Expediting the Implementation of Closed-Loop Supply Chain Management: a Facilitated Case Study on Re-using Timber in Construction Projects.

An increasing number of firms are aiming to implement closed-loop supply chain (CLSC) management to contribute to a more circular economy. However, for many of these firms, it is difficult to translate this strategic aim into fruitful operational decisions. They need to address many deep uncertainties and dynamic complexities in their supply chain system, which make their transition towards CLSC management challenging. This article aims to develop a better understanding of how supply chain actors taking steps towards CLSC management could be supported to reach higher levels of maturity in dealing with deep uncertainty and dynamic complexity. This is investigated in a single, facilitated, embedded case study: a future-oriented decision-making process regarding the use of timber with four real-world actors in the construction industry. The process is structured and supported with analyses, following a methodology based on the capability maturity approach. In this empirical context, the selected approach is shown to have positive effects on clarifying the potential impact of transitions to CLSC management. Furthermore, it stimulates important learning processes during the transition, and as such supports actors to achieve higher levels of maturity and to take further steps towards CLSC management. In this context, a conceptual distinction is made between 'situational maturity' and 'mental maturity', which enriches double-loop learning theory in the context of transitions.

Demonstration of atomic force microscopy imaging using an integrated opto-electro-mechanical transducer.

The low throughput of atomic force microscopy (AFM) is the main drawback in its large-scale deployment in industrial metrology. A promising solution would be based on the parallelization of the scanning probe system, allowing acquisition of the image by an array of probes operating simultaneously. A key step for reaching this goal relies on the miniaturization and integration of the sensing mechanism. Here, we demonstrate AFM imaging employing an on-chip displacement sensor, based on a photonic crystal cavity, combined with an integrated photodetector and coupled to an on-chip waveguide. This fully-integrated sensor allows high-sensitivity and high-resolution in a very small footprint and its readout is compatible with current commercial AFM systems.

Integrated nano-opto-electro-mechanical sensor for spectrometry and nanometrology.

Spectrometry is widely used for the characterization of materials, tissues, and gases, and the need for size and cost scaling is driving the development of mini and microspectrometers. While nanophotonic devices provide narrowband filtering that can be used for spectrometry, their practical application has been hampered by the difficulty of integrating tuning and read-out structures. Here, a nano-opto-electro-mechanical system is presented where the three functionalities of transduction, actuation, and detection are integrated, resulting in a high-resolution spectrometer with a micrometer-scale footprint. The system consists of an electromechanically tunable double-membrane photonic crystal cavity with an integrated quantum dot photodiode. Using this structure, we demonstrate a resonance modulation spectroscopy technique that provides subpicometer wavelength resolution. We show its application in the measurement of narrow gas absorption lines and in the interrogation of fiber Bragg gratings. We also explore its operation as displacement-to-photocurrent transducer, demonstrating optomechanical displacement sensing with integrated photocurrent read-out.

Photonic crystal cavity on optical fiber facet for refractive index sensing.

Using a micromanipulation technique, a planar photonic crystal nanocavity made from a thin semiconductor membrane is released from the host semiconductor and attached to the end facet of a standard single-mode optical fiber. The cavity spectrum can be read out through the fiber by detecting the photoluminescence of embedded quantum dots. The modified fiber end serves as a fiber-optic refractive index sensor.

Linking biological activity with herbal constituents by systems biology-based approaches: effects of Panax ginseng in type 2 diabetic Goto-Kakizaki rats.

Although a number of animal experiments and clinical trials have investigated the effects of ginseng roots on diabetes, the relationship between their therapeutic effects on diabetes and the quality and the growth age of this herb have not yet been reported. This study systematically investigated the effects of 3- to 6-year-old ginseng roots on glycemic and plasma lipid control in a rat model of type 2 diabetes. Six groups of male Goto-Kakizaki (GK) rats received either metformin, 3- to 6-year-old ginseng roots, or no treatment. The treatments were administered twice daily for 9 weeks. A combined approach was used that involved applying liquid chromatography-mass spectrometry-based lipidomics, measuring biochemical parameters and profiling the components of ginseng roots of different ages. Compared to the untreated controls, treatment with 4- and 6-year-old ginseng roots significantly improved glucose disposal, and 5-year-old ginseng treatment significantly increased high density lipoprotein cholesterol. Treatment with 6-year-old ginseng significantly decreased total plasma triacylglyceride (TG) and very-low-density lipoprotein cholesterol and improved plasma glycated hemoglobin (HbA1c). In addition, treatment with 4- to 6-year-old ginseng influenced plasma lipidomics in diabetic GK rats by reducing TG lipid species. Metformin significantly reduced fasting blood glucose by 41% and reduced HbA1c by 11%, but showed no effects on the plasma lipid parameters. The present study demonstrates that ginseng roots show growth age-dependent therapeutic effects on hyperlipidemia and hyperglycemia in diabetic GK rats. These age-dependent effects may be linked with the variation in both the ratios and concentrations of specific bioactive ginsenosides in ginseng roots of different growth ages. This study introduced novel systems biology-based approaches for linking biological activities with potential active components in herbal mixtures.

