Miracle-dz/UniFAR-FTUs huggingface dataset:
Whole-brain mapping of long-range inputs to the VIP-expressing inhibitory neurons in the primary motor cortex

The primary motor cortex (MOp) is an important site for motor skill learning. Interestingly, neurons in MOp possess reward-related activity, presumably to facilitate reward-based motor learning. While pyramidal neurons (PNs) and different subtypes of GABAergic inhibitory interneurons (INs) in MOp all undergo cell-type specific plastic changes during motor learning, the vasoactive intestinal peptide-expressing inhibitory interneurons (VIP-INs) in MOp have been shown to preferentially respond to reward and play a critical role in the early phases of motor learning by triggering local circuit plasticity. To understand how VIP-INs might integrate various streams of information, such as sensory, pre-motor, and reward-related inputs, to regulate local plasticity in MOp, we performed monosynaptic rabies tracing experiments and employed an automated cell counting pipeline to generate a comprehensive map of brain-wide inputs to VIP-INs in MOp. We then compared this input profile to the brain-wide inputs to somatostatin-expressing inhibitory interneurons (SST-INs) and parvalbumin-expressing inhibitory interneurons (PV-INs) in MOp. We found that while all cell types received major inputs from sensory, motor, and prefrontal cortical regions, as well as from various thalamic nuclei, VIP-INs received more inputs from the orbital frontal cortex (ORB) – a region associated with reinforcement learning and value predictions. Our findings provide insight on how the brain leverages microcircuit motifs by both integrating and partitioning different streams of long-range input to modulate local circuit activity and plasticity.
A trajectory of social innovations for the direct purchase of organic food by food services: a case study in Florianópolis, Brazil

Introduction Although interest in the so-called short food supply chains (SFSC) has grown in recent decade, studies and social innovations that emerged from this phenomenon have made little progress in involving food actors outside the home. The article analyzes the conditioning factors for forming short food supply chains involving food services and organic farmers’ organizations, understanding them as potential social innovations. Methods The research used questionnaires with food services, participant and non-participant observations, and secondary data analysis with regional farmers’ organizations in the Greater Florianópolis region. Results Food services, which mostly do not yet purchase organic products from local producers, are interested in integrating purchasing initiatives directly from farmers and their organizations. However, they have presented several conditions for this. Nevertheless, farmers have the capacity, at least in part, to respond to the required conditions due to their innovative trajectory and socio-organizational capacity. Discussion The provision of food services, associated with the trajectory of social innovations in SFSC by farmers around Florianópolis, shows a potential to converge different interests for the generation of new initiatives, following the innovative trajectory led by social actors who work with the rural area. This could increase the impact of ongoing SFSC initiatives, ensuring consumers access local food, even when eating out.
Lecture notes: harmonic analysis

7 Littlewood-Paley theory 61 7.1 A square function that characterizes L 13 Bessel functions 127 14 Restriction to the sphere 129 15 The uniform sobolev inequality 131 16 Inverse problems: potentials in L n/2 133 17 Scattering for a two-dimensional system 135 17.
Accurate frequency of the 119 mu m methanol laser from tunable far-infrared absorption spectroscopy

High-accuracy absorption spectroscopy of CH/sub 3/OH in the far infrared is discussed. In addition to 22 transitions in the ground state, the frequency of the (n, tau , J, K), (0, 1, 16, 8) to (0, 2, 15, 7) transition in the nu /sub 5/ excited vibrational level, which is responsible for the laser emission at 119 mu m, was measured. The measured frequency is 2,522,782.57(10) MHz at zero pressure, with a pressure shift of 6.1(32) kHz/Pa (0.805
A Dynamic Analysis of Retail Infrastructure and Tourism Demand: Evidence from a Casino Destination

