Miracle-dz/UniFAR-FTUs huggingface dataset:
Planar Location Problems with Barriers under Polyhedral Gauges

The Weber problem for a given finite set of existing facilities {cal E}x = {Ex_1,Ex_2, . ,Ex_M} subset R^2 with positive weights w_m (m = 1, . ,M) is to find a new facility X* in R^2 such that sum_{m=1}^{M} w_{m}d(X,Ex_m) is minimized for some distance function d. In this paper we consider distances defined by polyhedral gauges. A variation of this problem is obtained if barriers are introduced which are convex polygonal subsets of the plane where neither location of new facilities nor traveling is allowed. Such barriers like lakes, military regions, national parks or mountains are frequently encountered in practice.From a mathematical point of view barrier problems are difficult, since the prensence of barriers destroys the convexity of the objective function. Nevertheless, this paper establishes a descretization result: One of the grid points in the grid defined by the existing facilities and the fuundamental directions of the gauge distances can be proved to be an optimal location. Thus the barrier problem can be solved with a polynomial algorithm.
The impact of incidental anxiety on the neural signature of mentalizing

While the effects of anxiety on various cognitive processes, including memory, attention, and learning, have been relatively well documented, the neurobiological effects of anxiety on social cognitive processes remain largely unknown. We address this gap using threat-of-shock to induce incidental anxiety while participants performed two false-belief tasks, a standard and an economic-games version. During belief formation and belief inferences, regions in a canonical social cognition network showed activation reflecting mentalizing, including the temporoparietal junction (TPJ), precuneus, and dorsomedial prefrontal cortex (dmPFC). At the same time, we found threat-related suppression of social cognition regions during belief inferences. A conjunction analysis confirmed that a network of regions was simultaneously engaged during mentalizing and suppressed by anxiety: bilateral TPJ, bilateral IFG, and putamen. We examined how threat impacted the connectivity between seed regions from the conjunction analyses and its targets. During belief formation, we found that anxiety suppressed the connectivity between the precuneus seed and two key mentalizing nodes, the dmPFC and right TPJ. Moreover, during belief inferences threat specificallty suppressed belief-based connectivity between putamen and its targets in IPS and dlPFC, and dispositional distress significantly modulated threat-related suppression of connectivity between the left TPJ seed and left IPS. Our results highlight important effects of incidental and dispositional anxiety on specific nodes of the social cognition network. Taken together, our study uncovers novel interactions between the reward, social cognition, and attentional systems, indicating that social cognitive processes rely on support from other large-scale networks, and that these network interactions are disrupted under incidental anxiety.
Molecular Basis of Kv1 Channel Downregulation and Its Epileptogenic Implications in Lgi1 Knock-out Mice

The Kv1 members (KCNA, Shaker) of the voltage-gated potassium channels are implicated in determining key functional neuronal properties from spike generation at axonal initial segments to the control of synaptic strength at nerve terminals. In animal models of LGI1-dependent autosomal dominant lateral temporal lobe epilepsy (ADTLE), Kv1 channels are downregulated, suggesting their crucial involvement in epileptogenesis. The molecular basis of Kv1 channel-downregulation in LGI1 knock-out mice has not been elucidated and how the absence of this extracellular protein induces an important modification in the expression of Kv1 remains unknown. In this study we analyse by immunofluorescence the detailed modifications in neuronal Kv1.1 and Kv1.2 distribution throughout the hippocampal formation of LGI1 knock-out mice. We show that Kv1 downregulation is not restricted to the axonal compartment, but also takes place in the somatodendritic region and is accompanied by a drastic decrease in Kv2 expression levels. Moreover, we find that the downregulation of these Kv channels is associated with an important increase in bursting patterns. Finally, mass spectrometry uncovered key important modifications in the Kv1 interactome that highlight the epileptogenic implication of Kv1 downregulation in LGI1 knock-out animals.
How Veeries vary: Whole genome sequencing resolves fine-scale genetic structure in a long-distance migratory bird, Catharus fuscescens

Fine-scale resolution of spatial genetic structure is important for understanding a species’ evolutionary history and contemporary genetic diversity. For high-latitude species with high dispersal ability, such as long-distance migratory birds, populations typically exhibit little genetic structure due to high gene flow and recent postglacial expansion. Some migratory birds, however, show high breeding site fidelity, which might reduce gene flow such that population genetic structure could be detectable with sufficient genomic data. We sequenced over 120 low-coverage whole genomes from across the breeding range of a long-distance migratory bird, the Veery (Catharus fuscescens). As this species’ breeding range extends across both historically glaciated and unglaciated regions in North America, we evaluated whether contemporary patterns of structure and genetic diversity are consistent with historical population isolation in glacial refugia. We found strong evidence for isolation by distance across the breeding range, as well as significant population structure between southern Appalachian and northern populations. However, patterns of genetic diversity did not support southern Appalachia as a glacial refugium. Resolution of isolation by distance across the breeding range was sufficient to assign likely breeding origins of individuals sampled in this species’ poorly understood South American nonbreeding range, demonstrating the potential to assess migratory connectivity in this species using genomic data. Overall, our findings suggest that isolation by distance yields subtle associations between genetic structure and geography across the breeding range even in the absence of obvious historical vicariance or contemporary barriers to dispersal.
Mathematical Discourse in Elementary Classrooms

