Transition of elastomers from a rubber to glassy state under laser shock conditions.

The mechanical behaviour of polycarbonate and polydimethylsiloxane (Sylgard184) is studied in this work under laser shock conditions that induce high pressure and strain rates. Laser shock, usually used to reinforce metals, is chosen here because of its capacity to produce strain rates in the 106 s1 range and pressures of GPa order. The pressure and strain rates produced are extracted from the backface velocity profiles and reproduced with the FEM simulation on Abaqus for each laser shot. These two parameters lead to a glass transition shift in the polymers that can induce significant behaviour modifications. We show that Sylgard184, an elastomer with a glass transition temperature of 147 K, exhibits glassy behaviour under such laser shock conditions. By contrast, polycarbonate is already a glassy polymer in its normal state with a glass transition temperature of 415 K; no drastic change in behaviour under shock is evidenced. To discuss these findings in relation to the different mobility domains of the polymer chains under extreme conditions, dielectric relaxation spectroscopy (DRS) measurements are performed to characterize the limits of the rubbery and glassy behaviour for both polymers. As a result, the coupling of the two techniques provides a deeper understanding of the contribution of both the strain rate and pressure to the dynamic glass transition in polymers and thus expands the experimental study range of the two polymers to a strain rate that had not previously been reached.

Bone marrow mesenchymal stem cells stabilize already-formed aortic aneurysms more efficiently than vascular smooth muscle cells in a rat model.

PURPOSE: Abdominal aortic aneurysms (AAAs) expand because of aortic wall destruction. Enrichment in Vascular Smooth Muscle Cells (VSMCs) stabilizes expanding AAAs in rats. Mesenchymal Stem Cells (MSCs) can differentiate into VSMCs. We have tested the hypothesis that bone marrow-derived MSCs (BM-MSCs) stabilizes AAAs in a rat model. MATERIAL AND METHODS: Rat Fischer 344 BM-MSCs were isolated by plastic adhesion and seeded endovascularly in experimental AAAs using xenograft obtained from guinea pig. Culture medium without cells was used as control group. The main criteria was the variation of the aortic diameter at one week and four weeks. We evaluated the impact of cells seeding on inflammatory response by immunohistochemistry combined with RT-PCR on MMP9 and TIMP1 at one week. We evaluated the healing process by immunohistochemistry at 4 weeks. RESULTS: The endovascular seeding of BM-MSCs decreased AAA diameter expansion more powerfully than VSMCs or culture medium infusion (6.5% ± 9.7, 25.5% ± 17.2 and 53.4% ± 14.4; p = .007, respectively). This result was sustained at 4 weeks. BM-MSCs decreased expression of MMP-9 and infiltration by macrophages (4.7 ± 2.3 vs. 14.6 ± 6.4 mm(2) respectively; p = .015), increased Tissue Inhibitor Metallo Proteinase-1 (TIMP-1), compared to culture medium infusion. BM-MSCs induced formation of a neo-aortic tissue rich in SM-alpha active positive cells (22.2 ± 2.7 vs. 115.6 ± 30.4 cells/surface units, p = .007) surrounded by a dense collagen and elastin network covered by luminal endothelial cells. CONCLUSIONS: We have shown in this rat model of AAA that BM-MSCs exert a specialized function in arterial regeneration that transcends that of mature mesenchymal cells. Our observation identifies a population of cells easy to isolate and to expand for therapeutic interventions based on catheter-driven cell therapy.

Management of obstructive sleep apnea in children: a Canada-wide survey.

