A Case Study in Application of the Risk Knowledge Infinity Cycle.

The Risk Knowledge Infinity (RKI) Cycle Framework was featured as part of the ICH-sanctioned training materials supporting the recent issuance of ICH Q9(R1) Quality Risk Management To support ICH Q9(R1) understanding and adoption, this paper presents a case study on the application of the RKI Cycle, based on an underlying out-of-specification investigation. This case study provides a stepwise walk-through of the cycle to illustrate how key concepts within the ICH Q9(R1) revision can be achieved through better connecting quality risk management and knowledge management with a framework such as the RKI Cycle.

Synthesis of micro- and nanosheets of CrCl3-RuCl3 solid solution by chemical vapour transport.

Solid solutions of 2D transition metal trihalides are rapidly growing in interest for the search for new 2D materials with novel properties at nanoscale dimensions. In this regard, we present a synthesis method for the Cr1-xRuxCl3 solid solution and describe the behaviour of the unit cell parameters over the whole composition range, which in general follows Vegard's law in the range of a = 5.958(6)CrCl3 … 5.9731(5)RuCl3 Å, b = 10.3328(20)CrCl3 … 10.34606(21)RuCl3 Å, c = 6.110(5)CrCl3 … 6.0385(5)RuCl3 Å and ß = 108.522(15)CrCl3 … 108.8314(14)RuCl3 °. The synthesized solid solution powder was subsequently used to deposit micro- and nanosheets directly on a substrate by applying chemical vapour transport in a temperature gradient of 575 °C → 525 °C for 2 h and 650 °C → 600 °C for 0.5 h as a bottom-up approach without the need for an external transport agent. The observed chromium chloride enrichment of the deposited crystals is predicted by thermodynamic simulation. The results allow for a nanostructure synthesis of this solid solution with a predictable composition down to about 30 nm in height and lateral size of several µm. When applying a quick consecutive delamination step, it is possible to obtain few- and monolayer structures, which could be used for further studies of downscaling effects for the CrCl3-RuCl3 solid solution. X-ray photoelectron spectroscopy, transmission electron microscopy and Raman spectroscopy were used to confirm the purity and quality of the synthesized crystals.

Temperature Driven Transformation of the Flexible Metal-Organic Framework DUT-8(Ni).

DUT-8(Ni) metal-organic framework (MOF) belongs to the family of flexible pillared layer materials. The desolvated framework can be obtained in the open pore form (op) or in the closed pore form (cp), depending on the crystal size regime. In the present work, we report on the behaviour of desolvated DUT-8(Ni) at elevated temperatures. For both, op and cp variants, heating causes a structural transition, leading to a new, crystalline compound, containing two interpenetrated networks. The state of the framework before transition (op vs. cp) influences the transition temperature: the small particles of the op phase transform at significantly lower temperature in comparison to the macroparticles of the cp phase, transforming close to the decomposition temperature. The new compound, confined closed pore phase (ccp), was characterized by powder X-ray diffraction and spectroscopic techniques, such as IR, EXAFS, and positron annihilation lifetime spectroscopy (PALS). Thermal effects of structural transitions were studied using differential scanning calorimetry (DSC), showing an overall exothermic effect of the process, involving bond breaking and reformation. Theoretical calculations reveal the energetics, driving the observed temperature induced phase transition.

Reactivity of Ionic Liquids: Reductive Effect of [C4 C1 im]BF4 to Form Particles of Red Amorphous Selenium and Bi2 Se3 from Oxide Precursors.

Temperature-induced change in reactivity of the frequently used ionic liquid 1-butyl-3-methylimidazolium tetrafluoroborate ([C4 C1 im]BF4 ) is presented as a prerequisite for the rational screening of reaction courses in material synthesis. [C4 C1 im]BF4 becomes active with oxidic precursor compounds in reduction reaction at ϑ≥200 °C, even without the addition of an external reducing agent. The reaction mechanism of forming red amorphous selenium from SeO2 is investigated as a model system and can be described similarly to the Riley oxidation. The reactive species but-1-ene, which is formed during the decomposition of [C4 C1 im]BF4 , reacts with SeO2 and form but-3-en-2-one, water, and selenium. Elucidation of the mechanism was achieved by thermoanalytical investigations. The monotropic phase transition of selenium was analyzed by the differential scanning calorimetry. Beyond, the suitability of the single source oxide precursor Bi2 Se3 O9 for the synthesis of Bi2 Se3 particles was confirmed. Identification, characterization of formed solids succeeded by using light microscopy, XRD, SEM, and EDX.

Chemical vapor growth and delamination of α-RuCl3 nanosheets down to the monolayer limit.