ABSTRACT This study used a panel cointegration approach to investigate the effect of retail infrastructure/facilities on tourism demand in the casino gaming destination, Macao, from 23 provinces (and municipalities) of mainland China. Numbers of retail outlets in general and retail establishments in integrated resorts (IRs) are used as proxies for retail infrastructure/facilities. Dynamic Ordinary Least Square (DOLS) estimations reveal that a positive long-run relationship exists between tourism demand and retail from both dimensions. Heterogeneous results on the individual province estimates suggest visitors from the emerging central and western regions of China respond more strongly to retail facilities than the more saturated southern and eastern regions. The bidirectional causality between retail infrastructure and tourism demand also validates a positive cycle in the long-term growth of the destination. The results suggest that casino gaming destinations should seek to diversify entertainment and capitalize on the competitive advantage of their non-gaming facilities to sustain long-term development.
HAF-Net: A Fully Convolutional Segmentation Network Based on Hybrid Attention for Skin Lesion Segmentation

Abstract Skin cancer has become one of the leading causes of life threatening, and accurate segmentation of lesion regions from dermoscopic images is an effective aid to diagnosis. The lack of obvious lesion features and the large variations in the shape of lesion areas lead to the inability of many convolutional neural networks (CNNs) to accurately identify lesion pixels. In this paper, we propose a fully convolutional segmentation network based on hybrid attention (HAF-Net) for skin lesion segmentation. The model integrates the residual-dense block (RDB) in the encoding stage to improve the efficiency of feature extraction. Furthermore, channel attention block (CAB) and position attention block (PAB) are embedded at the end of the encoding stage, and the semantic relevance of the same class of features is integrated by hybrid attention to highlight the feature representation. In addition, we use channel separable convolution to reduce the number of parameters of the model. Test results on the publicly available skin lesion datasets ISIC 2016 and ISIC 2017 illustrate the superiority of the proposed model.
Gametophytic epigenetic regulators MEA and DME synergistically suppress 2 ectopic shoot formation in Arabidopsis 3

28 The gametophyte to sporophyte transition is an important event facilitating the alter- 29 nation of generations in a plant life cycle. The paternally imprinted epigenetic regula- 30 tors DEMETER(DME) and MEDEA(MEA) synergistically control central cell prolifera- 31 tion and differentiation, ensuring proper gametophyte to sporophyte transition 32 in Arabidopsis . Mutant alleles of DME and MEA are maternal lethal, eluding the re- 33 covery of recessive homozygotes to examine their role in the sporophyte. Here, we 34 exploited the paternal transmission of these mutant alleles coupled with CENH3- 35 haploid inducer to generate mea -1; dme -2 sporophytes. Strikingly, the simultaneous 36 loss of function of MEA and DME leads to the emergence of multiple shoot meri- 37 stems at the apical pole of the plant body axis. DME and MEA are expressed in the 38 developing shoot apex and regulate the expression of various shoot-promoting fac- 39 tors. Chromatin immunoprecipitation(ChIP) and DNA methylation analysis revealed 40 several shoot regulators as potential targets of MEA and DME, with mea -1 -/- ; dme -2 -/- 41 seedlings showcasing their misexpression. Knockdown of upregulated shoot- 42 promoting factors STM, CUC2, and PLT5 rescued the ectopic shoot phenotypes. 43 Our findings reveal a previously unrecognized synergistic role of MEA and DME in 44 restricting the meristematic activity at the shoot apex during sporophytic develop- 45 ment to orchestrate the plant architecture.
Aneurysmal growth in type-B aortic dissection: assessing the impact of patient-specific inlet conditions on key haemodynamic indices

Type-B Aortic Dissection is a cardiovascular disease in which a tear develops in the intimal layer of the descending aorta, allowing pressurized blood to delaminate the layers of the vessel wall. In medically managed patients, long-term aneurysmal dilatation of the false lumen (FL) is considered virtually inevitable and is associated with poorer disease outcomes. While the pathophysiological mechanisms driving FL dilatation are not yet understood, hemodynamic factors are believed to play a key role. Computational Fluid Dynamics (CFD) and 4D-Flow MRI (4DMR) analyses have revealed correlations between flow helicity, oscillatory wall shear stress, and aneurysmal dilatation of the FL. In this study, we compare CFD simulations using a patient-specific, three-dimensional, three-component inlet velocity profile (3D IVP) extracted from 4DMR data against simulations with flow rate-matched uniform and axial velocity profiles that remain widely used in the absence of 4DMR. We also evaluate the influence of measurement errors in 4DMR data by scaling the 3D IVP to the degree of imaging error detected in prior studies. We observe that oscillatory shear and helicity are highly sensitive to inlet velocity distribution and flow volume throughout the FL and conclude that the choice of IVP may greatly affect the future clinical value of simulations.
Visible-Light Optical Coherence Tomography Fibergraphy of the Tree Shrew Retinal Ganglion Cell Axon Bundles