BACKGROUND: Obstructive sleep apnea frequently persists in children following adenotonsillectomy, which is the first-line treatment recommended for obstructive sleep apnea with adenotonsillar hypertrophy. Drug-induced sleep endoscopy (DISE) is a diagnostic tool increasingly used to assess pediatric obstructive sleep apnea, but its use has not been standardized. The overarching goal of this study was to document the current practice of Canadian otolaryngologists managing this population. METHODS: A nation-wide online cross-sectional survey of Canadian otolaryngologist members of the Canadian Society of Otolaryngology - Head and Neck Surgery and the Association d'otorhinolaryngologie et chirurgie cervico-faciale du Québec. The 58-question electronic survey was developed based on a validated survey redaction guide with the aim to assess management and treatment of pediatric obstructive sleep apnea, as well as indications and performance of DISE. Consensus on practice items was defined by a minimum of 75% similar answers. RESULTS: One hundred and nine Canadian otolaryngologists completed the survey on management of pediatric obstructive sleep apnea, among which 12 of them completed the questions on DISE. Overall, there was a poor rate of agreement of 55% among the respondents for the 58 questions altogether. There was a consensus to assess pediatric obstructive sleep apnea clinically ± with videos (82.6%), to assess adenotonsillar hypertrophy clinically (93.6%) and with flexible scope in the office (80.7%), as well as for the airway sites examined endoscopically during DISE. However, there was no consensus regarding anesthetic protocol and scoring system. DISE was mostly performed in cases of persistent obstructive sleep apnea after adenotonsillectomy rather than before performing any surgical procedure. There was no difference in the management of obstructive sleep apnea between otolaryngologists who perform DISE and those who do not. The only difference between otolaryngologists who practice in community centers versus in tertiary care centers was the more frequently use of the Brodsky tonsil scale by the latter ones. CONCLUSION: This Canadian-wide survey highlighted a lack of consensus in the management of pediatric obstructive sleep apnea and DISE. Certain aspects regarding DISE remain unclear, including establishment of its ideal timing in order to eventually avoid unnecessary tonsillectomies.

Senegalin, a new phenylpropanoid and other secondary metabolites from the stem bark of Ekebergia senegalensis A. Juss. (Meliaceae).

Senegalin (1), a new phenylpropanoid has been isolated from the stem bark of Ekebergia senegalensis A. Juss. along with twelve known secondary metabolites including coumarins 2-5, 4-hydroxy-3,5-methylbenzoic acid (6), pentacyclic triterpenoids 7-9, acyclic triterpenoids 10 and 11 and steroids 12 and 13, respectively. Their structures were elucidated with the help of spectroscopic techniques including 1 D- and 2 D-NMR. The antibacterial activity of the major compounds (2, 9-11) was evaluated on five bacterial strains. However, only compounds 2 and 11 showed a weak inhibition against Bacillus subtilis and Pseudomonas agarici. Furthermore, the chemotaxonomic significance of these compounds has also been elaborated.

Aortic length changes during abdominal aortic aneurysm formation, expansion and stabilisation in a rat model.

BACKGROUND: Determinants of extracellular matrix (ECM) destruction/reconstruction balance influencing abdominal aortic aneurysm (AAA) diameter may impact length. OBJECTIVE: Document aortic lengthening, its correlation to diameter, and determine how treatments that impact diameter also affect length. METHODS: Three hundred and fifty-five diameter and length measurements were performed in 308 rats during AAA formation, expansion and stabilisation in guinea pig aortas xenografted in rats. Impact of modulation of ECM destructive/reconstructive balance by endovascular Vascular Smooth Muscle Cell (VSMCs) seeding, TIMP-1, PAI-1 and TGF-beta1 overexpression on length has been assessed. RESULTS: Length increased in correlation with diameter during formation (correlation coefficient (cc): 0.584, P<0.0001) and expansion (cc: 0.352, P=0.0055) of AAAs. Overexpression of TIMP-1 and PAI-1 decreased lengthening (P=0.02 and 0.014, respectively) demonstrating that elongation is driven by matrix metalloproteinases and their activation by the plasmin pathway. Overexpression of TGF-beta1 controlled length in formed AAAs (17.3 ± 9.6 vs. 5.9 ± 7.4mm, P=0.022), but not VSMC seeding, although both therapies efficiently prevented further diameter increase. Length and diameter correlation was lost after biotherapies. CONCLUSION: Length increases in correlation with diameter during AAA formation and expansion, as a consequence of ECM injury driven by MMPs activated by the plasmin pathway. Correlation between length and diameter increases is not universally preserved.