The 2D layered honeycomb magnet α-ruthenium(iii) chloride (α-RuCl3) is a promising candidate to realize a Kitaev spin model. As alteration of physical properties on the nanoscale is additionally intended, new synthesis approaches to obtain phase pure α-RuCl3 nanocrystals have been audited. Thermodynamic simulations of occurring gas phase equilibria were performed and optimization of synthesis conditions was achieved based on calculation results. Crystal growth succeeded via chemical vapor transport (CVT) in a temperature gradient of 973 K to 773 K on YSZ substrates. Single crystal sheets of high crystallinity with heights ≤30 nm were obtained via pure CVT. The crystal properties were characterized by means of optical and electron microscopy, AFM, SAED, micro-Raman and XPS proving their composition, morphology, crystallinity and phase-purity. A highlight of our study is the successful individualization of nanocrystals and the delamination of nanosheets on YSZ substrates down to the monolayer limit (≤1 nm) which was realized by means of substrate exfoliation and ultrasonication in a very reproducible way.

Thermal Resilience of Imidazolium-Based Ionic Liquids-Studies on Short- and Long-Term Thermal Stability and Decomposition Mechanism of 1-Alkyl-3-methylimidazolium Halides by Thermal Analysis and Single-Photon Ionization Time-of-Flight Mass Spectrometry.

Ionic liquids are often considered as green alternatives of volatile organic solvents. The thermal behavior of the ionic liquids is relevant for a number of emerging large-scale applications at elevated temperature. Knowledge about the degradation products is indispensable for treatment and recycling of the used ionic liquids. The objective of this paper was an investigation of the short- and long-term stability of several 1-alkyl-3-methylimidazolium halides, determination of the degradation products, and the elucidation of their decomposition patterns and structure-stability relations. Short-term stability and mechanism of thermal degradation were investigated by a self-developed, innovative thermal analysis single-photon ionization time-of-flight mass spectrometry device with Skimmer coupling. The applied technology provides real-time monitoring of the forming species and allows tracing their change during the course of the decomposition. Therein, the almost fragment-free soft ionization with vacuum ultraviolet photons plays a crucial role. We have detected unfragmented molecules whose formation was only assumed by electron ionization. Nevertheless, the main decomposition products of the selected ionic liquids were alkyl imidazoles, alkenes, alkyl halides, and hydrogen halides. From the decomposition products, we have deduced the fragmentation patterns and discussed their interrelation with the length of the alkyl chain and the type of the halide anion. Our results did not suggest the evaporation of the investigated ionic liquids prior to their decomposition under atmospheric conditions. Long-term thermal stability and applicability were determined based on thermogravimetric analysis evaluated with a kinetic model. Thus, the time-dependent maximum operation temperature (MOT) for the respective ionic liquids has been calculated. As a rule, the short-term stability overestimates the long-term decomposition temperatures; the calculated MOT are significantly lower (at least 100 K) than the standardly obtained decomposition temperatures.

Inorganic Double Helices in Semiconducting SnIP.

SnIP is the first atomic-scale double helical semiconductor featuring a 1.86 eV bandgap, high structural and mechanical flexibility, and reasonable thermal stability up to 600 K. It is accessible on a gram scale and consists of a racemic mixture of right- and left-handed double helices composed by [SnI] and [P] helices. SnIP nanorods <20 nm in diameter can be accessed mechanically and chemically within minutes.

The extended stability range of phosphorus allotropes.

Phosphorus displays fascinating structural diversity and the discovery of new modifications continues to attract attention. In this work, a complete stability range of known and novel crystalline allotropes of phosphorus is described for the first time. This includes recently discovered tubular modifications and the prediction of not-yet-known crystal structures of [P12] nanorods and not-yet-isolated [P14] nanorods. Despite significant structural differences, all P allotropes consist of covalent substructures, which are held together by van der Waals interactions. Their correct reproduction by ab initio calculations is a core issue of current research. While some predictions with the established DFT functionals GGA and LDA differ significantly from experimental data in the description of the P allotropes, consistently excellent agreement with the GGA-D2 approach is used to predict the solid structures of the P nanorods.

Temperature initiated P-polymerization in solid [Cd3Cu]CuP10.

[Cd3Cu]CuP10, a polyphosphide containing adamantine-analogue [P10] unit undergoes a solid-state polymerization to form [P6] rings and tubular [P26] polymer units at elevated temperatures. This reaction represents the rare case of a polyphosphide polymerization in the solid state. The formation of such a polymeric unit starting from a molecular precursor is the first evidence of the general possibility to perform a bottom-up route to the well-known tubular polyphosphide units of elemental phosphorus in a solid material. Temperature-dependent X-ray powder diffraction experiments substantiate the solid phase transformation of [Cd3Cu]CuP10 starting at 550 °C to the polymerized form via an additional intermediate step. A single crystal structure determination of the quenched product at room temperature was performed to evaluate the structural properties and the resulting polyphosphide units. The full polymerization and decomposition mechanism has been analyzed by thermogravimetric experiments and subsequent X-ray powder phase analyses. The present [P26] polymer unit represents a former unseen one-dimensional cut-out of the two-dimensional polyphosphide substructure of Ag3P11 and can be directly related to the tubular polyphosphide substructures of violet or fibrous phosphorus.

Cd4Cu7As, the first representative of a fully ordered, orthorhombically distorted MgCu2 Laves phase.

