Miracle-dz/UniFAR-FTUs huggingface dataset:
Island Cells Control Temporal Association Memory

Entorhinal Cell Clusters There is considerable interest in understanding the function of neurons in layer 2 of the medial entorhinal cortex and how they generate their unique firing patterns, which are important in the recall of facts and past events (see the Perspective by Blair). Ray et al. (p. 891, published online 23 January) investigated principal cells in layer 2 by immunoreactivity, projection patterns, microcircuit analysis, and assessment of temporal discharge properties in awake, freely moving animals. In tangential sections, pyramidal neurons were clustered into patches arranged in a hexagonal grid—very similar to the patterns observed in grid cell spatial firing. These patches received selective cholinergic innervation, which is critical for sustaining grid cell activity. Kitamura et al. (p. 896, published online 23 January) found that these cells drive a hippocampal circuit by projecting directly to the hippocampal CA1 area and synapsing with a distinct class of inhibitory neurons. This circuit provides feed-forward inhibition in combination with excitatory inputs from layer 3 cells of the medial entorhinal cortex, projecting to CA1 pyramidal cells to determine the strength and time window of temporal associative inputs. A distinct set of excitatory neurons in the entorhinal cortex projects directly to specific interneurons in the hippocampus. [Also see Perspective by Blair] Episodic memory requires associations of temporally discontiguous events. In the entorhinal-hippocampal network, temporal associations are driven by a direct pathway from layer III of the medial entorhinal cortex (MECIII) to the hippocampal CA1 region. However, the identification of neural circuits that regulate this association has remained unknown. In layer II of entorhinal cortex (ECII), we report clusters of excitatory neurons called island cells, which appear in a curvilinear matrix of bulblike structures, directly project to CA1, and activate interneurons that target the distal dendrites of CA1 pyramidal neurons. Island cells suppress the excitatory MECIII input through the feed-forward inhibition to control the strength and duration of temporal association in trace fear memory. Together, the two EC inputs compose a control circuit for temporal association memory.
Principal-principal conflicts and family firm growth: The moderating role of business family identity

Purpose Drawing on the principal-principal conflict and identity literatures, the purpose of this paper is to investigate the Agency Problem Type II-bis in the context of family business. Specifically, the authors hypothesize that the size of the family owner group is related to firm growth and that this relationship is moderated by the extent to which the family identifies with the firm. Design/methodology/approach The hypotheses are tested on a sample of 265 medium and large German family firms (FFs) via moderated hierarchical regression analysis. Findings The main findings suggest that business family identity moderates the inverted U-shaped relationship between the size of the family owner group and firm growth in such a way that FFs with medium-sized family owner groups and high levels of business family identity reach higher firm growth. Practical implications In the context of FFs fully owned by one family, family owners might have different strategic preferences, goals, and identities, thus potentially making them subject to the conflict that could arise among the different family owners in relation to growth expectations. Recognizing this problem could help family owners find potential solutions to ensure the well-being of both the family and the business. Originality/value The combination of family ownership structure and family ownership dynamics affects firm growth. Challenging the homogeneity of the family owner group, the authors highlight the role of Agency Problem Type II-bis in hindering growth of FFs. A finer-grained view of principal-principal conflicts in FFs is thus discussed.
Long-term channelrhodopsin-2 (ChR2) expression can induce abnormal axonal morphology and targeting in cerebral cortex

