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This paper presents the results of the Power To Melt and Maneuverability (P2M) Simulation Exercise on past fuel melting irradiation experiments, organized within the Organisation for Economic Co-operation and Development/Nuclear Energy Agency Framework for IrraDiation ExperimentS (FIDES) framework by the Core Group (CEA, EDF, and SCK‧CEN) and open to all FIDES members. The exercise consisted in simulating two past power ramps where fuel melting was detected: (1) the xM3 staircase power transient [ramp terminal level (RTL) 70 kW‧m−1, average burnup 27 GWd‧tU−1], carried out in 2005 in the R2 reactor at Studsvik (Sweden), where the rodlet maintained its integrity, and (2) the HBC4 fast power transient (RTL 66 kW‧m−1, average burnup 48 GWd‧tU−1), carried out in 1987 in the BR2 reactor at SCK‧CEN (Belgium), where the cladding failed during the experiment. The exercise was joined by 13 organizations from 9 countries using 11 different fuel performance codes. In this paper, the main results of the Simulation Exercise are presented and compared to available postirradiation examinations (PIE) or on-line measurements during the power ramps (fuel and clad diameters, rod elongation, pellet-clad gap, and fission gas release). Since the focus of the Simulation Exercise is on fuel melting assessment, determination of the boundary between melted/nonmelted fuel and the consequent definition of a melting radius from PIE are first discussed. During the HBC4 ramp, fuel melting was predicted by most of the codes despite differences in the melting models. Higher discrepancies were observed for the xM3 rod that can be attributed partly to power uncertainty and partly to the limited capability of the models to describe partial melting of the fuel during this ramp. Finally, possible code developments to improve simulation results are presented. [ABSTRACT FROM AUTHOR]

We report a novel synthesis strategy to prepare precision polymers providing exact chain lengths, molecular weights and monomer sequences that allow post modifications by convenient DNA hybridization. Two grafted single strand DNA (ssDNA) side chains serve as a versatile platform for sequence-specific attachment of chromophores, proteins, cell-targeting peptide, and a Y-shape DNA linker. This approach resembles a LEGO®-type incorporation of functionalities to create functional biopolymers of high structure definition under mild conditions.

CRISPR/Cas9-based approaches have greatly facilitated targeted genomic deletions. Contrary to coding genes however, which can be functionally knocked out by frame-shift mutagenesis, non-coding RNA (ncRNA) gene knockouts have remained challenging. Here we present a universal ncRNA knockout approach guided by epigenetic hallmarks, which enables robust gene silencing even in provisionally annotated gene loci. We build on previous work reporting the presence of overlapping histone H3 lysine 4 tri-methylation (H3K4me3) and DNaseI hypersensitivity sites around the transcriptional start sites of most genes. We demonstrate that excision of this gene-proximal signature leads to loss of microRNA and lincRNA transcription and reveals ncRNA phenotypes. Exemplarily we demonstrate silencing of the constitutively transcribed MALAT1 lincRNA gene as well as of the inducible miR-146a and miR-155 genes in human monocytes. Our results validate a role of miR-146a and miR-155 in negative feedback control of the activity of inflammation master-regulator NFκB and suggest that cell-cycle control is a unique feature of miR-155. We suggest that our epigenetically guided CRISPR approach may improve existing ncRNA knockout strategies and contribute to the development of high-confidence ncRNA phenotyping applications.

The attachment of two different functionalities in a site-selective fashion represents a great challenge in protein chemistry. We report site specific dual functionalizations of peptides and proteins capitalizing on reactivity differences of cysteines in their free (thiol) and protected, oxidized (disulfide) forms. The dual functionalization of interleukin 2 and EYFP proceeded with no loss of bioactivity in a stepwise fashion applying maleimide and disulfide rebridging allyl-sulfone groups. In order to ensure broader applicability of the functionalization strategy, a novel, short peptide sequence that introduces a disulfide bridge was designed and site-selective dual labeling in the presence of biogenic groups was successfully demonstrated.

In osteoporosis, bone structure can be improved by the introduction of therapeutic molecules inhibiting bone resorption by osteoclasts. Here, biocompatible hydrogels represent an excellent option for the delivery of pharmacologically active molecules to the bone tissue because of their biodegradability, injectability, and manifold functionalization capacity. The present study reports the preparation of a multifunctional hybrid hydrogel from chemically modified human serum albumin and rationally designed DNA building blocks. The hybrid hydrogel combines advantageous characteristics, including rapid gelation through DNA hybridization under physiological conditions and a self-healing and injectable nature with the possibility of specific loading and spatiotemporally controlled release of active proteins, making it an advanced biomaterial for the local treatment of bone diseases, for example, osteoporosis. The hydrogels are loaded with a recombinant Rho-inhibiting C3 toxin, C2IN-C3lim-G205C. This toxin selectively targets osteoclasts and inhibits Rho-signaling and, thereby, actin-dependent processes in these cells. Application of C2IN-C3lim-G205C toxin-loaded hydrogels effectively reduces osteoclast formation and resorption activity in vitro, as demonstrated by tartrate-resistant acid phosphatase staining and the pit resorption assay. Simultaneously, osteoblast activity, viability, and proliferation are unaffected, thus making C2IN-C3lim-G205C toxin-loaded hybrid hydrogels an attractive pharmacological system for spatial and selective modulation of osteoclast functions to reduce bone resorption., (© 2017 The Authors. Published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