Validity of the sonographic measurement of the diameters of the ascending aorta in rats.

PURPOSE: The objective of this investigation was to compare transthoracic ultrasound (US) determinations of ascending aortic diameters in rats with video microscopy (VM), the current standard for measuring aortic diameters in rats. MATERIALS AND METHODS: The diameter of the ascending aorta was measured in 111 adult Lewis male rats, by VM and US, with a 9 MHz probe, before and after intervention for induction of experimental aneurysm of the ascending aorta. RESULTS: The Bland-Altman test showed a high degree of agreement between the two methods, with a bias of only 0.23 mm (95 % confidence limits - 0.86 - 0.39 mm). Also, the measurements obtained by US correlated highly (r = 0.83, p < 0.0001) with those obtained by VM. Rat ascending aortic diameters obtained both by VM and US correlated significantly with the weight (r = 0.62 and r = 0.39, respectively), and with the age of the animals (r = 0.74 and r = 0.49, respectively). CONCLUSION: This study demonstrates that noninvasive US ascending aortic measurements are a reliable supplement to VM for the development of an ascending aortic aneurysm model, and for monitoring the efficiency of novel therapeutic agents.

Tumour response 3 months after neoadjuvant single-fraction radiotherapy for low-risk breast cancer.

Introduction: Standard treatment for early-stage invasive breast cancer (bca) consists of breast-conserving surgery and several weeks of adjuvant radiotherapy (rt). Neoadjuvant single-fraction rt is a novel approach for early-stage bca. We sought to investigate the effect of delaying surgery after neoadjuvant rt with respect to the rate of pathologic response (pr). Methods: Women 65 years of age or older with a new diagnosis of stage i luminal A bca were eligible for inclusion. A single 20 Gy dose to the primary breast tumour was given, followed by breast-conserving surgery 3 months later. The primary endpoint was the pr rate assessed by microscopic evaluation using the Miller-Payne system. Results: To date, 10 patients have been successfully treated. Median age of the patients was 72 years (range: 65-84 years). In 8 patients, neoadjuvant rt resulted in a tumour pr with median residual cellularity of 3%. No immediate rt complications other than mild dermatitis were noted. Conclusions: This study demonstrates a method for delivering single-fraction rt that can lead to a high level of pr in most patients. Continued accrual to this study and subsequent trials are needed to determine the feasibility, safety, and role of this novel technique in the management of early-stage bca.

New insight in aetiopathogenesis of aortic diseases.

BACKGROUND: Knowledge in the aetiopathogeny of aortic disease helps to characterise aortic lesions better and determine the risk of evolution and therapeutic strategies as well. This article focusses on aneurysms and dissections, and excludes causes related to infection, systemic inflammatory diseases and trauma. METHODS AND RESULTS: The biomedical literature of the past 10 years has been reviewed here. Aortic diseases are heterogeneous along the aorta as far as their genetic determinants, contribution of smooth muscle cells, inflammation and thrombus formation are concerned. Degradation of extracellular matrix by proteases causing aortic disease is a 'terminal' event, modulated by genetic background, haemodynamic strain, cellular events and thrombus formation. New genetic determinants of aortic disease have been identified. Proteases degrading the aortic wall are derived from a variety of cell types in addition to macrophages, including neutrophils on the luminal thrombus, mesenchymal and endothelial cells in the wall. Smooth muscle cells contribute to aortic wall homeostasis against inflammation and proteolysis. The degradation of the wall is followed by, or paralleled with, a failure of aortic reconstruction. CONCLUSIONS: Aortic diseases are diverse, and involve a multiplicity of biological systems in the vascular wall and at the interface with blood. Future research needs to unravel distinct cellular and molecular mechanisms causing the clinical events, in particular, dissection, expansion of already formed aneurysms and rupture.

ERRα promotes breast cancer cell dissemination to bone by increasing RANK expression in primary breast tumors.

