Stabilized Radiation Pressure Acceleration and Neutron Generation in Ultrathin Deuterated Foils.

Premature relativistic transparency of ultrathin, laser-irradiated targets is recognized as an obstacle to achieving a stable radiation pressure acceleration in the "light sail" (LS) mode. Experimental data, corroborated by 2D PIC simulations, show that a few-nm thick overcoat surface layer of high Z material significantly improves ion bunching at high energies during the acceleration. This is diagnosed by simultaneous ion and neutron spectroscopy following irradiation of deuterated plastic targets. In particular, copious and directional neutron production (significantly larger than for other in-target schemes) arises, under optimal parameters, as a signature of plasma layer integrity during the acceleration.

Inducing signal-verified lucid dreams in 40% of untrained novice lucid dreamers within two nights in a sleep laboratory setting.

Dreams in which the dreamer is aware of the dream state (lucid dreams, LD) are difficult to induce in naïve subjects in-laboratory. Recently, Stumbrys and Erlacher (2014) used a combination of existing induction techniques together with a self-developed experiment protocol and achieved comparatively high LD induction rates. In this study, we simplified their methodology slightly and repeated their experiment with twenty naïve subjects who spent one or two nights in our sleep laboratory. After about six hours of sleep, they were woken up during REM sleep and engaged in a series of cognitive tasks before going back to bed. Ten subjects reported a LD during the following period of sleep in one of the nights. Eight of these subjects gave a predefined eye signal, which was clearly visible in the electrooculogram during REM sleep. In summary, we replicated Stumbrys and Erlacher's results using a simplified version of their induction protocol.

Maximum Proton Energy above 85 MeV from the Relativistic Interaction of Laser Pulses with Micrometer Thick CH_{2} Targets.

We present a study of laser-driven ion acceleration with micrometer and submicrometer thick plastic targets. Using laser pulses with high temporal contrast and an intensity of the order of 10^{20} W/cm^{2} we observe proton beams with cutoff energies in excess of 85 MeV and particle numbers of 10^{9} in an energy bin of 1 MeV around this maximum. We show that applying the target normal sheath acceleration mechanism with submicrometer thick targets is a very robust way to achieve such high ion energies and particle fluxes. Our results are backed with 2D particle in cell simulations furthermore predicting cutoff energies above 200 MeV for acceleration based on relativistic transparency. This predicted regime can be probed after a few technically feasible adjustments of the laser and target parameters.

Spatially invariant coding of numerical information in functionally defined subregions of human parietal cortex.

Macaque electrophysiology has revealed neurons responsive to number in lateral (LIP) and ventral (VIP) intraparietal areas. Recently, fMRI pattern recognition revealed information discriminative of individual numbers in human parietal cortex but without precisely localizing the relevant sites or testing for subregions with different response profiles. Here, we defined the human functional equivalents of LIP (feLIP) and VIP (feVIP) using neurophysiologically motivated localizers. We applied multivariate pattern recognition to investigate whether both regions represent numerical information and whether number codes are position specific or invariant. In a delayed number comparison paradigm with laterally presented numerosities, parietal cortex discriminated between numerosities better than early visual cortex, and discrimination generalized across hemifields in parietal, but not early visual cortex. Activation patterns in the 2 parietal regions of interest did not differ in the coding of position-specific or position-independent number information, but in the expression of a numerical distance effect which was more pronounced in feLIP. Thus, the representation of number in parietal cortex is at least partially position invariant. Both feLIP and feVIP contain information about individual numerosities in humans, but feLIP hosts a coarser representation of numerosity than feVIP, compatible with either broader tuning or a summation code.

Transfer of the chemokine receptor CCR5 between cells by membrane-derived microparticles: a mechanism for cellular human immunodeficiency virus 1 infection.

