External and internal electrostatic potentials of cholinesterase models

The electrostatic potentials for the three-dimensional structures of cholinesterases from various species were calculated, using the Delphi algorithm, on the basis of the Poisson–Boltzmann equation. We used structures for Torpedo californica and mouse acetylcholinesterase, and built homology models of the human, Bungarus fasciatus, and Drosophila melanogaster acetylcholinesterases and human butyrylcholinesterase. All these structures reveal a negative external surface potential, in the area around the entrance to the active-site gorge, that becomes more negative as the rim of the gorge is approached. Moreover, in all cases, the potential becomes increasingly more negative along the central axis running down the gorge, and is largest at the base of the gorge, near the active site. Ten key acidic residues conserved in the sequence alignments of AChE from various species, both in the surface area near the entrance of the active-site gorge and at its base, appear to be primarily responsible for these potentials. The potentials are highly correlated among the structures examined, down to sequence identities as low as 35%. This indicates that they are a conserved property of the cholinesterase family, could serve to attract the positively charged substrate into and down the gorge to the active site, and may play other roles important for cholinesterase function.     

The SL synchronous language

We present SL, a new programming language of the synchronous reactive family in which hypotheses about signal presence/absence are disallowed. One can decide that a signal is absent during an instant only at the end of this instant, and so reaction to this absence is delayed to the next instant. Sources of causal circularities are avoided, while only weak preemption remains. A structural operational semantics is provided through rewrite rules, and an implementation is described. In addition to directly executing programs, this implementation can also be used to produce automata by symbolic evaluation     

Nachweis von Maillard-Produkten in Malzen, Bieren und Braucouleuren

Zusammenfassung Bei der Maillard-Reaktion reagieren primär reduzierende Zucker mit den freien Aminogruppen der Aminosäuren. Dabei entstehen aus Aldosen als erste stabile Zwischenprodukte die 1-Aminosäure-1-desoxy-ketosen (Amadori-Verbindungen). In Malzen konnten zehn Amadori-Verbindungen quantitativ bestimmt werden. Sie entstehen während des Darrens des Malzes. Aufgrund unterschiedlicher Darrbedingungen unterscheiden sich die Malztypen im Gehalt und im Muster dieser Substanzen. Während der Erhitzungsvorgänge beim Brauprozeß (Maischen, Würzekochung) werden die Amadori-Verbindungen etwa zur Hälfte abgebaut, dagegen sind bei der an schließenden Gärung keine Veränderungen zu beobachten. Aus dem Gehalt und dem Muster der Amadori-Verbindungen im Bier können somit Rückschlüsse auf das verwendete Malz gezogen werden. Bei der Herstellung von Braucouleuren werden Ammoniak bzw. Ammoniumverbindungen als Aminokomponenten eingesetzt. Die Couleure enthalten deshalb keine 1-Aminosäure-l-desoxy-ketosen, dafür aber Desoxyfructosazine, die bei der Reaktion von Zuckern mit Ammoniak entstehen. Diese Pyrazinderivate wurden in Braucouleuren in hohen Mengen (2–6 g/100 g) gefunden. Es wird eine Methode vorgestellt, mit der ein Zusatz von Braucouleuren zum Bier über die Bestimmung der Desoxyfructosazine eindeutig nachgewiesen werden kann.

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Detection of Maillard products in malts, beers, and brewing couleurs

During the Maillard reaction, the reducing sugars first react with the free amino groups of the amino acids. With aldoses, 1-amino-l-deoxyketoses (ketose-amino acids, Amadori compounds) are the first stable intermediates to be formed. In malts ten different Amadori compounds could be determined that formed during the kiln-drying of malt. Dependent on the kiln-drying conditions, the different types of malt contain different amounts and proportions of these compounds. During the brewing process (mashing, mash wort cooking) about half of the Amadori compounds are decomposed, whereas during fermentation no changes can be observed. Therefore the amount and composition of Amadori compounds detected in beer may indicate the type of malt used. During the production of brewing couleurs, ammonia or ammonium compounds react with sugars and deoxyfructosazines are formed. In brewing coleurs, relatively high amount of these pyrazine derivatives (2–6 g/100 g) could be found. An analytical method is described for the quantitative determination of deoxyfructosazines, indicating an addition of brewing couleur to beer.

