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Healthy adults show better memory for low-arousal positive versus negative stimuli, but depression compromises this positive memory advantage. Existing studies are limited by small samples or analyses that provide limited insight into underlying mechanisms. Our study addresses these concerns by using a multistaged analysis, including diffusion modeling, to identify precise psychological processes underlying the positive memory advantage and its disruption by depression in a large sample. A total of 1,358 participants completed the BDI-II (Beck et al., 1996) and an emotional memory task. At encoding, participants judged whether positive and negative words were positive or self-descriptive. After a free recall test, participants viewed an equal mix of studied and unstudied words and judged whether each was "old" or "new"; if judged "old," they indicated whether the study source was a valence or self-reference judgment. We replicate the positive memory advantage and its decrease in depression in recall, recognition, and source accuracy. The hierarchical drift diffusion model (HDDM; Wiecki et al., 2013) revealed that higher BDI-II scores are associated with more efficient evidence accumulation for negative words in the recognition and source memory tasks. By contrast, evidence accumulation for positive words is unaffected by BDI-II during the recognition task but becomes less efficient with increased BDI-II during the source memory task. In conclusion, in a well-controlled design with a large sample, we find that depression reduces the positive memory advantage. HDDM analyses suggest that this reflects differential effects of depression on the speed of evidence accumulation during the retrieval of positive versus negative memories. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

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Muonic atom X-ray Emission Spectroscopy (µ-XES) is a novel technique based on the detection of high-energy X-rays emitted after the interaction of a negative muon beam with matter. Thanks to the multi-elemental range, negligible self-absorption of the x-rays and the possibility of performing depth profile studies, the technique is a very powerful probe for the analysis of cultural heritage artefacts. By tuning the energy of the incident muon beam, indeed, it is possible to investigate the different layers that constitute a sample. In this work, we report preliminary results of the analysis on two fire-gilded surfaces, in which the data analysis is coupled with Monte Carlo-based simulation software. Here, to perform a depth profile characterization, the samples were analysed at different beam energies (or momentum). Each of the resulting x-ray spectra was then analysed and compared with the output of the simulations software and a remarkably good agreement was reached. The results of the work are promising and with this approach, it will be possible to enhance the capability offered by the technique, both in terms of data analysis and data interpretation.

Previous work suggests that subordinate-level object training improves exemplar-level perceptual discrimination over basic-level training. However, the extent to which visual fixation strategies and the use of visual features, such as color and spatial frequency (SF), change with improved discrimination was not previously known. In the current study, adults (n = 24) completed 6 days of training with 2 families of computer-generated novel objects. Participants were trained to identify one object family at the subordinate level and the other object family at the basic level. Before and after training, discrimination accuracy and visual fixations were measured for trained and untrained exemplars. To examine the impact of training on visual feature use, image color and SF were manipulated and tested before and after training. Discrimination accuracy increased for the object family trained at the subordinate-level, but not for the family trained at the basic level. This increase was seen for all image manipulations (color, SF) and generalized to untrained exemplars within the trained family. Both subordinate- and basic-level training increased average fixation duration and saccadic amplitude and decreased the number of total fixations. Collectively, these results suggest a dissociation between discrimination accuracy, indicative of recognition, and the associated pattern of changes present for visual fixations.

Lysosomal trafficking and maturation in neurons remain poorly understood and are unstudied in vivo despite high disease relevance. We generated neuron-specific transgenic mice to track vesicular CTSD acquisition, acidification, and traffic within the autophagic-lysosomal pathway in vivo, revealing that mature lysosomes are restricted from axons. Moreover, TGN-derived transport carriers (TCs), not lysosomes, supply lysosomal components to axonal organelles. Ultrastructurally distinctive TCs containing TGN and lysosomal markers enter axons, engaging autophagic vacuoles and late endosomes. This process is markedly upregulated in dystrophic axons of Alzheimer models. In cultured neurons, most axonal LAMP1 vesicles are weakly acidic TCs that shuttle lysosomal components bidirectionally, conferring limited degradative capability to retrograde organelles before they mature fully to lysosomes within perikarya. The minor LAMP1 subpopulation attaining robust acidification are retrograde Rab7(+) endosomes/amphisomes, not lysosomes. Restricted lysosome entry into axons explains the unique lysosome distribution in neurons and their vulnerability toward neuritic dystrophy in disease.

