Structure prediction based on ab initio simulated annealing for boron nitride

Possible crystalline modifications of chemical compounds at low temperatures correspond to local minima of the energy landscape. Determining these minima via simulated annealing is one method for the prediction of crystal structures, where the number of atoms per unit cell is the only information used. It is demonstrated that this method can be applied to covalent systems, at the example of boron nitride, using ab initio energies in all stages of the optimization, i.e. both during the global search and the subsequent local optimization. Ten low lying structure candidates are presented, including both layered structures and 3d-network structures such as the wurtzite and zinc blende types, as well as a structure corresponding to the beta-BeO type

Report of the JRC’s Descriptor 1 workshop to support the review of the Commission Decision 2010/477/EU concerning MSFD criteria for assessing Good Environmental Status

The MSFD workshop on biodiversity (MSFD D1), held in Ispra JRC (7th-9th of September 2015) aimed to provide clear proposals and conclusions on some of the outstanding issues identified in the D1 review manual (May 2015 consultation version: https://circabc.europa.eu/w/browse/46d2b7ba-d2fd-4b3c-9eaf-18c7cb702b53) in the broader context of support to the review of Commission Decision 2010/477/EU. This report is complementing the Commission Decision 2010/477/EU review manual (JRC96521) and presents the result of the scientific and technical review concluding phase 1 of the review of the Commission Decision 2010/477/EU in relation to Descriptor 1. The review has been carried out by the EC JRC together with experts nominated by EU Member States, and has considered contributions from the GES Working Group in accordance with the roadmap set out in the MSFD implementation strategy (agreed on at the 11th CIS MSCG meeting). The main issues addressed and tackled in this workshop’s report are: - Common lists of elements for the biodiversity assessments (species & habitats) o Review of the “Biological Features” in Table 1 in the MSFD Annex III in relation to D1 requirements o Review of the “Habitat Types” entries in Table 1 in the MSFD Annex III in relation to D1 requirements - Selection/deselection criteria for the inclusion of species and habitats in a group - Updated criteria and indicators for D1 - Habitat/Bird Directives, WFD, Common Fisheries Policy and D1 o Use of species and habitats for the MSFD needs that are already included in other legislation and agreements o Links between status classification approaches (FCS vs GES, GEcS vs GES) - Streamlining of assessments, including scales of assessments - Cross-cutting issues related to D1 implementation o Aggregation rules within D1 criteria/indicators o Final GES integration across descriptors assessments Steps forward and technical needs for D1.JRC.H.1-Water Resource

Auswirkungen von Wärmebehandlungen von Mangan-Aluminium-Bronzen auf Gefüge und Korrosionsverhalten

Due to a much lower nickel content, manganese aluminum bronzes (MAB) are a cost-effective alternative to nickel aluminum bronzes (NAB). When the material is processed, different microstructures are observable in the material which have an impact on the corrosion resistance of MAB alloys. MAB samples were annealed at 900 °C and quenched in water. After that, annealing treatments at 600, 500, 400 and 300 °C for up to 24 h were performed and the samples were again quenched in water. Metallographic sections were prepared from all samples and potentiostatic corrosion tests at different potentials were performed in synthetic seawater. It was found that the sample annealed at 900 °C and quenched in water as well as those samples which underwent a second annealing treatment at low temperatures for shorter times exhibited a greater corrosion tendency than those undergoing a second annealing treatment at higher temperatures. X-ray diffraction measurements revealed that phase transformations and changes in grain size occurred during the annealing treatments. The increase in corrosion resistance as a result of annealing at higher temperatures is probably due to the strong intergrowth of the phases that are formed.Mangan-Aluminium-Bronze (MAB) ist aufgrund des viel geringeren Nickelgehalts eine kostengünstigere Alternative zu Nickel-Aluminium-Bronze (NAB). Bei der Werkstoffverarbeitung treten unterschiedliche Gefüge im Werkstoff auf, welche die Korrosionsbeständigkeit von MAB-Legierungen beeinflussen. MAB-Proben wurden bei 900 °C geglüht und in Wasser abgeschreckt. Danach wurden Glühungen bei 600, 500, 400 und 300 °C für bis zu 24 h durchgeführt und abermals in Wasser abgeschreckt. Von allen Proben wurden metallographische Schliffe angefertigt und potentiostatische Korrosionstests bei unterschiedlichen Potentialen, in künstlichem Meerwasser durchgeführt. Es wurde festgestellt, dass bei der bei 900 °C geglühten und abgeschreckten Probe, sowie jenen Proben die bei niedrigen Temperaturen und kürzeren Zeiten nachgeglüht wurden, eine stärkere Korrosionsneigung besteht, als bei den bei höheren Temperaturen nachgeglühten Proben. Röntgenbeugung-Messungen haben ergeben, dass es während der Temperungen zur Umwandlung von Phasen kommt und dabei auch die Korngrößen verändert werden. Die Erhöhung der Korrosionsbeständigkeit durch Tempern bei höheren Temperaturen ist vermutlich auf die starke Verwachsung der gebildeten Phasen zurückzuführen

