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Biomedical subjects

P Mora

Publications and source records attributed to P Mora.

At least 19 recordsLinked to original sources

Effect of rolling on dissipation in fault gouges.

Sliding and rolling are two outstanding deformation modes in granular media. The first one induces frictional dissipation whereas the latter one involves deformation with negligible resistance. Using numerical simulations on two-dimensional shear cells, we investigate the effect of the grain rotation on the energy dissipation and the strength of granular materials under quasistatic shear deformation. Rolling and sliding are quantified in terms of the so-called Cosserat rotations. The observed spontaneous formation of vorticity cells and clusters of rotating bearings may provide an explanation for the long standing heat flow paradox of earthquake dynamics.

Journal Article↗

Biodegradable scleral implants as new triamcinolone acetonide delivery systems.

The goal of this study was to develop ocular scleral implants able to release triamcinolone acetonide (TA) overall several months. Scleral discs were manufactured by a compression-molding method using a new synthetic polymer, poly(methylidene malonate) (PMM2.1.2), as matrix. Implants with good mechanical properties adapted for in vivo implantation have been obtained when using high M(w) PMM2.1.2 (100,000 - 150,000 Da) associated with ethoxylated derivatives of stearic acid (Simulsol) or oligomers of methylidene malonate as plasticizer. After implantation in rabbit eyes, scleral implants showed a good ocular biocompatibility. Indeed, the clinical follow-up and ocular inflammation parameters, such as inflammatory cell number and protein content in aqueous humor, demonstrated that implants were well tolerated and did not provoke abnormal inflammation. Implants were able to release significant concentrations of TA in the vitreous and the sclera throughout 5 weeks.

Absorbable Implants↗

Thin-foil expansion into a vacuum.

The collisionless expansion into a vacuum of a thin foil heated by an ultrashort laser pulse and adiabatically cooling down is studied with a particular emphasis on the structure of the accelerating field and on the resultant ion energy spectrum. For late times, a double layer structure at the ion front becomes the dominant feature. The dependence of the maximum ion velocity on the thin foil width is established. The effect of a two-temperature electron distribution function is discussed.

Journal Article↗

Dynamics of electric fields driving the laser acceleration of multi-MeV protons.

The acceleration of multi-MeV protons from the rear surface of thin solid foils irradiated by an intense (approximately 10(18) W/cm2) and short (approximately 1.5 ps) laser pulse has been investigated using transverse proton probing. The structure of the electric field driving the expansion of the proton beam has been resolved with high spatial and temporal resolution. The main features of the experimental observations, namely, an initial intense sheath field and a late time field peaking at the beam front, are consistent with the results from particle-in-cell and fluid simulations of thin plasma expansion into a vacuum.

Journal Article↗

Plasma expansion into a vacuum.

The charge separation effects in the collisionless plasma expansion into a vacuum are studied in great detail. Accurate results are obtained concerning the structure of the ion front, the resultant ion energy spectrum, and more specifically the maximum ion energy. These are of crucial importance for the interpretation of recent experiments, where high-energy ion jets were produced from short pulse interaction with solid targets.

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Steady ion momentum in nonlinear plasma waves.

The analysis of a one-dimensional two-fluid hydrodynamic model with relativistic electrons and nonrelativistic ions shows that the propagation of a nonlinear plasma wave is accompanied by a steady currentless plasma drift. Ions, due to their larger mass, appear to be the main carriers of the average momentum of the plasma wave. Two examples of nonlinear plasma waves generated by moving sources (short laser pulses and electron bunches) are analyzed to show details of the energy and momentum conservation laws.

Journal Article↗

The role of the symbiotic fungus in the digestive metabolism of two species of fungus-growing ants.

