Computed Ultrasound Tomography in Echo mode (CUTE) of speed of sound for diagnosis and for aberration correction in pulse-echo sonography

Sound speed as a diagnostic marker for various diseases of human tissue has been of interest for a while. Up to now, mostly transmission ultrasound computed tomography (UCT) was able to detect spatially resolved sound speed, and its promise as a diagnostic tool has been demonstrated. However, UCT is limited to acoustically transparent samples such as the breast. We present a novel technique where spatially resolved detection of sound speed can be achieved using conventional pulse-echo equipment in reflection mode. For this purpose, pulse-echo images are acquired under various transmit beam directions and a two-dimensional map of the sound speed is reconstructed from the changing phase of local echoes using a direct reconstruction method. Phantom results demonstrate that a high spatial resolution (1 mm) and contrast (0.5 % of average sound speed) can be achieved suitable for diagnostic purposes. In comparison to previous reflection-mode based methods, CUTE works also in a situation with only diffuse echoes, and its direct reconstruction algorithm enables real-time application. This makes it suitable as an addition to conventional clinical ultrasound where it has the potential to benefit diagnosis in a multimodal approach. In addition, knowledge of the spatial distribution of sound speed allows full aberration correction and thus improved spatial resolution and contrast of conventional B-mode ultrasound. © (2014) COPYRIGHT Society of Photo-Optical Instrumentation Engineers (SPIE). Downloading of the abstract is permitted for personal use only.

Functionally Optimized Neuritogenic Farinosone C Analogs: SAR-Study and Investigations on Their Mode of Action

Several natural products derived from entomopathogenic fungi have been shown to initiate neuronal differentiation in the rat pheochromocytoma PC12 cell line. After the successful completion of the total synthesis program, the reduction of structural complexity while retaining biological activity was targeted. In this study, farinosone C served as a lead structure and inspired the preparation of small molecules with reduced complexity, of which several were able to induce neurite outgrowth. This allowed for the elaboration of a detailed structure-activity relationship. Investigations on the mode of action utilizing a computational similarity ensemble approach suggested the involvement of the endocannabinoid system as potential target for our analogs and also led to the discovery of four potent new endocannabinoid transport inhibitors.

Procedure for short-lived particle detection in the OPERA experiment and its application to charm decays

The OPERA experiment, designed to perform the first observation of νμ→ντ oscillations in appearance mode through the detection of the τ leptons produced in ντ charged current interactions, has collected data from 2008 to 2012. In the present paper, the procedure developed to detect τ particle decays, occurring over distances of the order of 1 mm from the neutrino interaction point, is described in detail. The results of its application to the search for charmed hadrons are then presented as a validation of the methods for ντ appearance detection.

Models of hybridization during range expansions and their application to recent human evolution

Several lines of genetic, archeological and paleontological evidence suggest that anatomically modern humans (Homo sapiens) colonized the world in the last 60,000 years by a series of migrations originating from Africa (e.g. Liu et al., 2006; Handley et al., 2007; Prugnolle, Manica, and Balloux, 2005; Ramachandran et al. 2005; Li et al. 2008; Deshpande et al. 2009; Mellars, 2006a, b; Lahr and Foley, 1998; Gravel et al., 2011; Rasmussen et al., 2011). With the progress of ancient DNA analysis, it has been shown that archaic humans hybridized with modern humans outside Africa. Recent direct analyses of fossil nuclear DNA have revealed that 1–4 percent of the genome of Eurasian has been likely introgressed by Neanderthal genes (Green et al., 2010; Reich et al., 2010; Vernot and Akey, 2014; Sankararaman et al., 2014; Prufer et al., 2014; Wall et al., 2013), with Papua New Guineans and Australians showing even larger levels of admixture with Denisovans (Reich et al., 2010; Skoglund and Jakobsson, 2011; Reich et al., 2011; Rasmussen et al., 2011). It thus appears that the past history of our species has been more complex than previously anticipated (Alves et al., 2012), and that modern humans hybridized several times with local hominins during their expansion out of Africa, but the exact mode, time and location of these hybridizations remain to be clarifi ed (Ibid.; Wall et al., 2013). In this context, we review here a general model of admixture during range expansion, which lead to some predictions about expected patterns of introgression that are relevant to modern human evolution.

Unusual Southern Hemisphere tree growth patterns induced by changes in the Southern Annular Mode

Recent changes in the summer climate of the Southern Hemisphere extra-tropics are primarily related to the dominance of the positive phase of the Southern Annular Mode1, 2. This shift in the behaviour of the Southern Annular Mode—essentially a measure of the pressure gradient between Southern Hemisphere mid and high latitudes—has been predominantly induced by polar stratospheric ozone depletion2, 3, 4. The concomitant southward expansion of the dry subtropical belts5, 6 could have consequences for forest growth. Here, we use tree-ring records from over 3,000 trees in South America, Tasmania and New Zealand to identify dominant patterns of tree growth in recent centuries. We show that the foremost patterns of growth between 1950 and 2000 differed significantly from those in the previous 250 years. Specifically, growth was higher than the long-term average in the subalpine forests of Tasmania and New Zealand, but lower in the dry-mesic forests of Patagonia. We further demonstrate that variations in the Southern Annular Mode can explain 12–48% of the tree growth anomalies in the latter half of the twentieth century. Tree-ring-based reconstructions of summer Southern Annular Mode indices suggest that the high frequency of the positive phase since the 1950s is unprecedented in the past 600 years. We propose that changes in the Southern Annular Mode have significantly altered tree growth patterns in the Southern Hemisphere.