Sardinian metallurgy produced samples of high artistic and historical value. In particular, ship models are rare and unmatched examples of the mastery reached by Sardinian metallurgists and their production process deserves an in-depth analysis of all the phases involved in the making. In this work, we examined a Sardinian boat model to obtain information about its composition, microstructure and manufacturing technique. The object is a small bronze ship model that was found near the Nuraghe Colovros, located in north-east Sardinia (Italy). It was analysed by means of neutron imaging and neutron diffraction experiments at the ISIS Pulsed Neutron and Muon Source laboratory (Harwell, UK). Neutron techniques are relatively new in the field of archaeometry, but they are a very effective tool for the study of archaeological objects: they permit to survey complete artefacts, determine compositions and structures, assess the conservation status and address questions of effective use and casting techniques. This type of data can add new and different insights to existing archaeological information, especially where sampling is not permitted. The outcome of the study reveals a peculiar approach to the manufacturing of the boat model.

We analyze the effect of the barrier motion on the Bose-Hubbard Hamiltonian of a ring-shaped Bose-Einstein condensate interrupted by a pair of Josephson junctions, a configuration which is the cold atom analog of the well-known dc superconducting quantum interference device (SQUID). Such an effect is also shown to modify the Heisenberg equation of motion of the boson field operator in the two-mode approximation, where a hysteretic contribution that could affect the dynamics for accelerated or overlapping barriers is identified. By studying the energy landscape as a function of order and control parameters, we determine the diagram with the location of the dc and ac Josephson regimes, along with the critical points that are shown to depend on the junctions position. We analyze the dc to ac Josephson transition for adiabatic barrier trajectories that lead to a final uniform velocity, or which perform symmetric velocity paths. We show that such symmetric trajectories may induce, when reaching the critical point, highly hysteretic oscillating return paths within the dc regime, similar to the underdamped hysteresis loops arising from the action of a resistive flow in the ac regime. We also consider nonequilibrium initial conditions resulting from a finite phase difference on either side of the junctions, along with the critical features of such a parameter. An excellent agreement between the Gross-Pitaevskii simulations and the two-mode results is found in all cases., Typos in Eq. (6) corrected

H.E.S.S. has recently completed a systematic survey of the Galactic plane in the TeV energy domain. We analyze the flux, latitude and longitude distributions of $\gamma-$ray sources observed by H.E.S.S. in order to infer the properties of Galactic TeV source population. We show that the total Milky-Way luminosity in the 1-100 TeV energy range is $L_{\rm MW} = 1.7^{+0.5}_{-0.4}\times 10^{37} {\rm ergs}\,{\rm sec}^{-1}$. Evaluating the cumulative flux expected at Earth by the considered population, we show that H.E.S.S. unresolved sources provide a relevant contribution to the diffuse Galactic emission. Finally, in the hypothesis that the majority of bright sources detected by H.E.S.S. are powered by pulsar activity, like e.g. Pulsar Wind Nebulae or TeV halos, we estimate the main properties of the pulsar population., Comment: 11 pages, 5 figures

Background The majority of eyewitness lineup studies are laboratory-based. How well the conclusions of these studies, including the relationship between confidence and accuracy, generalize to real-world police lineups is an open question. Signal detection theory (SDT) has emerged as a powerful framework for analyzing lineups that allows comparison of witnesses’ memory accuracy under different types of identification procedures. Because the guilt or innocence of a real-world suspect is generally not known, however, it is further unknown precisely how the identification of a suspect should change our belief in their guilt. The probability of guilt after the suspect has been identified, the posterior probability of guilt (PPG), can only be meaningfully estimated if we know the proportion of lineups that include a guilty suspect, P(guilty). Recent work used SDT to estimate P(guilty) on a single empirical data set that shared an important property with real-world data; that is, no information about the guilt or innocence of the suspects was provided. Here we test the ability of the SDT model to recover P(guilty) on a wide range of pre-existing empirical data from more than 10,000 identification decisions. We then use simulations of the SDT model to determine the conditions under which the model succeeds and, where applicable, why it fails. Results For both empirical and simulated studies, the model was able to accurately estimate P(guilty) when the lineups were fair (the guilty and innocent suspects did not stand out) and identifications of both suspects and fillers occurred with a range of confidence levels. Simulations showed that the model can accurately recover P(guilty) given data that matches the model assumptions. The model failed to accurately estimate P(guilty) under conditions that violated its assumptions; for example, when the effective size of the lineup was reduced, either because the fillers were selected to be poor matches to the suspect or because the innocent suspect was more familiar than the guilty suspect. The model also underestimated P(guilty) when a weapon was shown. Conclusions Depending on lineup quality, estimation of P(guilty) and, relatedly, PPG, from the SDT model can range from poor to excellent. These results highlight the need to carefully consider how the similarity relations between fillers and suspects influence identifications.