Bone is the most common metastatic site for breast cancer. Estrogen-related-receptor alpha (ERRα) has been implicated in cancer cell invasiveness. Here, we established that ERRα promotes spontaneous metastatic dissemination of breast cancer cells from primary mammary tumors to the skeleton. We carried out cohort studies, pharmacological inhibition, gain-of-function analyses in vivo and cellular and molecular studies in vitro to identify new biomarkers in breast cancer metastases. Meta-analysis of human primary breast tumors revealed that high ERRα expression levels were associated with bone but not lung metastases. ERRα expression was also detected in circulating tumor cells from metastatic breast cancer patients. ERRα overexpression in murine 4T1 breast cancer cells promoted spontaneous bone micro-metastases formation when tumor cells were inoculated orthotopically, whereas lung metastases occurred irrespective of ERRα expression level. In vivo, Rank was identified as a target for ERRα. That was confirmed in vitro in Rankl stimulated tumor cell invasion, in mTOR/pS6K phosphorylation, by transactivation assay, ChIP and bioinformatics analyses. Moreover, pharmacological inhibition of ERRα reduced primary tumor growth, bone micro-metastases formation and Rank expression in vitro and in vivo. Transcriptomic studies and meta-analysis confirmed a positive association between metastases and ERRα/RANK in breast cancer patients and also revealed a positive correlation between ERRα and BRCA1mut carriers. Taken together, our results reveal a novel ERRα/RANK axis by which ERRα in primary breast cancer promotes early dissemination of cancer cells to bone. These findings suggest that ERRα may be a useful therapeutic target to prevent bone metastases.

Cross-pinning: the philosophy of retrievability applied practically to fixed, implant-supported prostheses.

Biologic and technical complications are widely reported in the dental literature and often compromise the functional and/or aesthetic features of fixed, implant-supported prostheses. Managing complications without damaging or destroying a restoration is an obvious advantage of implant-based dentistry where the option of prosthetic retrievability is almost always available. The technique of cross-pinning uses a transverse screw to secure a prosthesis to a milled implant abutment, allowing prosthetic retrievability irrespective of dental implant alignment. This study presents guidelines for cross-pinning implant-supported prostheses based on resistance form, screw mechanics and natural tooth contours. The technical aspects of cross-pinning are also discussed using examples from four implant systems.

Glycan conformational change in mesomorphic structures of ternary systems: liposaccharide/phospholipid/water.

An amphipatic liposaccharide, beta 16, has been synthesized by condensation of the glycoamino acid beta of ovomucoid with the palmitic acid to serve as a model on which the properties of the saccharide chains can be studied. This paper reports the ternary system beta 16/dipalmitoylphosphatidylcholine (DPPC)/water. Using X-ray diffraction and freeze-fracture electron microscopy, it was shown that the ternary system exhibits mesomorphic structures in the temperature range over which the aliphatic chains of the DPPC are in a liquid-like conformation. A phase diagram of the system was drawn at 75 degrees C in terms of the water concentration and of the beta 16 content. As the molar fraction in beta 16 increases from about 0.08 to 1, the ternary system displays successively two lamellar structures analogous to that exhibited by the system DPPC/H2O, then a hexagonal structure similar to that exhibited by the system beta 16/H2O. The two types of lamellar structure were shown to differ by the T or Y conformation adopted by their saccharide chains.

Liposomes injected intravenously into mice associate with liver mitochondria.

Liposomes encapsulating uranyl acetate or ferritin were injected intravenously into mice. At periods of 20 min, 1 h and 4 h post-injection, animals were killed, and livers were excised. Transmission electron micrographs of liver tissue showed association of oligolamellar liposomes with mitochondria for each time period. At 1 h post-injection, an average of one out of ten mitochondria was associated with liposomes. In most cases, the liposomes were clearly enclosed in a cytoplasmic vacuole. Phagocytosis by Kupffer cells as well as fusion with primary lysosomes and inclusion in secondary lysosomes was observed. No difference in intracellular fate was observed when lactosylceramide was incorporated in the liposome bilayers, suggesting that the differences observed in biochemical studies are at the level of liposome-plasma membrane interaction. When liposomes containing uranyl acetate were intravenously injected and hepatocytes were isolated by collagenase perfusion one hour later, transmission EM revealed the presence of liposomes in these cells, in cytoplasmic vacuoles in the cytoplasm and in association with mitochondria. A freeze-fracture-etching analysis of liver tissue excised 20 min after injection of liposomes encapsulating ferritin, further supported the observation that liposomes associate with mitochondria in the liver.

