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Line sampling (LS) stands as a powerful stochastic simulation method for structural reliability analysis, especially for assessing small failure probabilities. To further improve the performance of traditional LS, a Bayesian active learning idea has recently been pursued. This work presents another Bayesian active learning alternative, called 'Bayesian active learning line sampling with log-normal process' (BAL-LS-LP), to traditional LS. In this method, we assign an LP prior instead of a Gaussian process prior over the distance function so as to account for its non-negativity constraint. Besides, the approximation error between the logarithmic approximate distance function and the logarithmic true distance function is assumed to follow a zero-mean normal distribution. The approximate posterior mean and variance of the failure probability are derived accordingly. Based on the posterior statistics of the failure probability, a learning function and a stopping criterion are developed to enable Bayesian active learning. In the numerical implementation of the proposed BAL-LS-LP method, the important direction can be updated on the fly without re-evaluating the distance function. Four numerical examples are studied to demonstrate the proposed method. Numerical results show that the proposed method can estimate extremely small failure probabilities with desired efficiency and accuracy. • BAL-LS-LP is proposed for estimating extremely small failure probabilities. • Log-normal process is used as a prior distribution for the distance function. • Approximation error and non-negativity of the distance function are considered. • Approximate posterior mean and variance of the failure probability are derived. • Learning function and stopping criterion are proposed to enable active learning. [ABSTRACT FROM AUTHOR]

Summary: DNA methylation plays crucial roles in cellular development and stress responses through gene regulation and genome stability control. Precise regulation of DOMAINS REARRANGED METHYLTRANSFERASE 2 (DRM2), the de novo Arabidopsis DNA methyltransferase, is crucial to maintain DNA methylation homeostasis to ensure genome integrity. Compared with the extensive studies on DRM2 targeting mechanisms, little information is known regarding the quality control of DRM2 itself.Here, we conducted yeast two‐hybrid screen assay and identified an E3 ligase, COP9 INTERACTING F‐BOX KELCH 1 (CFK1), as a novel DRM2‐interacting partner and targets DRM2 for degradation via the ubiquitin‐26S proteasome pathway in Arabidopsis thaliana. We also performed whole genome bisulfite sequencing (BS‐seq) to determine the biological significance of CFK1‐mediated DRM2 degradation.Loss‐of‐function CFK1 leads to increased DRM2 protein abundance and overexpression of CFK1 showed reduced DRM2 protein levels. Consistently, CFK1 overexpression induces genome‐wide CHH hypomethylation and transcriptional de‐repression at specific DRM2 target loci.This study uncovered a distinct mechanism regulating de novo DNA methyltransferase by CFK1 to control DNA methylation level. [ABSTRACT FROM AUTHOR]

Perfluorooctane sulfonates (PFOS) are the persistent organic pollutants. In the present study, 0, 0.3, or 3-mg/kg PFOS were administered to pregnant mice from GD 11 to GD 18. The histopathology of liver and intestine, serum and hepatic lipid levels, lipid metabolism related genes, and gut microbiota were examined in adult female offspring. The results suggested that maternal PFOS exposure increased serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and induced F4/80+ macrophage infiltration in adult female offspring, in addition to the elevation of TNF-α and IL-1β mRNA levels in low-dose and high-dose groups, respectively. Furthermore, maternal exposure to PFOS increased serum triglyceride (TG) and hepatic total cholesterol (TC) levels, which was associated with the alteration of the process of fatty acid transport and β-oxidation, TG synthesis and transport, cholesterol synthesis and excretion in the liver. The AMPK/mTOR/autophagy signaling was also inhibited in the liver of adult female offspring. Moreover, changes in gut microbiota were also related to lipid metabolism, especially for the Desulfovibrio, Ligilactobacillus , Enterorhabdus , HT002 and Peptococcaceae_unclassified. Additionally, maternal exposure to PFOS decreased mRNA expressions of the tight junction protein and AB+ goblet cells in the colon, while increasing the overproduction of lipopolysaccharides (LPS) and F4/80+ macrophage infiltration. Collectively, maternal PFOS exposure induced liver lipid accumulation and inflammation, which strongly correlated with the disruption of the gut-liver axis and autophagy in adult female offspring, highlighting the persistent adverse effects in offspring exposed to PFOS. [Display omitted] • Maternal PFOS exposure induced hepatic lipid accumulation and inflammation in adult female offspring. • PFOS induced intestinal microbiota homeostasis, triggering overproduction of LPS. • Hepatic autophagy induced by PFOS was related to lipid accumulation and inflammation. [ABSTRACT FROM AUTHOR]