The release of microparticles from eukaryotic cells is a well-recognized phenomenon. We demonstrate here that the chemokine receptor CCR5, the principal co-receptor for macrophage-tropic human immunodeficiency virus (HIV)-1, can be released through microparticles from the surface of CCR5+ Chinese hamster ovary cells and peripheral blood mononuclear cells. Microparticles containing CCR5 can transfer the receptor to CCR5- cells and render them CCR5+. The CCR5 transfer to CCR5-deficient peripheral blood mononuclear cells homozygous for a 32-base-pair deletion in the CCR5 gene enabled infection of these cells with macrophage-tropic HIV-1. In monocytes, the transfer of CCR5 could be inhibited by cytochalasin D, and transferred CCR5 could be downmodulated by chemokines. A transfer of CCR5 from peripheral blood mononuclear cells to endothelial cells during transendothelial migration could be demonstrated. Thus, the transfer of CCR5 may lead to infection of tissues without endogenous CCR5 expression. Moreover, the intercellular transfer of membrane proteins by microparticles might have broader consequences for intercellular communication beyond the effects seen for HIV-1.

Time-resolved study of holeboring in realistic experimental conditions.

The evolution of dense plasmas prior to the arrival of the peak of the laser irradiation is critical to understanding relativistic laser plasma interactions. The spectral properties of a reflected laser pulse after the interaction with a plasma can be used to gain insights about the interaction itself, whereas the effect of holeboring has a predominant role. Here we developed an analytical model, describing the non-relativistic temporal evolution of the holeboring velocity in the presence of an arbitrary overdense plasma density and laser intensity profile. We verify this using two-dimensional particle-in-cell simulations, showing a major influence on the holeboring dynamic depending on the density profile. The influence on the reflected laser pulse has been verified during an experiment at the PHELIX laser. We show that this enables the possibility to determine the sub-micrometer scale length of the preplasma by measuring the maximum holeboring velocity and acceleration during the laser-plasma interaction.

A group model for stable multi-subject ICA on fMRI datasets.

Spatial Independent Component Analysis (ICA) is an increasingly used data-driven method to analyze functional Magnetic Resonance Imaging (fMRI) data. To date, it has been used to extract sets of mutually correlated brain regions without prior information on the time course of these regions. Some of these sets of regions, interpreted as functional networks, have recently been used to provide markers of brain diseases and open the road to paradigm-free population comparisons. Such group studies raise the question of modeling subject variability within ICA: how can the patterns representative of a group be modeled and estimated via ICA for reliable inter-group comparisons? In this paper, we propose a hierarchical model for patterns in multi-subject fMRI datasets, akin to mixed-effect group models used in linear-model-based analysis. We introduce an estimation procedure, CanICA (Canonical ICA), based on i) probabilistic dimension reduction of the individual data, ii) canonical correlation analysis to identify a data subspace common to the group iii) ICA-based pattern extraction. In addition, we introduce a procedure based on cross-validation to quantify the stability of ICA patterns at the level of the group. We compare our method with state-of-the-art multi-subject fMRI ICA methods and show that the features extracted using our procedure are more reproducible at the group level on two datasets of 12 healthy controls: a resting-state and a functional localizer study.

Blockade of "NMDA" receptors disrupts experience-dependent plasticity of kitten striate cortex.

Intracortical infusion of the "N-methyl-D-aspartate" (NMDA) receptor blocker D,L-2-amino-5-phosphonovaleric acid (APV) renders kitten striate cortex resistant to the effects of monocular deprivation. In addition, 1 week of continuous APV treatment (50 nanomoles per hour) produces a striking loss of orientation selectivity in area 17. These data support the hypothesis that crucial variables for the expression of activity-dependent synaptic modifications are a critical level of postsynaptic activation and calcium entry through ion channels linked to NMDA receptors.

Acetyl coenzyme A carboxylase: filamentous nature of the animal enzymes.

Acetyl coenzyme A carboxylases purified from several animal tissues exist as enzymatically active polymeric filaments of high molecular weight and have simillar electron microscopic, hydrodynamic, and catalytic properties. These filaments reversibly dissociate into inactive protomers of uniform size. Their re-assembly into catalytically active filaments is promoted by the presence of an allosteric activator.

