Miracle-dz/UniFAR-FTUs huggingface dataset:
Depletion of a Microtubule-Associated Motor Protein Induces the Loss of Dendritic Identity

Dendrites are short stout tapering processes that are rich in ribosomes and Golgi elements, whereas axons are long thin processes of uniform diameter that are deficient in these organelles. It has been hypothesized that the unique morphological and compositional features of axons and dendrites result from their distinct patterns of microtubule polarity orientation. The microtubules within axons are uniformly oriented with their plus ends distal to the cell body, whereas microtubules within dendrites are nonuniformly oriented. The minus-end-distal microtubules are thought to arise via their specific transport into dendrites by the motor protein known as CHO1/MKLP1. According to this model, CHO1/MKLP1 transports microtubules with their minus ends leading into dendrites by generating forces against the plus-end-distal microtubules, thus creating drag on the plus-end-distal microtubules. Here we show that depletion of CHO1/MKLP1 from cultured neurons causes a rapid redistribution of microtubules within dendrites such that minus-end-distal microtubules are chased back to the cell body while plus-end-distal microtubules are redistributed forward. The dendrite grows significantly longer and thinner, loses its taper, and acquires a progressively more axon-like organelle composition. These results suggest that the forces generated by CHO1/MKLP1 are necessary for maintaining the minus-end-distal microtubules in the dendrite, for antagonizing the anterograde transport of the plus-end-distal microtubules, and for sustaining a pattern of microtubule organization necessary for the maintenance of dendritic morphology and composition. Thus, we would conclude that dendritic identity is dependent on forces generated by CHO1/MKLP1.
The thioredoxin-1 inhibitor 1-methylpropyl 2-imidazolyl disulfide (PX-12) decreases vascular permeability in tumor xenografts monitored by dynamic contrast enhanced magnetic resonance imaging.

PURPOSE The purpose of this study was to use dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) to measure changes in tumor xenograft permeability produced by the antitumor thioredoxin-1 (Trx-1) inhibitor 1-methylpropyl 2-imidazolyl disulfide (PX-12) and to assess the relationship to Trx-1 and vascular endothelial growth factor (VEGF) levels. EXPERIMENTAL DESIGN DCE-MRI was used to monitor the dynamics of gadolinium-diethylenetriaminepentaacetic acid coupled bovine serum albumin as a macromolecular contrast reagent to measure hemodynamic changes in HT-29 human colon xenografts in immunodeficient mice treated with PX-12. Blood vessel permeability was estimated from the slope of the enhancement curves, and tumor vascular volume fraction from the ordinate. Tumor Trx-1 and VEGF was also measured. RESULTS PX-12 caused a rapid 63% decrease in the average tumor blood vessel permeability within 2 hours of administration. The decrease lasted 24 hours and had returned to pretreatment values by 48 hours. The changes in vascular permeability were not accompanied by alterations in average tumor vascular volume fraction. There was a decrease in tumor and tumor-derived VEGF in plasma at 24 hours after treatment with PX-12, but not at earlier time points. However, tumor redox active Trx-1 showed a rapid decline within 2 hours following PX-12 administration that was maintained for 24 hours. CONCLUSION The rapid decrease in tumor vascular permeability caused by PX-12 administration coincided with a decrease in tumor redox active Trx-1 and preceded a decrease in VEGF. DCE-MRI responses to PX-12 in patients of Trx-1 inhibition at early time points and decreased VEGF at later times, may be useful to follow tumor response and even therapeutic benefit.
Mission accomplished?: Research methods in the first five years of Leadership

Taking its lead from a growing literature dealing with the research methods employed in management and adjacent disciplines and from the editors’ goal of encouraging a diversity of methodological positions in the pages of Leadership, this article reports the findings of a content analysis of the research methods employed in empirical articles during the journal’s first five years of publication. Particularly in comparison with a comparable study of the North American journal, The Leadership Quarterly, the content analysis findings reveal a greater tendency to employ a qualitative than a quantitative research approach and for qualitative interviewing and the qualitative analysis of documents to be predominant methods of data collection. At the same time, the findings also reveal similarities with traditional journals in terms of the methods employed, such as a relatively low take up of mixed-methods research.
Fast Receive Antenna Subset Selection for Pre-Coding Aided Spatial Modulation