     

The Contribution of Small Vessel Disease to Neurodegeneration: Focus on Alzheimer’s Disease,Parkinson’s Disease and Multiple Sclerosis

Brain small vessel disease (SVD) refers to a variety of structural and functional changes affecting small arteries and micro vessels, and manifesting as white matter changes, microbleeds and lacunar infarcts. Growing evidence indicates that SVD might play a significant role in the neurobiology of central nervous system (CNS) neurodegenerative disorders, namely Alzheimer’s disease (AD) and Parkinson’s disease (PD), and neuroinflammatory diseases, such as multiple sclerosis (MS). These disorders share different pathophysiological pathways and molecular mechanisms (i.e., protein misfolding, derangement of cellular clearance systems, mitochondrial impairment and immune system activation) having neurodegeneration as biological outcome. In these diseases, the actual contribution of SVD to the clinical picture, and its impact on response to pharmacological treatments, is not known yet. Due to the high frequency of SVD in adult-aged patients, it is important to address this issue. In this review, we report preclinical and clinical data on the impact of SVD in AD, PD and MS, with the main aim of clarifying the predictability of SVD on clinical manifestations and treatment response.     

Molecular Mechanisms of Fetal Tendon Regeneration Versus Adult Fibrous Repair

Tendinopathies are painful, disabling conditions that afflict 25% of the adult human population. Filling an unmet need for realistic large-animal models, we here present an ovine model of tendon injury for the comparative study of adult scarring repair and fetal regeneration. Complete regeneration of the fetal tendon within 28 days is demonstrated, while adult tendon defects remained macroscopically and histologically evident five months post-injury. In addition to a comprehensive histological assessment, proteome analyses of secretomes were performed. Confirming histological data, a specific and pronounced inflammation accompanied by activation of neutrophils in adult tendon defects was observed, corroborated by the significant up-regulation of pro-inflammatory factors, neutrophil attracting chemokines, the release of potentially tissue-damaging antimicrobial and extracellular matrix-degrading enzymes, and a response to oxidative stress. In contrast, secreted proteins of injured fetal tendons included proteins initiating the resolution of inflammation or promoting functional extracellular matrix production. These results demonstrate the power and relevance of our novel ovine fetal tendon regeneration model, which thus promises to accelerate research in the field. First insights from the model already support our molecular understanding of successful fetal tendon healing processes and may guide improved therapeutic strategies.     

Resolution proof transformation for compression and interpolation

Verification methods based on SAT, SMT, and theorem proving often rely on proofs of unsatisfiability as a powerful tool to extract information in order to reduce the overall effort. For example a proof may be traversed to identify a minimal reason that led to unsatisfiability, for computing abstractions, or for deriving Craig interpolants. In this paper we focus on two important aspects that concern efficient handling of proofs of unsatisfiability: compression and manipulation. First of all, since the proof size can be very large in general (exponential in the size of the input problem), it is indeed beneficial to adopt techniques to compress it for further processing. Secondly, proofs can be manipulated as a flexible preprocessing step in preparation for interpolant computation. Both these techniques are implemented in a framework that makes use of local rewriting rules to transform the proofs. We show that a careful use of the rules, combined with existing algorithms, can result in an effective simplification of the original proofs. We have evaluated several heuristics on a wide range of unsatisfiable problems deriving from SAT and SMT test cases.     