Context effects are changes in preference that occur when alternatives are added to a choice set. Models that account for context effects typically assume a within-dimension comparison process; however, the presentation format of a choice set can influence comparison strategies. The present study jointly tests the influence of presentation format on the attraction, compromise, and similarity effects in a within-subjects design. Participants completed a series of choices designed to elicit each of the three context effects, with either a by-alternative or by-dimension format. Whereas the by-alternative format elicited a standard similarity effect, but null attraction and reverse compromise effects, the by-dimension format elicited standard attraction and compromise effects, but a reverse similarity effect. These novel results are supported by a re-analysis of the eye-tracking data collected by Noguchi and Stewart (Cognition, 132(1), 44-56, 2014) and demonstrate that flexibility in the comparison process should be incorporated into theories of preferential choice.

Perceptual expertise is marked by subordinate-level recognition of objects in the expert domain. In this study, participants learned one family of full-color, artificial objects at the subordinate (species) level and another family at the basic (family) level. Discrimination of trained and untrained exemplars was tested before and after training across several image manipulations [full-color, grayscale, low spatial frequency (LSF) and high spatial frequency (HSF)] while event-related potentials (ERPs) were recorded. Regardless of image manipulation, discrimination (indexed by d') of trained and of untrained exemplars was enhanced after subordinate-level training, but not after basic-level training. Enhanced discrimination after subordinate-level training generalized to untrained exemplars and to grayscale images and images in which LSF or HSF information was removed. After training, the N170 and N250, recorded over occipital and occipitotemporal brain regions, were both more enhanced after subordinate-level training than after basic-level training. However, the topographic distribution of enhanced responses differed across components. The N170 latency predicted reaction time after both basic-level training and subordinate-level training, highlighting an association between behavioral and neural responses. These findings further elucidate the role of the N170 and N250 as ERP indices of subordinate-level expert object processing and demonstrate how low-level manipulations of color and spatial frequency impact behavior and the N170 and N250 components independent of training or expertise.

Harmful algal blooms (HAB) release microtoxins that contaminate drinking water supplies and risk the health of millions annually. Crystalline ferrate(VI) is a powerful oxidant capable of removing algal microtoxins. We investigate in-situ electrochemically produced ferrate from common carbon steel as an on-demand alternative to crystalline ferrate for the removal of microcystin-LR (MC-LR) and compare the removal efficacy for both electrochemical (EC) and chemical dosing methodologies. We report that a very low dose of EC-ferrate in deionized water (0.5 mg FeO42− L−1) oxidizes MC-LR (MC-LR0 = 10 μg L−1) to below the guideline limit (1.0 μg L−1) within 10 minutes' contact time. With bicarbonate or natural organic matter (NOM), doses of 2.0–5.0 mg FeO42− L−1 are required, with lower efficacy of EC-ferrate than crystalline ferrate due to loss of EC-ferrate by water oxidation. To evaluate the EC-ferrate process to concurrently oxidize micropollutants, coagulate NOM, and disinfect drinking water, we spiked NOM-containing real water with MC-LR and Escherichia coli, finding that EC-ferrate is effective at 10.0 mg FeO42− L−1 under normal operation or 2.0 mg FeO42− L−1 if the test water has initial pH optimized. We suggest in-situ EC-ferrate may be appropriate for sporadic HAB events in small water systems as a primary or back-up technology.

