How to statistically analyze nano exposure measurement results: using an ARIMA time series approach

Measurement strategies for exposure to nano-sized particles differ from traditional integrated sampling methods for exposure assessment by the use of real-time instruments. The resulting measurement series is a time series, where typically the sequential measurements are not independent from each other but show a pattern of autocorrelation. This article addresses the statistical difficulties when analyzing real-time measurements for exposure assessment to manufactured nano objects. To account for autocorrelation patterns, Autoregressive Integrated Moving Average (ARIMA) models are proposed. A simulation study shows the pitfalls of using a standard t-test and the application of ARIMA models is illustrated with three real-data examples. Some practical suggestions for the data analysis of real-time exposure measurements conclude this article.     

Sensor–actuator system for dynamic chloride ion determination

Chloride is a crucial anion for various analytical applications from biological to environmental applications. In order to measure the chloride ion concentration, a measurement system is needed which can detect this concentration for prolonged times reliably. Chronopotentiometry is a technique which does not need a long term stable reference electrode and is therefore very suitable for prolonged ion concentration measurements. As the used electrode might be fouled by reaction products, this work focuses on a chronopotentiometric approach with a separated sensing electrode (sensor) and actuating electrode (actuator). Both actuation and sensor electrode are made of Ag/AgCl. A constant current is applied to the actuator and will start the reaction between Ag and Clˉ, while the resulting Clˉ ion concentration change is observed through the sensor, which is placed close to the actuator. The time it takes to locally deplete the Clˉ ions is called transition time. Experiments were performed to verify the feasibility of this approach. The performed experiments show that the sensor detects the local concentration changes resulting from the current applied to the actuator. A linear relation between the Clˉ ion concentration and the square root of the transition time was observed, just as was predicted by theory. The calibration curves for different chips showed that both a larger sensor and a larger distance between sensor and actuator resulted in a larger time delay between the transition time detected at the actuator and the sensor.     

Comparing Cyclophellitol N‐Alkyl and N‐Acyl Cyclophellitol Aziridines as Activity‐Based Glycosidase Probes

The synthesis and evaluation as activity‐based probes (ABPs) of three configurationally distinct, fluorescent N‐alkyl cyclophellitol aziridine isosteres for profiling GH1 β‐glucosidase (GBA), GH27 α‐galactosidase (GLA) and GH29 α‐fucosidase (FUCA) is described. In comparison with the corresponding acyl aziridine ABPs reported previously, the alkyl aziridine ABPs are synthesized easily and are more stable in mild acidic and basic media, and are thus easier to handle. The β‐glucose‐configured alkyl aziridine ABP proves equally effective in labeling GBA as its N‐acyl counterpart, whereas the N‐acyl aziridines targeting GLA and FUCA outperform their N‐alkyl counterparts. Alkyl aziridines can therefore be an attractive alternative in retaining glycosidase ABP design, but in targeting a new retaining glycosidase both N‐alkyl and N‐acyl aziridines are best considered at the onset of a new study.     

Patterning functional materials using channel diffused plasma-etched self-assembled monolayer templates

A simple and cost-effective methodology for large-area micrometer-scale patterning of a wide range of metallic and oxidic functional materials is presented. Self-assembled monolayers (SAM) of alkyl thiols on Au were micropatterned by channel-diffused oxygen plasma etching, a method in which selected areas of SAM were protected from plasma oxidation via a soft lithographic stamp. The patterned SAMs were used as templates for site-selective electrodeposition, electroless deposition and solution-phase deposition of functional materials such as ZnO, Ni, Ag thin films, and ZnO nanowires. The patterned SAMs and functional materials were characterized by scanning electron microscopy (SEM), X-ray diffraction (XRD), atomic force microscopy (AFM), and tunneling AFM (TUNA).     

Nanopatterning of functional materials by gas phase pattern deposition of self-assembled molecular thin films in combination with electrodeposition

We present a general methodology to pattern functional materials on the nanometer scale using self-assembled molecular templates on conducting substrates. A soft lithographic gas phase edge patterning process using poly(dimethylsiloxane) molds was employed to form electrically isolating organosilane patterns of a few nanometer thickness and a line width that could be tuned by varying the time of deposition. Electrodeposition was employed to deposit patterns of Ni and ZnO on these prepatterned substrates. Deposition occurred only on patches of the substrate where no organosilane monolayer was present. The process is simple, inexpensive, and scalable to large areas. We achieved formation of metallic and oxide material patterns with a lateral resolution of 80 nm.     

Exceptional Stability of Artemin Neurotrophic Factor Dimers: Effects of Temperature, pH, Buffer and Storage Conditions on Protein Integrity and Activity

Artemin (ARTN) is a neurotrophic growth factor of the GDNF ligand family that signals through the specific GFRα-3 coreceptor/cRet tyrosine kinase-mediated signaling cascade. Its expression and signaling action in adults are restricted to nociceptive sensory neurons in the dorsal root ganglia. Consequently, Artemin supports survival and growth of sensory neurons and has been studied as a possible treatment for neuropathic pain. We have developed a robust and sensitive cellular assay to measure ARTN biological activity. Using recombinant Artemin produced in Escherichia coli bacteria together with this specific assay, we demonstrate that ARTN is an exceptionally stable polypeptide. Multiple freeze-thaw cycles, incubation at elevated temperatures (up to 90 °C) for 0.5 h, prolonged storage at 4 °C, and exposure to conditions of different pH, salt concentration, and additives had no measurable effect on the biological activity of ARTN. In some of the tested conditions, partial removal of nine NH(2)-terminal amino acids of the ARTN protein occurred, but this truncation had no important effect on the ARTN signaling response. Consequently, we postulate that formulation and storage for in vivo testing of ARTN in neuropathic pain paradigms in animals and humans should be straightforward.     

