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During severe septic shock and/or severe acute respiratory distress syndrome (ARDS) patients present with a limited cardio-ventilatory reserve (low cardiac output and blood pressure, low mixed venous saturation, increased lactate, low PaO2/FiO2 ratio, etc.), especially when elderly patients or co-morbidities are considered. Rescue therapies (low dose steroids, adding vasopressin to noradrenaline, proning, almitrine, NO, extracorporeal membrane oxygenation, etc.) are complex. Fever, above 38.5-39.5°C, increases both the ventilatory (high respiratory drive: large tidal volume, high respiratory rate) and the metabolic (increased O2 consumption) demands, further limiting the cardio-ventilatory reserve. Some data (case reports, uncontrolled trial, small randomized prospective trials) suggest that control of elevated body temperature (“fever control”) leading to normothermia (35.5-37°C) will lower both the ventilatory and metabolic demands: fever control should simplify critical care management when limited cardio-ventilatory reserve is at stake. Usually fever control is generated by a combination of general anesthesia (“analgo-sedation”, light total intravenous anesthesia), antipyretics and cooling. However general anesthesia suppresses spontaneous ventilation, making the management more complex. At variance, alpha-2 agonists (clonidine, dexmedetomidine) administered immediately following tracheal intubation and controlled mandatory ventilation, with prior optimization of volemia and atrio-ventricular conduction, will reduce metabolic demand and facilitate normothermia. Furthermore, after a rigorous control of systemic acidosis, alpha-2 agonists will allow for accelerated emergence without delirium, early spontaneous ventilation, improved cardiac output and micro-circulation, lowered vasopressor requirements and inflammation. Rigorous prospective randomized trials are needed in subsets of patients with a high fever and spiraling toward refractory septic shock and/or presenting with severe ARDS. [ABSTRACT FROM AUTHOR]

Progress over the last 50 years has led to a decline in mortality from ≈70% to ≈20% in the best series of patients with septic shock. Nevertheless, refractory septic shock still carries a mortality close to 100%. In the best series, the mortality appears related to multiple organ failure linked to comorbidities and/or an intense inflammatory response: shortening the period that the subject is exposed to circulatory instability may further lower mortality. Treatment aims at reestablishing circulation within a “central” compartment (i.e., brain, heart, and lung) but fails to reestablish a disorganized microcirculation or an adequate response to noradrenaline, the most widely used vasopressor. Indeed, steroids, nitric oxide synthase inhibitors, or donors have not achieved overwhelming acceptance in the setting of septic shock. Counterintuitively, α2-adrenoceptor agonists were shown to reduce noradrenaline requirements in two cases of human septic shock. This has been replicated in rat and sheep models of sepsis. In addition, some data show that α2-adrenoceptor agonists lead to an improvement in the microcirculation. Evidence-based documentation of the effects of alpha-2 agonists is needed in the setting of human septic shock. [ABSTRACT FROM AUTHOR]

Abstract: Alpha-2 adrenergic agonists (“alpha-2 agonists”) present multiple pharmacodynamic effects: rousable sedation, decreased incidence of delirium in the setting of critical care, preservation of respiratory drive, decreased whole body oxygen consumption, decreased systemic and pulmonary arterial impedance, improved left ventricular systolic and diastolic function, preserved vascular reactivity to exogenous catecholamines, preserved vasomotor baroreflex with lowered set point, preserved kidney function, decreased protein catabolism. These pharmacodynamic effects explain the interest for these drugs in the critical care setting. However, their exact role for sedation in critically ill-patients remains open for further studies. Given the few double-blind randomized multicentric trials available, the present non exhaustive analysis of the literature aims at presenting the utilization of alpha-2 agonists as potential first-line sedative agents, in the critical care setting. Suggestions regarding the use of alpha-2 agonists as sedatives are detailed. [Copyright &y& Elsevier]