Line sampling has been demonstrated to be a promising simulation method for structural reliability analysis, especially for assessing small failure probabilities. However, its practical performance can still be significantly improved by taking advantage of, for example, Bayesian active learning. Along this direction, a recently proposed 'partially Bayesian active learning line sampling' (PBAL-LS) method has shown to be successful. This paper aims at offering a more complete Bayesian active learning treatment of line sampling, resulting in a new method called 'Bayesian active learning line sampling' (BAL-LS). Specifically, we derive the exact posterior variance of the failure probability, which can measure our epistemic uncertainty about the failure probability more precisely than the upper bound given in PBAL-LS. Further, two essential components (i.e., learning function and stopping criterion) are proposed to facilitate Bayesian active learning, based on the uncertainty representation of the failure probability. In addition, the important direction can be automatically updated throughout the simulation, as one advantage directly inherited from PBAL-LS. The performance of BAL-LS is illustrated by four numerical examples. It is shown that the proposed method is capable of evaluating extremely small failure probabilities with desired efficiency and accuracy. • Classical line sampling is treated by Bayesian active learning. • Bayesian active learning line sampling is proposed for structural reliability analysis. • Posterior variance of the failure probability is derived in an analytic expression. • A learning function and stopping criterion are proposed to enable Bayesian active learning. • Numerical studies indicate the efficiency and accuracy of the proposed method. [ABSTRACT FROM AUTHOR]

This work investigated the significantly weakened anisotropy of tensile properties of selective laser melted Ti6Al4V by heat treatment and represented a new perspective into the weakening mechanism. For the as-deposited sample, the tensile strength showed an evident improvement as the oriented angle θ (the angle between the tensile axis and the substrate plane) increased from 0° to 90° while the elongation showed the opposite trend. Nevertheless, the heat treatment weakened the anisotropy of strength as the deviation was reduced from 167 to 39 MPa, while the anisotropy of ductility was also remarkably declined. An algorithm, based on the EBSD data, was newly adopted to determine the most likely active slip system of each grain and evaluate the area-weighted average Schmid factors (SFs). The statistical results presented the distinct difference in the SFs of the as-deposited sample as θ changed while the SFs of the heat-treated sample showed similar values, quantitatively explaining the anisotropy of strength and the weakening mechanism. Besides, the high dependence of SF on the primary β grains, the number of primary β grains in the tensile specimen at different θ , and the existence of equiaxed grain boundary α together explained that ductility was worst at θ = 90° and increased as θ decreased. • Heat treatment eliminated the anisotropy of strength and weakened the anisotropy of ductility. • The area-weighted average Schmid Factor agreed well with the change of the anisotropy of strength. • The dependence of Schmid factors on primary grains accounted for the anisotropy of ductility. [ABSTRACT FROM AUTHOR]

The titanium powder embedded with 2.5 vol% TiB was in-situ fabricated by gas atomization and applied for direct laser deposited (DLD) titanium matrix composites. Consistent with the network distributed boron-rich zone in composite powder, a three-dimensional (3D) in-situ ultrafine network structure, consisting of nano-TiB whiskers (TiBw), was characterized throughout the as-fabricated composite (DLDed TiB–Ti). Both the dendritic and equiaxed network, attributed to the boron-induced constitutional supercooling and subsequent nucleation and growth of primary β-Ti, existed in the composite. The addition of boron (B) had a positive effect on the equiaxial transition and grain refinement of both primary β-Ti grains and α grains. Tensile tests showed an enhancement of strength compared with conventionally fabricated homogeneous TiB–Ti composites and selective laser melted CP-Ti. Analyzing the strength mechanism of the DLDed TiB–Ti, apart from the fine-grain strengthening and load-bearing effect of TiBw, the TiB network was found to have an additional contribution to the improvement of strength. Fracture morphology and in situ tensile observation showed the role of network structure in plastic deformation limitation, crack deflection and blunting, which was mainly attributed to the ultrafine cell size and revealed the significance of network structure. • Titanium powder embedded with TiB was applied for direct laser deposited titanium matrix composite. • The composite presented both the dendritic network and equiaxed network structure consisting of nano-TiB whiskers. • The microstructure evolution was controlled by the development of constitutional supercooling induced by boron addition. • The tensile test showed a superior strength due to the extra strengthening effect of the TiB network structure. [ABSTRACT FROM AUTHOR]

