Development and preliminary evaluation of a pediatric measure of community integration: The Pediatric Community Participation Questionnaire (PCPQ).

Objective: To develop and evaluate a new pediatric measure of community integration: the Pediatric Community Participation Questionnaire (PCPQ). Participants: 105 youths with physical disabilities. Measures: In addition to the PCPQ, demographic and disability-related questions and the Functional Disability Inventory (FDI) were administered. Results: The PCPQ demonstrated convergent validity through its high association with functional ability, discriminant validity through its ability to discriminate between ambulatory and nonambulatory participants, and excellent internal consistency. Conclusions: Community participation, an important component of positive overall development, may be particularly important for youths with physical disabilities. The findings from this study provide preliminary support for the validity and reliability of the PCPQ, supporting its use as a measure of community participation with this population. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Disturbances of nuclear condensation in human spermatozoa: search for mutations in the genes for protamine 1, protamine 2 and transition protein 1

During spermiogenesis, the successive replacement of the somatic histones by basic proteins, the transition proteins and protamines, allows normal sperm nuclear condensation. It was suggested that disturbances in nuclear condensation may result in male infertility. Here we report the first molecular analysis of the structure of three genes which code for germ cell-specific nuclear proteins, namely protamine 1 (PRM1), protamine 2 (PRM2) and transition protein 1 (TNP1) in infertile men with disturbed sperm chromatin condensation. In 36 infertile men whose spermatozoa showed a positive reaction with aniline blue, which is an indication for the presence of histones in the nuclei, the complete nucleotide sequences of the coding regions and 5' and 3' untranslated regions of the three genes were evaluated. In addition, 10 infertile patients with oligoasthenoteratozoospermia were studied in the same way, as well as nine infertile patients whose spermatozoa showed a reduction of the protamine 2 content. We did not detect any mutation in the three genes in any of the patients. We assume that the disturbances in the sperm chromatin condensation of our patients, and those described in the literature, are not primarily due to mutations in the genes for PRM1, PRM2 and TNP1.     

Contact stress analysis for an elastic cylinder indenting a slab in the presence of friction

In an earlier paper the authors discussed numerical methods of contact stress analysis for rigid indenters pressed against rough elastic slabs. In this sequel, they include the deformation of the cylindrical indenter using numerical methods of analysis similar to those adopted in the previous article. Examples which demonstrate the effects of indenter deformation and adhesion in the contact area are presented.     

The Reactivity of Difluorocarbene with Hydroxylamines: Synthesis of Carbamoyl Fluorides

Carbamoyl fluorides are formed in reactions of hydroxylamines with difluorocarbene generated from sodium bromodifluoroacetate as readily available and non‐toxic carbene precursor. The process shows a high functional group tolerance, and the reaction path has been rationalized by computational calculations.

     

Determination of the absolute configurations of 4-mercapto-2-alkanones using the <Superscript>1</Superscript>H NMR anisotropy method and enzyme-catalyzed kinetic resolution of the corresponding 4-acetylthio-2-alkanones

To determine the capillary gas chromatographic (GC) elution order of the enantiomers of 4-mercapto-2-alkanones, racemic 4-acetylthio-2-alkanones were synthesized and hydrolyzed by lipases to get enantio-enriched 4-mercapto-2-alkanones that were resolved by capillary gas chromatography using a chiral stationary phase. The obtained enantio-enriched 4-mercapto-2-alkanones were esterified with (S)-2-methoxy-2-(1-naphthyl)propionic acid ((S)-MαNP acid), and the HPLC analysis of MαNP thioesters revealed the same isomeric ratios as the chiral GC analysis of the corresponding thiol enantiomers. The diastereoisomeric thioesters obtained were resolved by HPLC, and the absolute configurations were determined on the basis of ¹H NMR anisotropy effects. On the basis of these results, the GC elution order of the enantiomers of 4-mercapto-2-alkanones and of the corresponding 4-acetylthio-2-alkanones could be determined. The combination of enzymatic resolution and MαNP thioesterification proved to be a useful tool to determine the absolute configuration of secondary thiols.     

Prevalence of gastrointestinal disorders recorded at postmortem inspection in white veal calves and associated risk factors

The study aimed at assessing the prevalence of poor rumen development, presence of rumen plaques, rumen papillae hyperkeratinization, and abomasal lesions in veal calves and to investigate risk factors for their occurrence at the farm level. Within a wide cross-sectional study, a sample of 170 veal farms representative of the European veal meat production systems was considered in the 3 major producing countries (99 in the Netherlands, 47 in France, and 24 in Italy). An average of 59 ± 10 (SD) rumens and abomasa belonging to calves from a single batch per farm were inspected at the abattoir by trained observers to assess the incidence of these gastrointestinal disorders. Potential risk factors for their occurrence related to farm management, housing, and to the feeding plan were obtained by a questionnaire submitted to the stockperson. Prevalence of poor rumen development (almost no papillae present), rumen plaques, and hyperkeratinization were 60.4, 31.4, and 6.1% of rumens, respectively, whereas abomasal lesions in the pyloric area were recorded in 74.1% of abomasa. Independent variables related to the feeding system confirmed to be the main risk factors for the occurrence of gastrointestinal disorders in veal calves. However, additional risk sources for each given problem were identified among housing and management variables. The provision of a low amount of solid feed (≤50 kg of dry matter/head per cycle) was a relevant risk for rumen underdevelopment. Rumen wall alterations (plaques and hyperkeratinization) and abomasal lesions were instead associated with the administration of large quantities of solids (151-300 kg of dry matter/head per cycle) in calves receiving milk replacer during the entire fattening cycle. Among the types of solid feed, cereal grain acted as a preventive measure for low rumen development, whereas it was a risk factor for the occurrence of rumen plaques, papillae hyperkeratinization, and abomasal lesions. Some housing and management options adopted to improve veal calf welfare (i.e., higher space allowance and use of heating) were associated with lower risk for gastrointestinal disorders.     

One Question,Multiple Answers: Biochemical and Biophysical Screening Methods Retrieve Deviating Fragment Hit Lists

Fragment‐based lead discovery is gaining momentum in drug development. Typically, a hierarchical cascade of several screening techniques is consulted to identify fragment hits which are then analyzed by crystallography. Because crystal structures with bound fragments are essential for the subsequent hit‐to‐lead‐to‐drug optimization, the screening process should distinguish reliably between binders and non‐binders. We therefore investigated whether different screening methods would reveal similar collections of putative binders. First we used a biochemical assay to identify fragments that bind to endothiapepsin, a surrogate for disease‐relevant aspartic proteases. In a comprehensive screening approach, we then evaluated our 361‐entry library by using a reporter‐displacement assay, saturation‐transfer difference NMR, native mass spectrometry, thermophoresis, and a thermal shift assay. While the combined results of these screening methods retrieve 10 of the 11 crystal structures originally predicted by the biochemical assay, the mutual overlap of individual hit lists is surprisingly low, highlighting that each technique operates on different biophysical principles and conditions.     

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.