Validation of a new 60 MeV proton beam-line for radiation hardness testing

A 60 MeV proton beam-line has been developed in Nice, France, in collaboration with the Centre National d'Etudes Spatiales (CNES). Experimental results are presented here to validate the beam-line for radiation hardness testing.Comment: RADECS conference 202

High-Yielding Diastereoselective syn -Dihydroxylation of Protected HBO: An Access to D-(+)-Ribono-1,4-lactone and 5- O -Protected Analogues

International audienceA diastereoselective chemoenzymatic synthetic pathway to D‐(+)‐ribono‐1,4‐lactone, a versatile chiral sugar derivative widely used for the synthesis of various natural products, has been designed from cellulose‐based levoglucosenone (LGO). This route involves a sustainable Baeyer‐Villiger oxidation of LGO to produce enantiopure (S)‐γ‐hydroxymethyl‐α,β‐butenolide (HBO) that is further functionalized with various protecting groups to provide 5‐O‐protected γ‐hydroxymethyl‐α,β‐butenolides. The latter then undergo a diastereoselective and high‐yielding syn‐dihydroxylation of the α,β‐unsaturated lactone moiety followed by a deprotection step to give D‐(+)‐ribono‐1,4‐lactone. Through this 4‐step synthetic route from LGO, D‐(+)‐ribono‐1,4‐lactone is obtained with d.r. varying from 82:18 to 97:3 and in overall yields between 32 and 41 % depending on the protecting group used. Moreover, valuable synthetic intermediates 5‐O‐tert‐butyldimethylsilyl‐, 5‐O‐tert‐butyldiphenylsilyl‐ as well as 5‐O‐benzyl‐ribono‐1,4‐lactones are obtained in 3 steps from LGO in 58, 61 and 40 %, respectively

Oxide phosphors for light upconversion; Yb3+ and Tm3+ co-doped Y2BaZnO5

Copyright 2011 American Institute of Physics. This article may be downloaded for personal use only. Any other use requires prior permission of the author and the American Institute of Physics. This article appeared in Journal of Applied Physics 109, 063104 (2011) and may be found at

Is There a Role for Hematopoietic Growth Factors During Sepsis?

Sepsis is a complex syndrome characterized by simultaneous activation of pro- and anti-inflammatory processes. After an inflammatory phase, patients present signs of immunosuppression and possibly persistent inflammation. Hematopoietic growth factors (HGFs) are glycoproteins that cause immune cells to mature and/or proliferate. HGFs also have a profound effect on cell functions and behavior. HGFs play crucial role in sepsis pathophysiology and were tested in several clinical trials without success to date. This review summarizes the role played by HGFs during sepsis and their potential therapeutic role in the Management of sepsis-related immune disturbances

Sensory contribution to vocal emotion deficit in patients with cerebellar stroke

In recent years, there has been increasing evidence of cerebellar involvement in emotion processing. Difficulties in the recognition of emotion from voices (i.e., emotional prosody) have been observed following cerebellar stroke. However, the interplay between sensory and higher-order cognitive dysfunction in these deficits, as well as possible hemispheric specialization for emotional prosody processing, has yet to be elucidated. We investigated the emotional prosody recognition performances of patients with right versus left cerebellar lesions, as well as of matched controls, entering the acoustic features of the stimuli in our statistical model. We also explored the cerebellar lesion-behavior relationship, using voxel-based lesion-symptom mapping. Results revealed impairment of vocal emotion recognition in both patient subgroups, particularly for neutral or negative prosody, with a higher number of misattributions in patients with right-hemispheric stroke. Voxel-based lesion-symptom mapping showed that some emotional misattributions correlated with lesions in the right Lobules VIIb and VIII and right Crus I and II. Furthermore, a significant proportion of the variance in this misattribution was explained by acoustic features such as pitch, loudness, and spectral aspects. These results point to bilateral posterior cerebellar involvement in both the sensory and cognitive processing of emotions

Identification of functionally-related adaptations in the trabecular network of the proximal femur and tibia of a bipedally-trained Japanese macaque

