A new approach for open‐end sequential change point monitoring

We propose a new sequential monitoring scheme for changes in the parameters of a multivariate time series. In contrast to procedures proposed in the literature which compare an estimator from the training sample with an estimator calculated from the remaining data, we suggest to divide the sample at each time point after the training sample. Estimators from the sample before and after all separation points are then continuously compared calculating a maximum of norms of their differences. For open‐end scenarios our approach yields an asymptotic level $\alpha$ procedure, which is consistent under the alternative of a change in the parameter. By means of a simulation study it is demonstrated that the new method outperforms the commonly used procedures with respect to power and the feasibility of our approach is illustrated by analyzing two data examples.     

A nanoscopic view at the spherulitic morphology of isotactic polypropylene by atomic force microscopy

Summary The spherulitic morphology of isotactic polypropylene (i-PP) was investigated by a combination of optical and atomic force microscopes. Thin films of i-PP were prepared in situ by using a hot stage. The crystallization conditions were carefully selected to produce different types of spherulites including -I, -II, mixed, and -III types. Atomic force microscopy (AFM) scans unveiled morphological details such as mother/daughter lamellae, cross-hatching, and thickness and orientation of the lamellae. In a few cases, macromolecules were visualized. However, due to poor resolution, only the expected chain direction within the lamellae could be determined. The advantages and disadvantages of using AFM to study the surface of spherulites is discussed.     

Visual exploration and retrieval of XML document collections with the generic system X2

This article reports on the XML retrieval system x² that has been developed at the University of Munich over the last 5 years. In a typical session with x², the user first browses a structural summary of the XML database in order to select interesting elements and keywords occurring in documents. Using this intermediate result, queries combining structure and textual references are composed semiautomatically. After query evaluation, the full set of answers is presented in a visual and structured way. x² largely exploits the structure found in documents, queries and answers to enable new interactive visualization and exploration techniques that support mixed IR and database-oriented querying, thus bridging the gap between these three views on the data to be retrieved. Another salient characteristic of x² that distinguishes it from other visual query systems for XML is that it supports various degrees of detailedness in the presentation of answers, as well as techniques for dynamically reordering, grouping and ranking retrieved elements once the complete answer set has been computed.     

Monitoring cache behavior on parallel SMP architectures and related programming tools

This paper describes the ideas and developments of the project EP-CACHE. Within this project new methods and tools are developed to improve the analysis and the optimization of programs for cache architectures, especially for SMP clusters. The tool set comprises the semi-automatic instrumentation of user programs, the monitoring of the cache behavior, the visualization of the measured data, and optimization techniques for improving the user program for better cache usage.

As current hardware performance counters do not give sufficient user relevant information, new hardware monitors are designed that provide more detailed information about the cache utilization related to the data structures and code blocks in the user program. The expense of the hardware and software realization will be assessed to minimize the risk of a real implementation of the investigated monitors. The usefulness of the hardware monitors is evaluated by a cache simulator.     

Comparison of analytical and theoretical pharmaceutical concentrations in human urine in Germany

Urine is considered as a valuable plant fertiliser due to its high nutrient content. However, urine also contains pharmaceuticals. Currently, little is known regarding expected pharmaceutical concentrations in urine and the resulting risks. Through series of analyses in Hamburg and Berlin and results from the development of a concentration prediction model this knowledge gap was intended to be filled. To which extent the theoretical calculations can substitute analyses of pharmaceuticals was also tested. Results showed that the model fits well for bezafibrate, carbamazepine, diclofenac, ibuprofen, phenazone, and pentoxifylline. In Hamburg an R(2) value of 0.98 and in Berlin of 0.90 was achieved for correlations between predicted and analysed concentrations. Additionally, it was shown that a sufficient number of people discharging their urine to the respective collection system are important to allow for reasonable predictions via calculation. Also, comparisons of predicted pharmaceutical concentrations to those determined in other projects showed good correlations. Overall, it can be concluded that in any case the calculated concentrations exceed the measured ones and are therefore conservative. This overestimation can be explained by several factors discussed in this article.     

Exposure to ultrafine carbon particles at levels below detectable pulmonary inflammation affects cardiovascular performance in spontaneously hypertensive rats

Background

Exposure to particulate matter is a risk factor for cardiopulmonary disease but the underlying molecular mechanisms remain poorly understood. In the present study we sought to investigate the cardiopulmonary responses on spontaneously hypertensive rats (SHRs) following inhalation of UfCPs (24 h, 172 μg·m^-3), to assess whether compromised animals (SHR) exhibit a different response pattern compared to the previously studied healthy rats (WKY).

Methods

Cardiophysiological response in SHRs was analyzed using radiotelemetry. Blood pressure (BP) and its biomarkers plasma renin-angiotensin system were also assessed. Lung and cardiac mRNA expressions for markers of oxidative stress (hemeoxygenase-1), blood coagulation (tissue factor, plasminogen activator inhibitor-1), and endothelial function (endothelin-1, and endothelin receptors A and B) were analyzed following UfCPs exposure in SHRs. UfCPs-mediated inflammatory responses were assessed from broncho-alveolar-lavage fluid (BALF).