Aromatic A-ring analogues of orobanchol, new germination stimulants for seeds of parasitic weeds

Strigolactones are signaling compounds in plants of increasing importance. In this paper the focus is on their activity as germinating agents for seeds of parasitic weeds. The syntheses of aromatic A-ring analogues of the germination stimulant orobanchol have been described. Starting substrate is the ABC unit of the stimulant GR24. Oxidation at the C-4 position gives a 4-oxo derivative which on subsequent reduction produces two C-4 epimeric alcohols, syn and anti in a ratio of 82 : 3. For practical access of the C-4 anti alcohol, the predominant syn epimer is inverted by a Mitsunobu procedure. The anti C-4 alcohol is then coupled with the D-ring in a one-pot two-step process involving a formylation and a reaction with bromobutenolide to give a mixture of the diastereomeric aromatic A-ring analogues of orobanchol. In contrast, the syn C-4 alcohol cannot be coupled directly with the D-ring. Protection of the C-4 syn OH is a prequisite. The best protecting function is the SEM group as deprotection after coupling with the D-ring can then readily be achieved. The structures of these new analogues have been ascertained by X-ray analyses. Both diastereomers of the C-4 syn as well as the C-4 anti orobanchol analogues have been tested as germination agents of seeds of Striga hermonthica and Orobanche ramosa. In addition, the acetates of both epimeric C-4 alcohols have been prepared and tested. Both diastereomers of the 4-oxo derivative have been prepared and bioassayed as well. The bioassays reveal that the diastereomers having the natural relative configuration are most active. The data also suggest that hydrogen bonding is not an important factor in the binding of the stimulant molecules in the receptor.     

Mid-infrared spectrometry of milk for dairy metabolomics: a comparison of two sampling techniques and effect of homogenization

Milk production is a dominant factor in the metabolism of dairy cows involving a very intensive interaction with the blood circulation. As a result, the extracted milk contains valuable information on the metabolic status of the cow. On-line measurement of milk components during milking two or more times a day would promote early detection of systemic and local alterations, thus providing a great input for strategic and management decisions. The objective of this study was to investigate the potential of mid-infrared (mid-IR) spectroscopy to measure the milk composition using two different measurement modes: micro attenuated total reflection (μATR) and high throughput transmission (HTT). Partial least squares (PLS) regression was used for prediction of fat, crude protein, lactose and urea after preprocessing IR data and selecting the most informative wavenumber variables. The prediction accuracies were determined separately for raw and homogenized copies of a wide range of milk samples in order to estimate the possibility for on-line analysis of the milk. In case of fat content both measurement modes resulted in an excellent prediction for homogenized samples (R(2)>0.92) but in poor results for raw samples (R(2)<0.70). Homogenization was however not mandatory to achieve good predictions for crude protein and lactose with both μATR and HTT, and urea with μATR spectroscopy. Excellent results were obtained for prediction of crude protein, lactose and urea content (R(2)>0.99, 0.98 and 0.86 respectively) in raw and homogenized milk using μATR IR spectroscopy. These results were significantly better than those obtained by HTT IR spectroscopy. However, the prediction performance of HTT was still good for crude protein and lactose content (R(2)>0.86 and 0.78 respectively) in raw and homogenized samples. However, the detection of urea in milk with HTT spectroscopy was significantly better (R(2)=0.69 versus 0.16) after homogenization of the milk samples. Based on these observations it can be concluded that μATR approach is most suitable for rapid at line or even on-line milk composition measurement, although homogenization is crucial to achieve good prediction of the fat content.     

Halogen bonding to a divalent sulfur atom: an experimental study of the interactions of CF3X (X = Cl, Br, I) with dimethyl sulfide

Using FTIR and Raman spectroscopy, the formation of halogen bonded complexes of the trifluorohalomethanes CF(3)Cl, CF(3)Br and CF(3)I with dimethyl sulfide (DMS) dissolved in liquid krypton has been investigated. For CF(3)Br and CF(3)I, evidence was found for the formation of C-XS halogen bonded 1:1 complexes. At higher concentrations of CF(3)I weak absorptions due to a 2:1 complex were also observed. Using spectra recorded at temperatures between 118 and 163 K, the complexation enthalpies for the complexes were determined to be -9.5(5) kJ mol(-1) for CF(3)Br·DMS, -17.4(1) kJ mol(-1) for CF(3)I·DMS and -30.8(16) kJ mol(-1) for (CF(3)I·)(2)DMS. The results from the cryospectroscopic study are compared with ab initio calculations at the MP2/aug-cc-pVDZ(-PP) level. Apart from vibrational modes localized in the trifluorohalomethanes and the DMS moieties, for both CF(3)Br and CF(3)I, an additional band, which we assign as the intermolecular stretching mode in the complex, was identified in the infrared and Raman spectra.     

A theoretical description of elastic pillar substrates in biophysical experiments.

Arrays of elastic pillars are used in biophysical experiments as sensors for traction forces. The evaluation of the forces can be complicated if they are coupled to the pillar displacements over large distances. This is the case if many of the pillars are interconnected by elastic linkages as, for example, in fiber networks that are grown on top of pillars. To calculate the traction forces in such a network, we developed a set of nonlinear inhomogeneous equations relating the forces in the linking elements to the resulting pillar deflections. We chose a homogeneous, activated two-dimensional network of cytoskeletal actin filaments to illustrate that a pillar substrate is generally not a force sensor but a force-gradient sensor. In homogeneous networks the forces acting along the filaments can be approximated by analyzing only pillar deflections in the edge zones of the substrate and by integration over the corresponding force gradients.