In the literature, the pre-coding aided spatial modulation (PSM) is designed only for the symmetric and the underdetermined multiple-input multiple-output (MIMO) systems. In this letter, we study the PSM in the over-determined MIMO system where the receive antenna subset (RAS) selection is considered. The optimal selection criterion is first given, and a fast greedy incremental algorithm is then proposed. The proposed algorithm constructs the RAS by adding antennas one by one, where the low-complexity recursive computation of the matrix inverse can be further employed. Simulation results show that the proposed fast algorithm can achieve most of the antenna selection gain with very low complexity.
Reputation and identity conflict in management consulting

Based on a case study of a large consulting firm, this article makes two contributions to the literature on reputation and identity by examining how an organization responds when its identity is substantially misaligned with the experience and perceptions of external stakeholders that form the basis of reputational judgments. First, rather than triggering some form of identity adaptation, it outlines how other forms of identity can come into play to remediate this gap, buffering the organization’s identity from change. This shift to other individual identities is facilitated by a low organizational identity context even when the identity of the firm is coherent and strong. The second contribution concerns the conceptualization of consulting and other professional service firms. We explain how reputation and identity interact in the context of the distinctive organizational features of these firms. Notably, their loosely coupled structure and the central importance of expert knowledge claims enable individual consultants both to reinforce and supplement corporate reputation via individual identity work.
Combining eye movements and collaborative filtering for proactive information retrieval

We study a new task, proactive information retrieval by combining implicit relevance feedback and collaborative filtering. We have constructed a controlled experimental setting, a prototype application, in which the users try to find interesting scientific articles by browsing their titles. Implicit feedback is inferred from eye movement signals, with discriminative hidden Markov models estimated from existing data in which explicit relevance feedback is available. Collaborative filtering is carried out using the User Rating Profile model, a state-of-the-art probabilistic latent variable model, computed using Markov Chain Monte Carlo techniques. For new document titles the prediction accuracy with eye movements, collaborative filtering, and their combination was significantly better than by chance. The best prediction accuracy still leaves room for improvement but shows that proactive information retrieval and combination of many sources of relevance feedback is feasible.
Seamless utilisation of GPU resources for runtime and energy reduction in the Actor Model Yaroslav Hayduk

The Doctoral Workshop on Distributed Systems has been held at Le Louverain, Neuchâtel, Switzerland, from June 21-23, 2015. Ph.D. students from the Universities of Neuchâtel and Bern as well as the University of Applied Sciences of Fribourg presented their current research work and discussed recent research results. This technical report includes the extended abstracts of the talks given during the workshop.
Critical importance of appropriate fixation conditions for faithful imaging of receptor microclusters

ABSTRACT Receptor clustering is known to trigger signalling events that contribute to critical changes in cellular functions. Faithful imaging of such clusters by means of fluorescence microscopy relies on the application of adequate cell fixation methods prior to immunolabelling in order to avoid artefactual redistribution by the antibodies themselves. Previous work has highlighted the inadequacy of fixation with paraformaldehyde (PFA) alone for efficient immobilisation of membrane-associated molecules, and the advantages of fixation with PFA in combination with glutaraldehyde (GA). Using fluorescence microscopy, we here highlight how inadequate fixation can lead to the formation of artefactual clustering of receptors in lymphatic endothelial cells, focussing on the transmembrane hyaluronan receptors LYVE-1 and CD44, and the homotypic adhesion molecule CD31, each of which displays their native diffuse surface distribution pattern only when visualised with the right fixation techniques, i.e. PFA/GA in combination. Fluorescence recovery after photobleaching (FRAP) confirms that the artefactual receptor clusters are indeed introduced by residual mobility. In contrast, we observed full immobilisation of membrane proteins in cells that were fixed and then subsequently permeabilised, irrespective of whether the fixative was PFA or PFA/GA in combination. Our study underlines the importance of choosing appropriate sample preparation protocols for preserving authentic receptor organisation in advanced fluorescence microscopy. Summary: Commonly used fixation protocols during immunolabelling can result in artefactual protein distribution. We highlight the artefacts in images and provide fixation conditions for studying membrane receptor organisation.
UNDERSTANDINGS OF EMOTIONAL SALIENCE IN A PRESCHOOL CLASSROOM