We seek to develop techniques for high-resolution imaging of the tree shrew retina for visualizing and parameterizing retinal ganglion cell (RGC) axon bundles in vivo. We applied visible-light optical coherence tomography fibergraphy (vis-OCTF) and temporal speckle averaging (TSA) to visualize individual RGC axon bundles in the tree shrew retina. For the first time, we quantified individual RGC bundle width, height, and cross-sectional area and applied vis-OCT angiography (vis-OCTA) to visualize the retinal microvasculature in tree shrews. Throughout the retina, as the distance from the optic nerve head (ONH) increased from 0.5 mm to 2.5 mm, bundle width increased by 30%, height decreased by 67%, and cross-sectional area decreased by 36%. We also showed that axon bundles become vertically elongated as they converge toward the ONH. Ex vivo confocal microscopy of retinal flat-mounts immunostained with Tuj1 confirmed our in vivo vis-OCTF findings.
CParty: Conditional Partition Function for Density-2 RNA Pseudoknots

RNA molecules fold into biologically important functional structures. Efficient dynamic programming RNA (secondary) structure prediction algorithms restrict the search space to evade NP-hardness of general pseudoknot prediction. While such prediction algorithms can be extended to provide a stochastic view on RNA ensembles, they are either limited to pseudoknot-free structures or extremely complex. To overcome this dilemma, we provide the theoretical framework and implementation for our algorithm, CParty, that follows the hierarchical folding hypothesis, i.e., the bio-physically well-motivated assumption that non-crossing structures fold relatively fast prior to the formation of pseudoknot interactions. Thus, we efficiently compute the conditional partition function (CPF) given a non-crossing structure G for a subset of pseudoknotted structures, i.e., density-2 structures G ∪ G′ for non-crossing disjoint structure G′. Notably, this can enable sampling from the hierarchical distribution P (G′ | G). With CParty we develop for the first time an unambiguous scheme based on HFold, i.e., the minimum free energy hierarchical folding algorithm based on a realistic pseudoknot energy model. Thus, we develop the first partition function variant for density-2 structures. Compared to the only other available pseudoknot partition function algorithm, which covers simple pseudoknots (and follows a different strategy, mapped from a pure minimum free energy structure prediction), our method covers a much larger structure class; at the same time, it is significantly more efficient—reducing the time as well as the space complexity by a quadratic factor. Summarizing, we provide an efficient, cubic time, algorithm for the stochastic analysis of pseudoknotted RNAs, which enables novel applications. We discuss one such application, i.e., how the CPF for a pseudoknotted therapeutic target in SARS-CoV-2 can provide insight into RNA structure formation.
SARS-CoV-2 infection leads to Tau pathological signature in neurons

Background The coronavirus disease 19 (COVID-19) has represented an issue for global health since its outbreak in March 2020. It is now evident that the SARS-CoV-2 infection results in a wide range of long-term neurological symptoms and is worryingly associated with the aggravation of Alzheimer’s disease. Little is known about the molecular basis of these manifestations. Methods Several SARS-CoV-2 strain variants were used to infect SH-SY5Y neuroblastoma cells and K18-hACE C57BL/6J mice. The Tau phosphorylation profile and aggregation propensity upon infection were investigated using immunoblot and immunofluorescence on cellular extracts, subcellular fractions, and brain tissue. The viral proteins Spike, Nucleocapsid, and Membrane were overexpressed in SH-SY5Y cells and the direct effect on Tau phosphorylation was checked using immunoblot experiments. Results Upon infection, Tau is phosphorylated at several pathological epitopes associated with Alzheimer’s disease and other tauopathies. Moreover, this event increases Tau’s propensity to form insoluble aggregates and alters its subcellular localization. Conclusions Our data support the evidence that SARS-CoV-2 infection in the Central Nervous System triggers downstream effects altering Tau function, eventually leading to the impairment of neuronal function.
Interruption of the Intratumor CD8:Treg Crosstalk Improves the Efficacy of PD-1 Immunotherapy