In the critical care setting, α-2 agonists present a multifaceted profile: sedation combined with arousability, suppression of delirium, preservation of respiratory drive, reduced O2 consumption, preserved renal function, and reduced protein metabolism. In addition, this review details the reduced arterial impedance, improved left ventricular performance, preserved vascular reactivity to exogenous amines, preserved cardiac baroreflex reactivity, preserved vasomotor baroreflex activity combined with a lowered pressure set point: these features may explain the good tolerance observed when α-2 agonists are used as continuous infusion without any loading dose. Reviewing the literature allows one to suggest that a new management appears possible with arousable sedation. However, it remains to be demonstrated whether this arousable sedation can be combined with the preservation of spontaneous ventilation, in the setting of severe respiratory distress, as opposed to conventional controlled mechanical ventilation combined with conventional sedation. Should such a speculative view be confirmed, then α-2 agonists will move from second-line sedative agents to first-line sedative agents. However, key studies are lacking to demonstrate the effect of α-2 agonists on physiological endpoints and outcome. Presently, the existing body of data suggests a niche for the use of α-2 agonists in the critical care setting. [ABSTRACT FROM PUBLISHER]

We investigated the variation and short-term evolution of the selfing rate and inbreeding depression (ID) across three generations within a cedar forest that was established from admixture ca 1860. The mean selfing rate was 9.5%, ranging from 0 to 48% among 20 seed trees (estimated from paternally inherited chloroplast DNA). We computed the probability of selfing for each seed and we investigated ID by comparing selfed and outcrossed seeds within progenies, thus avoiding maternal effects. In all progenies, the germination rate was high (88-100%) and seedling mortality was low (0-12%). The germination dynamics differed significantly between selfed and outcrossed seeds within progenies in the founder gene pool but not in the following generations. This transient effect of selfing could be attributed to epistatic interactions in the original admixture. Regarding the seedling growth traits, the ID was low but significant: 8 and 6% for height and diameter growth, respectively. These rates did not vary among generations, suggesting minor gene effects. At this early stage, outcrossed seedlings outcompeted their selfed relatives, but not necessarily other selfed seedlings from other progenies. Thus, purging these slightly deleterious genes may only occur through within-family selection. Processes that maintain a high level of genetic diversity for fitness-related traits among progenies also reduce the efficiency of purging this part of the genetic load. [ABSTRACT FROM AUTHOR]

Background: Src family kinases control multiple cancer cell properties including cell cycle progression, survival, and metastasis. Recent studies suggest that the Src inhibitor dasatinib blocks these critical cancer cell functions.Methods: Because the molecular mechanism of action of dasatinib in breast cancers has not been investigated, we evaluated the effects of dasatinib as a single agent and in combination with the commonly used chemotherapeutic doxorubicin, on the proliferation, viability, and invasive capacity of breast cancer cells lines earlier categorised as dasatinib-sensitive (MDA-MB-231) and moderately resistant (MCF7 and T47D). We also tested the effects of these drugs on the actin cytoskeleton and associated signalling pathways.Results: The cell lines tested varied widely in sensitivity to growth inhibition (IC(50)=0.16-12.3 microM), despite comparable Src kinase inhibition by dasatinib (IC(50)=17-37 nM). In the most sensitive cell line, MDA-MB-231, dasatinib treatment induced significant G(1) accumulation with little apoptosis, disrupted cellular morphology, blocked migration, inhibited invasion through Matrigel (P<0.01), and blocked the formation of invadopodia (P<0.001). Importantly, combination treatment with doxorubicin resulted in synergistic growth inhibition in all cell lines and blocked the migration and invasion of the highly metastatic, triple-negative MDA-MB-231 cell line.Conclusion: The observed synergy between dasatinib and doxorubicin warrants the re-evaluation of dasatinib as an effective agent in multi-drug regimens for the treatment of invasive breast cancers. [ABSTRACT FROM AUTHOR]