We study the collisional dynamics of multiple dark solitons in a Bose-Einstein condensate confined by a toroidal trap. We assume a tight enough confinement in the radial direction to prevent possible dissipative effects due to the presence of solitonic vortices. Analytical expressions for the initial order parameters with imprinted phases are utilized to generate different initial arrays of solitons, for which the time-dependent Gross-Pitaevskii equation is numerically solved. Given that the soliton velocity is conserved due to the lack of dissipation, we are able to apply a simple quasiparticle description of the soliton dynamics. In fact, the trajectory equations are written in terms of the velocities and the angular shifts produced at each collision, in analogy to the infinite one-dimensional system. To calculate the angular shifts, we directly extract them from the trajectories given by the Gross-Pitaevskii simulations and, on the other hand, we show that accurate values can be analytically obtained by adapting a formula valid for the infinite one-dimensional system that involves the healing length, which in our inhomogeneous system must be evaluated in terms of the sound velocity along the azimuthal direction. We further show that very good estimates of such a sound velocity can be directly determined by using the ground state density profile and the values of the imprinted phases. We discuss the possible implementation of the system here proposed using the current experimental techniques., 13 pages, 8 figures

We study the dynamics of three-dimensional weakly linked Bose-Einstein condensates using a multimode model with an effective interaction parameter. The system is confined by a ring-shaped four-well trapping potential. By constructing a two-mode Hamiltonian in a reduced highly symmetric phase space, we examine the periodic orbits and calculate their time periods both in the self-trapping and Josephson regimes. The dynamics in the vicinity of the reduced phase space is investigated by means of a Floquet multiplier analysis, finding regions of different linear stability and analyzing their implications on the exact dynamics. The numerical exploration in an extended region of the phase space demonstrates that two-mode tools can also be useful for performing a partition of the space in different regimes. Comparisons with Gross-Pitaevskii simulations confirm these findings and emphasize the importance of properly determining the effective on-site interaction parameter governing the multimode dynamics., 12 pages, 13 figures

We study the dynamics of three-dimensional Bose-Einstein condensates confined by double-well potentials using a two-mode model with an effective on-site interaction energy parameter. The effective on-site interaction energy parameter is evaluated for different numbers of particles ranging from a low experimental value to larger ones approaching the Thomas-Fermi limit, yielding important corrections to the dynamics. We analyze the time periods as functions of the initial imbalance and find a closed integral form that includes all interaction-driven parameters. A simple analytical formula for the self-trapping period is introduced and shown to accurately reproduce the exact values provided by the two-mode model. Systematic numerical simulations of the problem in 3D demonstrate the excellent agreement of the two-mode model for experimental parameters., Comment: 7 pages, 5 figures

Training of subjects and execution of flintknapping sessions followed a written protocol strictly followed by a skilled tutor. The general protocol is presented as well as its treatment-specific variants.

We evaluate the diffuse gamma-ray flux at TeV energies produced by hadronic interactions of cosmic rays with the gas contained in the galactic disk. We consider different assumptions for the cosmic ray distribution, including the recently emerged possibility of a harder cosmic ray spectrum in the inner Galaxy. We show that observational data provided by Argo-YBJ, HESS, HAWC and Milagro, can already discriminate among different hyphoteses. The constraints can be strengthened if the contribution of sources not resolved by HESS is taken into account.

Despite the well-documented association between aggression and NSSI among adolescents, relatively little research has been conducted on the mechanisms underlying this relationship. The purpose of this study was to investigate potential socio-cognitive mechanisms through which aggression and NSSI are related. Participants were 186 adolescents (ages 13–18) recruited from a psychiatric inpatient facility in the northeastern United States. According to teen report, 57.5% of the sample endorsed NSSI in the previous year. Mediation was tested using the modern bootstrapping technique described by Hayes, using 5,000 re-samples with replacement, including sex and depression diagnosis as covariates. Results demonstrated that greater negative self-talk, a more negative cognitive style, and lower perceived family support were all significant mediators of the relationship between aggression and greater frequency of NSSI, whereas perceived social support from friends was not a significant mediator. Limitations, clinical implications, and future research directions of the current research are discussed.

The distribution of cosmic rays in the Galaxy is still uncertain and this affects the expectations for the diffuse gamma-ray emission produced by hadronic interactions of cosmic rays with the interstellar gas. We evaluate the diffuse gamma-ray flux at TeV energies by considering different assumptions for the cosmic ray distribution, including the recently emerged possibility of a decreasing cosmic ray spectral index in the inner Galaxy. The diffuse emission from the galactic central region (i.e. in the longitude range | l | ≤ 60o) changes in the different scenarios by a relatively large factor and can be probed by TeV scale gamma-ray observations. By comparing the total flux produced by diffuse emission and point-like and extended sources resolved by HESS with the gamma-ray flux observed by Argo-YBJ, HESS, HAWC and Milagro, we show that experimental data can already discriminate among different hyphoteses for cosmic ray distribution. The constraints can be strengthened if the contribution of sources not resolved by HESS is taken into account.