PD-1 blockade unleashes the potent antitumor activity of CD8 cells but can also promote immunosuppressive T regulatory (Treg) cells, which may worsen response to immunotherapy. Tumor Treg inhibition is a promising strategy to overcome therapeutic resistance; however, the mechanisms supporting tumor Tregs during PD-1 immunotherapy are largely unexplored. Here, we report that PD-1 blockade increases tumor Tregs in mouse models of immunogenic tumors, including melanoma, and metastatic melanoma patients. Unexpectedly, Treg accumulation was not caused by Treg-intrinsic inhibition of PD-1 signaling but instead depended on an indirect effect of activated CD8 cells. CD8 cells colocalized with Tregs within tumors and produced IL-2, especially after PD-1 immunotherapy. IL-2 upregulated the anti-apoptotic protein ICOS on tumor Tregs, causing their accumulation. ICOS signaling inhibition before PD-1 immunotherapy resulted in increased control of immunogenic melanoma. Thus, interrupting the intratumor CD8:Treg crosstalk is a novel strategy that may enhance the efficacy of immunotherapy in patients.
High-bit-rate data transmission with short-wavelength oxidized VCSELs, toward bias-free operation

Efficient oxide-confined vertical-cavity surface-emitting laser diodes are investigated as light sources for optical interconnection. Data rates of 2.5 Gb/s with bit-error rates (BERs) smaller than 10/sup -11/ are routinely achieved with 980-nm as well as 850-nm short-wavelength devices for transmission over several hundred meters of graded index multimode fiber. A bias-free modulation scheme is applied to vertical-cavity lasers for the first time and 1-Gb/s data links are established in both wavelength regimes. Successful demonstration of data transmission with rates up to 10 Gb/s with proton-implanted devices is briefly reviewed.
Modeling and Simulation of Neocortical Micro- and Mesocircuitry. Part II: Physiology and Experimentation

Cortical dynamics underlie many cognitive processes and emerge from complex multi-scale interactions, which can be studied in large-scale, biophysically detailed models. We present a model comprising eight somatosensory cortex subregions, 4.2 million morpho-logical and electrically-detailed neurons, and 13.2 billion local and long-range synapses. In silico tools enabled reproduction and extension of complex laboratory experiments under a single parameterization, providing strong validation. We reproduced millisecond-precise stimulus-responses, stimulus-encoding under targeted optogenetic activation, and selective propagation of stimulus-evoked activity to downstream areas. The model’s di-rect correspondence with biology generated predictions about how multiscale organisation shapes activity. We predict that structural and functional recurrency increases towards deeper layers and that stronger innervation by long-range connectivity increases local correlated activity. The model also predicts the role of inhibitory interneuron types in stimulus encoding, and of different layers in driving layer 2/3 stimulus responses. Simu-slation tools and a large subvolume of the model are made available.
Memory at your fingertips: how viscoelasticity affects tactile neuron signaling

Human skin and its underlying tissues constitute a viscoelastic medium, implying that any deformation depends not only on the currently applied force, but also the recent loading history. The extent to which this physical memory influences the signaling of first-order tactile neurons during natural hand use is not well understood. Here, we examined the effect of past loading on the responses of fast-adapting (FA-1) and slowly-adapting (SA-1 and SA-2) first-order tactile neurons innervating the human fingertip to loadings applied in different directions representative of object manipulation tasks. We found that variation in the preceding loading affected neurons’ overall signaling of force direction. Some neurons kept signaling the current direction, while others signaled both the current and preceding direction, or even primarily the preceding direction. In addition, ongoing impulse activity in SA-2 neurons between loadings signaled information related to the fingertip’s viscoelastic deformation state between loadings. We conclude that tactile neurons at the population level signal continuous information about the fingertip’s viscoelastic deformation state, which is shaped by both its recent history and current loading. Such information might be sufficient for the brain to correctly interpret current force loading and help in computing accurate motor commands for interactions with objects in manipulation and haptic tasks.
Evidence that ultrafast non-quantal transmission underlies short-latency vestibular evoked potentials