Accurate and efficient 3' processing of U2 small nuclear RNA precursor in a fractionated cytoplasmic extract.

The small nuclear RNAs U1, U2, U4, and U5 are cofactors in mRNA splicing and, like the pre-mRNAs with which they interact, are transcribed by RNA polymerase II. Also like mRNAs, mature U1 and U2 RNAs are generated by 3' processing of their primary transcripts. In this study we have investigated the in vitro processing of an SP6-transcribed human U2 RNA precursor, the 3' end of which matches that of authentic human U2 RNA precursor molecules. Although the SP6-U2 RNA precursor was efficiently processed in an ammonium sulfate-fractionated HeLa cytoplasmic S100 extract, the product RNA was unstable. Further purification of the processing activity on glycerol gradients resolved a 7S activity that nonspecifically cleaved all RNAs tested and a 15S activity that efficiently processed the 3' end of pre-U2 RNA. The 15S activity did not process the 3' end of a tRNA precursor molecule. As demonstrated by RNase protection, the processed 3' end of the SP6-U2 RNA maps to the same nucleotides as does mature HeLa U2 RNA.

An intron-containing Schizosaccharomyces pombe U6 RNA gene can be transcribed by human RNA polymerase III.

A Schizosaccharomyces pombe U6 small nuclear RNA gene containing an intron has been described. We find that the S. pombe U6 gene is transcribed in a human (HeLa) cell S100 extract with an alpha-amanitin sensitivity characteristic of RNA polymerase III. The S. pombe U6 gene is also transcribed after transfection into human cells. The transcription of vertebrate U6 RNA genes by RNA polymerase III does not require intragenic control elements. The intron of the S. pombe U6 gene disrupts a "box A"-like intragenic sequence that is typically an RNA polymerase III transcription control element. This, together with the transcription of the S. pombe U6 gene by human RNA polymerase III, suggests that it is recognized by human U6 gene-specific transcription machinery.

Effects of arousing emotional scenes on the distribution of visuospatial attention: changes with aging and early subcortical vascular dementia.

BACKGROUND: The modulation of attention by emotionally arousing stimuli is highly important for each individual's social function. Disturbances of emotional processing are a supportive feature for the diagnosis of subcortical vascular dementia (SVD). We address here whether these disturbances might be useful as an early disease marker. METHODS: In order to examine the modulation of visual attention by emotionally arousing stimuli of different valence, 12 elderly patients with early SVD, 12 age-comparable healthy adults and 12 young healthy subjects were studied while looking at pairs of pictures from the International Affective Picture Battery that were either neutral-neutral, neutral-positive or neutral-negative in terms of emotional content. Eye movements were recorded with an infrared eye-tracking system. The direction of the first saccade and the dwell time during the 10 s of presentation were measured and compared among groups with parametric tests. RESULTS: All subjects showed a modulation of initial attentional orienting as well as a higher percentage of dwell time towards the pictures containing emotional material. Patients with SVD and old controls did not differ in either experimental measure. Young patients showed a stronger bias towards emotionally negative material than both groups of older individuals. CONCLUSIONS: Modulation of visuospatial attention is preserved in early SVD. This might have implications for therapeutic interventional approaches. A weakened sustained attention towards negative but not positive emotional pictures in the elderly is in accordance with the socioemotional selectivity theory, describing a relative selection of positive stimuli with aging.

Calibration of time of flight detectors using laser-driven neutron source.

Calibration of three scintillators (EJ232Q, BC422Q, and EJ410) in a time-of-flight arrangement using a laser drive-neutron source is presented. The three plastic scintillator detectors were calibrated with gamma insensitive bubble detector spectrometers, which were absolutely calibrated over a wide range of neutron energies ranging from sub-MeV to 20 MeV. A typical set of data obtained simultaneously by the detectors is shown, measuring the neutron spectrum emitted from a petawatt laser irradiated thin foil.