Mitochondrial transplantation is currently being explored as a means to repair and restore proper organelle function in a variety of inherited and acquired disorders of energy metabolism. The optimal preparation and application of donor mitochondria is unknown, but most studies in vivo have used injection techniques or, for tissue studies, unpackaged mitochondria (organelles isolated and suspended in buffer) in transplant experiments. Packaging in lipid rafts can increase recipient cell uptake of some compounds and objects. We present the first data comparing recipient cell uptake of unpackaged mitochondria to recipient cell uptake of mitochondria packaged in cell membrane lipids. Mitochondria and membranes were prepared from autologous cells and applied to cells (fibroblasts) in culture. Both unpackaged and lipid-packaged mitochondria were taken into recipient cells and the donor mitochondria showed evidence, in each case, of retained functionality and the ability to merge with the recipient mitochondrial matrix. However, lipid packaging appeared to enhance the uptake of functional mitochondria. Current studies of mitochondrial transplantation in animal models might fruitfully explore the utility and efficacy of lipid-packaged mitochondria in transplant experiments.

During the last ten years, the fish consumption is increased about 27%. This increase depending from several factors, such as: population growth (+12%); greater awareness of the nutritional value of fish products; development of new aquaculture technologies; improvement of distribution channels. In order to safeguard humankind’s heritage, innovation strategies for food industry need to be concerned not only with technological changes but also with the scientific (nutritional, medical), social and environmental changes (sustainability, transparency). Aquaculture is an expansion industry and has the potential to satisfy the worldwide demand of fish production related to the global population growth. Technological and methodological innovations are needed not only to optimize the production but also to assure its sustainability. With this point of view, in this work, researchers, engineers and enterprises worked together to develop a system to be placed in sea aquaculture plants. The system is composed by several devices that work following IoT paradigm, and is able to solve practical issues emerged from a case study in South of Italy. The data collected by the system, conveniently enriched by other specific information, will be used for traceability purpose in order to satisfy the emerging information needs of Food Citizenship. The system’ devices, the production process (as-is and to-be), the plant maintenance process (as-is) and the traced data are described.

The present study has investigated the performance of electrocoagulation, to produce drinking water, using aluminum electrodes to remove nickel (Ni) and chromium (Cr) from two different water well samples from the north of Italy. Different experimental parameters, such as stirring and distance between the electrodes and current density, have been examined for both water samples. The series of experiments carried out on these two water samples has shown that the removal process of Ni is faster than that of Cr. In the case of water poisoned by Ni, a final concentration of 5 ppb was achieved starting from 41 ppb, while the Cr case showed a final concentration of 10 ppb compared to an initial 20 ppb. The electrocoagulation treatment presented in this study has shown very promising results and a high potential to remove very low amounts of heavy metals from water for drinking water production purposes.

Immersive experiences contribute to and enhance diverse curricula. Although more commonly applied to language curricula, student travel has much to offer science courses as well. Here, several options are described for secondary and college-level biology courses to participate in field-based study. The experience of one high school with one Amazonian field station is considered in detail, and several alternative opportunities for science-based student travel are provided as well. Traveling to the Amazon as an extension of classroom-based hypothesis generation and experimental design contextualized content for one high school biology course in a way that is powerful and repeatable.