The purpose of this research was to examine the ways in which preschoolers use artistic, kinaesthetic and linguistic modes of expression to recognize, label and understand feeling words of varied salience within a classroom environment. The ways in which a multi-modal approach towards emotional literacy in the classroom supported emotional literacy is examined. The research site was an urban preschool classroom in the lower mainland of British Columbia. Seventeen three-and-four-year-old children created drawings, kinaesthetically posed, and discussed feeling words of varied salience: ‘calm’, ‘happy’, and ‘ecstatic’, which served as the primary data source, supplemented with teacher observation notes. Analysis found that each mode offered unique insights into how young children recognize, understand and label feeling words of varied salience. Limitations of this study are discussed and suggestions for further research are offered.
Historical Contingency and Animal Diets: The Origins of Egg Eating in Snakes

Evolutionary changes in animal diets must often begin through the inclusion of a novel food type as a minor component of the diet. An aspect of this initial change that has rarely been studied is the relationship between the existing diet and the use of specific novel foods. We used comparative analyses to test the hypothesis that, in snakes, feeding on squamate (lizard and snake) eggs or bird eggs—items that represent evolutionarily derived and, in most cases, minor components of the diet—is associated with feeding on squamates or birds, respectively. Phylogenetic concentrated‐changes tests indicate a significant tendency for predation on eggs to arise in snake lineages characterized by feeding on the corresponding animals. These results also generally hold for analyses including only snake species that are likely to encounter eggs and are large enough to ingest them. The inferred histories of specialized egg eaters also support the hypothesis. Because snakes often use chemical cues to recognize prey, the observed phylogenetic patterns might be explained by chemical similarities between eggs and adult animals. Our results suggest broad effects of predispositions on snake diets and thus illustrate how historical contingencies can shape the ecology of organisms.
Independent component analysis using Gaussian mixture models

This paper discusses a method for performing independent component analysis exploiting Gaussian mixture models (GMMs). Previously most techniques that combine these methods have used GMMs to model the source signals. This paper considers a parsimonious method for modelling the observed signals. The GMM is fitted to the observed data using a modified version of the expectation maximisation algorithm.
Neural Recording Front-End Designs for Fully Implantable Neuroscience Applications and Neural Prosthetic Microsystems

An implantable neural recording front-end has been designed in two versions. The first is a multi-channel signal-conditioning ASIC for use with any neural recording probe technology. This ASIC was implemented in a commercial 0.5 mum CMOS process, includes 16 parallel amplifier channels, and measures 2.3 mm2 The amplifiers have a gain of 59.5 dB, a high cutoff frequency at 9.1 kHz and consume 75 muW per channel. The low cutoff frequency is independently tunable on each channel to accept or reject field potentials. This chip is small enough to be chronically packaged for experiments in awake behaving animals or it can be integrated into a fully implantable neural recording microsystem. The second version of the front-end is a neural recording probe with integrated signal conditioning circuitry on the back-end implemented in a 3 mum CMOS process. This version dissipates 142 muW and includes 64 to 8 site selection, 8 per-channel amplifiers each having a gain of 50.2 dB, a tunable low cutoff frequency, and a 7 kHz upper cutoff frequency. Real-time site impedance and circuit testing has been integrated in this design
Efficient Estimation of Firm-Specific Betas and its Benefits for Asset Pricing Tests and Portfolio Choice