Long-term expression of optogenetic proteins including channelrhodopsin-2 (ChR2) is widely used to study neural circuit function, but whether ChR2 expression itself perturbs circuits is not known. We expressed a common construct, CAG::ChR2 (H134R)-EYFP-WPRE, in L2/3 pyramidal cells in rat somatosensory cortex via in utero DNA electroporation (IUE). L2/3 pyramidal cells expressed ChR2-EYFP, but histology revealed abnormal morphology and targeting of ChR2-EYFP expressing axons, beginning at postnatal day (P) 33 and increasing with age. Axonal abnormalities included cylinders that enveloped pyramidal cell proximal apical dendrites, and spherical, calyx-like structures that surrounded neuronal cell bodies, including in L4. These are abnormal subcellular and laminar targets for L2/3 pyramidal cell synapses. Abnormalities did not occur in cells expressing GFP instead of ChR2, or in intermixed ChR2-negative axons. Long-term viral-mediated expression (80 d) did not cause axonal abnormalities when the CAG promoter was used, but produced some abnormalities with the stronger αCaMKII promoter (albeit much less than with in utero electroporation). Thus, under some circumstances high-level, long-term expression of ChR2-EYFP can perturb the structural organization of cortical circuits.
Behavioral / Systems / Cognitive Hippocampal Inactivation Disrupts the Acquisition and Contextual Encoding of Fear Extinction

In recent studies, inactivation of the dorsal hippocampus before the retrieval of extinguished fear memories disrupted the contextdependent expression of these memories. In the present experiments, we examined the role of the dorsal hippocampus in the acquisition of extinction. After pairing an auditory conditional stimulus (CS) with an aversive footshock [unconditional stimulus (US)], rats received an extinction session in which the CS was presented without the US. In experiment 1, infusion of muscimol, a GABAA receptor agonist, into the dorsal hippocampus before the extinction training session decreased the rate of extinction. Moreover, when later tested for fear to the extinguished CS, all rats that had received hippocampal inactivation before extinction training demonstrated renewed fear regardless of the context in which testing took place. This suggests a role for the dorsal hippocampus in both acquiring the extinction memory and encoding the CS– context relationship that yields the context dependence of extinction. In experiment 2, inactivation of the dorsal hippocampus before testing also disrupted the context dependence of fear to the extinguished CS. In experiment 3, quantitative autoradiography revealed the boundaries of muscimol diffusion after infusion into the dorsal hippocampus. Together, these results reveal that the dorsal hippocampus is involved in the acquisition, contextual encoding, and context-dependent retrieval of fear extinction. Learning and remembering when and where aversive events occur is essential for adaptive emotional regulation.
A latent neurogenic program in astrocytes regulated by Notch signaling in the mouse

Neurogenesis is restricted in the adult mammalian brain; most neurons are neither exchanged during normal life nor replaced in pathological situations. We report that stroke elicits a latent neurogenic program in striatal astrocytes in mice. Notch1 signaling is reduced in astrocytes after stroke, and attenuated Notch1 signaling is necessary for neurogenesis by striatal astrocytes. Blocking Notch signaling triggers astrocytes in the striatum and the medial cortex to enter a neurogenic program, even in the absence of stroke, resulting in 850 ± 210 (mean ± SEM) new neurons in a mouse striatum. Thus, under Notch signaling regulation, astrocytes in the adult mouse brain parenchyma carry a latent neurogenic program that may potentially be useful for neuronal replacement strategies. Astrocytes can produce neuroblasts in response to stroke and can be artificially triggered to do so in the absence of injury. Astrocytes' hidden ability to generate neurons New neurons could be useful in the brain to respond to damage done by disease, trauma, or just plain age. But the adult brain does not produce many new neurons. Working in mice, Magnusson et al. hunted for intrinsic genetic programs that can help adult brains produce replacement neurons. They found that astrocytes, spidery cells that are interspersed between neurons, carry a latent neurogenic program. The ability to entice astrocytes to replace neurons could obviate the need for neuronal replacement strategies. Science, this issue p. 237
The effects of ellipticity and substructure on estimates of cluster density profiles based on lensing and kinematics