There is a continuous demand for imaging probes offering excellent performance in various microscopy techniques for comprehensive investigations of cellular processes by more than one technique. Fluorescent nanodiamond-gold nanoparticles (FND-Au) constitute a new class of "all-in-one" hybrid particles providing unique features for multimodal cellular imaging including optical imaging, electron microscopy, and, and potentially even quantum sensing. Confocal and optical coherence microscopy of the FND-Au allow fast investigations inside living cells via emission, scattering, and photothermal imaging techniques because the FND emission is not quenched by AuNPs. In electron microscopy, transmission electron microscopy (TEM) and scanning transmission electron microscopy (STEM) analysis of FND-Au reveals greatly enhanced contrast due to the gold particles as well as an extraordinary flickering behavior in three-dimensional cellular environments originating from the nanodiamonds. The unique multimodal imaging characteristics of FND-Au enable detailed studies inside cells ranging from statistical distributions at the entire cellular level (micrometers) down to the tracking of individual particles in subcellular organelles (nanometers). Herein, the processes of endosomal membrane uptake and release of FNDs were elucidated for the first time by the imaging of individual FND-Au hybrid nanoparticles with single-particle resolution. Their convenient preparation, the availability of various surface groups, their flexible detection modalities, and their single-particle contrast in combination with the capability for endosomal penetration and low cytotoxicity make FND-Au unique candidates for multimodal optical-electronic imaging applications with great potential for emerging techniques, such as quantum sensing inside living cells.

Retroviral vectors are common tools for introducing genes into the genome of a cell. However, low transduction rates are a major limitation in retroviral gene transfer, especially in clinical applications. We generated cationic human serum albumin (cHSA) protected by a shell of poly(ethylene glycol) (PEG); this significantly enhanced retroviral gene transduction with potentially attractive pharmacokinetics and low immunogenicity. By screening a panel of chemically optimized HSA compounds, we identified a very potent enhancer that boosted the transduction rates of viral vectors. Confocal microscopy revealed a drastically increased number of viral particles attached to the surfaces of target cells. In accordance with the positive net charge of cationic and PEGylated HSA, this suggests a mechanism of action in which the repulsion of the negatively charged cellular and viral vector membranes is neutralized, thereby promoting attachment and ultimately transduction. Importantly, the transduction-enhancing PEGylated HSA derivative evaded recognition by HSA-specific antibodies and macrophage activation. Our findings hold great promise for facilitating improved retroviral gene transfer., (© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

We discuss fastest effectively adiabatic transitions (FEATs) for a collection of noninteracting harmonic oscillators with shared controllable real frequencies. The construction of such transitions is presented for given initial and final equilibrium states, and the dependence of the minimum time control on the interval of achievable frequencies is discussed. While the FEAT times and associated FEAT processes are important in their own right as optimal controls, the FEAT time is an added feature which provides a measure of the quality of a shortcut to adiabaticity (STA). The FEAT time is evaluated for a previously reported experiment, wherein a cloud of Rb atoms is cooled following a STA recipe that took about twice as long as the FEAT speed limit, a time efficiency of 50%.

Cells as the smallest unit of life rely on precise macromolecules and programmable supramolecular interactions to accomplish the various vital functions. To translate such strategies to precisely control architectures and interactions into the synthetic world represents an exciting endeavor. Polymers with distinct structures, sequences and architectures are still challenging to achieve. However, in particular for biomedical applications, reproducible synthesis, narrow dispersities, tunable functionalities and additionally biocompatibility of the polymeric materials are crucial. Polymers derived from protein precursors provide many advantages of proteins such as precise monomer sequences and contour lengths, biodegradability and multiple functionalities, which can be synergistically combined with the valuable features of synthetic polymers e.g. stability, tunable solubility and molecular weights. The resulting polymeric biohybrid materials offer many applications ranging from drug delivery to biosensing and therapeutic hydrogels. This minireview summarizes the most recent advances in this field.

A modular approach for the precise assembly of multi-component hydrogels consisting of protein and DNA building blocks is described for the first time. Multi-arm DNA is designed for crosslinking and stepwise, non-covalent assembly of active proteins inside the hydrogel.

Standard wafer solar cells are made of near-semiconductor quality silicon. This high quality material makes up a significant part of the total costs of a solar module. Therefore, new concepts with less expensive so called solar grade silicon directly based on physiochemically upgraded metallurgical grade silicon are investigated. Metallurgical grade silicon contains large amounts of impurities, mainly transition metals like Fe, Cr, Mn, and Co, which degrade the minority carrier lifetime and thus the solar cell efficiency. A major reduction of the transition metal content occurs during the unidirectional crystallization due to the low segregation coefficient between the solid and liquid phase. A further reduction of the impurity level has to be done by gettering procedures applied to the silicon wafers. The efficiency of such cleaning procedures of metallurgical grade silicon is studied by instrumental neutron activation analysis (INAA). Small sized silicon wafers of approximately 200mg with and without gettering step were analyzed. To accelerate the detection of transition metals in a crystallized silicon ingot, experiments of scanning whole vertical silicon columns with a diameter of approximately 1cm by gamma spectroscopy were carried out. It was demonstrated that impurity profiles can be obtained in a comparably short time. Relatively constant transition metal ratios were found throughout an entire silicon ingot. This led to the conclusion that the determination of several metal profiles might be possible by the detection of only one "leading element". As the determination of Mn in silicon can be done quite fast compared to elements like Fe, Cr, and Co, it could be used as a rough marker for the overall metal concentration level. Thus, a fast way to determine impurities in photovoltaic silicon material is demonstrated., (Copyright © 2011 Elsevier Ltd. All rights reserved.)