First set of gated x-ray imaging diagnostics for the Laser Megajoule facility.

The Laser Megajoule (LMJ) facility located at CEA/CESTA started to operate in the early 2014 with two quadruplets (20 kJ at 351 nm) focused on target for the first experimental campaign. We present here the first set of gated x-ray imaging (GXI) diagnostics implemented on LMJ since mid-2014. This set consists of two imaging diagnostics with spatial, temporal, and broadband spectral resolution. These diagnostics will give basic measurements, during the entire life of the facility, such as position, structure, and balance of beams, but they will also be used to characterize gas filled target implosion symmetry and timing, to study x-ray radiography and hydrodynamic instabilities. The design requires a vulnerability approach, because components will operate in a harsh environment induced by neutron fluxes, gamma rays, debris, and shrapnel. Grazing incidence x-ray microscopes are fielded as far as possible away from the target to minimize potential damage and signal noise due to these sources. These imaging diagnostics incorporate microscopes with large source-to-optic distance and large size gated microchannel plate detectors. Microscopes include optics with grazing incidence mirrors, pinholes, and refractive lenses. Spatial, temporal, and spectral performances have been measured on x-ray tubes and UV lasers at CEA-DIF and at Physikalisch-Technische Bundesanstalt BESSY II synchrotron prior to be set on LMJ. GXI-1 and GXI-2 designs, metrology, and first experiments on LMJ are presented here.

Gut ecosystem: how microbes help us.

The human gut houses one of the most complex and abundant ecosystems composed of up to 1013-1014 microorganisms. Although the anthropocentric concept of life has concealed the function of microorganisms inside us, the important role of gut bacterial community in human health is well recognised today. Moreover, different microorganims, which are commonly present in a large diversity of food products, transit through our gut every day adding in some cases a beneficial effect to our health (probiotics). This crosstalk is concentrated mainly in the intestinal epithelium, where microbes provide the host with essential nutrients and modulation of the immune system. Furthermore, microorganisms also display antimicrobial activities maintaining a gut ecosystem stable. This review summarises some of the recent findings on the interaction of both commensal and probiotic bacteria with each other and with the host. The aim is to highlight the cooperative status found in healthy individuals as well as the importance of this crosstalk in the maintenance of human homeostasis.

Diffusion tensor imaging and tractography in Brown-Sequard syndrome.

STUDY DESIGN: Case report. OBJECTIVE: To demonstrate the utility of diffusion tensor imaging and tractography in two patients with Brown-Sequard syndrome after penetrating cervical cord injury. SETTING: Milwaukee, WI, USA. METHODS: Two patients, who presented with features of Brown-Sequard syndrome after sustaining stab wounds to the neck, underwent DTI and tractography of the cervical cord within a week of the injury. DTI metrics were measured within the left and right hemicord around the level of injury. Diffusion tensor tractography was performed to visualize the site of injury and injured fiber tracts. RESULTS: Axial fractional anisotropy maps at the site of injury showed unilateral damage to the cord structure, and FA was significantly reduced within the injured hemicord in both patients. Tractography allowed for visualization of the injured fiber tracts around the level of injury. Both DTI metrics and tractography showed an asymmetry that corresponded to the neurological deficits exhibited by the patients. CONCLUSION: This report illustrates the utility of DTI and DTT in delineating regions of cord injury in two patients with traumatic Brown-Sequard syndrome. Our results indicate that DTI provides clinically relevant information that supplements conventional MR imaging for patients with acute SCI.

Assessment of temporal state-dependent interactions between auditory fMRI responses to desired and undesired acoustic sources.

