Top-down attention shifts behavioral and neural event boundaries in narratives with overlapping event scripts.

Understanding and remembering the complex experiences of everyday life relies critically on prior schematic knowledge about how events in our world unfold over time. How does the brain construct event representations from a library of schematic scripts, and how does activating a specific script impact the way that events are segmented in time? We developed a novel set of 16 audio narratives, each of which combines one of four location-relevant event scripts (restaurant, airport, grocery store, and lecture hall) with one of four socially relevant event scripts (breakup, proposal, business deal, and meet cute), and presented them to participants in an fMRI study and a separate online study. Responses in the angular gyrus, parahippocampal gyrus, and subregions of the medial prefrontal cortex (mPFC) were driven by scripts related to both location and social information, showing that these regions can track schematic sequences from multiple domains.

A High-Resolution Discrete-Time Second-Order ΣΔ ADC with Improved Tolerance to KT/C Noise Using Low Oversampling Ratio.

This work presents a novel ΣΔ analog-to-digital converter (ADC) architecture for a high-resolution sensor interface. The concept is to reduce the effect of kT/C noise generated by the loop filter by placing the gain stage in front of the loop filter. The proposed architecture effectively reduces the kT/C noise power from the loop filter by as much as the squared gain of the added gain stage.

A cerebellar granule cell-climbing fiber computation to learn to track long time intervals.

In classical cerebellar learning, Purkinje cells (PkCs) associate climbing fiber (CF) error signals with predictive granule cells (GrCs) that were active just prior (∼150 ms). The cerebellum also contributes to behaviors characterized by longer timescales. To investigate how GrC-CF-PkC circuits might learn seconds-long predictions, we imaged simultaneous GrC-CF activity over days of forelimb operant conditioning for delayed water reward.

Precise Filtration of Chronic Myeloid Leukemia Cells by an Ultrathin Microporous Membrane with Backflushing to Minimize Fouling.

A cell filtration platform that affords accurate size separation and minimizes fouling was developed. The platform features an ultra-thin porous membrane (UTM) filter, a pumping head filtration with backflush (PHF), and cell size measurement (CSM) software. The UTM chip is an ultrathin free-standing membrane with a large window area of 0.

Isolation of Bovine Milk Exosome Using Electrophoretic Oscillation Assisted Tangential Flow Filtration with Antifouling of Micro-ultrafiltration Membrane Filters.

Tangent flow-driven ultrafiltration (TF-UF) is an efficient isolation process of milk exosomes without morphological deformation. However, the TF-UF approach with micro-ultrafiltration SiN membrane filters suffers from the clogging and fouling of micro-ultrafiltration membrane filter pores with large bioparticles. Thus, it is limited in the long term, continuous isolation of large quantities of exosomes.

Reexamining event attributes, benefits, and values in a time of pandemic: A multi-faceted approach.

The COVID-19 pandemic increased attention to product/service-customer relationships in the context of events where social gatherings take place. Event attributes have been a topic of continued interest in research and practice. Due to COVID-19, however, event attendees' preferences and requirements related to personal values and satisfaction may be changing.

Fluorescence imaging of large-scale neural ensemble dynamics.

Recent progress in fluorescence imaging allows neuroscientists to observe the dynamics of thousands of individual neurons, identified genetically or by their connectivity, across multiple brain areas and for extended durations in awake behaving mammals. We discuss advances in fluorescent indicators of neural activity, viral and genetic methods to express these indicators, chronic animal preparations for long-term imaging studies, and microscopes to monitor and manipulate the activity of large neural ensembles. Ca imaging studies of neural activity can track brain area interactions and distributed information processing at cellular resolution.

A Reference-Sampling Based Calibration-Free Fractional-N PLL with a PI-Linked Sampling Clock Generator.

Sampling-based PLLs have become a new research trend due to the possibility of removing the frequency divider (FDIV) from the feedback path, where the FDIV increases the contribution of in-band noise by the factor of dividing ratio square (N). Between two possible sampling methods, sub-sampling and reference-sampling, the latter provides a relatively wide locking range, as the slower input reference signal is sampled with the faster VCO output signal. However, removal of FDIV makes the PLL not feasible to implement fractional-N operation based on varying divider ratios through random sequence generators, such as a Delta-Sigma-Modulator (DSM).

A neural circuit state change underlying skilled movements.