The axial and appendicular skeleton of Japanese macaques (Macacca fuscata) trained to adopt ipedal posture and locomotion display a number of functionally-related external and internal macro- and micro-morphological changes, including site-specific cortical and trabecular bone adaptations. In this study we use high-resolution microtomography scanning to analyse the 3D distribution of trabecular architecture of the proximal femur and proximal tibia of Sansuke, a male individual trained in bipedal performances for eight years, as well as five wild individuals. The distribution and architecture of trabecular bone in the femoral head of Sansuke is distinct from that found in wild M. fuscata individuals, with a unique bone reinforcement around the region of the fovea capitis. Conversely, wild individuals exhibit two pillar-like, high-density structures (converging in an inverted cone) that reach distinct regions of the posterior and anterior surfaces of the femoral head. For Sansuke’s proximal tibia, contrary to previous observations from the cortico-trabecular complex distribution at the plateau, our results do not show a more asymmetric distribution between medial and lateral condyles with a medial reinforcement. Additionally, relative bone volume in this region is not significantly higher in Sansuke. However, we observed a slightly more medially placed bone reinforcement in the lateral condyle compared to the wild individuals as well as a slightly higher trabecular bone anisotropy in the medial than in the lateral condyle not observed in the wild individuals. These analyses provide new evidence about the nature and extent of functionally-related adaptive arrangements of the trabecular network at the coxofemoral and the knee joints in individuals recurrently experiencing atypical load

Polyhexamethylene biguanide promotes adaptive cross-resistance to gentamicin in Escherichia coli biofilms

Antimicrobial resistance is a critical public health issue that requires a thorough understanding of the factors that influence the selection and spread of antibiotic-resistant bacteria. Biocides, which are widely used in cleaning and disinfection procedures in a variety of settings, may contribute to this resistance by inducing similar defense mechanisms in bacteria against both biocides and antibiotics. However, the strategies used by bacteria to adapt and develop cross-resistance remain poorly understood, particularly within biofilms –a widespread bacterial habitat that significantly influences bacterial tolerance and adaptive strategies. Using a combination of adaptive laboratory evolution experiments, genomic and RT-qPCR analyses, and biofilm structural characterization using confocal microscopy, we investigated in this study how Escherichia coli biofilms adapted after 28 days of exposure to three biocidal active substances and the effects on cross-resistance to antibiotics. Interestingly, polyhexamethylene biguanide (PHMB) exposure led to an increase of gentamicin resistance (GenR) phenotypes in biofilms formed by most of the seven E. coli strains tested. Nevertheless, most variants that emerged under biocidal conditions did not retain the GenR phenotype after removal of antimicrobial stress, suggesting a transient adaptation (adaptive resistance). The whole genome sequencing of variants with stable GenR phenotypes revealed recurrent mutations in genes associated with cellular respiration, including cytochrome oxidase (cydA, cyoC) and ATP synthase (atpG). RT-qPCR analysis revealed an induction of gene expression associated with biofilm matrix production (especially curli synthesis), stress responses, active and passive transport and cell respiration during PHMB exposure, providing insight into potential physiological responses associated with adaptive crossresistance. In addition, confocal laser scanning microscopy (CLSM) observations demonstrated a global effect of PHMB on biofilm architectures and compositions formed by most E. coli strains, with the appearance of dense cellular clusters after a 24h-exposure. In conclusion, our results showed that the PHMB exposure stimulated the emergence of an adaptive cross-resistance to gentamicin in biofilms, likely induced through the activation of physiological responses and biofilm structural modulations altering gradients and microenvironmental conditions in the biological edifice

Intracardiac electrophysiology to characterize susceptibility to ventricular arrhythmias in murine models

Introduction: Sudden cardiac death (SCD) and ventricular fibrillation are rare but severe complications of many cardiovascular diseases and represent a major health issue worldwide. Although the primary causes are often acute or chronic coronary diseases, genetic conditions, such as inherited channelopathies or non-ischemic cardiomyopathies are leading causes of SCD among the young. However, relevant experimental models to study the underlying mechanisms of arrhythmias and develop new therapies are still needed. The number of genetically engineered mouse models with cardiac phenotype is growing, making electrophysiological studies in mice essential tools to study arrhythmogenicity and arrhythmia mechanisms and to test novel treatments. Recently, intracardiac catheterization via the jugular vein was described to induce and record ventricular arrhythmias in living anesthetized mice. Several strategies have been reported, developed in healthy wild-type animals and based on aggressive right ventricular stimulation.Methods: Here, we report a protocol based on programmed electrical stimulation (PES) performed in clinical practice in patients with cardiac rhythm disorders, adapted to two transgenic mice models of arrhythmia - Brugada syndrome and cardiolaminopathy.Results: We show that this progressive protocol, based on a limited number of right ventricular extrastimuli, enables to reveal different rhythmic phenotypes between control and diseased mice. In this study, we provide detailed information on PES in mice, including catheter positioning, stimulation protocols, intracardiac and surface ECG interpretation and we reveal a higher susceptibility of two mouse lines to experience triggered ventricular arrhythmias, when compared to control mice.Discussion: Overall, this technique allows to characterize arrhythmias and provides results in phenotyping 2 arrhythmogenic-disease murine models