We address the question of how well the density profile of galaxy clusters can be determined by combining strong lensing and velocity dispersion data. We use cosmological dark matter simulations of clusters to test the reliability of the method, producing mock catalogues of tangential and radial gravitational arcs and simulating the radial velocity dispersion profile of the cluster brightest central galaxy. The density profiles of the simulated clusters closely follow the Navarro, Frenk & White (NFW) form, but we find that the recovered values of the inner slope are systematically underestimated, by about 0.4 in the mean, if the lens is assumed to be axially symmetric. However, if the ellipticity and orientation of the isocontours of the cluster lensing potential are taken into account, then the inner slopes can be recovered quite accurately for a significant subset of the clusters whose central surface density profiles appear the most regular. These have lensing potentials with ellipticities in the range 0.15‐0.4. Further simulations projecting one cluster along many random lines of sight show that, even for lower ellipticities, the central slopes are underestimated by ∼10‐35 per cent. These simulations closely mimic past observations, suggesting that existing estimates of the central slopes may be biased towards low values. For the remaining clusters, where the lensing potential is strongly perturbed by active merging or by substructure, the correct determination of the inner slope requires a more accurate model for the lens. When the halo profile is modelled by a generalized NFW profile, we find that the inferred scale radius and characteristic density, unlike the inner slope, are generally poorly constrained, since there is a strong degeneracy between these two
The “Artistic Image” Concept Applied to a Fugue at the Early Stage of Piano Practice: An Observational Study

This article presents the results of an investigation on the concept of “artistic image of a musical composition” proposed by Heinrich Neuhaus (1888-1964) at the initial stage of learning a fugue by J.S. Bach. The data was gathered during the first practice session of six undergraduate piano majors learning a fugue, all from two public universities in southern Brazil. The concepts proposed by Neuhaus served as a parameter for an observational study of the students’ behavior and the technical-musical activities undertaken during their practice. The aim was to verify if the concept of artistic image had been used during practice and, if so, how it was established. We also examined the study strategies that helped comprehend the musical content, guiding the learning process and organization of practice. The results should assist in increasing our knowledge of the processes involving piano practice and the strategies linked to the concept of artistic image, stressing empirical observation as an important tool to validate theoretical concepts.
More human than human: does the uncanny curve really matter?

Anthropomorphism is a common phenomenon known already in ancient times. It is not a thing of the past, but still has a profound impact on major aspects of our lives and on research in AI and HRI. Its importance in the field of HRI is emphasized by the hotly-discussed uncanny valley hypothesis. However, in spite of its popularity, the uncanny valley hypothesis lacks empirical evidence. In this paper we suggest that the community should stop trying to fit data to this hypothesis, but rather, based on the available evidence, start talking about the 'uncanny curve'. Moreover, we point out mistakes in the previous studies of the uncanny curve and strongly encourage exploring it in a real HRI for it to be really relevant. We suggest that understanding the opposite process of anthropomorphisation, known as dehumanization, can help to cross the uncanny bottom of the graph.
Salivary Gland Branching Morphogenesis — Recent Progress and Future Opportunities

Salivary glands provide saliva to maintain oral health, and a loss of salivary gland function substantially decreases quality‐of‐life. Understanding the biological mechanisms that generate salivary glands during embryonic development may identify novel ways to regenerate function or design artificial salivary glands. This review article summarizes current research on the process of branching morphogenesis of salivary glands, which creates gland structure during development. We highlight exciting new advances and opportunities in studies of cell‐cell interactions, mechanical forces, growth factors, and gene expression patterns to improve our understanding of this important process.
On counting position weight matrix matches in a sequence, with application to discriminative motif finding