Long-term care (LTC) grading services refers to professional assessors using specific tools to systematically evaluate people with long-term care needs,develop and implement graded service standards that align with the care needs of individuals based on their varying levels of disability.It has been nearly a decade since China initiated home-based long-term care for the disabled elderly; however, challenges remain, such as the lack of detailed graded service standards and inadequate allocation of medical and nursing resources. This study aimed to gain insights into factors about influencing the current system by understanding the perspectives of those directly involved in providing care and to promote LTC services for older adults with disabilities in China.Using purposive sampling, nurses and certified nursing assistants were selected as participants for this qualitative study. Data were analysed using deductive method, guided by the Association Standard for Long-Term Care Grading Services for the Elderly, the Consolidated Framework for Implementation Research, and the Capability, Opportunity, and Motivation-Behavior (COM-B) model.This study identifies five themes-innovation, external and internal environmental factors, personal characteristics, and implementation process-along with five promoting and six obstacle factors. It explores nurses and certified nursing assistants perspectives on home-based long-term care grading for individuals with disabilities, offering a theoretical basis for a Chinese-specific long-term care model., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025 Elsevier Inc. All rights reserved.)

Lateral nanoarchitectonics is a method of precisely designing functional materials from atoms, molecules, and nanomaterials (so-called nanounits) in two-dimensional (2D) space using knowledge of nanotechnology. Similar strategies can be seen in biological systems; in particular, biological membranes ingeniously arrange and organise functional units within a single layer of units to create powerful systems for photosynthesis or signal transduction and others. When our major lateral nanoarchitectural approaches such as layer-by-layer (LbL) assembly and Langmuir-Blodgett (LB) films are compared with biological membranes, one finds that lateral nanoarchitectonics has potential to become a powerful tool for designing advanced functional nanoscale systems; however, it is still rather not well-developed with a great deal of unexplored possibilities. Based on such a discussion, this review article examines the current status of lateral nanoarchitectonics from the perspective of in-plane functional structure organisation at different scales. These include the extension of functions at the molecular level by on-surface synthesis, monolayers at the air-water interface, 2D molecular patterning, supramolecular polymers, macroscopic manipulation and functionality of molecular machines, among others. In many systems, we have found that while the targets are very attractive, the research is still in its infancy, and many challenges remain. Therefore, it is important to look at the big picture from different perspectives in such a comprehensive review. This review article will provide such an opportunity and help us set a direction for lateral nanotechnology toward more advanced functional organization., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Background: Liver surgery during the perioperative period often leads to a significant complication known as hepatic ischemia-reperfusion (I/R) injury. Hepatic I/R injury is linked to the innate immune response. The cGAS-STING pathway triggers the activation of innate immune through the detection of DNA within cells. Nevertheless, the precise mechanism and significance of the cGAS-STING pathway in hepatic I/R injury are yet to be investigated., Methods: Mouse model of hepatic I/R injury was used in the C57BL/6 WT mice and the STING knockout (STING-KO) mice. In addition, purified primary hepatocytes were used to construct oxygen-glucose deprivation reperfusion (OGD-Rep) treatment models., Results: Our research revealed a notable increase in mRNA and protein levels of cGAS and STING in liver during I/R injury. Interestingly, the lack of STING exhibited a safeguarding impact on hepatic I/R injury by suppressing the elevation of liver enzymes, liver cell death, and inflammation. Furthermore, pharmacological cGAS and STING inhibition recapitulated these phenomena. Macrophages play a crucial role in the activation of the cGAS-STING pathway during hepatic I/R injury. The cGAS-STING pathway experiences a significant decrease in activity and hepatic I/R injury is greatly diminished following the elimination of macrophages. Significantly, we demonstrate that the activation of the cGAS-STING pathway is primarily caused by the liberation of mitochondrial DNA (mtDNA) rather than nuclear DNA (nDNA). Moreover, the safeguarding of the liver against I/R injury is also attributed to the hindrance of mtDNA release through the utilization of inhibitors targeting mPTP and VDAC oligomerization., Conclusions: The results of our study suggest that the release of mtDNA plays a significant role in causing damage to liver by activating the cGAS-STING pathway during I/R injury. Furthermore, inhibiting the release of mtDNA can provide effective protection against hepatic I/R injury., (© 2024. The Author(s).)