Mathematic reasoning of elementary aged students in the United States is low compared to other like nations. For students living in poverty the disparity is even greater. Previous research has linked mathematical discourse with the improvement of mathematic conceptual understanding and reasoning. This research, which employed a qualitative case study methodology, examined six elementary classrooms, to investigate the complex nature of including mathematical discourse in instruction. The purpose of examining mathematical discourse in elementary classrooms was to provide contextual insight into teacher beliefs about mathematical discourse, how instruction was prepared and facilitated by the teacher, and how students responded through participation. Interview, observation, and artifact data were gathered, and cross analyzed. First, this study suggested that a combination of post-graduate coursework, adopted curriculum, and district professional development supported participating teachers to develop the content and pedagogical knowledge needed to include mathematical discourse in their instruction. Secondly, this study indicated that a teacher’s personal experience with mathematic learning influenced his or her beliefs and impacted his or her instructional practices. Finally, a discrepancy in the cognitive level of discussions between high and low poverty 4 and 6 grade classrooms was noted, but no difference in participation was noted in 2 grade classrooms. This study supports current research by cross analyzing six in-depth case studies and providing insights into commonalities and differences in teacher beliefs, instructional preparation and facilitation, as well as, student participation.
Single-cell gene expression prediction from DNA sequence at large contexts

Human genetic variants impacting traits such as disease susceptibility frequently act through modulation of gene expression in a highly cell-type-specific manner. Computational models capable of predicting gene expression directly from DNA sequence can assist in the interpretation of expression-modulating variants, and machine learning models now operate at the large sequence contexts required for capturing long-range human transcriptional regulation. However, existing predictors have focused on bulk transcriptional measurements where gene expression heterogeneity can be drowned out in broadly defined cell types. Here, we use a transfer learning framework, seq2cells, leveraging a pre-trained epigenome model for gene expression prediction from large sequence contexts at single-cell resolution. We show that seq2cells captures cell-specific gene expression beyond the resolution of pseudo-bulked data. Using seq2cells for variant effect prediction reveals heterogeneity within annotated cell types and enables in silico transfer of variant effects between cell populations. We demonstrate the challenges and value of gene expression and variant effect prediction at single-cell resolution, and offer a path to the interpretation of genomic variation at uncompromising resolution and scale.
processus fractionnaires via le calcul de Malliavin et applications en statistique

Cette these se decompose en six chapitres plus ou moins distincts. Cependant, tous font appel au calcul de Malliavin, aux notions de processus gaussien et processus de Levy, et a leur utilisation en statistique. Chacune des trois parties a fait l'objet de deux articles. Dans la premiere partie, nous etablissons les theoremes d'Ito et deTanaka pour le mouvement brownien bifractionnaire multidimensionnel. Ensuite nous etudions l'existence de la densite d'occupation pour certains processus en relation avec le mouvement brownien fractionnaire. Dans la deuxieme partie, nous analysons, dans un premier temps, le comportement asymptotique de la variation cubique pour le processus de Rosenblatt. Dans un deuxieme temps, nous construisons d'une part des estimateurs efficace pour la derive de mouvement brownien fractionnaire et d'autre part des estimateurs biaises de type James-Stein qui dominent, sous le riqsue quadratique usuel, l'estimateur du maximum de vraisemblance. La derniere partie presente deux travaux. Dans le premier, nous utilisons une approche menant a un calcul de Malliavin pour les processus de Levy, qui a ete developpee recemment par Sole et al. , et nous etudions des processus anticipes de type integrale d'Ito-Skorohod sur l'espace de Levy. Dans le deuxieme, nous etudions le lien entre les processus stables et les processus auto-similaires, a travers des processus qui sont infiniment divisibles en temps.
Tartrolon sensing and detoxification by the Listeria monocytogenes timABR resistance operon