A confounding factor in auditory functional magnetic resonance imaging (fMRI) experiments is the presence of the acoustic noise inherently associated with the echo planar imaging acquisition technique. Previous studies have demonstrated that this noise can induce unwanted neuronal responses that can mask stimulus-induced responses. Similarly, activation accumulated over multiple stimuli has been demonstrated to elevate the baseline, thus reducing the dynamic range available for subsequent responses. To best evaluate responses to auditory stimuli, it is necessary to account for the presence of all recent acoustic stimulation, beginning with an understanding of the attenuating effects brought about by interaction between and among induced unwanted neuronal responses, and responses to desired auditory stimuli. This study focuses on the characterization of the duration of this temporal memory and qualitative assessment of the associated response attenuation. Two experimental parameters--inter-stimulus interval (ISI) and repetition time (TR)--were varied during an fMRI experiment in which participants were asked to passively attend to an auditory stimulus. Results present evidence of a state-dependent interaction between induced responses. As expected, attenuating effects of these interactions become less significant as TR and ISI increase and in contrast to previous work, persist up to 18s after a stimulus presentation.

Diffusion tensor MR imaging in chronic spinal cord injury.

BACKGROUND AND PURPOSE: Diffusion tensor MR imaging is emerging as an important tool for displaying anatomic changes in the brain after injury or disease but has been less widely applied to disorders of the spinal cord. The aim of this study was to characterize the diffusion properties of the entire human spinal cord in vivo during the chronic stages of spinal cord injury (SCI). These data provide insight into the structural changes that occur as a result of long-term recovery from spinal trauma. MATERIALS AND METHODS: Thirteen neurologically intact subjects and 10 subjects with chronic SCI (>4 years postinjury) were enrolled in this study. A single-shot twice-refocused spin-echo diffusion-weighted echo-planar imaging pulse sequence was used to obtain axial images throughout the entire spinal cord (C1-L1) in <60 minutes. RESULTS: Despite heterogeneity in SCI lesion severity and location, diffusion characteristics of the chronic lesion were significantly elevated compared with those of uninjured controls. Fractional anisotropy was significantly lower at the chronic lesion and appeared dependent on the completeness of the injury. Conversely, mean diffusivity measurements in the upper cervical spinal cord in subjects with SCI were significantly lower than those in controls. These trends suggest that the entire neuraxis may be affected by long-term recovery from spinal trauma. CONCLUSION: These results suggest that diffusion tensor imaging may be useful in the assessment of SCI recovery.

Diffusion tensor MR imaging of the neurologically intact human spinal cord.

BACKGROUND AND PURPOSE: The aim of this study was to characterize the diffusion properties of the entire human spinal cord in vivo. These data are essential for comparisons to pathologic conditions as well as for comparisons of different pulse sequence design parameters aimed to reduce scan time and more accurately determine diffusion coefficients. MATERIALS AND METHODS: A total of 13 neurologically intact subjects were enrolled in this study. A single-shot, twice-refocused, spin-echo, diffusion-weighted, echo-planar imaging (EPI) pulse sequence was used to obtain axial images throughout the entire spinal cord (C1-L1) in 45 minutes. RESULTS: Diffusion images indicated slight geometric distortions; however, gray and white matter contrast was observed. All measurements varied across the length of the cord. Whole cord diffusion coefficients averaged 0.5-1.3 x 10(-3) mm(2)/s depending on orientation, mean diffusivity (MD) averaged 0.83 +/- 0.06 x 10(-3) mm(2)/s, fractional anisotropy (FA) averaged 0.49 +/- 0.05, and volume ratio (VR) averaged 0.73 +/- 0.05. CONCLUSION: This study provided normative diffusion values for the entire spinal cord for use in comparisons with pathologic conditions as well as improvements in pulse sequence design.

Heterologous prime-boost strategy to immunize very young infants against measles: pre-clinical studies in rhesus macaques.

Infants in developing countries are at high risk of developing severe clinical measles if they become infected during the "window of vulnerability" (age 4-9 months), when declining maternal antibodies do not protect against wild virus, yet impede successful immunization by attenuated measles vaccine. We developed two Sindbis replicon-based DNA vaccines expressing measles virus hemagglutinin and fusion protein with the goal of priming young infants to respond safely and effectively to subsequent boosting with attenuated measles vaccine. Intradermal prime with DNA vaccines by needle-free injection followed by aerosol or parenteral boost with licensed measles vaccine was well tolerated by juvenile and young infant rhesus macaques, and protected against clinical measles and viremia on wild-type virus challenge. A proteosome-measles vaccine administered alone (three doses) or as a boost following DNA vaccine priming was also safe and protective. These promising results pave the way for clinical trials to assess this prime-boost strategy.