Background Endocytic dysfunction and neurotrophin signaling deficits may underlie the selective vulnerability of hippocampal neurons during the progression of Alzheimer's disease (AD), although there is little direct in vivo and biochemical evidence to support this hypothesis. Methods Microarray analysis of hippocampal CA1 pyramidal neurons acquired via laser capture microdissection was performed using postmortem brain tissue. Validation was achieved using real-time quantitative polymerase chain reaction and immunoblot analysis. Mechanistic studies were performed using human fibroblasts subjected to overexpression with viral vectors or knockdown via small interference RNA. Results Expression levels of genes regulating early endosomes ( rab5 ) and late endosomes ( rab7 ) are selectively upregulated in homogeneous populations of CA1 neurons from individuals with mild cognitive impairment and AD. The levels of these genes are selectively increased as antemortem measures of cognition decline during AD progression. Hippocampal quantitative polymerase chain reaction and immunoblot analyses confirmed increased levels of these transcripts and their respective protein products. Elevation of select rab GTPases regulating endocytosis paralleled the downregulation of genes encoding the neurotrophin receptors TrkB and TrkC. Overexpression of rab5 in cells suppressed TrkB expression, whereas knockdown of TrkB expression did not alter rab5 levels, suggesting that TrkB downregulation is a consequence of endosomal dysfunction associated with elevated rab5 levels in early AD. Conclusions These data support the hypothesis that neuronal endosomal dysfunction is associated with preclinical AD. Increased endocytic pathway activity, driven by elevated rab GTPase expression, may result in long-term deficits in hippocampal neurotrophic signaling and represent a key pathogenic mechanism underlying AD progression.

Postmortem, genetic, brain imaging, and peripheral cell studies all support decreased mitochondrial activity as a factor in the manifestation of Bipolar Disorder (BD). Because abnormal mitochondrial morphology is often linked to altered energy metabolism, we investigated whether changes in mitochondrial structure were present in brain and peripheral cells of patients with BD. Mitochondria from patients with BD exhibited size and distributional abnormalities compared with psychiatrically-healthy age-matched controls. Specifically, in brain, individual mitochondria profiles had significantly smaller areas, on average, in BD samples (P = 0.03). In peripheral cells, mitochondria in BD samples were concentrated proportionately more within the perinuclear region than in distal processes (P = 0.0008). These mitochondrial changes did not appear to be correlated with exposure to lithium. Also, these abnormalities in brain and peripheral cells were independent of substantial changes in the actin or tubulin cytoskeleton with which mitochondria interact. The observed changes in mitochondrial size and distribution may be linked to energy deficits and, therefore, may have consequences for cell plasticity, resilience, and survival in patients with BD, especially in brain, which has a high-energy requirement. The findings may have implications for diagnosis, if they are specific to BD, and for treatment, if they provide clues as to the underlying pathophysiology of BD.

An additional copy of the β-amyloid precursor protein (APP) gene causes early-onset Alzheimer’s disease (AD) in trisomy 21 (DS). Endosome dysfunction develops very early in DS and AD and has been implicated in the mechanism of neurodegeneration. Here, we show that morphological and functional endocytic abnormalities in fibroblasts from individuals with DS are reversed by lowering the expression of APP or β-APP-cleaving enzyme 1 (BACE-1) using short hairpin RNA constructs. By contrast, endosomal pathology can be induced in normal disomic (2N) fibroblasts by overexpressing APP or the C-terminal APP fragment generated by BACE-1 (βCTF), all of which elevate the levels of βCTFs. Expression of a mutant form of APP that cannot undergo β-cleavage had no effect on endosomes. Pharmacological inhibition of APP γ-secretase, which markedly reduced Aβ production but raised βCTF levels, also induced AD-like endosome dysfunction in 2N fibroblasts and worsened this pathology in DS fibroblasts. These findings strongly implicate APP and the βCTF of APP, and exclude Aβ and the αCTF, as the cause of endocytic pathway dysfunction in DS and AD, underscoring the potential multifaceted value of BACE-1 inhibition in AD therapeutics.

We develop a microscopic model of mutual friction represented by the dissipative dynamics of a normal fluid flow which interacts with the helical normal modes of vortices comprising a lattice in thermal equilibrium. Such vortices are assumed to interact with the quasiparticles forming the normal fluid through a pseudomomentum-conserving scattering Hamiltonian. We study the approach to equilibrium of the normal fluid flow for temperatures below 1 K, deriving an equation of motion for the quasiparticle pseudomomentum which leads to the expected form predicted by the HVBK equations. We obtain an expression for the mutual friction coefficient $B$ in terms of microscopic parameters, which turns out to be practically independent of the vortex mass for values arising from diverse theories. By comparing our expression of $B$ with previous theoretical estimates, we deduce interesting qualitative features about the excitation of Kelvin modes by the quasiparticle scattering., Minor changes, enlarged version of the journal article

We numerically study properties of the dynamics of vortices in nonrotating Bose-Einstein condensates in the Thomas-Fermi regime. On the one hand, we compute the vortex energy as a function of its position and we predict, using the expression of the Magnus force, the vortex precession velocity. On the other hand, we calculate the temporal evolution of the vortex-state and test the accuracy of the previous prediction. We also investigate the validity of analytical formulae of this velocity involving the healing length. In addition, we analyze the velocity field and the angular momentum and we compare them to available analytical expressions.