Listeria monocytogenes is a foodborne bacterium that naturally occurs in the soil. Originating from there, it contaminates crops and infects farm animals and their consumption by humans may lead to listeriosis, a systemic life-threatening infectious disease. The adaptation of L. monocytogenes to such contrastive habitats is reflected by the presence of virulence genes for host infection and other genes for survival under environmental conditions. Among the latter are ABC transporters for excretion of antibiotics produced by environmental competitors, however, most of these transporters have not been characterized. Here, we generated a collection of promoter-lacZ fusions for genes encoding ABC-type drug transporters of L. monocytogenes and screened this reporter strain collection for induction using a library of natural compounds produced by various environmental microorganisms. We found that the timABR locus (lmo1964-lmo1962) was induced by the macrodiolide antibiotic tartrolon B, which is synthesized by the soil myxobacterium Sorangium cellulosum. Tartrolon B resistance of L. monocytogenes was dependent on timAB, encoding the ATPase and the permease component of a novel ABC transporter. Moreover, transplantation of timAB was sufficient to confer tartrolon B resistance to Bacillus subtilis. Expression of the timABR locus was found to be auto-repressed by the TimR repressor, whose repressing activity was lost in the presence of tartrolon B. We also demonstrate that tartrolon sensitivity was suppressed by high external potassium concentrations, suggesting that tartrolon acts as potassium ionophore. Our results help to map the ecological interactions of an important human pathogen with its co-residing species within their joint natural reservoir. Importance Listeria monocytogenes is an environmental bacterium that can cause listeriosis in humans when ingested. The genome of this bacterium contains many genes encoding putative ATP binding cassette transporters with unknown function. Presumably, these transporters serve the excretion of antimicrobial compounds produced by co-residing species competing with L. monocytogenes for nutrients and habitats. We here fused the lacZ reporter gene to the promoters of these transporter genes and screened a natural compound library for activating substances. We discovered that tartrolon B activates expression of the L. monocytogenes timABR operon, encoding the TimAB exporter and the TimR repressor. Tartrolon B is an antibiotic produced by the soil-dwelling myxobacterium Sorangium cellulosum. We elucidate how the timABR genes mediate sensing and detoxification of this antibiotic. This represents the first known mechanism of tartrolon resistance and may help to better define the natural reservoir of L. monocytogenes.
Inducing a meditative state by artificial perturbations: A causal mechanistic understanding of brain dynamics underlying meditation

Contemplative neuroscience has increasingly explored meditation using neuroimaging. However, the brain mechanisms underlying meditation remain elusive. Here, we implemented a causal mechanistic framework to explore the spatiotemporal dynamics of expert meditators during meditation and rest. We first applied a model-free approach by defining a probabilistic metastable substate (PMS) space for each state, consisting of different probabilities of occurrence from a repertoire of dynamic patterns. Different brain signatures were mainly found in the triple-network model (i.e., the executive control, salience, and default-mode networks). Moreover, we implemented a model-based approach by adjusting the PMS of the resting state to a whole-brain model, which enabled us to explore in silico perturbations to transition to the meditation state. Consequently, we assessed the sensitivity of different brain areas regarding their perturbability and their mechanistic local-global effects. Using a synchronous protocol, we successfully transitioned from the resting state to the meditative state by shifting areas mainly from the somatomotor and dorsal attention networks. Overall, our work reveals distinct whole-brain dynamics in meditation compared to rest, and how the meditation state can be induced with localized artificial perturbations. It motivates future work regarding meditation as a practice in health and as a potential therapy for brain disorders.
Genetic context drives age‐related disparities in synaptic maintenance and structure across cortical and hippocampal neuronal circuits

The disconnection of neuronal circuits through synaptic loss is presumed to be a major driver of age-related cognitive decline. Age-related cognitive decline is heterogeneous, yet whether genetic mechanisms differentiate successful from unsuccessful cognitive decline through synaptic structural mechanisms remains unknown. Previous work using rodent and primate models leveraged various techniques to suggest that age-related synaptic loss is widespread on pyramidal cells in prefrontal cortex (PFC) circuits but absent on those in area CA1 of the hippocampus. Here, we examined the effect of aging on synapses on projection neurons forming a hippocampal-cortico-thalamic circuit important for spatial working memory tasks from two genetically distinct mouse strains that exhibit susceptibility (C57BL/6J) or resistance (PWK/PhJ) to cognitive decline during aging. Across both strains, synapses on the CA1-to-PFC projection neurons appeared completely intact with age. In contrast, we found synapse loss on PFC-to-nucleus reuniens (RE) projection neurons from aged C57BL/6J but not PWK/PhJ mice. Moreover, synapses from aged PWK/PhJ mice but not from C57BL/6J exhibited morphological changes that suggest increased synaptic efficiency to depolarize the parent dendrite. Our findings suggest resistance to age-related cognitive decline results in part by age-related synaptic adaptations, and identification of these mechanisms in PWK/PhJ mice could uncover new therapeutic targets for promoting successful cognitive aging and extending human health span.
Visual feature tuning properties of stimulus-driven saccadic inhibition in macaque monkeys