Development of a low energy ion source for ROSINA ion mode calibration

The European Rosetta mission on its way to comet 67P/Churyumov-Gerasimenko will remain for more than a year in the close vicinity (1 km) of the comet. The two ROSINA mass spectrometers on board Rosetta are designed to analyze the neutral and ionized volatile components of the cometary coma. However, the relative velocity between the comet and the spacecraft will be minimal and also the velocity of the outgassing particles is below 1km∕s. This combination leads to very low ion energies in the surrounding plasma of the comet, typically below 20eV. Additionally, the spacecraft may charge up to a few volts in this environment. In order to simulate such plasma and to calibrate the mass spectrometers, a source for ions with very low energies had to be developed for the use in the laboratory together with the different gases expected at the comet. In this paper we present the design of this ion source and we discuss the physical parameters of the ion beam like sensitivity, energy distribution, and beam shape. Finally, we show the first ion measurements that have been performed together with one of the two mass spectrometers.

Prestimulus default mode activity influences depth of processing and recognition in an emotional memory task

Low self-referential thoughts are associated with better concentration, which leads to deeper encoding and increases learning and subsequent retrieval. There is evidence that being engaged in externally rather than internally focused tasks is related to low neural activity in the default mode network (DMN) promoting open mind and the deep elaboration of new information. Thus, reduced DMN activity should lead to enhanced concentration, comprehensive stimulus evaluation including emotional categorization, deeper stimulus processing, and better long-term retention over one whole week. In this fMRI study, we investigated brain activation preceding and during incidental encoding of emotional pictures and on subsequent recognition performance. During fMRI, 24 subjects were exposed to 80 pictures of different emotional valence and subsequently asked to complete an online recognition task one week later. Results indicate that neural activity within the medial temporal lobes during encoding predicts subsequent memory performance. Moreover, a low activity of the default mode network preceding incidental encoding leads to slightly better recognition performance independent of the emotional perception of a picture. The findings indicate that the suppression of internally-oriented thoughts leads to a more comprehensive and thorough evaluation of a stimulus and its emotional valence. Reduced activation of the DMN prior to stimulus onset is associated with deeper encoding and enhanced consolidation and retrieval performance even one week later. Even small prestimulus lapses of attention influence consolidation and subsequent recognition performance. Hum Brain Mapp, 2015. © 2015 Wiley Periodicals, Inc.

Towards clinical computed ultrasound tomography in echo-mode: Dynamic range artefact reduction

Computed ultrasound tomography in echo-mode (CUTE) allows imaging the speed of sound inside tissue using hand-held pulse-echo ultrasound. This technique is based on measuring the changing local phase of beamformed echoes when changing the transmit beam steering angle. Phantom results have shown a spatial resolution and contrast that could qualify CUTE as a promising novel diagnostic modality in combination with B-mode ultrasound. Unfortunately, the large intensity range of several tens of dB that is encountered in clinical images poses difficulties to echo phase tracking and results in severe artefacts. In this paper we propose a modification to the original technique by which more robust echo tracking can be achieved, and we demonstrate in phantom experiments that dynamic range artefacts are largely eliminated. Dynamic range artefact reduction also allowed for the first time a clinical implementation of CUTE with sufficient contrast to reproducibly distinguish the different speed of sound in different tissue layers of the abdominal wall and the neck.

Mode of action of claudin peptidomimetics in the transient opening of cellular tight junction barriers

In epithelial/endothelial barriers, claudins form tight junctions, seal the paracellular cleft, and limit the uptake of solutes and drugs. The peptidomimetic C1C2 from the C-terminal half of claudin-1's first extracellular loop increases drug delivery through epithelial claudin-1 barriers. However, its molecular and structural mode of action remains unknown. In the present study, >100 μM C1C2 caused paracellular opening of various barriers with different claudin compositions, ranging from epithelial to endothelial cells, preferentially modulating claudin-1 and claudin-5. After 6 h incubation, C1C2 reversibly increased the permeability to molecules of different sizes; this was accompanied by redistribution of claudins and occludin from junctions to cytosol. Internalization of C1C2 in epithelial cells depended on claudin-1 expression and clathrin pathway, whereby most C1C2 was retained in recyclosomes >2 h. In freeze-fracture electron microscopy, C1C2 changed claudin-1 tight junction strands to a more parallel arrangement and claudin-5 strands from E-face to P-face association - drastic and novel effects. In conclusion, C1C2 is largely recycled in the presence of a claudin, which explains the delayed onset of barrier and junction loss, the high peptide concentration required and the long-lasting effect. Epithelial/endothelial barriers are specifically modulated via claudin-1/claudin-5, which can be targeted to improve drug delivery.