Indoloazepinone‐Constrained Oligomers as Cell‐Penetrating and Blood–Brain‐Barrier‐Permeating Compounds

Non‐cationic and amphipathic indoloazepinone‐constrained (Aia) oligomers have been synthesized as new vectors for intracellular delivery. The conformational preferences of the [l ‐Aia‐Xxx]_n oligomers were investigated by circular dichroism (CD) and NMR spectroscopy. Whereas Boc‐[l ‐Aia‐Gly]_2,4‐OBn oligomers 12 and 13 and Boc‐[l ‐Aia‐β³‐h‐l ‐Ala]_2,4‐OBn oligomers 16 and 17 were totally or partially disordered, Boc‐[l ‐Aia‐l ‐Ala]₂‐OBn ( 14 ) induced a typical turn stabilized by C₅‐ and C₇‐membered H‐bond pseudo‐cycles and aromatic interactions. Boc‐[l ‐Aia‐l ‐Ala]₄‐OBn ( 15 ) exhibited a unique structure with remarkable T‐shaped π‐stacking interactions involving the indole rings of the four l ‐Aia residues forming a dense hydrophobic cluster. All of the proposed FITC‐6‐Ahx‐[l ‐Aia‐Xxx]₄‐NH₂ oligomers 19 – 23 , with the exception of FITC‐6‐Ahx‐[l ‐Aia‐Gly]₄‐NH₂ ( 18 ), were internalized by MDA‐MB‐231 cells with higher efficiency than the positive references penetratin and Arg₈. In parallel, the compounds of this series were successfully explored in an in vitro blood–brain barrier (BBB) permeation assay. Although no passive diffusion permeability was observed for any of the tested Ac‐[l ‐Aia‐Xxx]₄‐NH₂ oligomers in the PAMPA model, Ac‐[l ‐Aia‐l ‐Arg]₄‐NH₂ ( 26 ) showed significant permeation in the in vitro cell‐based human model of the BBB, suggesting an active mechanism of cell penetration.     

Abstraction and resolution modulo AC: How to verify Diffie–Hellman-like protocols automatically

We show how cryptographic protocols using Diffie–Hellman primitives, i.e., modular exponentiation on a fixed generator, can be encoded in Horn clauses modulo associativity and commutativity. In order to obtain a sufficient criterion of security, we design a complete (but not sound in general) resolution procedure for a class of flattened clauses modulo simple equational theories, including associativity–commutativity. We report on a practical implementation of this algorithm in the MOP modular platform for automated proving; in particular, we obtain the first fully automated proof of security of the IKA.1 initial key agreement protocol in the so-called pure eavesdropper model.     

Competency assessment models.

This article describes characteristics of alternative assessment models deployed in the measurement of professional competencies across the professional life span based on the work of the American Psychological Association Task Force on the Assessment of Competence in Professional Psychology. Assessments of knowledge, decision making, performance and personal attributes, as well as integrated practice-based skills and tasks are described and compared on the basis of their validity, feasibility and practicality, fidelity, and relevance at difference stages of professional development. It is acknowledged that no single assessment can evaluate all competencies and that assessments can be combined in complementary ways. Assessments deployed in the nursing, dental, and medical professions are reviewed and contrasted with current practices in psychology. At the licensure level, differences in the assessments deployed among the 4 healthcare professions are described, and their candidate fees and number of candidates assessed annually are documented. Ideas for developing new assessments in psychology are discussed on the basis of the needs and financial resources available to psychology and the experiences of other healthcare professions. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Modelling knowledge related to the allocation of modular jigs for part fixturing using fuzzy reasoning

One the problems a workholder designer faces in attempting to gain knowledge about the modelling of the “wear” in a positioning system by means of allocating positioning devices to each “virtual”locating point is that this knowledge is often verbalized by experts in an imprecise and uncertain way. Knowledge comes from technological know-how, and is developed through experience, personal habits and production-specific requirements. Nevertheless, current modelling of “expert knowledge” does not allow us to represent the different semantics (such as imprecision and uncertainty) that are related to it. In this paper, we present a method based on fuzzy reasoning that is able to support the modelling of these different knowledge semantics .     