Characterization of N-myristoyl transferase inhibitors and their effect on HIV release.

Acylation of virus proteins is an important covalent modification which has been shown, in many cases, to be necessary for their normal function. Furthermore, it has been shown that cerulenin, an inhibitor of this process, inhibits formation of vesicular stomatitis virus and Rous sarcoma virus in infected cultures, as well as acylation of HIV proteins. However, in agreement with earlier reports, we found that the acylating enzyme, N-myristoyl transferase, was unaffected by cerulenin which did, however, inhibit protein synthesis, thereby making interpretation of its effects difficult. Analogues of myristic acid were found to inhibit acylation in intact cells without toxic effects on protein synthesis or mitochondrial function. Myristic acid analogues were also shown by an in vitro assay to act directly on the acylating activity (N-myristoyl transferase). Furthermore, myristic acid analogues were found to inhibit HIV release from HIV-infected cells and glucosamine, which has recently been shown to be a non-competitive inhibitor of N-myristoyl-transferase, also inhibited HIV release.

Infection of human fibroblasts and osteoblast-like cells with HIV-1.

Primary human skin- and lung-derived fibroblast cell cultures and continuous human osteoblast-like and fibroblast-like cell lines were infected with different strains of HIV-1. Infection was measured at the single-cell level using the immunoperoxidase staining method to detect viral proteins. No cytopathic effects were observed in HIV-1-infected cell cultures. One continuous cell line (LC5), derived from embryonic lung, was readily infectable with HIV-1 and showed continuous production of infectious virus. Infection of LC5 cells could be blocked with anti-CD4 monoclonal antibodies. These findings indicate that fibroblasts of skin and lung, and osteogenic cells may be considered as potential target cells for HIV-1, thereby possibly contributing to the establishment of local HIV reservoirs.

Infection of human brain cells by HIV-1: restricted virus production in chronically infected human glial cell lines.

OBJECTIVE: To study expression of HIV-1 in human glial cell lines. DESIGN: Chronically HIV-1-infected glial cell lines were established to evade potential artefacts resulting from unphysiological viral entry (i.e., transfection). These cell lines were used to study viral expression and regulation. METHODS: Chronically infected glial cell lines were established by terminal dilution cloning of human glioma cells exposed to HIV-1. Virus production and expression were assayed by measuring reverse transcriptase activity, p24-antigen levels and syncytia-inducing capacity in C8166 target cells (extracellular), or by indirect immunoperoxidase staining, immunoblot analysis, and p24- and Nef-antigen-capture enzyme-linked immunosorbent assays (intracellular). HIV-long terminal repeat (LTR)-dependent expression of the chloramphenicol acetyltransferase reporter gene was determined in transient transfection assays. RESULTS: Culture supernatant from chronically HIV-1-infected glial cells contained only low levels of virus compared with chronically HIV-infected fibroblasts and T-lymphoma cells. Detailed study of HIV-antigen expression in representative glial cell line TH4-7-5 indicated the presence of all major structural proteins, albeit at low levels, and of Vif, Tat, Rev and Nef. Intracellular levels of Nef exceeded p24-antigen levels by approximately 10-fold. Virus was recovered from TH4-7-5 cells by cocultivation with blood-derived target cells, indicating that low-level virus production is not due to defective provirus. Prominent negative regulatory element (NRE)-mediated suppression of exogenous HIV-LTR activity was observed in TH4-7-5 cells and was unequalled by chronically HIV-producing fibroblast cells or by uninfected fibroblast and glial cells. CONCLUSIONS: Our results suggest that restricted virus production by chronically infected glial cells involves LTR-mediated regulation of virus expression.

Correlational imaging of thalamocortical coupling in the primary visual pathway of the human brain.