Role of anionic and nonionic surfactants on the control of particle size and latex colloidal stability in the seeded emulsion polymerization of butyl methacrylate

The evolution of the main colloidal parameters in the seeded starved‐feed semi‐continuous emulsion polymerization of butyl methacrylate (BMA) was investigated, with the main purpose of assessing the effectiveness of the semi‐empirical relationship S = K · S_S · ΔA/A_S as a tool to define the surfactant/monomer feed ratio (∝ K) best suited to achieve a target particle size. In particular, the effect of the type and amount of surfactant [i.e., anionic, sodium dodecyl sulfate (SDS), or nonionic, Brij 58P] added during the semi‐continuous stage was considered. Coagulum formation was never observed under the adopted experimental conditions. To detect the occurrence of secondary nucleation or particle aggregation, or both, the particle size and number of particles, the surface tension and the particle surface coverage ratio were correlated. The best results were obtained with SDS and 0.8 ≤ K ≤ 3. In fact, under the selected experimental conditions, only with SDS did the number of particles remain nearly constant throughout the polymerization at the value defined by the seed latex; the particle size distribution was highly monodisperse, and the final particle diameter closely matched the calculated one (～ 120 nm). The above semi‐empirical relationship based on the adjustable parameter K was validated by running test polymerizations aimed at lattices with well‐defined particle size. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 102: 3083–3094, 2006     

With a little help from my friends

In this paper, we propose a content-based method the for semi-automatic organization of photo albums based on the analysis of how different users organize their own pictures. The goal is to help the user in dividing his pictures into groups characterized by a similar semantic content. The method is semi-automatic: the user starts to assign labels to the pictures and unlabeled pictures are tagged with proposed labels. The user can accept the recommendation or made a correction. To formulate the suggestions is exploited the knowledge encoded in how other users have partitioned their images. The method is conceptually articulated in two parts. First, we use a suitable feature representation of the images to model the different classes that the users have collected, second, we look for correspondences between the criteria used by the different users. Boosting is used to integrate the information provided by the analysis of multiple users. A quantitative evaluation of the proposed approach is obtained by simulating the amount of user interaction needed to annotate the albums of a set of members of the flickr^® photo-sharing community.     

Upcycling of polypropylene with various concentrations of peroxydicarbonate and dilauroyl peroxide and two processing steps

The influence of two peroxides (peroxydicarbonate/dilauroyl peroxide) with various concentrations (10–200 mmol/kg PP) and their effective opportunity to introduce long chain branched (LCB) were investigated. The dependence of a single and double extrusion step and the changes of the properties were studied. Experiments were carried out in a single screw extruder at 180°C for the first extrusion step (modification) and at 240°C for the second extrusion step (processing simulation). Melt flow rate and dynamic rheological properties were studied at a measuring temperature of 230°C. For the definitive determination of long chain branched polypropylene (LCB-PP) served the extensional rheology measurements. The mechanical properties were examined via tensile test and impact tensile test. Summarized, LCB (melt strength) could be observed via extensional rheology for all modified specimens and the mechanical properties were maintained or even improved for the modified samples. Particularly, samples containing dilauroyl peroxide display excellent mechanical properties in this study.     

When simulated environments make the difference: the effectiveness of different types of training of car service procedures

An empirical analysis was performed to compare the effectiveness of different approaches to training a set of procedural skills to a sample of novice trainees. Sixty-five participants were randomly assigned to one of the following three training groups: (1) learning-by-doing in a 3D desktop virtual environment, (2) learning-by-observing a video (show-and-tell) explanation of the procedures, and (3) trial-and-error. In each group, participants were trained on two car service procedures. Participants were recalled to perform a procedure either 2 or 4 weeks after the training. The results showed that: (1) participants trained through the virtual approach of learning-by-doing performed both procedures significantly better (i.e. p < .05 in terms of errors and time) than people of non-virtual groups, (2) the virtual training group, after a period of non-use, were more effective than non-virtual training (i.e. p < .05) in their ability to recover their skills, (3) after a (simulated) long period from the training—i.e. up to 12 weeks—people who experienced 3D environments consistently performed better than people who received other kinds of training. The results also suggested that independently from the training group, trainees’ visuospatial abilities were a predictor of performance, at least for the complex service procedure, adj R ² = .460, and that post-training performances of people trained through virtual learning-by-doing are not affected by learning styles. Finally, a strong relationship (p < .001, R ² = .441) was identified between usability and trust in the use of the virtual training tool—i.e. the more the system was perceived as usable, the more it was perceived as trustable to acquire the competences.