Fusion of negatively charged liposomes with clathrin-uncoated vesicles.

The interaction of lipid vesicles with uncoated vesicles from bovine brain has been studied by fluorescence energy transfer between fluorescent lipid analogs (NBD-PE, Rh-DOPE), by loss of fluorescence self-quenching (NBD-PE, carboxyfluorescein) and by freeze-fracture electron microscopy. The fluorescence techniques monitor the mixing of membranous lipids and the induced release of encapsulated material. The results demonstrate a mixing of the negatively charged lipid (PA, PS) vesicles with the uncoated vesicles. In parallel with the lipid mixing a release of intravesicularly encapsulated material takes place. Lipid vesicles composed of zwitterionic lipids (PC, DOPC, PC:PE) do not specifically interact with uncoated vesicles. The electron micrographs reveal single fusion events. Studies on the kinetics are consistent with a fusional mechanism of the negatively charged lipid vesicles with uncoated vesicles.

1H, 15N resonance assignment and three-dimensional structure of CYP1 (HAP1) DNA-binding domain.

CYP1(HAP1) is a transcriptional activator involved in the aerobic metabolism of the yeast Saccharomyces cerevisiae. The amino acid sequence of its DNA-binding domain suggests that it belongs to the "zinc cluster" class. This region is indeed characterized by a pattern known to form a bimetal thiolate cluster where two zinc ions are coordinated by six cysteine residues. Structures of two such domains, those from GAL4 and PPR1, have been solved as complexes with DNA. These domains consist of the zinc cluster connected to a dimerization helix by a linker peptide. They recognize, as a dimer, an inverted repeat of a CGG motif that is separated by a specific number of bases. Interestingly, the specificity of that interaction seems not to be due to the interaction between the cluster region and the DNA but rather to a fine tune between the structure of the linker peptide and the number of base-pairs separating the two CGGs. However, the CYP1 target sites fail to display such a consensus sequence. One of the two CGG sites is poorly conserved and some experiments suggest a direct rather than an inverted repeat. Using 1H, 15N and 113Cd NMR spectroscopy, we have undertaken the analysis of the structural properties of the CYP1(56-126) fragment that consists of the zinc-cluster region, the linker peptide and a part of the dimerization helix. We have demonstrated that the six cysteine residues of the peptide chelate two cadmium ions as in GAL4 and PPR1. Fifteen structures of the zinc-cluster region (residues 60 to 100) were calculated, the linker peptide and the dimerization helix being unstructured under the conditions of our study. This region possesses the same overall fold as in GAL4 and PPR1, and most of the side-chains involved in the interaction with DNA are structurally conserved. This suggests that the CYP1 zinc-cluster region recognizes a CGG triplet in the same way as GAL4 and PPR1. In this case, the particular properties of CYP1 seem to be due to the structure of the linker peptide and/or of the dimerization helix.

Nitrite reductase from Pseudomonas aeruginosa: sequence of the gene and the protein.

The gene coding for nitrite reductase of Pseudomonas aeruginosa has been cloned and its sequence determined. The coding region is 1707 bp long and contains information for a polypeptide chain of 568 amino acids. The sequence of the mature protein has been confirmed independently by extensive amino acid sequencing. The amino-terminus of the mature protein is located at Lys-26; the preceding 25 residue long extension shows the features typical of signal peptides. Therefore the enzyme is probably secreted into the periplasmic space. The mature protein is made of 543 amino acid residues and has a molecular mass of 60,204 Da. The c-heme-binding domain, which contains the only two Cys of the molecule, is located at the amino-terminal region. Analysis of the protein sequence in terms of hydrophobicity profile gives results consistent with the fact that the enzyme is fully water soluble and not membrane bound; the most hydrophilic region appears to correspond to the c-heme domain. Secondary structure predictions are in general agreement with previous analysis of circular dichroic data.