In motor neuroscience, state changes are hypothesized to time-lock neural assemblies coordinating complex movements, but evidence for this remains slender. We tested whether a discrete change from more autonomous to coherent spiking underlies skilled movement by imaging cerebellar Purkinje neuron complex spikes in mice making targeted forelimb-reaches. As mice learned the task, millimeter-scale spatiotemporally coherent spiking emerged ipsilateral to the reaching forelimb, and consistent neural synchronization became predictive of kinematic stereotypy.

Kratom pharmacology: Clues from planarians exposed to mitragynine.

Mitragynine (MG), the most prevalent bioactive alkaloid in kratom, displays nanomolar affinity for µ, κ and δ opioid receptors and produces opioid-dependent antinociception and dependence in rats. Here, using a battery of behavioral assays, we investigated MG effects in planarians. Acute MG exposure (< 100 μM) did not affect planarian motility or environmental preference, but reduced motility was detected during abstinence from chronic MG (1, 10 μM).

The relationship between birth timing, circuit wiring, and physiological response properties of cerebellar granule cells.

Cerebellar granule cells (GrCs) are usually regarded as a uniform cell type that collectively expands the coding space of the cerebellum by integrating diverse combinations of mossy fiber inputs. Accordingly, stable molecularly or physiologically defined GrC subtypes within a single cerebellar region have not been reported. The only known cellular property that distinguishes otherwise homogeneous GrCs is the correspondence between GrC birth timing and the depth of the molecular layer to which their axons project.

Tear-Based Aqueous Batteries for Smart Contact Lenses Enabled by Prussian Blue Analogue Nanocomposites.

Batteries for contact lenses fabricated by conventional methods could cause severe damage to the eyes if broken. Herein, we present flexible aqueous batteries that operate in tears and provide a safe power supply to smart contact lenses. Nanocomposite flexible electrodes of carbon nanotubes and Prussian blue analogue nanoparticles for cathode and anode were embedded in UV-polymerized hydrogel as not only a soft contact lens but also an ion-permeable separator.

Direct-acting oral anti-coagulants in dental practice: A Retrospective Observational Study (Part 1).

Objectives: The objective of this retrospective observational study was to determine the incidence of direct-acting oral anti-coagulant (DOA) use in patients receiving invasive dental procedures. The secondary objective was to investigate the precautionary measures implemented and the post/intraoperative complications associated with DOA use.

Methods: Electronic record database, Axium, was retrospectively reviewed, and patients using NGOA and treated between 2010 and 2017 were identified.

Time-Interleaved SAR ADC with Background Timing-Skew Calibration for UWB Wireless Communication in IoT Systems.

Ultra-wideband (UWB) wireless communication is prospering as a powerful partner of the Internet-of-things (IoT). Due to the ongoing development of UWB wireless communications, the demand for high-speed and medium resolution analog-to-digital converters (ADCs) continues to grow. The successive approximation register (SAR) ADCs are the most powerful candidate to meet these demands, attracting both industries and academia.

Skilled reaching tasks for head-fixed mice using a robotic manipulandum.

Skilled forelimb behaviors are among the most important for studying motor learning in multiple species including humans. This protocol describes learned forelimb tasks for mice using a two-axis robotic manipulandum. Our device provides a highly compact adaptation of actuated planar two-axis arms that is simple and inexpensive to construct.

Development of a Handheld Volumetric Photoacoustic Imaging System With a Central-Holed 2D Matrix Aperture.

Objective: Photoacoustics has been evolving rapidly in the recent several decades. With the aim of clinical translation, a photoacoustic imaging platform with a portable system size, a miniaturized imaging probe, and convenient handheld capability is of great demand.

Methods: In this work, by adopting an ultrathin central-holed matrix array and a compact coaxial photoacoustic design, a water-free handheld photoacoustic imager is developed (weight: 44 g).

Shared Cortex-Cerebellum Dynamics in the Execution and Learning of a Motor Task.

Throughout mammalian neocortex, layer 5 pyramidal (L5) cells project via the pons to a vast number of cerebellar granule cells (GrCs), forming a fundamental pathway. Yet, it is unknown how neuronal dynamics are transformed through the L5→GrC pathway. Here, by directly comparing premotor L5 and GrC activity during a forelimb movement task using dual-site two-photon Ca imaging, we found that in expert mice, L5 and GrC dynamics were highly similar.