Leaf-cutting ants live in an obligatory symbiosis with a fungus which they grow on fresh leaves harvested by workers. This study attempts to clarify the respective role of ants and fungus in the degradation of plant material, in order to highlight the evolutionary basis of this mutualistic association. The symbiotic system of two ant species, Acromyrmex subterraneus subterraneus and Acromyrmex crassispinus, was investigated. To identify the digestive carbohydrases, a total of 19 specific and synthetic plant material substrates were tested on workers from different castes (major and minor), larvae and fungus. Extracts of A. subterraneus and A. crassispinus workers showed high enzymatic activity particularly on starch, maltose, sucrose and alpha-1,4 glucoside. Larvae degraded starch, sucrose, maltose but also laminarin, and all the detected activities were higher than those found for workers. The symbiotic fungus of A. subterraneus was mostly active on laminarin, xylan and cellulose, while the symbiotic fungus of A. crassispinus was mostly active on laminarin, starch, maltose and sucrose. The enzymatic activities of ants and fungus belonging to the same symbiotic system tended not to overlap, suggesting that the association is highly evolved and of an ancient origin.

Animal Feed↗

Femtosecond laser-guided electric discharge in air.

The filament due to the self-guided propagation of an infrared femtosecond laser pulse in atmospheric-pressure air is used to trigger and guide an electric discharge. The long low density plasma channel due to the filament is first heated by the Joule effect during an initial transient plasma stage. The heated channel of recombined gas then hydrodynamically expands radially. The onset of a discharge starts when the density depression on axis reaches the threshold discharge value. This model is supported by detailed experimental and numerical analysis.

Journal Article↗

Dynamics of Raman instabilities using chirped laser pulses.

Time resolved measurements of the growth of Raman instabilities were performed using a picosecond chirped laser pulse. It was observed experimentally that for a short laser pulse (<10 ps), forward and 30 degrees Raman scattering occur at the back of the pulse. The growth of the instabilities was found to be independent of the sign of the chirp. In addition, a simple temporal model was developed and shows good agreement with the experimental results. This model also indicates that the plasma wave driven by forward Raman scattering is severely damped in the case of pulses longer than a few picoseconds. Damping by the modulational instability is compatible with the experimental results.

Journal Article↗

Plasma ions dynamics in the wake of a short laser pulse.

A new physical effect of a plasma channel formation by the ponderomotive force of a wakefield generated by a laser pulse with a length of the order of the electron plasma wavelength is discussed. For a narrow pulse, wherein the width is less than c/omega(pe) ( omega(pe) and c are the plasma frequency and light velocity, respectively), the channel has an annular form with on-axis density maximum. The depth of the channel increases with the distance from the pulse until the phase mixing arises and the wake starts to break. The linear fluid theory is used to obtain the scaling for wave-breaking conditions. The results of numerical simulations for high intensity laser pulses are in good agreement with theoretical predictions.

Journal Article↗

Compressing and focusing a short laser pulse by a thin plasma lens.

We consider the possibility of using a thin plasma slab as an optical element to both focus and compress an intense laser pulse. By thin we mean that the focal length is larger than the lens thickness. We derive analytic formulas for the spot size and pulse length evolution of a short laser pulse propagating through a thin uniform plasma lens. The formulas are compared to simulation results from two types of particle-in-cell code. The simulations give a greater final spot size and a shorter focal length than the analytic formulas. The difference arises from spherical aberrations in the lens which lead to the generation of higher-order vacuum Gaussian modes. The simulations also show that Raman side scattering can develop. A thin lens experiment could provide unequivocal evidence of relativistic self-focusing.

Journal Article↗

Discerning malignancy in adrenocortical tumors: are molecular markers useful?