Plasma and liver lipidomics response to an intervention of rimonabant in ApoE*3Leiden.CETP transgenic mice.

BACKGROUND: Lipids are known to play crucial roles in the development of life-style related risk factors such as obesity, dyslipoproteinemia, hypertension and diabetes. The first selective cannabinoid-1 receptor blocker rimonabant, an anorectic anti-obesity drug, was frequently used in conjunction with diet and exercise for patients with a body mass index greater than 30 kg/m(2) with associated risk factors such as type II diabetes and dyslipidaemia in the past. Less is known about the impact of this drug on the regulation of lipid metabolism in plasma and liver in the early stage of obesity. METHODOLOGY/PRINCIPAL FINDINGS: We designed a four-week parallel controlled intervention on apolipoprotein E3 Leiden cholesteryl ester transfer protein (ApoE*3Leiden.CETP) transgenic mice with mild overweight and hypercholesterolemia. A liquid chromatography-linear ion trap-Fourier transform ion cyclotron resonance-mass spectrometric approach was employed to investigate plasma and liver lipid responses to the rimonabant intervention. Rimonabant was found to induce a significant body weight loss (9.4%, p<0.05) and a significant plasma total cholesterol reduction (24%, p<0.05). Six plasma and three liver lipids in ApoE*3Leiden.CETP transgenic mice were detected to most significantly respond to rimonabant treatment. Distinct lipid patterns between the mice were observed for both plasma and liver samples in rimonabant treatment vs. non-treated controls. This study successfully applied, for the first time, systems biology based lipidomics approaches to evaluate treatment effects of rimonabant in the early stage of obesity. CONCLUSION: The effects of rimonabant on lipid metabolism and body weight reduction in the early stage obesity were shown to be moderate in ApoE*3Leiden.CETP mice on high-fat diet.

Traditional processing strongly affects metabolite composition by hydrolysis in Rehmannia glutinosa roots.

The processing of biological raw materials is considered to have an important role in the therapeutic application in Traditional Chinese Medicine. The root of Rehmannia glutinosa has to be processed by nine cycles of rice wine immersing, steaming and drying before using in clinical applications. In order to understand the chemical changes resulting from the processing, a comprehensive analysis of Rehmanniae radix was made using (1)H-NMR and Fourier transform (FT)-mass spectrometry in combination with multivariate data analysis. After (1)H-NMR and principle component analysis, hydrolysis was found to be the major chemical process during the treatments. Catalpol, raffinose and stachyose levels gradually decreased during processing, whereas monosaccharides including galactose and glucose were found to be higher in processed roots. The metabolic profile changed gradually through the processing cycles although the differences became smaller after the fifth processing cycle. The positive and negative ion-mode mass spectra by high resolution FT-MS revealed several series of ion clusters with mass differences of 162.053 Da, indicating a difference of a hexose moiety. During the processing, the number and signal intensity of the smaller glycosides were increased. Therefore, these results indicate that the fresh Rehmanniae radix is rich in polysaccharides, which are hydrolyzed during the processing.

LC/MS analysis of stratum corneum lipids: ceramide profiling and discovery.

Ceramides (CERs) in the upper layer of the skin, the stratum corneum (SC), play a key role in the skin barrier function. In human SC, the literature currently reports 11 CER subclasses that have been identified. In this paper, a novel quick and robust LC/MS method is presented that allows the separation and analysis of all known human SC CER subclasses using only limited sample preparation. Besides all 11 known and identified subclasses, a 3D multi-mass chromatogram shows the presence of other lipid subclasses. Using LC/MS/MS with an ion trap (IT) system, a Fourier transform-ion cyclotron resonance system, and a triple quadrupole system, we were able to identify one of these lipid subclasses as a new CER subclass: the ester-linked ω-hydroxy fatty acid with a dihydrosphingosine base (CER [EOdS]). Besides the identification of a new CER subclass, this paper also describes the applicability and robustness of the developed LC/MS method by analyzing three (biological) SC samples: SC from human dermatomed skin, human SC obtained by tape stripping, and SC from full-thickness skin explants. All three biological samples showed all known CER subclasses and slight differences were observed in CER profile.