Abstract: Due to their outstanding properties, surface-functionalized polymer latexes proved to offer suitable colloidal supports in many biotechnological applications. At first, numerous polymerization methods in heterogeneous media, especially in aqueous medium, allow to synthesise a wide variety of polymer particles upon varying particle size, composition and morphology. Secondly, a broad selection of functionalities can be installed to the particle interface due to both the availability of a large amount of functional molecular and macromolecular species and versatility of manufacturing protocols. Surface functionalization with appropriate reactive groups has now become a prerequisite in the handling of polymer particles for biotechnological applications. The immobilization of a hydrophilic and sometimes stimuli-responsive hairy layer as well as the possibility of coating particles with specific ligands (saccharide moieties, lipids, biomolecules) open very attractive potentialities. More elaborated surface-functionalized (nano)particles can take much advantage of novel controlled radical polymerization techniques as well as the immobilization of complex organic or inorganic structures allowing an improved specificity in relevant applications. [Copyright &y& Elsevier]

Poly(d,l-lactic acid) (PLA) particles, obtained by the emulsification–diffusion process, were surface modified by electrostatic interactions with cationic poly(ethylenimine) (PEI). The charge inversion was evidenced by zeta potential measurements and the adsorption isotherms of PEI were established. No flocculation was observed by Quasi-Elastic Light Scattering (QELS) or Scanning Electron Microscopy (SEM) so long as the PEI amount in the adsorption medium was close to the surface saturation. With water as an adsorption medium, low PEI loading levels were achieved but, when salt was added, higher amounts of polymer were immobilized at the surface of the PLA particles, as proved by the positive value of the zeta potentials (+20–30 mV). Highly cationized latex particles complexed plasmid DNA under a compacted conformation, as evidenced by the ethidium bromide displacement results, similar to the PEI free in solution. With particles obtained by PEI adsorption from water, low amounts of DNA were loaded on the surface and the level of compaction was low. [Copyright &y& Elsevier]

This paper aims at reviewing recent work dedicated in this lab to the elaboration and applications in the biomedical domain of hydrophilic stimuli-responsive latex particles based on the use of various polyalkyl(meth)acrylamides together with functional monomers bearing bioreactive groups. At first, a brief description is provided on the synthesis of such particles, differing in their surface and internal morphology, through radical-initiated polymerization processes in heterogeneous media. Then, it is shown that several colloidal properties of these particles drastically change, not only as a function of temperature, but also vs. pH and salinity. Knowledge of these characteristics is a prerequisite for optimal control of the immobilization of various biologically-active macromolecules, mostly by covalent binding. Finally, some applications of these particles are described, especially for improving sensitivity in gene diagnostics or for the separation and concentration of biomolecules. [ABSTRACT FROM AUTHOR]

A method for reconstructing the complex permittivity profile of lossy dielectric objects from measured scattered far-field data is presented. An iterative reconstruction algorithm based on a conjugate gradient method is derived from an integral representation of the electric field and applying a moment method solution. Results obtained from experimental data are shown for both known and unknown targets. Then, a new regularization procedure is developed to enhance the quality of the reconstruction. This method, based on a Markov random fields approach, models the object to be reconstructed by homogeneous areas separated by borderlike discontinuities. Finally, the enhancement is shown by the reconstruction of a polystyrene square cylinder. © 1997 John Wiley & Sons, Inc. Int J Imaging Syst Technol, 8, 337–342, 1997 [ABSTRACT FROM AUTHOR]

The authors describe the case of a 48-year-old man admitted to the critical care unit (CCU) who presented with septic shock and treated conventionally with volume loading and noradrenaline, and then again with clonidine infusion upon experiencing hypotension following a cholecystectomy. It is presumed that clonidine administered slowly lessens the release of endogenous NA. It is found that in hypertensive patients, clonidine decreases the dose of phenylephrine needed to increase systolic blood pressure.