OBJECTIVE: Adrenocortical carcinoma (ACC) is a rare neoplasm with poor prognosis. Discerning ACCs from benign adenomas histologically may be difficult if invasion into surrounding tissues or metastases are missing. DESIGN: In order to establish molecular markers for malignancy, we analyzed seven normal adrenals, three massive macronodular ACTH-independent adrenocortical hyperplasias (MMAHs), 30 adrenocortical adenomas (ACAs) and ten ACCs. METHODS: All tissues were studied for the presence of alterations in the p53 tumor suppressor gene using the PAb 1801 antibody, which detects mutant p53 protein and the pYNZ22 microsatellite marker to show loss of heterozygosity (LOH) at 17p, for expression of the proliferation-associated antigen Ki67 using the MIB1 antibody, for the rate of apoptotic tumor cells with the TdT-mediated dUTP biotin nick end labeling (TUNEL) method, and for LOH of 11q13 (menin gene locus) with the D11S956 microsatellite marker. RESULTS: 0/3 MMAH, 1/28 ACA and 3/10 ACC revealed immunopositive staining for p53. LOH for pYNZ22 was observed in 1/3 MMAH, 1/23 informative ACA and 6/6 informative ACC. The rate of apoptotic cells was significantly higher in ACC (P<0.0001 by ANOVA) than in ACA but there was some overlap between groups. The Ki67 index (% immunopositive cells) was 1.9+/-1.30% (mean+/-s.d.) in normal adrenals, 3.47+/-1.37% in MMAH, and 2.11+/-1.01% in ACA. ACC had the highest Ki67 index of 11.94+/-7.58% distinguishing all ACC from the ACA and MMAH studied with a cut-off level of 5%. LOH for 11q13 was detected in 2/3 MMAH, 5/26 ACA and 6/8 ACC. CONCLUSIONS: We conclude that a Ki67 index above 5% is a sensitive and specific indicator of ACC and may be useful in the differentiation of adenomas from carcinomas.

Adenoma↗

Site-directed mutagenesis of the regulatory domain of Escherichia coli carbamoyl phosphate synthetase identifies crucial residues for allosteric regulation and for transduction of the regulatory signals.

Carbamoyl phosphate (CP), the essential precursor of pyrimidines and arginine, is made in Escherichia coli by a single carbamoyl phosphate synthetase (CPS) consisting of 41.4 and 117.7 kDa subunits, which is feed-back inhibited by UMP and activated by IMP and ornithine. The large subunit catalyzes CP synthesis from ammonia in three steps, and binds the effectors in its 15 kDa C-terminal domain. Fifteen site-directed mutations were introduced in 13 residues of this domain to investigate the mechanism of allosteric modulation by UMP and IMP. Two mutations, K993A and V994A, decreased significantly or abolished enzyme activity, apparently by interfering with the step of carbamate synthesis, and one mutation, T974A, negatively affected ornithine activation. S948A, K954A, T974A, K993A and K993W/H995A abolished or greatly hampered IMP activation and UMP inhibition as well as the binding of both effectors, monitored using photoaffinity labeling and ultracentrifugation binding assays. V994A also decreased significantly IMP and UMP binding. L990A, V991A, H995A, G997A and G1008A had more modest effects or affected more the modulation by and the binding of one than of the other nucleotide. K993W, R1020A, R1021A and K1061A were without substantial effects. The results confirm the independence of the regulatory and catalytic centers, and also confirm functional predictions based on the X-ray structure of an IMP-CPS complex. They prove that the inhibitor UMP and the activator IMP bind in the same site, and exclude that the previously observed binding of ornithine and glutamine in this site were relevant for enzyme activation. K993 and V994 appear to be involved in the transmission of the regulatory signals triggered by UMP and IMP binding. These effectors possibly change the position of K993 and V994, and alter the intermolecular contacts mediated by the regulatory domain.

Allosteric Regulation↗

Opacity of an underdense plasma slab due to the parametric instabilities of an ultraintense laser pulse

The interaction of ultraintense laser beams with underdense plasma slabs has been investigated with two-dimensional particle-in-cell numerical simulations, showing a strong absorption and a correlatively low transmission. Energetic electrons in the multi-MeV range are produced. At very high intensities the plasma transparency is recovered. These results are interpreted in terms of the development of electron parametric instabilities in the self-consistently heated plasma.

Journal Article↗

Identification of peptides that neutralize bacterial endotoxins using beta-hairpin conformationally restricted libraries.