Comparative transcriptional profiling and preliminary study on heterosis mechanism of super-hybrid rice.

Heterosis is a biological phenomenon whereby the offspring from two parents show improved and superior performance than either inbred parental lines. Hybrid rice is one of the most successful apotheoses in crops utilizing heterosis. Transcriptional profiling of F(1) super-hybrid rice Liangyou-2186 and its parents by serial analysis of gene expression (SAGE) revealed 1183 differentially expressed genes (DGs), among which DGs were found significantly enriched in pathways such as photosynthesis and carbon-fixation, and most of the key genes involved in the carbon-fixation pathway exhibited up-regulated expression in F(1) hybrid rice. Moreover, increased catabolic activity of corresponding enzymes and photosynthetic efficiency were also detected, which combined to indicate that carbon fixation is enhanced in F(1) hybrid, and might probably be associated with the yield vigor and heterosis in super-hybrid rice. By correlating DGs with yield-related quantitative trait loci (QTL), a potential relationship between differential gene expression and phenotypic changes was also found. In addition, a regulatory network involving circadian-rhythms and light signaling pathways was also found, as previously reported in Arabidopsis, which suggest that such a network might also be related with heterosis in hybrid rice. Altogether, the present study provides another view for understanding the molecular mechanism underlying heterosis in rice.

Controlling mode degeneracy in a photonic crystal nanocavity with infiltrated liquid crystal.

We demonstrate the control of the mode degeneracy when a liquid crystal (LC) is infiltrated into an InGaAsP membrane photonic crystal nanocavity with embedded InAs quantum dots. Mode splitting exists in the anisotropic nematic LC state, and not in the unfilled or isotropic LC state. The degeneracy lifting of the quadrupole mode is attributed to the different interactions of the two orthogonal basis modes of the degenerate mode with the two components of the refractive index of the LC. The interpretation is supported by the quantitative agreement between the experimental results and the three-dimensional finite-difference time-domain computations.

Sensitivities of InGaAsP photonic crystal membrane nanocavities to hole refractive index.

The sensitivities of resonant wavelengths of photonic crystal (PhC) membrane nanocavities with embedded InAs quantum dots to the ambient refractive index are reported for use in (bio) chemical sensing. The resonances for the different modes of several point-defect type cavities are obtained by photoluminescence measurements. Systematic trends of the variation of sensitivity with increase of the overlap of the modes with the PhC holes are observed for varying cavity type as well as for a given mode within a cavity type. A maximum sensitivity of approximately 300 nm/RIU (refractive index unit) is observed, corresponding to approximately 25% mode overlap with the holes and complete infiltration with the aqueous solution.

Quality and safety of Chinese herbal medicines guided by a systems biology perspective.

Chinese herbal medicines, often referred as Chinese materia medica (CMM), are comprised of a complex multicomponent nature. The activities are aimed at the system level via interactions with a multitude of targets in the human body. This review aims at the toxicity aspects of CMM and its preparations at the different steps of production; harvesting, processing and the final formulation. The historic perspective and today's issues of the safety of CMM are introduced briefly, followed by the descriptions of the toxic CMM in the current Chinese Pharmacopoeia (2005). Subsequently, several aspects of safety are illustrated using a typical example of a toxic CMM, Aconitum roots, and some recent findings of our own research are included to illustrate that proper processing and multi-herbs formulation can reduce the level of toxic components. This also explains that in CMM, some herbs, such as Aconitum, Ephedra species are never used as single herb for intervention and that aconite is only used when it is processed and in combination with specific matched other herbs. The formulation principle of multi-herbs intervention strategy is a systems approach for the treatment and prevention of disease. In this light, the role of systems toxicology in the safety and quality of Chinese herbal medicine is proposed as a promising method. Moreover the principles of practiced-based and evidence-based research are discussed from a symbiotic perspective.

Feasibility of electrodialysis as a fast and selective sample preparation method for the profiling of low-abundant peptides in biofluids.