MOTIVATION AND RESULTS The position weight matrix (PWM) is a popular method to model transcription factor binding sites. A fundamental problem in cis-regulatory analysis is to "count" the occurrences of a PWM in a DNA sequence. We propose a novel probabilistic score to solve this problem of counting PWM occurrences. The proposed score has two important properties: (1) It gives appropriate weights to both strong and weak occurrences of the PWM, without using thresholds. (2) For any given PWM, this score can be computed while allowing for occurrences of other, a priori known PWMs, in a statistically sound framework. Additionally, the score is efficiently differentiable with respect to the PWM parameters, which has important consequences for designing search algorithms. The second problem we address is to find, ab initio, PWMs that have high counts in one set of sequences, and low counts in another. We develop a novel algorithm to solve this "discriminative motif-finding problem", using the proposed score for counting a PWM in the sequences. The algorithm is a local search technique that exploits derivative information on an objective function to enhance speed and performance. It is extensively tested on synthetic data, and shown to perform better than other discriminative as well as non-discriminative PWM finding algorithms. It is then applied to cis-regulatory modules involved in development of the fruitfly embryo, to elicit known and novel motifs. We finally use the algorithm on genes predictive of social behavior in the honey bee, and find interesting motifs. AVAILABILITY The program is available upon request from the author.
Stationary states of quadratic diffusion equations with long-range attraction

We study the existence and uniqueness of nontrivial stationary solutions to a nonlocal aggregation equation with quadratic diusion arising in many contexts in population dynamics. The equation is the Wasserstein gradient ow generated by the energy E, which is the sum of a quadratic free energy and the interaction energy. The interaction kernel is taken radial and attractive, nonnegative and integrable, with further technical smoothness assumptions. The existence vs. nonexistence of such solutions is ruled by a threshold phenomenon, namely nontrivial steady states exist if and only if the diusivity constant is strictly smaller than the total mass of the interaction kernel. In the one dimensional case we prove that steady states are unique up to translations and mass constraint. The strategy is based on a strong version of the Krein-Rutman theorem. The steady states are symmetric with respect to their center of mass x0, compactly supported on sets of the form (x0 L;x0 + L), C 2 on their support, strictly decreasing on (x0;x0+L). Moreover, they are global minimizers of the energy functional E. The results are complemented by numerical simulations.
The Open University ’ s repository of research publications and other research outputs TGVizTab : An ontology visualisation extension for Prot Conference Item

Ontologies are gaining a lot of interest and many are being developed to provide a variety of knowledge services. There is an increasing need for tools to graphically and interactively visualise such modelling structures to enhance their clarification, verification and analysis. Protégé 2000 is one of the most popular ontology modelling tools currently available. This paper introduces TGVizTab; a new Protégé plugin based on TouchGraph technology to graphically visualise Protégé’s ontologies.
Section Ii-exercise Physiology & Sports Medicine the Effect of the Mthfr C677t Mutation on Athletic Performance and the Homocysteine Level of Soccer Players and Sedentary Individuals

This study investigated athletic performance and homocysteine (Hcy) levels in relation to the methylenetetrahydrofolate reductase (MTHFR) C677T mutation and explored the relationship between this mutation and other cardiac risk factors in soccer players and sedentary individuals. The study groups consisted of randomly selected soccer players (n=48) from the Turkish Super and Major League and sedentary male students (n=48) aged 18-27. Anthropometric variables, aerobic and anaerobic thresholds were measured, furthermore, biochemical assays were performed. The level of HDL cholesterol, LDL cholesterol, triglyceride, Hcy, folate, vitamin B12, hemogram and MTHFR C677T was investigated. The results showed that there was a statistical difference between the two groups in terms of body mass, body fat, the BMI, the aerobic threshold heart rate (ATHR), aerobic threshold velocity (ATVL) and anaerobic threshold velocity (ANTVL). The soccer players were found to have lower levels of triglyceride, total cholesterol and LDL cholesterol, and higher levels of folate than the sedentary participants. The analysis of the alleles of the MTHFR C677T polymorphism showed that the participants that carried TT genotypes had a lower level of vitamin B12 and folate, and a higher level of Hcy than the participants carrying CC and CT genotypes. In conclusion, the baseline homocysteine and cardiovascular fitness levels of healthy young males with the TT genotypes of the MTHFR C677T genotype were found to strongly correlate with their levels of Hcy.
Need Satisfaction Supportive Game Features as Motivational Determinants: An Experimental Study of a Self-Determination Theory Guided Exergame