Endocytic dysfunction is an early pathological change in Alzheimer's disease (AD) and Down's syndrome (DS). Using primary fibroblasts from DS individuals, we explored the interactions among endocytic compartments that are altered in AD and assessed their functional consequences in AD pathogenesis. We found that, like neurons in both AD and DS brains, DS fibroblasts exhibit increased endocytic uptake, fusion, and recycling, and trafficking of lysosomal hydrolases to rab5-positive early endosomes. Moreover, late endosomes identified using antibodies to rab7 and lysobisphosphatidic acid increased in number and appeared as enlarged, perinuclear vacuoles, resembling those in neurons of both AD and DS brains. In control fibroblasts, similar enlargement of rab5-, rab7-, and lysobisphosphatidic acid-positive endosomes was induced when endocytosis and endosomal fusion were increased by expression of either a rab5 or an active rab5 mutant, suggesting that persistent endocytic activation results in late endocytic dysfunction. Conversely, expression of a rab5 mutant that inhibits endocytic uptake reversed early and late endosomal abnormalities in DS fibroblasts. Our results indicate that DS fibroblasts recapitulate the neuronal endocytic dysfunction of AD and DS, suggesting that increased trafficking from early endosomes can account, in part, for downstream endocytic perturbations that occur in neurons in both AD and DS brains.

We study the dynamics of two gray solitons in a Bose-Einstein condensate confined by a toroidal trap with a tight confinement in the radial direction. Gross-Pitaevskii simulations show that solitons can be long living objects passing through many collisional processes. We have observed quite different behaviors depending on the soliton velocity. Very slow solitons, obtained by perturbing the stationary solitonic profile, move with a constant angular velocity until they collide elastically and move in the opposite direction without showing any sign of lowering their energy. In this case the density notches are always well separated and the fronts are sharp and straight. Faster solitons present vortices around the notches, which play a central role during the collisions. We have found that in these processes the solitons lose energy, as the outgoing velocity turns out to be larger than the incoming one. To study the dynamics, we model the gray soliton state with a free parameter that is related to the soliton velocity. We further analyze the energy, soliton velocity and turning points in terms of such a free parameter, finding that the main features are in accordance with the infinite one-dimensional system., Comment: 15 pages, 11 figures. Accepted in PRA

Kohut proposed that the narcissistic personality could be transformed in the therapeutic environment by an empathic approach on the part of the analyst. Within the analytic setting, specific transference phenomena arise spontaneously, allowing the analysand to confront infantile grandiose fantasies and unresolved narcissistic wounds. Using the story of the life of St. Francis of Assisi, this paper illustrates how religious experience––specifically the ongoing encounter with a transcendent other––can provide the “therapeutic” milieu in which the mirroring, idealizing, and twinship transferences described by Kohut can arise, and within which pathological narcissism can be transformed into the “cosmic narcissism” of the healthy personality.

Macroautophagy, which is a lysosomal pathway for the turnover of organelles and long-lived proteins, is a key determinant of cell survival and longevity. In this study, we show that neuronal macroautophagy is induced early in Alzheimer's disease (AD) and before β-amyloid (Aβ) deposits extracellularly in the presenilin (PS) 1/Aβ precursor protein (APP) mouse model of β-amyloidosis. Subsequently, autophagosomes and late autophagic vacuoles (AVs) accumulate markedly in dystrophic dendrites, implying an impaired maturation of AVs to lysosomes. Immunolabeling identifies AVs in the brain as a major reservoir of intracellular Aβ. Purified AVs contain APP and β-cleaved APP and are highly enriched in PS1, nicastrin, and PS-dependent γ-secretase activity. Inducing or inhibiting macroautophagy in neuronal and nonneuronal cells by modulating mammalian target of rapamycin kinase elicits parallel changes in AV proliferation and Aβ production. Our results, therefore, link β-amyloidogenic and cell survival pathways through macroautophagy, which is activated and is abnormal in AD.