Considerable interest exists in endogenous peptides as potential biomarkers, since they act as signaling molecules and are formed by degradation of proteins. A crucial step in the profiling of these peptides is the sample preparation, which aims to enrich the low-abundant peptides, while removing interfering matrix compounds. In a feasibility study we examined the suitability of electrodialysis (ED) for this purpose. A custom-made device was developed from the low-binding material Kel-F. It consisted of two compartments separated by a dialysis membrane, over which a voltage was applied. One compartment served as donor (containing the sample), while the smaller acceptor compartment collected the peptides. The procedure was optimized by investigating the effect of the applied voltage, ammonium acetate buffer concentration, and ED duration using model peptides. Optimum conditions were found at 300 V (150 V/cm), 25 mM ammonium acetate buffer (pH 3.8) containing 20% v/v DMSO, and 10 min, respectively. With these optimized parameters, recoveries for the model peptides were found to be 35-85% (average 64%). Additionally, ED was successfully applied to the challenging synovial fluid biological sample (due to its high viscosity). In a synovial fluid sample from a rheumatoid arthritis patient, 27 peptides originating from 12 proteins were identified, of which a considerable fraction was not identified before with other methods. This demonstrates the usefulness and complementary nature of combining ED with nanoLC-MS for biomarker discovery. These results indicate that ED is promising as a fast and selective sample preparation method for the profiling of endogenous peptides.

Towards heat-stable oxytocin formulations: analysis of degradation kinetics and identification of degradation products.

PURPOSE: To investigate degradation kinetics of oxytocin as a function of temperature and pH, and identify the degradation products. MATERIALS AND METHODS: Accelerated degradation of oxytocin formulated at pH 2.0, 4.5, 7.0 and 9.0 was performed at 40, 55, 70 and 80 degrees C. Degradation rate constants were determined from RP-HPLC data. Formulations were characterized by HP-SEC, UV absorption and fluorescence spectroscopy. Degradation products were identified by ESI-MS/MS. RESULTS: The loss of intact oxytocin in RP-HPLC was pH- and temperature-dependent and followed (pseudo) first order kinetics. Degradation was fastest at pH 9.0, followed by pH 7.0, pH 2.0 and pH 4.5. The Arrhenius equation proved suitable to describe the kinetics, with the highest activation energy (116.3 kJ/mol) being found for pH 4.5 formulations. At pH 2.0 deamidation of Gln(4), Asn(5), and Gly(9)-NH2, as well as combinations thereof were found. At pH 4.5, 7.0 and 9.0, the formation of tri- and tetrasulfide-containing oxytocin as well as different types of disulfide and dityrosine-linked dimers were found to occur. Beta-elimination and larger aggregates were also observed. At pH 9.0, mono-deamidation of Gln(4), Asn(5), and Gly(9)-NH2 additionally occurred. CONCLUSIONS: Multiple degradation products of oxytocin have been identified unequivocally, including various deamidated species, intramolecular oligosulfides and covalent aggregates. The strongly pH dependent degradation can be described by the Arrhenius equation.

Analytical strategies in lipidomics and applications in disease biomarker discovery.

Lipidomics is a lipid-targeted metabolomics approach aiming at comprehensive analysis of lipids in biological systems. Recently, lipid profiling, or so-called lipidomics research, has captured increased attention due to the well-recognized roles of lipids in numerous human diseases to which lipid-associated disorders contribute, such as diabetes, obesity, atherosclerosis and Alzheimer's disease. Investigating lipid biochemistry using a lipidomics approach will not only provide insights into the specific roles of lipid molecular species in health and disease, but will also assist in identifying potential biomarkers for establishing preventive or therapeutic approaches for human health. Recent technological advancements in mass spectrometry and rapid improvements in chromatographic techniques have led to the rapid expansion of the lipidomics research field. In this review, emphasis is given to the recent advances in lipidomics technologies and their applications in disease biomarker discovery.

Alkaloid profiling of the Chinese herbal medicine Fuzi by combination of matrix-assisted laser desorption ionization mass spectrometry with liquid chromatography-mass spectrometry.