Bacterial endotoxins are the major mediator of septic shock; therefore, endotoxin-neutralizing molecules could have biomedical applications. The septic shock cascade relies in a series of molecular recognition processes. The large contact-surface described for the interacting macromolecules, in most cases, prevents the identification of small molecules that could modulate such recognition events. Here we report on a beta-hairpin conformationally restricted combinatorial library that has been generated and screened towards the identification of new peptides that neutralize bacterial endotoxins. Starting with a de novo designed linear peptide that shows a beta-hairpin structure population of around 30%, (Ramirez-Alvarado, M., Blanco, F. J. and Serrano, L. Nat. Struc. Biol., 7, 604-612 (1996)), we selected four positions to build up a combinatorial library of 20(4) sequences. Deconvolution of the library reduced such a sequence complexity to 8 defined sequences. The newly identified peptides have a biological activity equivalent to that reported for peptides derived from natural endotoxin-binding proteins.

Amino Acid Sequence↗

Multiple endocrine neoplasia type 1 gene expression is normal in sporadic adrenocortical tumors.

Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant disorder with neoplasia of the anterior pituitary, the parathyroid, the endocrine pancreas and other endocrine tissues including the adrenal cortex. The tumor-suppressor gene causing this disease was identified at the gene locus 11q13. We recently reported that adrenocortical carcinomas frequently show loss of heterozygosity (LOH) of 11q13, but do not contain point mutations within the MEN1-coding region. To investigate whether reduced gene expression (for example by mutations within the MEN1 promoter) may contribute to the tumorigenesis of sporadic adrenocortical tumors, 24 adrenocortical specimen were studied by Northern blot analysis. This series included six adrenocortical carcinomas, four cortisol-producing adenomas, six aldosterone-producing adenomas, three endocrine-inactive adenomas and six normal adrenal glands. The presence of LOH of 11q13 was investigated using five polymorphic microsatellite markers (D11S956, PYGM, D11S4939, D11S4946 and D11S987) close to the MEN1 gene. Poly-A mRNA was hybridized with a PCR-generated cDNA probe of the MEN1 gene, a cDNA of the former MEN1 candidate gene phospholipase (PLC) beta3 and a mouse beta-actin cDNA for normalization. LOH of 11q13 was detected in five out of six carcinomas and two inactive adenomas, but in none of the hormone-producing adenomas. Compared with normal adrenals (100+/-6. 5%, mean+/-s.e.m.) MEN1 mRNA in adrenocortical tumors was expressed in similar amounts (carcinomas 109+/-11%, cortisol-producing adenomas 131+/-10%, aldosterone-producing adenomas 113+/-13%, endocrine-inactive adenomas 111+/-2%) with the exception of one adrenocortical carcinoma with low MEN1 mRNA expression (66%). PLCbeta3 mRNA expression showed a variable pattern without reaching significant differences between the groups. We conclude that since mRNA levels were unaltered in the majority of tumors, mutations of the MEN1 gene causing altered gene transcription is unlikely to be a major pathogenic factor of sporadic adrenocortical tumors.

Adenoma↗

[Esophageal perforation and postoperative fistulae of the upper digestive tract treated endoscopically with the application of Tissucol].

We present three patients with serious gastro-esophageal complications which were treated with Tissucol. The first patient developed a rare postoperative oesophago-pleural fistula. The second suffered a traumatic esophageal perforation (possibly iatrogenic) that was discovered at the end of the removal procedure of an alimentary bolus impacted in the distal esophagus. Attempts to close the high output oesophago-pleural fistula with standard treatment were unsuccessful. It was closed with Tissucol at the third attempt, in conjunction with oesophago-jejunal stenosis by means of endoscopic dilatation. In the second patient, early Tissucol application after detection of pneumomediastinum was an effective complementary treatment to the conservative approach and rapidly closed the perforation. The third patient developed a low debit postoperative gastro-cutaneous fistula that did not resolve with conservative treatment. It was closed with only one session of Tissucol sealing. We consider that the endoscopic application of fibrin glue should become the first step in the conservative treatment of small esophageal perforations or postoperative esophageal pleural fistulae, especially in cases of high output fistulae. The success of this technique depends on the localization and selective catheterization of the fistula and on brushing the fistular opening. Total resolution of any distal stenosis is necessary to prevent reopening of the fistula.

Adult↗