Aberrant phosphorylation of the neuronal cytoskeleton is an early pathological event in Alzheimer's disease (AD), but the underlying mechanisms are unclear. Here, we demonstrate in the brains of AD patients that neurofilament hyperphosphorylation in neocortical pyramidal neurons is accompanied by activation of both Erk1,2 and calpain. Using immunochemistry, Western blot analysis, and kinase activity measurements, we show in primary hippocampal and cerebellar granule (CG) neurons that calcium influx activates calpain and Erk1,2 and increases neurofilament phosphorylation on carboxy terminal polypeptide sites known to be modulated by Erk1,2 and to be altered in AD. Blocking Erk1,2 activity either with antisense oligonucleotides to Erk1,2 mRNA sequences or by specifically inhibiting its upstream activating kinase MEK1,2 markedly reduced neurofilament phosphorylation. Calpeptin, a cell-permeable calpain inhibitor, blocked both Erk1,2 activation and neurofilament hyperphosphorylation at concentrations that inhibit calpain-mediated cleavage of brain spectrin. By contrast, inhibiting Erk1,2 with U-0126, a specific inhibitor of Mek1,2, had no appreciable effect on ionomycin-induced calpain activation. These findings demonstrate that, under conditions of calcium injury in neurons, calpains are upstream activators of Erk1,2 signaling and are likely to mediate in part the hyperphosphorylation of neurofilaments and tau seen at early stages of AD as well as the neuron survival-related functions of the MAP kinase pathway.

The neuronal lysosomal system is a major degradative pathway, induced by cell stress and closely linked to Alzheimer disease (AD) and other neurodegenerative diseases. Here, we show that mutations of presenilin (PS) 1 and 2, which cause familial early-onset AD (FAD), induce more severe lysosomal system neuropathology in humans than does sporadic AD (SAD). Cathepsin D and B levels were higher in PS-FAD neocortex than in SAD and, unlike neurons in SAD, expressed higher levels of the cation-independent mannose-6-phosphate receptor. Lysosomal pathology was also evident in more populations of neurons in PS-FAD brains, including the less vulnerable neurons in laminae II and IV and affected neurons contained high numbers of hydrolase-positive vesicular compartments with a broader range of abnormal morphology. In transgenic mice expressing mutant amyloid precursor protein (APPswe), introducing mutant PSI significantly upregulated the lysosomal system in neocortical and hippocampal neurons. This upregulation, though milder in severity, resembled that seen in human PS-FAD. Accumulation of hydrolases in dystrophic neurites in senile plaques was particularly strong, suggesting that amyloid deposition may be a stimulus for local mobilization of the lysosomal system. PS1 mice lacking the APPswe transgene also had a mild lysosomal response in some neuronal populations, which was not seen in the APPswe mice. Our findings suggest that presenilin mutations have amyloid-independent effects on the lysosomal system, which are synergistic with the lysosomal system pathology that is associated with beta-amyloid.

We previously identified abnormalities of the endocytic pathway in neurons as the earliest known pathology in sporadic Alzheimer's disease (AD) and Down's syndrome brain. In this study, we modeled aspects of these AD-related endocytic changes in murine L cells by overexpressing Rab5, a positive regulator of endocytosis. Rab5-transfected cells exhibited abnormally large endosomes immunoreactive for Rab5 and early endosomal antigen 1, resembling the endosome morphology seen in affected neurons from AD brain. The levels of both Abeta40 and Abeta42 in conditioned medium were increased more than 2.5-fold following Rab5 overexpression. In Rab5 overexpressing cells, the levels of beta-cleaved amyloid precursor protein (APP) carboxyl-terminal fragments (betaCTF), the rate-limiting proteolytic intermediate in Abeta generation, were increased up to 2-fold relative to APP holoprotein levels. An increase in beta-cleaved soluble APP relative to alpha-cleaved soluble APP was also observed following Rab5 overexpression. BetaCTFs were co-localized by immunolabeling to vesicular compartments, including the early endosome and the trans-Golgi network. These results demonstrate a relationship between endosomal pathway activity, betaCTF generation, and Abeta production. Our findings in this model system suggest that the endosomal pathology seen at the earliest stage of sporadic AD may contribute to APP proteolysis along a beta-amyloidogenic pathway.