Einfluss von wärmebehandlungen auf das gefüge und die korrosionsbeständigkeit von mangan-aluminium-bronzen

The analyses have shown that the corrosion behavior of manganese-aluminum bronzes (MAB) can be improved by keeping the fraction of β phase low. As opposed to the cast structure, the sample annealed at 850 °C and water quenched does not only contain coarse α and β phase but also a fine α/β phase mixture. The κ phase is coarsened. After annealing at 600 °C, not only isolated coarse α phase but also a fine α/β phase mixture is present. The κ phase has a globular appearance. Since, at an Al content of 7 wt. %, the alloy is located in a three-phase region consisting of α, β, and κ phase, the β phase is preserved even at slow cooling. In both corrosive media, SFW and SSW, predominantly selective corrosion takes place after which, similar to the dezincification of brass, metallic copper remains (so-called dealloying). The heat treatments show different effects on the corrosion behavior in fresh water or sea water. In fresh water, both heat treatments result in a deterioration of the corrosion resistance. Here, the α-β phase mixture, the β phase, and the κ phase were attacked. Measurements in sea water revealed a deterioration of the durability after annealing at 850 °C, but an improvement after annealing at 600 °C. Since no coarse β phase is observed after slow cooling, the MAB corrosion resistance, especially to sea water, can thus be improved

Preparation and in vitro evaluation of 177Lu-iPSMA-RGD as a new heterobivalent radiopharmaceutical

This study aimed to synthesize a new 177Lu-iPSMA-RGD heterobivalent radiopharmaceutical, as well as to assess the in vitro radiopharmaceutical potential to target cancer cells overexpressing PSMA and a(v) b(3) integrins. The radiotracer prepared with a radiochemical purity of 98.8 ± 1.0% showed stability in human serum, specific recognition with suitable affinity to PSMA and a(v)b(3) integrins, and capability to inhibit cancer cell proliferation and VEGF signaling (antiangiogenic effect). Results warrant further preclinical studies to establish the 177Lu-iPSMA-RGD potential as a dual therapeutic radiopharmaceutical.CONACyT-CB-2016-01-28152

PET imaging of αvβ3 integrin expression in tumours with 68Ga-labelled mono-, di- and tetrameric RGD peptides

Contains fulltext : 97195.pdf (publisher's version ) (Closed access)PURPOSE: Due to the restricted expression of alpha(v)beta(3) in tumours, alpha(v)beta(3) is considered a suitable receptor for tumour targeting. In this study the alpha(v)beta(3)-binding characteristics of (68)Ga-labelled monomeric, dimeric and tetrameric RGD peptides were determined and compared with their (111)In-labelled counterparts. METHODS: A monomeric (E-c(RGDfK)), a dimeric (E-[c(RGDfK)](2)) and a tetrameric (E{E[c(RGDfK)](2)}(2)) RGD peptide were synthesised, conjugated with DOTA and radiolabelled with (68)Ga. In vitro alpha(v)beta(3)-binding characteristics were determined in a competitive binding assay. In vivo alpha(v)beta(3)-targeting characteristics of the compounds were assessed in mice with subcutaneously growing SK-RC-52 xenografts. In addition, microPET images were acquired using a microPET/CT scanner. RESULTS: The IC(50) values for the Ga(III)-labelled DOTA-E-c(RGDfK), DOTA-E-[c(RGDfK)](2) and DOTA-E{E[c(RGDfK)](2)}(2) were 23.9 +/- 1.22, 8.99 +/- 1.20 and 1.74 +/- 1.18 nM, respectively, and were similar to those of the In(III)-labelled mono-, di- and tetrameric RGD peptides (26.6 +/- 1.15, 3.34 +/- 1.16 and 1.80 +/- 1.37 nM, respectively). At 2 h post-injection, tumour uptake of the (68)Ga-labelled mono-, di- and tetrameric RGD peptides (3.30 +/- 0.30, 5.24 +/- 0.27 and 7.11 +/- 0.67%ID/g, respectively) was comparable to that of their (111)In-labelled counterparts (2.70 +/- 0.29, 5.61 +/- 0.85 and 7.32 +/- 2.45%ID/g, respectively). PET scans were in line with the biodistribution data. On all PET scans, the tumour could be clearly visualised. CONCLUSION: The integrin affinity and the tumour uptake followed the order of DOTA-tetramer > DOTA-dimer > DOTA-monomer. The (68)Ga-labelled tetrameric RGD peptide has excellent characteristics for imaging of alpha(v)beta(3) expression with PET