Excessive proliferation and migration of pulmonary arterial smooth muscle cells (PASMCs) represent key steps of pulmonary vascular remodeling, leading to the development of pulmonary arterial hypertension (PAH) and right ventricular failure. Niclosamide (NCL), an FDA-approved anthelmintic, has been shown to regulate cell proliferation, migration, invasion, and apoptosis through a variety of signaling pathways. However, its role on modulating the phenotypic switch and inflammatory responses in PASMCs remains unclear. In this study, cell proliferation assay showed that NCL inhibited PDGF-BB induced proliferation of human PASMCs in a dose-dependent manner. Western blot analysis further confirmed a notable reduction in the expression of cyclin D1 and PCNA proteins. Subsequently, flow cytometry analysis demonstrated that NCL induced an increased percentage of cells in the G1 phase while promoting apoptosis in PASMCs. Moreover, both scratch wound assay and transwell assay confirmed that NCL decreased PDGF-BB-induced migration of PASMCs. Mechanistically, western blot revealed that pretreatment of PASMCs with NCL markedly restored the protein levels of SMA, SM22, and calponin, while reducing phosphorylation of P38/STAT3 signaling in the presence of PDGF-BB. Interestingly, macrophages adhesion assay showed that NCL markedly reduced recruitment of Calcein-AM labeled RAW264.7 by TNFα-stimulated PASMCs. Western blot revealed that NCL suppressed TNFα-induced expression of both of VCAM-1 and ICAM-1 proteins. Furthermore, pretreatment of PASMCs with NCL significantly inhibited NLRP3 inflammasome activity through reducing NLRP3, AIM2, mature interleukin-1β (IL-β), and cleaved Caspase-1 proteins expression. Together, these results suggested versatile effects of NCL on controlling of proliferation, migration, and inflammatory responses in PASMCs through modulating different pathways, indicating that repurposing of NCL may emerge as a highly effective drug for PAH treatment., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Alternative polyadenylation (APA) enhances gene regulatory potential by increasing the diversity of mRNA transcripts. 3' UTR shortening through APA correlates with enhanced cellular proliferation and is a widespread phenomenon in tumor cells. Here, we show that the ubiquitously expressed transcription factor Sp1 binds RNA in vivo and is a common repressor of distal poly(A) site usage. RNA sequencing identified 2,344 genes (36% of the total mapped mRNA transcripts) with lengthened 3' UTRs upon Sp1 depletion. Sp1 preferentially binds the 3' UTRs of such lengthened transcripts and inhibits cleavage at distal sites by interacting with the subunits of the core cleavage and polyadenylation (CPA) machinery. The 3' UTR lengths of Sp1 target genes in breast cancer patient RNA-seq data correlate with Sp1 expression levels, implicating Sp1-mediated APA regulation in modulating tumorigenic properties. Taken together, our findings provide insights into the mechanism for dynamic APA regulation by unraveling a previously unknown function of the DNA-binding transcription factor Sp1., Competing Interests: Declaration of interests B.J.B. is a member of the Molecular Cell advisory board., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Stem cells and their microenvironment interact cooperatively to dictate their fates. Biomaterials are dynamically remodeled by stem cells, and stem cells sense and translate the changes into cell fate decisions. We have previously reported that adaptive biomaterials composed of fibronectin inserted into protein nanosheets at a liquid interface enhance neuronal differentiation of human mesenchymal stem cells (hMSCs). However, we could not decouple clearly the effect of ligand density from that of fibrillary structure on cellular function and fate. Here we present an adaptive biomaterial based on two-dimensional networks of protein nanofibrils at a liquid-liquid interface. Compared with flat protein nanosheets, this biomaterial enhances neuronal differentiation of hMSCs through a signaling mechanism involving focal adhesion kinase. Lipid raft microdomains in plasma membrane are found to play a central role in which hMSCs rapidly adapt to the dynamic microenvironment at the fluid interface. Our finding has substantial implications for regenerative medicine and tissue engineering., (© 2022. The Author(s).)