Unsupervised Discovery of Demixed, Low-Dimensional Neural Dynamics across Multiple Timescales through Tensor Component Analysis.

Perceptions, thoughts, and actions unfold over millisecond timescales, while learned behaviors can require many days to mature. While recent experimental advances enable large-scale and long-term neural recordings with high temporal fidelity, it remains a formidable challenge to extract unbiased and interpretable descriptions of how rapid single-trial circuit dynamics change slowly over many trials to mediate learning. We demonstrate a simple tensor component analysis (TCA) can meet this challenge by extracting three interconnected, low-dimensional descriptions of neural data: neuron factors, reflecting cell assemblies; temporal factors, reflecting rapid circuit dynamics mediating perceptions, thoughts, and actions within each trial; and trial factors, describing both long-term learning and trial-to-trial changes in cognitive state.

Diametric neural ensemble dynamics in parkinsonian and dyskinetic states.

Loss of dopamine in Parkinson's disease is hypothesized to impede movement by inducing hypo- and hyperactivity in striatal spiny projection neurons (SPNs) of the direct (dSPNs) and indirect (iSPNs) pathways in the basal ganglia, respectively. The opposite imbalance might underlie hyperkinetic abnormalities, such as dyskinesia caused by treatment of Parkinson's disease with the dopamine precursor L-DOPA. Here we monitored thousands of SPNs in behaving mice, before and after dopamine depletion and during L-DOPA-induced dyskinesia.

Cerebellar granule cells encode the expectation of reward.

The human brain contains approximately 60 billion cerebellar granule cells, which outnumber all other brain neurons combined. Classical theories posit that a large, diverse population of granule cells allows for highly detailed representations of sensorimotor context, enabling downstream Purkinje cells to sense fine contextual changes. Although evidence suggests a role for the cerebellum in cognition, granule cells are known to encode only sensory and motor context.

Long-Term Optical Access to an Estimated One Million Neurons in the Live Mouse Cortex.

A major technological goal in neuroscience is to enable the interrogation of individual cells across the live brain. By creating a curved glass replacement to the dorsal cranium and surgical methods for its installation, we developed a chronic mouse preparation providing optical access to an estimated 800,000-1,100,000 individual neurons across the dorsal surface of neocortex. Post-surgical histological studies revealed comparable glial activation as in control mice.

Pharmaceutical expenditure on drugs for rare diseases in Canada: a historical (2007-13) and prospective (2014-18) MIDAS sales data analysis.

Background: Health Canada has defined rare diseases as life-threatening, seriously debilitating, or serious chronic conditions affecting a very small number of patients (~1 in 2,000 persons). An estimated 9 % of Canadians suffer from a rare disease. Drugs treating rare diseases (DRDs) are also known as orphan drugs.

Camphorquinone inhibits odontogenic differentiation of dental pulp cells and triggers release of inflammatory cytokines.

Introduction: Camphorquinone (CQ) is a photoinitiator that triggers polymerization of light-curing materials such as dental adhesives and composites. CQ does not become a part of the polymer network, suggesting that CQ can be leached out into surrounding environment including dental pulp and exert adversary effects on tissues. In order to understand the mechanisms of CQ-induced side effects, we investigated the effect of CQ on cell viability, cytokine secretion, and odontogenic differentiation of dental pulp stem cells in vitro.

Itinerant ferromagnetism in a Fermi gas of ultracold atoms.

Can a gas of spin-up and spin-down fermions become ferromagnetic because of repulsive interactions? We addressed this question, for which there is not yet a definitive theoretical answer, in an experiment with an ultracold two-component Fermi gas. The observation of nonmonotonic behavior of lifetime, kinetic energy, and size for increasing repulsive interactions provides strong evidence for a phase transition to a ferromagnetic state. Our observations imply that itinerant ferromagnetism of delocalized fermions is possible without lattice and band structure, and our data validate the most basic model for ferromagnetism introduced by Stoner.

Effects of insulin treatment without and with recurrent hypoglycemia on hypoglycemic counterregulation and adrenal catecholamine-synthesizing enzymes in diabetic rats.

Untreated diabetic rats show impaired counterregulation against hypoglycemia. The blunted epinephrine responses are associated with reduced adrenomedullary tyrosine hydroxylase (TH) mRNA levels. Recurrent hypoglycemia further impairs epinephrine counterregulation and is also associated with reduced phenylethanolamine N-methyltransferase mRNA.