A matrix-assisted laser desorption ionization mass spectrometry (MALDI-MS) method was developed for the high throughput and robust qualitative profiling of alkaloids in Fuzi--the processed lateral roots of the Chinese herbal medicine Aconitum carmichaeli Debx (A. carmichaeli). After optimization, powdered roots--without any further sample preparation--could be used to screen for the presence of Aconitum alkaloids. Furthermore, the semi-quantitative potential of MALDI-MS was confirmed using liquid chromatography-mass spectrometry (LC-MS) as reference. In total over sixty alkaloids were detected by LC-MS and fifteen of them were tentatively identified. Both MALDI-MS and LC-MS analysis revealed significant variation in alkaloid content in different (commercial) samples. LC-MS analysis of three toxic alkaloids in 14 batches of Fuzi resulted in a variation of their concentrations expressed as RSDs of 138%, 99% and 221% for aconitine, hypaconitine and mesaconitine, respectively. The variation in concentrations (expressed as RSD) of about the ninety constituents detected were classified as follows: 13 constituents showed an RSD of 77-100%, 46 with an RSD of 100-150%, 21 with an RSD of 150-200% and 9 constituents with an RSD in concentration of 200-235%. These results demonstrate a strong difference in chemical composition of the various Fuzi and illustrate the necessity of adequate QA/QC procedures for both safety and efficiency of herbal medicine. The described analytical procedures for alkaloid profiling could play a role in these procedures.

Bioconversion of red ginseng saponins in the gastro-intestinal tract in vitro model studied by high-performance liquid chromatography-high resolution Fourier transform ion cyclotron resonance mass spectrometry.

A high-performance liquid chromatography-high resolution Fourier transform ion cyclotron resonance mass spectrometry (HPLC-FTICR-MS) method was developed to investigate the metabolism of ginsenosides in in vitro models of the gastro-intestinal tract. The metabolites were identified by high-resolution tandem mass spectrometry. Degradation and bioconversion routes of the different ginsenosides at acidic (gastric) conditions and in the presence of intestinal microbiota were elaborated. Besides hydrolysis (deglycosylation) also hydration reactions occurred at acidic conditions. The results illustrate the value of metabolite profiling by HPLC-FTICR-MS for understanding of the mechanisms in bioavailability of herbal drugs and their metabolites.

Systems toxicology study of doxorubicin on rats using ultra performance liquid chromatography coupled with mass spectrometry based metabolomics.

A metabolomics-based systems toxicology approach was used to profile the urinary metabolites for the toxicity related processes and pathogenesis induced by doxorubicin (DOX) to rats. Endogenous metabolite profiles were obtained with ultra performance liquid chromatography-mass spectrometry (UPLC-MS) for rats receiving different single dosages of DOX (5, 10 or 20 mg/kg) prior and at three time points after dosage. Principal components analysis (PCA) allowed detection of two major systemic metabolic changes with the time due to the induced toxicity. Furthermore, Analysis of variance (ANOVA) Simultaneous Component Analysis (ASCA) was applied to reveal the variation caused by time and dose, and their interaction in a multivariate way. Finally, various metabolites involved in the toxic processes could be identified using their accurate mass and MS(n) experiments, and possible mechanisms of the toxicity of DOX were postulated. In conclusion, metabolomics as a systems toxicology approach was able to provide comprehensive information on the dynamic process of drug induced toxicity. In addition, detection of the systemic toxic effects could be obtained with metabolomics at an earlier stage compared to the clinical chemistry and histopathological assessment.

RPLC-ion-trap-FTMS method for lipid profiling of plasma: method validation and application to p53 mutant mouse model.

A reversed-phase liquid chromatography-linear ion trap-Fourier transform ion cyclotron resonance-mass spectrometric method was developed for the profiling of lipids in human and mouse plasma. With the use of a fused-core C 8 column and a binary gradient, more than 160 lipids belonging to eight different classes were detected in a single LC-MS run. The method was fully validated and the analytical characteristics such as linearity ( R (2), 0.994-1.000), limit of detection (0.08-1.28 microg/mL plasma), repeatability (RSD, 2.7-7.9%) and intermediate precision (RSD, 2.7-15.6%) were satisfactory. The method was successfully applied to p53 mutant mice plasma for studying some phenotypic effects of p53 expression.

Recent methodology in the phytochemical analysis of ginseng.

This review summarises the most recent developments in ginseng analysis, in particular the novel approaches in sample pre-treatment and the use of high-performance liquid-chromatography-mass spectrometry. The review also presents novel data on analysing ginseng extracts by nuclear magnetic resonance spectroscopy and high-resolution mass spectrometry (Fourier transform mass spectrometry) in the context of metabolomics.