phosphopeptide dimers compared to the phosphopeptide alone (<1% ID/mg protein). In vivo biodistribution of F-18-labeled peptide dimers was determined with small animal PET revealing a superior biodistribution pattern of sC18-containing peptide dimer MQSpTPL-sC18 [F-18]4. Conclusion: [F-18]SFB labeling of the phosphopeptide-CPP dimers using a microfluidic system leads to an improved chemoselectivity towards the N-terminal NH2 group compared to the conventional labeling approach. Cell-penetrating peptide sC18 can be considered as an ideal molecular shuttle for intracellular delivery of the Plk1-PBD-binding hexaphosphopeptide as demonstrated by its favourable radiopharmacological profile. (C) 2012 Elsevier Inc. All rights reserved

Effect of [F-18]FMISO stratified dose-escalation on local control in FaDu hSCC in nude mice

Objective: To investigate the effect of radiation dose-escalation on local control in hypoxic versus non-hypoxic hypoxic tumours defined using [F-18]fluoromisonidazole ([F-18]FMISO) PET. Materials and methods: FaDu human squamous cell carcinomas (hSCCs) growing subcutaneously in nude mice were subjected to [F-18]FMISO PET before irradiation with single doses of 25 or 35 Gy under normal blood flow conditions. [F-18]FMISO hypoxic volume (HV) and maximum standardised uptake value (SUVmax) were used to quantify tracer uptake. The animals were followed up for at least 120 days after irradiation. The endpoints were permanent local tumour control and time to local recurrence. Results: HV varied between 38 and 291 mm(3) (median 105 mm(3)). Non-hypoxic tumours (HV below median) showed significantly better local control after single dose irradiation than hypoxic tumours (HV above median) (p = 0.046). The effect of dose was significant and not different in non-hypoxic and in hypoxic tumours (HR= 0.82 [95% Cl 0.71; 0.93], p = 0.002 and HR= 0.86 [0.78; 0.95], p = 0.001, respectively). Dose escalation resulted in an incremental increase of local tumour control from low-dose hypoxic, over low-dose non-hypoxic and high-dose hypoxic to high-dose non-hypoxic tumours. SUVmax did not reveal significant association with local control at any dose level. Conclusions: The negative effect of [F-18]FMISO HV on permanent local tumour control supports the prognostic value of the pre-treatment [F-18]FMISO HV. Making the assumption that variable [F-18]FMISO uptake in different FaDu tumours which all have the same genetic background may serve as an experimental model of intratumoural heterogeneity, the data support the concept of dose-escalation with inhomogeneous dose distribution based on pre-treatment [F-18]FMISO uptake. This result needs to be confirmed in other tumour models and using fractionated radiotherapy schedules

Die Befaehigung der Abgeordneten der oertlichen Volksvertretungen zur Erhoehung ihrer politischen Wirksamkeit in der sozialistischen Oeffentlichkeit

HUB(11) - 71 HB 270 / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekSIGLEDEGerman

Radiosynthesis of racemic and enantiomerically pure (-)-[18F]flubatine - A promising PET radiotracer for neuroimaging of alpha-4 beta-2 nicotinic acetylcholine receptors

(−)-[18F]flubatine is a promising agent for visualization by PET of cerebral α4β2 nicotinic acetylcholine receptors (nAChRs), which are implicated in psychiatric and neurodegenerative disorders. Here, we describe a substantially improved two-step radiosynthesis strategy for (−)-[18F]flubatine, based on the nucleophilic radiofluorination of an enantiomerically pure precursor followed by deprotection of the intermediate. An extensive leaving group/protecting group library of precursors was tested. Application of a trimethylammonium-iodide precursor with a Boc-protecting group provided the best results: labeling efficiencies of 80–95%, RCY of 60±5%, radiochemical purity of >98%, and a specific activity of >350 GBq/μmol. The radiosynthesis is easily transferable to an automated synthesis module