Presurgical and intraoperative mapping of the motor system in congenital truncation of the precentral gyrus.

A 43-year-old man presented with a grade II astrocytoma in the left postcentral gyrus and superior parietal lobule. Preoperative functional MR imaging and diffusion tensor imaging mapped distal upper-extremity primary motor cortex and white matter, respectively, adjacent to the tumor, within a congenitally truncated precentral gyrus. Because of the congenital anomaly, this region of primary motor cortex was inaccessible to direct visualization or intraoperative electrocortical stimulation. The integration of preoperative and intraoperative mapping data facilitated resection of the tumor while avoiding a postoperative motor deficit.

Characterizing the attenuation and/or saturation effect of the acoustic scanner noise in auditory event-related functional magnetic resonance imaging.

The analysis of event-related functional magnetic resonance imaging when presenting auditory stimuli and/or investigating auditory cortex and related areas is hindered by inherent acoustic scanner noise (ASN), which can alter the properties of the acquired time-series data. Therefore, it is necessary to account for ASN in the analysis, and one step towards this goal is to characterize the attenuation and/or saturation effect of the hemodynamic response due to ASN. Towards this end, this study examined how the effect of ASN is dependent on repetition time (TR) and the inter-stimulus interval (ISI), two experimental parameters that affect the acoustic signal-to-noise ratio of the experimental paradigm. Results indicate that a decrease in TR (e.g., 6 s to 1.5 s) results in an increase in saturation and an attenuation of the estimated hemodynamic response peak with respect to the baseline signal level. There was no statistical difference in peak response between the two ISI values used, 12 s and 18 s.

Characterizing the amplitude and spatial extent of the cortical response in auditory cortex to acoustic scanner noise generated during echo-planar image acquisition in functional magnetic resonance imaging.

Acoustic scanner noise produced during event-related functional magnetic resonance imaging (ER-fMRI) studies can hinder auditory fMRI research analysis by altering the properties of the acquired time-series data. Given the desire to obtain the most accurate results possible using ER-fMRI experiments, this study seeks to characterize the amplitude and spatial extent of the auditory fMRI cortical response, in isolation, generated by the acoustic scanner noise associated with echo-planar acquisition. Results from this study indicate that the pure cortical response is non-trivial, is comparable to a standard hemodynamic response function, and should be accounted for in analysis using ER-fMRI models.

Formation of focal adhesion-stress fibre complexes coordinated by adhesive and non-adhesive surface domains.

Cell motility consists of repeating cycles of protrusion of a leading edge in the direction of migration, attachment of the advancing membrane to the matrix, and pulling of the trailing edge forward. In this dynamic process there is a major role for the cytoskeleton, which drives the protrusive events via polymerisation of actin in the lamellipodium, followed by actomyosin contractility. To study the transition of the actin cytoskeleton from a 'protrusive' to 'retractive' form, we have monitored the formation of focal adhesions and stress fibres during cell migration on a micro-patterned surface. This surface consisted of parallel arrays of 2 microm-wide, fibronectin-coated gold stripes, separated by non-adhesive (poly(ethylene glycol)-coated) glass areas with variable width, ranging from 4-12 microm. Monitoring the spreading of motile cells indicated that cell spreading was equally effective along and across the adhesive stripes, as long as the non-adhesive spaces between them did not exceed 6 microm. When the width of the PEG region was 8 microm or more, cells became highly polarised upon spreading, and failed to reach the neighboring adhesive stripes. It was also noted that as soon as the protruding lamella successfully crossed the PEG-coated area and reached an adhesive region, the organisation of actin in that area was transformed from a diffuse meshwork into a bundle, oriented perpendicularly to the stripes and anchored at its ends in focal adhesions. This transition depends on actomyosin-based contractility and is apparently triggered by the adhesion to the rigid fibronectin surface.

Attenuated salmonella and Shigella as carriers for DNA vaccines.