Amniotes evolved a unique calyceal postsynaptic terminal in the vestibular organs of the inner ear that underpins quantal and non-quantal transmission at the synapse of sensory hair cells and vestibular afferent neurons. The non-quantal component is of particular interest as it includes an ultrafast synaptic current thought to underlie the exquisite synchronization of action potentials in vestibular afferent fibres to dynamic stimuli such as sound and vibration. Here we demonstrate evidence that non-quantal transmission is responsible for short latency vestibular evoked potentials (vCAPs) in the guinea pig utricle. We first show that, unlike auditory nerve responses which are completely abolished, vCAPs are insensitive to local administration of the AMPA receptor agonist CNQX. Moreover, latency comparisons between presynaptic hair cell and postsynaptic neural responses reveal that the vCAP occurs without measurable synaptic delay. Finally, using a paired-pulse stimulus designed to deplete the readily releasable pool of synaptic vesicles in hair cells, we reveal that forward masking is lacking in vestibular responses, compared to the equivalent cochlear responses. Our data support the hypothesis that the fast component of non-quantal transmission at calyceal synapses is indefatigable and responsible for ultrafast responses of vestibular organs evoked by transient stimulation. Significance The mammalian vestibular system drives some of the fastest reflex pathways in the nervous system, ensuring stable gaze and postural control for locomotion on land. To achieve this, terrestrial amniotes evolved a large, unique calyx afferent terminal which completely envelopes one or more pre-synaptic vestibular hair cells, which transmits mechanosensory signals mediated by quantal and nonquantal (NQ) synaptic transmission. We present several lines of data in the guinea pig that reveal the pre-synaptic transmission of the most sensitive vestibular afferents are faster than their auditory nerve counterparts. Here, we present neurophysiological and pharmacological evidence that this vestibular speed advantage arises from ultrafast NQ electrical synaptic transmission from Type I hair cells to their calyx partners.
Community-based Reconstruction and Simulation of a Full-scale Model of Region CA1 of Rat Hippocampus

The CA1 region of the hippocampus is one of the most studied regions of the rodent brain, thought to play an important role in cognitive functions such as memory and spatial navigation. Despite a wealth of experimental data on its structure and function, it has been challenging to reconcile information obtained from diverse experimental approaches. To address this challenge, we present a community-driven, full-scale in silico model of the rat CA1 that integrates a broad range of experimental data, from synapse to network, including the reconstruction of its principal afferents, the Schaffer collaterals, and a model of the effects that acetylcholine has on the system. We tested and validated each model component and the final network model, and made input data, assumptions, and strategies explicit and transparent. The unique flexibility of the model allows scientists to address a range of scientific questions. In this article, we describe the methods used to set up simulations that reproduce and extend in vitro and in vivo experiments. Among several applications in the article, we focus on theta rhythm, a prominent hippocampal oscillation associated with various behavioral correlates and use our computer model to reproduce and reconcile experimental findings. Finally, we make data, code and model available through the hippocampushub.eu portal, which also provides an extensive set of analyses of the model and a user-friendly interface to facilitate adoption and usage. This neuroscience community-driven model represents a valuable tool for integrating diverse experimental data and provides a foundation for further research into the complex workings of the hippocampal CA1 region.
SRF-deficient astrocytes provide neuroprotection in mouse models of excitotoxicity and neurodegeneration

Reactive astrogliosis is a common pathological hallmark of central nervous system (CNS) injury, infection, and neurodegeneration, where reactive astrocytes can be protective or detrimental to normal brain functions. Currently, the mechanisms regulating neuroprotective astrocytes and the extent of neuroprotection are poorly understood. Here, we report that conditional deletion of serum response factor (SRF) in adult astrocytes causes reactive-like hypertrophic astrocytes throughout the mouse brain. These SrfGFAP-ERCKO astrocytes do not affect neuron survival, synapse numbers, synaptic plasticity or learning and memory. However, the brains of Srf knockout mice exhibited neuroprotection against kainic-acid induced excitotoxic cell death. Relevant to human neurodegenerative diseases, SrfGFAP-ERCKO astrocytes abrogate nigral dopaminergic neuron death and reduce β-amyloid plaques in mouse models of Parkinson’s and Alzheimer’s disease, respectively. Taken together, these findings establish SRF as a key molecular switch for the generation of reactive astrocytes with neuroprotective functions that attenuate neuronal injury in the setting of neurodegenerative diseases.