A very accurate inverse scattering method for reconstructing the contours of perfectly conducting cylinders of arbitrary cross-section illuminated by electromagnetic waves under TM polarization with time-harmonic dependence is presented. No assumption is made on the shapes of the contours nor on their number. Inversion strategy consists in computing a special deformation velocity, defined on the contours of the objects, and allowing to decrease a cost function at each interation. Level set methods, used in as diverse fields as fluid dynamics, image processing and crystal growth, are used to perform the evolution of the contours. These methods allow to handle automatically topological changes by using a Eulerian point of view built on a level set representation of the contours. Hence, several objects can be retrieved from one single initial contour. Moreover, contours regularization is easily performed by adding a curvature term to the velocity. The inverse scattering method is based on a very accurate forward scattering algorithm characterized by the use of well-behaved pseudo-currents which are developed in Fourier series along the contours. The frequency hopping technique turns out to play a key role in the inversion process. The method is proved to be flexible, allowing to reconstruct accurately complex and multiple shape contours from one single initial guess. The deformation velocity is even able to retrieve very sharp corners and is quite robust with respect to high noise levels. [ABSTRACT FROM AUTHOR]

The preparation of well-defined (o/w) magnetic emulsions from an organic ferrofluid is reported. The ferrofluid synthesis is first described and a complete characterization is achieved by using numerous techniques. The ferrofluid is found to be composed of superparamagnetic maghemite nanoparticles, with a diameter below 10 nm, stabilized in octane by a surrounding oleic acid layer. This magnetic fluid is then emulsified in aqueous media in order to obtain stable ferrofluid droplets. The use of a couette mixer and a size sorting step under magnetic field allowed to produce magnetic emulsion with a narrow size distribution. Morphology and chemical composition of the magnetic emulsion are investigated. Magnetic properties of both ferrofluid and magnetic emulsion are also compared and discussed. In particular, it is showed that the superparamagnetic behavior is still observed after the emulsification process. [Copyright &y& Elsevier]

(Polymer-oligonucleotide) conjugates were obtained via direct ON synthesis from the poly(ethylene-alt-maleic anhydride: PEMA) grafted onto glass bead surfaces. The effect of the ON number per polymer chain on binding was evaluated through Tm experiments. Results were correlated with ELOSA (Enzyme Linked Oligosorbent Assay) tests run with conjugates in the capture step. [ABSTRACT FROM AUTHOR]

A single-layer reflector antenna combining eight and four correcting Fresnel zones is presented. The progressive phase shift is achieved by circular and annular patches. The choice of a quarter-wavelength thickness substrate provides naturally 0 and 180° correcting zones that simplify the reflector design. A prototype of reflector antenna working at 94 GHz has been designed, built and measured. Measurement results show 70% improvement of antenna aperture efficiency compared to the half-wave Fresnel zone plate reflector [1]. [ABSTRACT FROM AUTHOR]

Paternal apomixis was recently reported in the endangered Mediterranean cypress, Cupressus dupreziana. This species acts as a surrogate mother for the development of all-paternal embryos from pollen grains. C. dupreziana production of Cupressus sempervirens haploid or diploid seedlings from C. sempervirens pollen was also demonstrated. The haploid progeny was derived from the embryogenic development of haploid gametes, but the origin of the diploid progeny remained unknown. To determine the ontogenic origin of the diploid C. sempervirens progeny, we analyzed the heterozygozity of 63 diploid all-paternal C. sempervirens seedlings using highly variable co-dominant nuclear microsatellite markers. The bi-parental inheritance of the markers was checked in C. sempervirens controlled crosses. A high level of polymorphism was observed among the diploid all-paternal trees. All but three individuals exhibited single-band profiles as expected for homozygotes, which may originate from natural diploidization of a C. sempervirens haploid embryo or from the fusion of two male gametes produced by the same C. sempervirens microgametophyte. The three heterozygous seedlings must be derived from the fusion of male gametes produced by two different C. sempervirens microgametophytes. These findings offer a unique opportunity in conifers to produce homozygous lines, highly valuable for genetic analyses or breeding. [ABSTRACT FROM AUTHOR]

A wireframe implementation of the method of moments in time domain is presented, with particular attention to wire junctions. Peculiar base and weight functions will be defined at the junctions to implicitly account for current continuity and correctly take into account inter-wire coupling. This will allow implementation of both an explicit and an implicit solution. Results obtained are validated with existing frequency domain solutions. [ABSTRACT FROM AUTHOR]