We improve both the specification and estimation of firm-specific betas. Time variation in betas is modeled by combining a parametric specification based on economic theory with a non-parametric approach based on data-driven filters. We increase the precision of individual beta estimates by setting up a hierarchical Bayesian panel data model that imposes a common structure on parameters. We show that these accurate beta estimates lead to a large increase in the cross-sectional explanatory power of the conditional CAPM. Using the betas to forecast the covariance matrix of returns also results in a significant improvement in the out-of-sample performance of minimum variance portfolios.
Energy Efficiency with Adaptive Decoding Power and Wireless Backhaul Small Cell Selection

This paper considers the problem of maximizing energy efficiency on the downlink of two-tier wireless backhaul small cell heterogeneous networks, where an interference mitigation strategy that combines reverse time division duplexing and equally orthogonal spectrum splitting is proposed. By enabling the small cell access points with the capability of switching ON/OFF, we develop a joint design of transmit beamforming, power and small cell selection that maximizes the proposed weighted access energy efficiency metric. To better convey the total power consumption model, we assume the adaptive decoding power model at each small cell access point. The formulated problem is combinatorial and non-convex, which is NP-hard in general. Hence, to find a more realistic close-to-optimal feasible solution, we iteratively approximate the non-convex constraints in the formulated problem as second order cone ones based on the first order Taylor convex approximation and error-controlled second order cone approximation. The problem arrived at each iteration is a mixed integer second order cone programming, which can be solved optimally and efficiently by available dedicated solver to achieve the final result at convergence. Numerical results are studied to show the improvement of our proposed model compared to previous works.
Inconsistency of a recently proposed method for assessing magnetic field exposure for protection against peripheral nerve stimulation in occupational situations

A non-binding guide to practical implementation of European Directive 2013/35/EU concerning the limitation of occupational exposure against electromagnetic fields has been published recently. With regard to exposure assessment this guide proposes practically applicable assessment methods for non-uniform and non-sinusoidal environmental electric and magnetic fields, respectively. For non-sinusoidal magnetic fields in the low frequency range this guide proposes a time domain assessment (TDA) method, claimed to reduce the overestimation of exposure inherent to other assessment methods while being based on fundamental physiological principles regarding nerve stimulation. In the present paper we demonstrate that the proposed TDA method is not consistent with the obvious underlying principles of directive 2013/35/EU. Based on practically relevant waveforms and general considerations it can be shown that external magnetic fields may be deemed compliant by the TDA method although the underlying exposure limit values defined in 2013/35/EU may be exceeded. We therefore strongly recommend that the TDA method is removed from the guide for implementing 2013/35/EU as soon as possible.
3,4-Dicaffeoylquinic Acid, a Major Constituent of Brazilian Propolis, Increases TRAIL Expression and Extends the Lifetimes of Mice Infected with the Influenza A Virus

Brazilian green propolis water extract (PWE) and its chemical components, caffeoylquinic acids, such as 3,4-dicaffeoylquinic acid (3,4-diCQA), act against the influenza A virus (IAV) without influencing the viral components. Here, we evaluated the anti-IAV activities of these compounds in vivo. PWE or PEE (Brazilian green propolis ethanol extract) at a dose of 200 mg/kg was orally administered to Balb/c mice that had been inoculated with IAV strain A/WSN/33. The lifetimes of the PWE-treated mice were significantly extended compared to the untreated mice. Moreover, oral administration of 3,4-diCQA, a constituent of PWE, at a dose of 50 mg/kg had a stronger effect than PWE itself. We found that the amount of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) mRNA in the mice that were administered 3,4-diCQA was significantly increased compared to the control group, while H1N1 hemagglutinin (HA) mRNA was slightly decreased. These data indicate that PWE, PEE or 3,4-diCQA possesses a novel and unique mechanism of anti-influenza viral activity, that is, enhancing viral clearance by increasing TRAIL.
Effect of naturally-occurring gp41 HR1 variations on susceptibility of HIV-1 to fusion inhibitors