Volatile compounds of experimental liver pâté from pigs fed conjugated linoleic acid in combination with monounsaturated fatty acids

BACKGROUND: Feeding conjugated linoleic acid (CLA) to pigs leads to CLA‐enriched meat products, which are of current interest owing to the potential health properties of CLA. However, dietary CLA increases the ratio of saturated to monounsaturated fatty acids (MUFA) in pig tissues. Combining CLA with high MUFA levels in pig diets may counteract this effect. Owing to the modification of fatty acid composition, variation in the volatile profile of derived meat products might be expected. The aim of the present work was to study the volatile profile, and its change during storage, of experimental liver pâté manufactured from pigs fed different levels of CLA and MUFA. RESULTS: Regardless of the CLA or MUFA level, 98 compounds were identified. Lower area units were observed for most branched aldehydes, ketones and alcohols and some furans, sulfur compounds and nitrogen compounds with increasing CLA and MUFA contents. Levels of nonanal, propan‐2‐one, dodecane, 2‐pentylfuran and ethylbenzene were higher in CLA pâtes. The effect of experimental diets on the change in volatiles during storage was not significant. CONCLUSION: Supplementation of pig diets with CLA isomers in combination with low or high MUFA levels seems to have a significant effect on the volatile profile of pork liver pâté. Copyright © 2009 Society of Chemical Industry     

Selection by color and form in vision.

Whether attention to a local part of a visual display can prevent access to semantic information in form matching tasks with objects was studied. A first picture containing a line segment (the reference) was followed by 2 lateral objects also containing a line segment (a target and a distractor). Participants matched the line segments according to either their orientation or color. Effects of semantic information were assessed by manipulating the semantic relations among the pictures surrounding the reference, target, and distractor. Semantic information affected performance in the orientation matching task, but not in the color matching task. Results suggest the existence of separate selection mechanisms in vision. Selection of local colors for response purposes can be based on inhibition of the form pathway (eliminating semantic effects on matching). Selection within the form pathway can involve a bias toward global shape (the picture). Once attention is allocated to global shape, associated semantic representations are activated and semantic effects on matching emerge. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Photo-oxidation in an O2 atmosphere: A powerful tool to elucidate the mechanism of UV-visible light oxidation of polymers - Application to the photodegradation of MDMO-PPV

This article describes a new approach to improve the analysis of the chemical modifications that result from the degradation of polymers under UV-visible light exposure in the presence of oxygen. The tool which is used consists of an irradiation chamber whose atmosphere is composed of ¹⁸O₂. The ¹⁸O₂ pressure inside the chamber and the hygrometry can be adjusted. In this study, particular attention was paid to the photo-oxidation of poly[2-methoxy-5-(3′,7′-dimethyloctyloxy)-1,4-phenylenevinylene] (MDMO-PPV). Using infrared spectroscopy, irradiation under the oxygen 18 atmosphere allowed discrimination between compounds formed via fixation of oxygen from the atmosphere and those formed by reorganisation of the matrix. In addition, irradiation of MDMO-PPV in an ¹⁸O₂ wet atmosphere allowed for detection of the presence of phenyl formate and aromatic ketone functions. This permitted validating the mechanism of photo-oxidation previously proposed. Additionally, with regard to blends made with MDMO-PPV and methano-fullerene[6,6]-phenyl C₆₁-butyric acid methyl ester ([60] PCBM), it was demonstrated that this technique facilitates the identification of the photo-oxidation products formed.     

Optical pulse sequence transmission through single-mode fibers:interference signal analysis

The transmission of a pulse sequence through a single-mode fiber is considered under first- and second-order dispersion. An expression is given for the output power signal envelope in terms of the Fourier transform of a spectral function. The output envelope is composed of two terms: a linear one which is a distorted replica of the information sequence, and a nonlinear interference term. The latter is expressed in a more meaningful way and analyzed. The results allow a characterization and a classification of the interference pulses in terms of physically intuitive parameters     

Phase reconstruction from reflectivity in fiber Bragg gratings

We propose a method for phase, time delay, and impulse response reconstruction from the spectral power reflectance or reflectivity in fiber Bragg gratings (FBGs). This method is based on causality and stability conditions and uses the Hilbert and Wiener-Lee transforms. In order to obtain a complete study of the algorithm, we have applied it to uniform and nonuniform fiber Bragg gratings. Finally, we get a complete characterization of a experimental uniform fiber Bragg grating, from the measured reflectivity, by means of the phase reconstruction algorithm. Results show a good agreement between exact and reconstructed functions     

Attention to orientation, size, luminance, and color: Attentional failure within the form domain.

Whether Ss can attend to physical dimensions of objects without access to semantic information about them was examined. Ss decided which of 2 laterally presented pictures, a target and a distractor, had the same orientation (Exp 1), size (Exp 2), luminance (Exp 3), or color (Exp 4) as a reference picture. In each experiment, the matching stimuli were either physically identical, semantically related, or semantically unrelated. The reference stimulus and the distractor were either semantically related or unrelated. When matching was based on orientation or on size, performance was facilitated when the matching stimuli were semantically related, and it was disrupted when the distractor was semantically related to the reference stimulus. Semantic effects were eliminated when matching was based on luminance or color. The results are discussed in terms of physiological data, form and surface information, and global and local processing. (PsycINFO Database Record (c) 2010 APA, all rights reserved)