The ternary Laves phase Cd(4)Cu(7)As is the first intermetallic compound in the system Cu-Cd-As and a representative of a new substitution variant for Laves phases. It crystallizes orthorhombically in the space group Pnnm (No. 58) with lattice parameters a = 9.8833(7) Å; b = 7.1251(3) Å; c = 5.0895(4) Å. All sites are fully occupied within the standard deviations. The structure can be described as typical Laves phase, where Cu and As are forming vertex-linked tetrahedra and Cd adopts the structure motive of a distorted diamond network. Cd(4)Cu(7)As was prepared from stoichiometric mixtures of the elements in a solid state reaction at 1000 °C. Magnetic measurements are showing a Pauli paramagnetic behavior. During our systematical investigations within the ternary phase triangle Cd-Cu-As the cubic C15-type Laves phase Cd(4)Cu(6.9(1))As(1.1(1)) was structurally characterized. It crystallizes cubic in the space group Fd3m with lattice parameter a = 7.0779(8) Å. Typically for quasi-binary Laves phases Cu and As are both occupying the 16c site. Chemical bonding, charge transfer and atomic properties of Cd(4)Cu(7)As were analyzed by band structure, ELF, and AIM calculations. On the basis of the general formula for Laves phases AB(2), Cd is slightly positively charged forming the A substructure, whereas Cu and As represent the negatively charged B substructure in both cases. The crystal structure distortion is thus related to local effects caused by Arsenic that exhibits a larger atomic volume (18 Å(3) compared to 13 Å(3) for Cu) and higher ionicity in bonding.

Insights into the molecular basis of the microaerophily of three Campylobacterales: a comparative study.

The concentration of oxygen in the atmosphere is a common environmental factor which can also be a source of stress for microorganisms. Comparative analyses of the responses of the epsilon-proteobacteria Campylobacter jejuni, Helicobacter pylori and Wolinella succinogenes to elevated oxygen concentrations were carried out using transcriptomics. Microarray data were analysed to determine genes differentially expressed under elevated oxygen concentrations. The results indicated 158, 58 and 82 genes were upregulated and 46, 40 and 65 were downregulated in C. jejuni, H. pylori and W. succinogenes, respectively. The gene encoding the enzyme alkyl hydroperoxide reductase was the only one upregulated at higher oxygen tensions in all three bacterial species. No genes were found to be downregulated in all three species. Functional classification analyses were performed on the genes whose expression was modulated in order to identify common pathways and functional categories which were differentially expressed in the three organisms. Processes upregulated at higher oxygen tensions included translation, oxidative phosphorylation, antioxidation, and nucleic acid metabolism. ABC and ion-coupled transport proteins were generally downregulated at higher oxygen tensions. Finally, insights into the preferred environment were gained from the analyses of the bacterial responses, specifically motility and chemotaxis proteins. W. succinogenes preferred anaerobic conditions as opposed to C. jejuni and H. pylori preference for microaerobic conditions. These comparative studies provide a better understanding of bacterial adaptation to and interaction with their environment.

Au3SnP7@black phosphorus: an easy access to black phosphorus.

Black phosphorus can be prepared under low-pressure conditions at 873 K from red phosphorus via the addition of small quantities of gold, tin, and tin(IV) iodide. Au3SnP7, AuSn, and Sn4P3 were observed as additional phases. Tin(IV) iodide remains unreacted during the preparation process. The crystal structure of black phosphorus was redetermined from single crystals. P (295 K): a = 3.316(1) A, b = 10.484(2) A, c = 4.379(1) A, V = 152.24(6) A3, space group Cmce (No. 64). Solid-state 31P MAS NMR spectroscopy and X-ray powder diffraction were performed to substantiate the high crystal quality of black phosphorus. A possible mechanism for the formation is discussed in terms of the comparable structural features of black phosphorus and Au3SnP7. Thermodynamic calculations showed that the only relevant gas-phase species, P4, and the transport reactions are not suitable for the preparation of orthorhombic black phosphorus at temperatures above 773 K. A kinetically controlled mechanism must be favored instead of a thermodynamically controlled formation. The new preparation method of black phosphorus represents an easy and effective way to avoid complicated preparative setups, toxic catalysts, or "dirty" flux methods and is of general interest in elemental chemistry.

New weakly expressed cell cycle-regulated genes in yeast.

We present an approach combining bioinformatics prediction with experimental microarray validation to identify new cell cycle-regulated genes in Saccharomyces cerevisiae. We identify in the order of 100 new cell cycle-regulated genes and show by independent data that these genes in general tend to be more weakly expressed than the genes identified hitherto. Among the genes not previously suggested to be periodically expressed we find genes linked to DNA repair, cell size monitoring and transcriptional control, as well as a number of genes of unknown function. Several of the gene products are believed to be phosphorylated by Cdc28. For many of these new genes, homologues exist in Schizosaccharomyces pombe and Homo sapiens for which the expression also varies with cell cycle progression.