While the anatomy of the human brain is well defined, the functional connectivity of its structures is far less understood. Modern neuroimaging techniques offer the unique opportunity of visualizing physiologic activation in central nervous structures and of identifying the elements underlying distributed networks for information processing. Following improved spatial resolution of deoxyhemoglobin-sensitive magnetic resonance imaging, we were able to detect simultaneous signal changes in the lateral geniculate nucleus and primary visual cortex during periodic photic stimulation. Visualization of coupled activation by cross-correlation analysis resulted in the first demonstration of thalamocortical interaction in the primary visual pathway of the intact human brain.

The effect of acetazolamide on regional cerebral blood oxygenation at rest and under stimulation as assessed by MRI.

The sensitivity of gradient echo magnetic resonance imaging (MRI) to changes in cerebral blood oxygenation (CBO) has been introduced for mapping functional brain activation. Here, we report that this approach allows monitoring autoregulation in the human brain under vasodilatory stress. Following the administration of acetazolamide, signal intensities of deoxyhemoglobin-sensitive images increased in cortical and subcortical gray matter and to a lesser extent in white matter. This result reflects a venous hyperoxygenation stemming from an increase in cerebral perfusion with oxygen consumption remaining constant. In addition, pharmacologic induction of vasodilation attenuated activity-related MRI signal changes in the visual cortex under photic stimulation. Although intersubject variability was high, this finding indicates individually persisting autoregulatory responsiveness to functional challenge despite an "exhausted" reserve capacity. It is suggested that recording CBO by MRI will foster our understanding of modulation of vasomotor tone and cerebral perfusion. Furthermore, this technique may prove valuable for assessing the cerebrovascular reserve capacity in patients with carotid artery occlusive disease.

Simultaneous recording of cerebral blood oxygenation changes during human brain activation by magnetic resonance imaging and near-infrared spectroscopy.

Changes in cerebral blood oxygenation due to functional activation of the primary sensorimotor cortex during a unilateral finger opposition task were simultaneously mapped by deoxyhemoglobin-sensitive magnetic resonance imaging (MRI) and monitored by near-infrared spectroscopy (NIRS). Activation foci along the contralateral central sulcus displayed task-associated increases in MRI signal intensity, indicating a concomitant decrease of the focal concentration of deoxyhemoglobin. This interpretation was confirmed by simultaneous reductions in deoxyhemoglobin measured optically. Since observation of the latter effect required exact spatial matching of the MRI-detected activation foci and position of the fiber optic bundles ("optodes") used for transmitting and receiving light, it may be concluded that optical recordings of changes in deoxyhemoglobin during functional challenge probe only a restricted brain tissue region. While deoxyhemoglobin responses seen by NIRS were smaller for ipsi- than for contralateral finger movements, task-related increases in oxyhemoglobin were rather similar between both conditions and, thus, seem to be less specific. Furthermore, no consistent changes were obtained for total hemoglobin during task performance, possibly due to the short timing of the repetitive protocol. In general, results underline, in humans, the hitherto assumed signal physiology for functional brain mapping by oxygenation-sensitive MRI and allow assessment of both constraints and practicability of functional studies by NIRS.

Quantitation of regional cerebral blood flow with 15O-butanol and positron emission tomography in humans.

We describe the implementation and validation of a combined dynamic-autoradiographic approach for measuring the regional cerebral blood flow (rCBF) with 15O-butanol. From arterial blood data sampled at a rate of 1 s and list mode data of the cerebral radioactivity accumulated over 100 s, the time shift between blood and tissue curves, the dispersion constant DC, the partition coefficient p, and the CBF were estimated by least squares fitting. Using the fit results, a pixel-by-pixel parametrization of rCBF was computed for a single 40-s (autoradiographic) 15O-butanol uptake image. The mean global CBF found in 27 healthy subjects was 49 +/- 8 ml 100 g-1 min-1. Gray and white matter rCBF were 83 +/- 20 and 16 +/- 3 ml 100 g-1 min-1, respectively, with a corresponding partition coefficient p of 0.77 +/- 0.18 and 0.77 +/- 0.29 ml/g in both compartments. The quantitative images resulted in a significantly higher gray matter rCBF than the autoradiographic images.