Macropinocytosis is one of the major mechanisms by which cancer cells uptake extracellular nutrients from tumor microenvironment (TME) and plays very important roles in various steps of tumorigenesis. We previously reported the unexpected finding that intratumoral and extracellular ATP (eATP), as one of the major drastically upregulated extracellular nutrients and messengers in tumors, is taken up by cancer cells through macropinocytosis in large quantities and significantly contributing to cancer cell growth, survival, and increased resistance to chemo and target drugs. Inhibition of macropinocytosis substantially reduced eATP uptake by cancer cells and slowed down tumor growth in vivo. More recently, we have found the eATP also plays a very important role in inducing epithelial-to-mesenchymal transition (EMT), and that macropinocytosis is an essential facilitator in the induction. Thus, macropinocytosis and eATP, working in coordination, appear to play some previously unrecognized but very important roles in EMT and metastasis. As a result, they are likely to be interactive and communicative with each other, regulating each other's activity for various needs of host tumor cells. They are also likely to be an integral part of the future new anticancer therapeutic strategies. Moreover, it is undoubted that we have not identified all the important activities coordinated by ATP and macropinocytosis. This review describes our findings in how eATP and macropinocytosis work together to promote cancer cell growth, resistance, and EMT. We also list scientific challenges facing eATP research and propose to target macropinocytosis and eATP to reduce drug resistance and slow down metastasis., (© 2022. The Author(s), under exclusive license to Springer Nature Switzerland AG.)

Objective: Pulmonary vascular remodeling due to excessive growth factor production and pulmonary artery smooth muscle cells (PASMCs) proliferation is the hallmark feature of pulmonary arterial hypertension (PAH). Recent studies suggest that miR-663 is a potent modulator for tumorigenesis and atherosclerosis. However, whether miR-663 involves in pulmonary vascular remodeling is still unclear., Methods and Results: By using quantitative RT-PCR, we found that miR-663 was highly expressed in normal human PASMCs. In contrast, circulating level of miR-663 dramatically reduced in PAH patients. In addition, in situ hybridization showed that expression of miR-663 was decreased in pulmonary vasculature of PAH patients. Furthermore, MTT and cell scratch-wound assay showed that transfection of miR-663 mimics significantly inhibited platelet derived growth factor (PDGF)-induced PASMCs proliferation and migration, while knockdown of miR-663 expression enhanced these effects. Mechanistically, dual-luciferase reporter assay revealed that miR-663 directly targets the 3'UTR of TGF-β1. Moreover, western blots and ELISA results showed that miR-663 decreased PDGF-induced TGF-β1 expression and secretion, which in turn suppressed the downstream smad2/3 phosphorylation and collagen I expression. Finally, intratracheal instillation of adeno-miR-663 efficiently inhibited the development of pulmonary vascular remodeling and right ventricular hypertrophy in monocrotaline (MCT)-induced PAH rat models., Conclusion: These results indicate that miR-663 is a potential biomarker for PAH. MiR-663 decreases PDGF-BB-induced PASMCs proliferation and prevents pulmonary vascular remodeling and right ventricular hypertrophy in MCT-PAH by targeting TGF-β1/smad2/3 signaling. These findings suggest that miR-663 may represent as an attractive approach for the diagnosis and treatment for PAH., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Exposure to a single chemical does not exist in reality. Mixtures, which are the ecological norm, are often characterized by numerous intrinsic driving factors with unknown combined effects. Interactions between heterogeneous chemicals, or chemical and nonchemical stressors, could alter their toxicity traits relative to single exposure. Hence, revealing the hidden environmental effects affecting multiple stressor interactions is essential to expand our knowledge about uncertainty sources in chemical risk-based decision contexts. Global sensitivity analysis (GSA) techniques involving Morris method sampling and elementary effects (EE) sensitivity analysis was applied to investigate the driving factors underlying the combined effects on Scenedesmus obliquus, and identify the mode of interaction in mixtures at environmentally-relevant concentrations. One hundred mixed-exposure formulas were generated with 9 variables (8 chemicals and temperature) via the Morris method, representing environmental perspective in the field. Subsequently, EE sensitivity analysis combined with quantitative high-throughput screening (q-HTS) was adopted to identify the most critical mixture and its primary drivers. Combined exposure exerted significantly increased effects on S. obliquus compared to the effects of individual exposure. The critical drivers were identified and validated by the control variate method. For the mode of combined action, mixture toxicity did not match the additivity relationship, and a strong interaction existed among chemicals. Collectively, the data provides evidence that a combination of specific pesticides and emerging brominated flame retardants can produce comparable, or even stronger, bionegative effects than pure chemicals due to complicated interactions. The method used offers direct comparison of multifarious factors in a unified standard scale, bridges the actual interaction scenarios in the field to toxicity simulations in the laboratory, and fill a gap in ecotoxicology., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