Saccadic inhibition refers to a short-latency transient cessation of saccade generation after visual sensory transients. This oculomotor phenomenon occurs with a latency that is consistent with a rapid influence of sensory responses, such as stimulus-induced visual bursts, on oculomotor control circuitry. However, the neural mechanisms underlying saccadic inhibition are not well understood. Here, we exploited the fact that macaque monkeys experience robust saccadic inhibition to test the hypothesis that inhibition time and strength exhibit systematic visual feature tuning properties to a multitude of visual feature dimensions commonly used in vision science. We measured saccades in three monkeys actively controlling their gaze on a target, and we presented visual onset events at random times. Across six experiments, the visual onsets tested size, spatial frequency, contrast, motion direction, and motion speed dependencies of saccadic inhibition. We also investigated how inhibition might depend on the behavioral relevance of the appearing stimuli. We found that saccadic inhibition starts earlier, and is stronger, for large stimuli of low spatial frequencies and high contrasts. Moreover, saccadic inhibition timing depends on motion direction, with earlier inhibition systematically occurring for horizontally than for vertically drifting gratings. On the other hand, saccadic inhibition is stronger for faster motions, and when the appearing stimuli are subsequently foveated. Besides documenting a range of feature tuning dimensions of saccadic inhibition on the properties of exogenous visual stimuli, our results establish macaque monkeys as an ideal model system for unraveling the neural mechanisms underlying a highly ubiquitous oculomotor phenomenon in visual neuroscience. New and noteworthy Visual onsets dramatically reduce saccade generation likelihood with very short latencies. Such latencies suggest that stimulus-induced visual responses, normally jumpstarting perceptual and scene analysis processes, can also directly impact the decision of whether to generate saccades or not, causing saccadic inhibition. Consistent with this, we found that changing the appearance of the visual onsets systematically alters the properties of saccadic inhibition. These results constrain neurally-inspired models of coordination between saccade generation and exogenous sensory stimulation.
Species -Shared and -Unique Gyral Peaks on Human and Macaque Brains

Cortical folding is an important feature of primate brains that plays a crucial role in various cognitive and behavioral processes. Extensive research has revealed both similarities and differences in folding morphology and brain function among primates including macaque and human. The folding morphology is the basis of brain function, making cross-species studies on folding morphology important for understanding brain function and species evolution. However, prior studies on cross-species folding morphology mainly focused on partial regions of the cortex instead of the entire brain. Previously, we defined a whole-brain landmark based on folding morphology: the gyral peak. It was found to exist stably across individuals and ages in both human and macaque brains. In this study, we identified shared and unique gyral peaks in human and macaque, and investigated the similarities and differences in the spatial distribution, anatomical morphology, and functional connectivity of them.
Frequency-Domain Joint Motion and Disparity Estimation Using Steerable Filters

In this paper, the problem of joint disparity and motion estimation from stereo image sequences is formulated in the spatiotemporal frequency domain, and a novel steerable filter-based approach is proposed. Our rationale behind coupling the two problems is that according to experimental evidence in the literature, the biological visual mechanisms for depth and motion are not independent of each other. Furthermore, our motivation to study the problem in the frequency domain and search for a filter-based solution is based on the fact that, according to early experimental studies, the biological visual mechanisms can be modelled based on frequency-domain or filter-based considerations, for both the perception of depth and the perception of motion. The proposed framework constitutes the first attempt to solve the joint estimation problem through a filter-based solution, based on frequency-domain considerations. Thus, the presented ideas provide a new direction of work and could be the basis for further developments. From an algorithmic point of view, we additionally extend state-of-the-art ideas from the disparity estimation literature to handle the joint disparity-motion estimation problem and formulate an algorithm that is evaluated through a number of experimental results. Comparisons with state-of-the-art-methods demonstrate the accuracy of the proposed approach.
Theory of electronic transport through molecular nanostructures

The main issue of this work is to describe electronic transport through single molecule junctions. We implemented the "standard" approach to molecular conductance, namely transport calculations in a Landauer-Biittiker framework based on Kohn-Sham orbitals extracted from density functional theory (DFT). Our particular implementation ensures, that apart from approximations inherent in the exchange-correlation functional in DFT no further approximations are made. Comparison of our numerical calculations with available experimental data shows, that, while in some cases qualitative information on transport can be gained, the experimental conductance is two to three orders of magnitude below the theoretical estimate. Changes in bond geometry can not account for this discrepancy. We are led to the conclusion that approximations in the exchange-correlation functional may be the major underlying reason for the discrepancy. To this end, we formulated the condition under which the "standard" approach would be exact. Furthermore, we investigated three situations where despite these shortcomings quantitative results can be obtained. Thereby we, for first time, calculated the step positions in the I-V characteristics of a "diode-type" molecule quantitatively.