Background:Sequence variations in the gp41 heptad repeat 1 (HR1) region have been identified in some treatment-naive HIV-1-infected patients but it remained elusive whether they confer resistance to fusion inhibitors. Objective:To evaluate whether naturally occurring sequence variations in the HIV-1 group M gp41 HR1 region affect the sensitivity to inhibition by T-20 and T-1249. Methods:Site-directed mutagenesis was used to generate HIV-1 NL4-3 mutants containing changes in the gp41 HR1 domain which have been previously identified in treatment-naive patients infected with various HIV-1 group M subtypes. HIV-1 variants were produced by transient transfection of 293T cells and used to determine viral infectivity and sensitivity to the fusion inhibitors T-20 and T-1249. Results:Most naturally occurring sequence variations in the HR1 domain did not reduce viral infectivity. Three of the 10 HIV-1 variants analysed containing a single substitution of L33V, which is frequently present in subtype D isolates, or combined changes of L54M/Q56K or L34M/L54M/Q56R showed about fivefold reduced sensitivity to inhibition by T-20. In comparison, none of these HR1 sequence variations conferred resistance to T-1249. Conclusion:Some naturally occurring sequence variations in the gp41 HR1 region reduce sensitivity of HIV-1 to inhibition by T-20 but not T-1249.
Changes of spatial and temporal frequency tuning properties of neurons in the middle temporal area of aged rhesus monkeys

Aged humans exhibit severe deficits in visual motion perception and contrast sensitivity under various levels of spatial and temporal modulation. Previous studies indicated that many of these deficits are probably mediated by the neural degradation of the central visual system. To clarify the neuronal response mechanisms underlying the visual degradation during aging, we examined the spatial and temporal frequency tuning properties of neurons from anesthetised and paralysed aged monkeys at the middle temporal area (area MT), which is downstream of the primary visual cortex in the visual processing pathway and thought to be critical for motion perception. We found that the preferred spatial and temporal frequencies, spatial resolution and high temporal frequency cutoff of area MT neurons were reduced in aged monkeys, and were accompanied by the broadened tuning width of spatial frequency, elevated spontaneous activity, and decreased signal‐to‐noise ratio. These results showed that, for neurons in area MT, aging significantly changed both the spatial and temporal frequency response tuning properties. Such evidence provides new insight into the changes occurring at the electrophysiological level that may be related to the aging‐related visual deficits, especially in processing spatial and temporal information.
A novel 165-base-pair terminal repeat sequence is the sole cis requirement for the adeno-associated virus life cycle

Adeno-associated virus (AAV) replication is dependent on two copies of a 145-bp inverted terminal repeat (ITR) that flank the AAV genome. This is the primary cis-acting element required for productive infection and the generation of recombinant AAV (rAAV) vectors. We have engineered a plasmid (pDD-2) containing only 165 bp of AAV sequence: two copies of the D element, a unique sequence adjacent to the AAV nicking site, flanking a single ITR. When assayed in vivo, this modified hairpin was sufficient for the replication of the plasmid vector when Rep and adenovirus (Ad) helper functions were supplied in trans. pDD-2 replication intermediates were characteristic of the AAV replication scheme in which linear monomer, dimer, and other higher-molecular-weight replicative intermediates are generated. Compared to infectious AAV clones for replication, the modified hairpin vector replicated more efficiently independent of size. Further analysis demonstrated conversion of the input circular plasmid to a linear substrate with AAV terminal repeat elements at either end as an initial step for replication. This conversion was independent of both Rep and Ad helper genes, suggesting the role of host factors in the production of these molecules. The generation of these substrates suggested resolution of the modified terminal repeat through a Holliday-like structure rather than replication as a mechanism for rescue. Production of replicative intermediates via this plasmid substrate were competent not only for AAV DNA replication but also for encapsidation, infection, integration, and subsequent rescue from the chromosome when superinfected with Ad and wild-type AAV. These studies demonstrate that this novel 165-bp ITR substrate is sufficient in cis for the AAV life cycle and should provide a valuable reagent for further dissecting the cis sequences involved in AAV replication, packaging, and integration. In addition, this novel plasmid vector can be used as a substrate for both rAAV vector production and synthetic plasmid vector delivery.