AlthoughCupressus sempervirenshas been spread over southern Europe since antiquity, cypress pollen allergy has not been reported until 1945 (). In France, the very first case reports were published in 1962 (). Since then, the prevalence of cypress pollinosis seems to demonstrate an upward trend, concomitantly with the increased use of cypress trees as ornamental plants, as wind breaks and as hedges. Hyposensitization, using improved pollen extracts, is increasingly prescribed. Besides, prevention measures begin to be implemented. Such measures include avoidance of planting new cypress trees, especially near human populations’ centres, trimming of cypress hedges before the pollination season and agronomical research for hypoallergenic trees. Altogether, such new developments in cypress allergy deserve an update review. [ABSTRACT FROM AUTHOR]

The adsorption of a recombinant cutinase from Fusarium solani pisi onto the surface of 100 nm diameter poly(methyl methacrylate) (PMMA) latex particles was evaluated. Adsorption of cutinase is a fast process since more than 70% of protein molecules are adsorbed onto PMMA at time zero of experiment, irrespective of the tested conditions. A Langmuir-type model fitted both protein and enzyme activity isotherms at 25 °C. Γmax increased from 1.1 to 1.7 mg m−2 and Umax increased from 365 to 982 U m−2 as the pH was raised from 4.5 to 9.2, respectively. A decrease (up to 50%) in specific activity retention was observed at acidic pH values (pH 4.5 and 5.2) while almost no inactivation (ηact≅87–94%) was detected upon adsorption at pH 7.0 and 9.2. Concomitantly, far-UV circular dichroism (CD) spectra evidenced a reduction in the α-helical content of adsorbed protein at acidic pH values while at neutral and alkaline pH the secondary structure of adsorbed cutinase was similar to that of native protein. Fluorescence anisotropy decays showed the release of some constraints to the local motion of the Trp69 upon protein adsorption at pH 8.0, probably due to the disruption of the tryptophan–alanine hydrogen bond when the tryptophan interacts with the PMMA surface. Structural data associated with activity measurements at pH 7.0 and 9.2 showed that cutinase adsorbs onto PMMA particles in an end-on orientation with active site exposed to solvent and full integrity of cutinase secondary structure. Hydrophobic interactions are likely the major contribution to the adsorption mechanism at neutral and alkaline pH values, and a higher amount of protein is adsorbed to PMMA particles with increasing temperature at pH 9.2. The maximum adsorption increased from 88 to 140 mg cutinase per g PMMA with temperature raising from 25 to 50 °C, at pH 9.2. [Copyright &y& Elsevier]

The activation of various synthetic oligodeoxyribonucleotides (ODNs), bearing a hexamethylamine arm at their 5′-end, with the 2,4-phenylenediisothiocyanate (PDC) was studied. The activation reaction had to be performed within 40 min, because of competitive hydrolysis of the isothiocyanate functions. ODN modifications were then characterized by different analytical methods i.e. gel capillary electrophoresis, Matrix-Assisted Laser Desorption-Ionization-Time of Flight (MALDI-TOF) mass spectrometry. Moreover, activation of the amine groups of the nucleic bases was evidenced through the chemical analysis of the enzymatic-digested conjugate (PDC-ODN) by reverse phase HPLC. Preliminary results on the covalent grafting of activated ODN molecules onto the aminated latex particles showed that the amount of grafted ODNs was directly related to the number of potential grafting sites on the nucleic acid probe (primary amine group of hexamethyl arm and amine functions of the nucleic bases). [ABSTRACT FROM AUTHOR]

A new structure of a circularly polarized dielectric antenna fed by a single coaxial probe is proposed. The configuration includes four identical holes enclosed in a cylindrical resonator. The structure offers a bandwidth of 5% and a good purity of polarization. The effects of altering geometrical parameters on antenna behavior are presented. © 2005 Wiley Periodicals, Inc. Microwave Opt Technol Lett 45: 367–369, 2005; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/mop.20825 [ABSTRACT FROM AUTHOR]

Characterizes nuclear microsatellites in Pinus halepensis and their inheritance in Pinus halepensis and Pinus brutia. Genetic diversity observations; Levels of heterozygosities; Genetic polymorphisms identified.