Biological Designer Self-Assembling Peptide Nanofiber Scaffolds Significantly Enhance Osteoblast Proliferation, Differentiation and 3-D Migration

A class of self-assembling peptide nanofiber scaffolds has been shown to be an excellent biological material for 3-dimension cell culture and stimulating cell migration into the scaffold, as well as for repairing tissue defects in animals. We report here the development of several peptide nanofiber scaffolds designed specifically for osteoblasts. We designed one of the pure self-assembling peptide scaffolds RADA16-I through direct coupling to short biologically active motifs. The motifs included osteogenic growth peptide ALK (ALKRQGRTLYGF) bone-cell secreted-signal peptide, osteopontin cell adhesion motif DGR (DGRGDSVAYG) and 2-unit RGD binding sequence PGR (PRGDSGYRGDS). We made the new peptide scaffolds by mixing the pure RAD16 and designer-peptide solutions, and we examined the molecular integration of the mixed nanofiber scaffolds using AFM. Compared to pure RAD16 scaffold, we found that these designer peptide scaffolds significantly promoted mouse pre-osteoblast MC3T3-E1 cell proliferation. Moreover, alkaline phosphatase (ALP) activity and osteocalcin secretion, which are early and late markers for osteoblastic differentiation, were also significantly increased. We demonstrated that the designer, self-assembling peptide scaffolds promoted the proliferation and osteogenic differentiation of MC3T3-E1. Under the identical culture medium condition, confocal images unequivocally demonstrated that the designer PRG peptide scaffold stimulated cell migration into the 3-D scaffold. Our results suggest that these designer peptide scaffolds may be very useful for promoting bone tissue regeneration

Molecular imaging of angiogenesis with SPECT

Single-photon emission computed tomography (SPECT) and position emission tomography (PET) are the two main imaging modalities in nuclear medicine. SPECT imaging is more widely available than PET imaging and the radionuclides used for SPECT are easier to prepare and usually have a longer half-life than those used for PET. In addition, SPECT is a less expensive technique than PET. Commonly used gamma emitters are: 99mTc (Emax 141 keV, T1/2 6.02 h), 123I (Emax 529 keV, T1/2 13.0 h) and 111In (Emax 245 keV, T1/2 67.2 h). Compared to clinical SPECT, PET has a higher spatial resolution and the possibility to more accurately estimate the in vivo concentration of a tracer. In preclinical imaging, the situation is quite different. The resolution of microSPECT cameras (<0.5 mm) is higher than that of microPET cameras (>1.5 mm). In this report, studies on new radiolabelled tracers for SPECT imaging of angiogenesis in tumours are reviewed

Synthesis and Investigation of a Radioiodinated F3 Peptide Analog as a SPECT Tumor Imaging Radioligand

A radioiodinated derivative of the tumor-homing F3 peptide, (N-(2-{3-[125I]Iodobenzoyl}aminoethyl)maleimide-F3Cys peptide, [125I]IBMF3 was developed for investigation as a SPECT tumor imaging radioligand. For this purpose, we custom synthesized a modified F3 peptide analog (F3Cys) incorporating a C-terminal cysteine residue for site-specific attachment of a radioiodinated maleimide conjugating group. Initial proof-of-concept Fluorescence studies conducted with AlexaFluor 532 C5 maleimide-labeled F3Cys showed distinct membrane and nuclear localization of F3Cys in MDA-MB-435 cells. Additionally, F3Cys conjugated with NIR fluorochrome AlexaFluor 647 C2 maleimide demonstrated high tumor specific uptake in melanoma cancer MDA-MB-435 and lung cancer A549 xenografts in nude mice whereas a similarly labeled control peptide did not show any tumor uptake. These results were also confirmed by ex vivo tissue analysis. No-carrier-added [125I]IBMF3 was synthesized by a radioiododestannylation approach in 73% overall radiochemical yield. In vitro cell uptake studies conducted with [125I]IBMF3 displayed a 5-fold increase in its cell uptake at 4 h when compared to controls. SPECT imaging studies with [125I]IBMF3 in tumor bearing nude mice showed clear visualization of MDA-MB-435 xenografts on systemic administration. These studies demonstrate a potential utility of F3 peptide-based radioligands for tumor imaging with PET or SPECT techniques