How the loss of several residues, at the level of one interglobule junction, modulates the lactate dehydrogenase activity of yeast flavocytochrome b2: a study of the nicked enzymes resulting from clostripain and trypsin action.

The native chain of flavocytochrome b2 is folded into three globules linked together by two protease-sensitive bridges "a" and "cd". We show in this paper that zone "a" of H-flavocytochrome b2 is the first to be cleaved under clostripain action. The alpha c and beta c fragments thus formed are homologous to alpha T and beta'T trypsic fragments. The remaining activities of the resulting (alpha c beta c) and alpha T beta'T) forms are only 25 per cent and 4 per cent of the native flavocytochrome b2 one. The study of the catalytic properties of (alpha c beta'T) and (alpha T beta c) species resulting from the crossed reassociation of the isolated fragments show that the beta type fragment plays a critical role in the catalytic process. A dramatic activity decrease may be correlated with the loss of 6 amino acid residues at the N-terminal of beta c. Our best hypothesis is that these amino acids are involved in the active site, which may be located in the contact zone between alpha and beta. These results are in agreement with previous results obtained in this laboratory which showed the necessity of both alpha T and beta'T fragments for the correct conformation of the flavin binding site.

Gastro-cutaneous syndrome: peptic ulcer/hiatal hernia, multiple lentigines/café-au-lait spots, hypertelorism, and myopia.

We report the familial occurrence in a French Canadian family of peptic ulcer/hiatal hernia, multiple lentigines/café-au-lait spots, apparent hypertelorism, and myopia caused by a pleiotropic autosomal dominant gene with high penetrance and variable expressivity. Other probable but rarer components of the syndrome include ischemic heart disease, congenital heart disease, and maturity onset diabetes. Symptoms of peptic ulcer/hiatal hernia usually started in the second or third decade and were associated, as least in some examined individuals, with relatively increased acid secretion and abnormal dermatoglyphics.

Internal representation of visual texture as the basis for the judgment of similarity.

The relationship between Fourier spectra of visual textures (represented both by the actual frequency components and by the response of four hypothetical channels selectively sensitive to spatial frequency) and the perceptual appearance of the textures was investigated. Thirty textures were synthesized by combining seven spatial frequencies whose amplitudes were randomly chosen and then scaled to give an overall contrast of .9. Similarity judgments were collected using both the method of triadic comparison (two subjects, 4,060 trials each) and the method of paired comparison (six subjects, 435 trials each). The similarity judgments were subjected to MDSCAL and INDSCAL dimensions were found to be optimally oriented in terms of spatial frequency information without rotation. The seven spatial frequency components accounted for 90.6% of the variance in the 3-D INDSCAL space, while the four channels accounted for 91.8% of the variance in the first two dimensions. The data further suggest that the four channels may interact in an opponent process manner. The results support the idea that the visual internal representation of stimuli is based on spatial frequency analysis rather than feature extraction.

Identification confusions among letters of the alphabet.

Black, uppercase letters, subtending 6.0' of arc in height, were presented tachistoscopically to 6 subjects. An exposure duration was chosen to keep the subject's identification performance at about 50% correct. On each trial a single letter was presented, and the subject was required to identify the letter by verbal response. The resulting 26 X 26 confusion matrix was based on 3,900 trials (150 trials per letter). Several models of visual processing were used to generate predicted confusions among letter pairs. Models based on template overlap, geometric features, and two-dimensional spatial frequency content (Fourier transforms) were tested. The highest correlation (.70) between actual and predicted confusions was attained by the model based on the Fourier transformed letters filtered by the human contrast sensitivity function. These results demonstrate that the spatial frequency content of visual patterns can provide a valuable metric for predicting their psychological similarity. The results further suggest that spatial frequency models of visual processing are competitive with feature analysis models.