Empirical studies have validated that basic needs satisfaction supported by video game play predicts motivation and engagement outcomes. However, few studies specifically manipulated game features for each of the three basic needs specified in the self-determination theory (SDT) to examine how the game features impact players' need satisfaction and game experience. The current study employed an in-house developed exergame and manipulated the game features in a 2 (autonomy-supportive game features: on vs. off) × 2 (competence-supportive game features: on vs. off) experiment to predict need satisfaction, game enjoyment, motivation for future play, effort for gameplay, self-efficacy for exercise using the game, likelihood of game recommendation, and game rating. The manipulated game features led to the corresponding need satisfaction. Manipulated autonomy-supportive and competence-supportive game features had main effects on most motivation and engagement outcomes. Need satisfaction of autonomy and need satisfaction of competence were both found to be mediators for the relationships between the game features and the motivation and engagement outcomes. The findings add evidence to support the underlying mechanism postulated by SDT for media enjoyment and motivation as well as the emerging entertainment research conceptualizing enjoyment as need satisfaction. The findings also have practical implications for intervention effort that intends to capitalize the motivational pull of video games.
Positive curvature, local and global symmetry, and fundamental groups

A π1 -invariant torus-action on a manifold M is a T k -action on the universal covering which extends to the action of a semi-direct product π1 ( M )×ρ T k . In particular, the T k -action is the lift of a T k -action on M if ρ is the identity map. The main result asserts that if a compact manifold M n of positive sectional curvature admits a π1 -invariant isometric T k -action, then the fundamental group has a cyclic subgroup of index ≤ w ( n ). This refines the main result in [Ro1].
Total variation based 3D skull segmentation

Segmentation is widely used for determining tumor and other lesions and classifying tissues for various analysis purposes in medical images. However, being an ill-posed problem, there is no single segmentation method which can perform successfully for all kind of data. In this study, a novel total variation (TV) based skull segmentation method is proposed. Skull segmentation performance of the proposed method is shown using computed tomography (CT) images.
Intravitreal Triamcinolone Acetonide Inhibits Breakdown of the Blood-Retinal Barrier Through Differential Regulation of VEGF-A and Its Receptors in Early Diabetic Rat Retinas

OBJECTIVE To elucidate the mechanism of the unique beneficial effect of intravitreal steroid therapy on diabetic macular edema, we investigated the effect of locally administered triamcinolone acetonide (TA) on the expression of vascular endothelial growth factor (VEGF)-A and its receptors in retinas of rats with streptozotocin (STZ)-induced diabetes. We then correlated the expression of these proteins with breakdown of the blood-retinal barrier (BRB). RESEARCH DESIGN AND METHODS Thirty-two eyes of 16 diabetic and nondiabetic rats were divided into four groups. TA was injected into the vitreous of the right eye, and saline was injected into the left eye (control) 3.5 weeks after induction of diabetes. Retinas were harvested 48 h following treatment. mRNA and protein expression of VEGF-A, VEGF-A receptor 1 (fms-like tyrosine kinase [FLT]-1), and VEGF-A receptor 2 (fetal liver kinase [FLK]-1) were determined by real-time RT-PCR and immunohistochemistry. BRB permeability was quantitated by measuring extravasated endogenous albumin and retinal thickness. RESULTS Diabetes-induced retinal thickness and albumin extravasation were significantly reduced in TA-treated diabetic retinas to a level similar to that in sham-treated nondiabetic eyes. A close correlation between albumin leakage and increased expression of both Vegf-a and Flk-1 was noted in the diabetic retinas. TA downregulated the expression of Vegf-a and Flk-1 but upregulated the expression of Flt-1. TA did not alter the expression of these genes in nondiabetic retinas. CONCLUSIONS Intravitreal injection of TA stabilizes the BRB in association with regulation of Vegf-a, Flk-1, and Flt-1 expression in retinas in the early stages of diabetes.