The living cell can be regarded as an ideal functional material system in which many functional systems are working together with high efficiency and specificity mostly under mild ambient conditions. Fabrication of living cell-like functional materials is regarded as one of the final goals of the nanoarchitectonics approach. In this short review article, material-based approaches for regulation of living cell behaviors by external stimuli are discussed. Nanoarchitectonics strategies on cell regulation by various external inputs are first exemplified. Recent approaches on cell regulation with interfacial nanoarchitectonics are also discussed in two extreme cases using a very hard interface with nanoarchitected carbon arrays and a fluidic interface of the liquid-liquid interface. Importance of interfacial nanoarchitectonics in controlling living cells by mechanical and supramolecular stimuli from the interfaces is demonstrated., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2020 The Author(s).)

Incorporation of non-equilibrium actions in the sequence of self-assembly processes would be an effective means to establish bio-like high functionality hierarchical assemblies. As a novel methodology beyond self-assembly, nanoarchitectonics, which has as its aim the fabrication of functional materials systems from nanoscopic units through the methodological fusion of nanotechnology with other scientific disciplines including organic synthesis, supramolecular chemistry, microfabrication, and bio-process, has been applied to this strategy. The application of non-equilibrium factors to conventional self-assembly processes is discussed on the basis of examples of directed assembly, Langmuir-Blodgett assembly, and layer-by-layer assembly. In particular, examples of the fabrication of hierarchical functional structures using bio-active components such as proteins or by the combination of bio-components and two-dimensional nanomaterials, are described. Methodologies described in this review article highlight possible approaches using the nanoarchitectonics concept beyond self-assembly for creation of bio-like higher functionalities and hierarchical structural organization., (© 2020 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

There is a real need for new antibiotics against self-evolving bacteria. One option is to use biofriendly broad-spectrum and mechanically tunable antimicrobial hydrogels that can combat multidrug-resistant microbes. Whilst appealing, there are currently limited options. Herein, broad-spectrum antimicrobial biometallohydrogels based on the self-assembly and local mineralization of Ag + -coordinated Fmoc-amino acids are reported. Such biometallohydrogels have the advantages of localized delivery and sustained release, reduced drug dosage and toxicity yet improved bioavailability, prolonged drug effect, and tunable mechanical strength. Furthermore, they can directly interact with the cell walls and membrane, resulting in the detachment of the plasma membrane and leakage of the cytoplasm. This leads to cell death, triggering a significant antibacterial effect against both Gram-negative (Escherichia coli) and Gram-positive (Staphylococcus aureus) bacteria in cells and mice. This study paves the way for developing a multifunctional integration platform based on simple biomolecules coordinated self-assembly toward a broad range of biomedical applications., (© 2020 The Authors. Published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)