Results

Increased BP and heart rate (HR) by about 5% with a lag of 1–3 days were detected in UfCPs exposed SHRs. Inflammatory markers of BALF, lung (pulmonary) and blood (systemic) were not affected. However, mRNA expression of hemeoxygenase-1, endothelin-1, endothelin receptors A and B, tissue factor, and plasminogen activator inhibitor showed a significant induction (~2.5-fold; p < 0.05) with endothelin 1 being the maximally induced factor (6-fold; p < 0.05) on the third recovery day in the lungs of UfCPs exposed SHRs; while all of these factors – except hemeoxygenase-1 – were not affected in cardiac tissues. Strikingly, the UfCPs-mediated altered BP is paralleled by the induction of renin-angiotensin system in plasma.

Conclusion

Our finding shows that UfCPs exposure at levels which does not induce detectable pulmonary neutrophilic inflammation, triggers distinct effects in the lung and also at the systemic level in compromised SHRs. These effects are characterized by increased activity of plasma renin-angiotensin system and circulating white blood cells together with moderate increases in the BP, HR and decreases in heart rate variability. This systemic effect is associated with pulmonary, but not cardiac, mRNA induction of biomarkers reflective of oxidative stress; activation of vasoconstriction, stimulation of blood coagulation factors, and inhibition of fibrinolysis. Thus, UfCPs may cause cardiovascular and pulmonary impairment, in the absence of detectable pulmonary inflammation, in individuals suffering from preexisting cardiovascular diseases.     

Intramolecular carbon and nitrogen isotope analysis by quantitative dry fragmentation of the phenylurea herbicide isoproturon in a combined injector/capillary reactor prior to GC separation

Potentially, compound-specific isotope analysis may provide unique information on source and fate of pesticides in natural systems. Yet for isotope analysis, LC-based methods that are based on the use of organic solvents often cannot be used and GC-based analysis is frequently not possible due to thermolability of the analyte. A typical example of a compound with such properties is isoproturon (3-(4-isopropylphenyl)-1,1-dimethylurea), belonging to the worldwide extensively used phenylurea herbicides. To make isoproturon accessible to carbon and nitrogen isotope analysis, we developed a GC-based method during which isoproturon was quantitatively fragmented to dimethylamine and 4-isopropylphenylisocyanate. Fragmentation occurred only partially in the injector but was mainly achieved on a heated capillary column. The fragments were then chromatographically separated and individually measured by isotope ratio mass spectrometry. The reliability of the method was tested in hydrolysis experiments with three isotopically different batches of isoproturon. For all three products, the same isotope fractionation factors were observed during conversion and the difference in isotope composition between the batches was preserved. This study demonstrates that fragmentation of phenylurea herbicides does not only make them accessible to isotope analysis but even enables determination of intramolecular isotope fractionation.     

Non-colinear polyketide biosynthesis in the aureothin and neoaureothin pathways: an evolutionary perspective

Aureothin and neoaureothin (spectinabilin) represent rare nitroaryl-substituted polyketide metabolites from Streptomyces thioluteus and Streptomyces orinoci, respectively, which only differ in the lengths of the polyene backbones. Cloning and sequencing of the 39 kb neoaureothin (nor) biosynthesis gene cluster and its comparison with the aureothin (aur) pathway genes revealed that both polyketide synthase (PKS) assembly lines are remarkably similar. In both cases the module architecture breaks with the principle of colinearity, as individual PKS modules are used in an iterative fashion. Parsimony and neighbour-joining phylogenetic studies provided insights into the evolutionary process that led to the programming of these unusual type I PKS systems and to prediction of which modules act iteratively. The iterative function of the first module in the neoaureothin pathway, NorA, was confirmed by a successful cross-complementation.     

Macrocyclic statine-based inhibitors of BACE-1

Minimal sequence requirements for binding of substrate-derived statine peptides to the aspartyl enzyme were established on the basis of the X-ray cocrystal structure of the hydroxyethylene-octapeptide OM00-3 in complexation with BACE-1. With this information to hand, macrocyclic compounds that conformationally restrict and preorganize the peptide backbone for an entropically favoured binding to the enzyme active site cleft were designed. By means of a side chain-to-side chain ring closure between two aspartyl residues in the P2 and P3' positions through phenylene-1,3-dimethanamine, a 23-membered ring structure was obtained; this structure retained an extended conformation of the peptide backbone, including the transition state analogue statine for tight interactions with the two aspartyl residues of the active centre. The conformational preorganization of the inhibitor molecule was verified by NMR structural analysis and was then confirmed by the crystal structure of the BACE-1/inhibitor complex. Detailed insights into the binding mode of this macrocyclic inhibitor explained its moderate binding affinity in cell-free assays (K(i)=2.5 microM) and yielded precious information for possible structural optimization in view of the lack of steric clashes of the macrocycle with the flap domain of the enzyme.