The discovery that genes can be functionally transferred from bacteria to mammalian cells has suggested the possible use of bacterial vectors as gene delivery vehicles for vaccines. Attenuated invasive human intestinal bacteria, such as Salmonella and Shigella, have been used as plasmid DNA vaccine carriers and their potency has been evaluated in several animal models. This delivery system allows the administration of DNA vaccines together with associated bacterial immunostimulators directly to professional antigen presenting cells via human mucosal surfaces. Various strategies have been taken to improve the use of this delivery system to achieve robust immune responses at both mucosal and systemic sites of the immunized animals.

Multipotent hematopoietic cell lines derived from C/EBPalpha(-/-) knockout mice display granulocyte macrophage-colony-stimulating factor, granulocyte- colony-stimulating factor, and retinoic acid-induced granulocytic differentiation.

The transcription factor C/EBPalpha is an important mediator of granulocyte differentiation and regulates the expression of multiple granulocyte-specific genes including the granulocyte-colony-stimulating factor (G-CSF) receptor, neutrophil elastase, and myeloperoxidase. Indeed C/EBPalpha knockout mice display a profound block in granulocyte differentiation. To study this block in granulocytic differentiation in more detail, retroviral vector-mediated transduction of a dominant-negative retinoic acid receptor was used to establish hematopoietic growth factor-dependent, lympho-myeloid progenitor cell lines from the fetal livers of both the C/EBPalpha knockout animals (C/EBPalpha(-/-)) and their heterozygous littermates (C/EBPalpha(+/-)). Surprisingly, the C/EBPalpha(-/-) cell lines displayed significant spontaneous granulocytic differentiation, and this differentiation was markedly enhanced when the cells were stimulated with granulocyte macrophage (GM)-CSF. This GM-CSF-mediated differentiation was associated with the up-regulation of G-CSF receptor mRNA, and the combination of GM-CSF and G-CSF generated more than 95% mature neutrophils in the C/EBPalpha(-/-) cultures. The addition of all-trans retinoic acid also enhanced this granulocytic differentiation of the cultured C/EBPalpha(-/-) cells, indicating that the activated retinoic acid receptors can enhance granulocytic differentiation through a molecular pathway that is independent of C/EBPalpha. These studies clearly indicate that terminal granulocytic differentiation associated with the up-regulation of C/EBPalpha-responsive genes can occur in the absence of C/EBPalpha, and they indicate the existence of multiple independent molecular pathways potentially used by primitive hematopoietic precursors that can lead to the development of mature granulocytes.

Induction of potent immune responses by cationic microparticles with adsorbed human immunodeficiency virus DNA vaccines.

The effectiveness of cationic microparticles with adsorbed DNA at inducing immune responses was investigated in mice, guinea pigs, and rhesus macaques. Plasmid DNA vaccines encoding human immunodeficiency virus (HIV) Gag and Env adsorbed onto the surface of cationic poly(lactide-coglycolide) (PLG) microparticles were shown to be substantially more potent than corresponding naked DNA vaccines. In mice immunized with HIV gag DNA, adsorption onto PLG increased CD8(+) T-cell and antibody responses by approximately 100- and approximately 1,000-fold, respectively. In guinea pigs immunized with HIV env DNA adsorbed onto PLG, antibody responses showed a more rapid onset and achieved markedly higher enzyme-linked immunosorbent assay and neutralizing titers than in animals immunized with naked DNA. Further enhancement of antibody responses was observed in animals vaccinated with PLG/DNA microparticles formulated with aluminum phosphate. The magnitude of anti-Env antibody responses induced by PLG/DNA particles was equivalent to that induced by recombinant gp120 protein formulated with a strong adjuvant, MF-59. In guinea pigs immunized with a combination vaccine containing HIV env and HIV gag DNA plasmids on PLG microparticles, substantially superior antibody responses were induced against both components, as measured by onset, duration, and titer. Furthermore, PLG formulation overcame an apparent hyporesponsiveness of the env DNA component in the combination vaccine. Finally, preliminary data in rhesus macaques demonstrated a substantial enhancement of immune responses afforded by PLG/DNA. Therefore, formulation of DNA vaccines by adsorption onto PLG microparticles is a powerful means of increasing vaccine potency.