Functional organization of posterior parietal cortex circuitry based on inferred information flow.

Many studies infer the role of neurons by asking what information can be decoded from their activity or by observing the consequences of perturbing their activity. An alternative approach is to consider information flow between neurons. We applied this approach to the parietal reach region (PRR) and the lateral intraparietal area (LIP) in posterior parietal cortex. Two complementary methods imply that across a range of reaching tasks, information flows primarily from PRR to LIP. This indicates that during a coordinated reach task, LIP has minimal influence on PRR and rules out the idea that LIP forms a general purpose spatial processing hub for action and cognition. Instead, we conclude that PRR and LIP operate in parallel to plan arm and eye movements, respectively, with asymmetric interactions that likely support eye-hand coordination. Similar methods can be applied to other areas to infer their functional relationships based on inferred information flow.

Droplet microfluidics for time-resolved serial crystallography.

Serial crystallography requires large numbers of microcrystals and robust strategies to rapidly apply substrates to initiate reactions in time-resolved studies. Here, we report the use of droplet miniaturization for the controlled production of uniform crystals, providing an avenue for controlled substrate addition and synchronous reaction initiation. The approach was evaluated using two enzymatic systems, yielding 3 µm crystals of lysozyme and 2 µm crystals of Pdx1, an Arabidopsis enzyme involved in vitamin B6 biosynthesis. A seeding strategy was used to overcome the improbability of Pdx1 nucleation occurring with diminishing droplet volumes. Convection within droplets was exploited for rapid crystal mixing with ligands. Mixing times of <2 ms were achieved. Droplet microfluidics for crystal size engineering and rapid micromixing can be utilized to advance time-resolved serial crystallography.

Arthroscopic treatment of chronic calcific tendinitis with intraosseous migration: a case report.

We present a case of calcific tendinitis in the shoulder, where calcifications were observed within both the tendon and the adjacent bone. At the time of acute onset, radiographs (including a plain radiograph) and magnetic resonance imaging revealed calcific tendinitis with intraosseous migration. The patient's symptoms did not improve after 5 months of conservative treatment. The patient underwent arthroscopic debridement of the calcific deposits, and the defect was repaired using the double-row repair technique. The patient's symptoms improved 3 months after arthroscopic treatment. We share our unusual experience with arthroscopic debridement in the treatment of chronic calcific tendinitis with intraosseous migration.

A magnetically powered nanomachine with a DNA clutch.

Machines found in nature and human-made machines share common components, such as an engine, and an output element, such as a rotor, linked by a clutch. This clutch, as seen in biological structures such as dynein, myosin or bacterial flagellar motors, allows for temporary disengagement of the moving parts from the running engine. However, such sophistication is still challenging to achieve in artificial nanomachines. Here we present a spherical rotary nanomotor with a reversible clutch system based on precise molecular recognition of built-in DNA strands. The clutch couples and decouples the engine from the machine's rotor in response to encoded inputs such as DNA or RNA. The nanomotor comprises a porous nanocage as a spherical rotor to confine the magnetic engine particle within the nanospace (∼0.004 µm3) of the cage. Thus, the entropically driven irreversible disintegration of the magnetic engine and the spherical rotor during the disengagement process is eliminated, and an exchange of microenvironmental inputs is possible through the nanopores. Our motor is only 200 nm in size and the clutch-mediated force transmission powered by an embedded ferromagnetic nanocrystal is high enough (∼15.5 pN at 50 mT) for the in vitro mechanical activation of Notch and integrin receptors, demonstrating its potential as nano-bio machinery.

Nanoscale Magneto-mechanical-genetics of Deep Brain Neurons Reversing Motor Deficits in Parkinsonian Mice.

Here, we introduce the magneto-mechanical-genetic (MMG)-driven wireless deep brain stimulation (DBS) using magnetic nanostructures for therapeutic benefits in the mouse model of Parkinson's disease (PD). Electrical DBS of the subthalamic nucleus (STN) is an effective therapy for mitigating Parkinson's motor symptoms. However, its broader application is hampered by the requirement for implanted electrodes and the lack of anatomical and cellular specificity. Using the nanoscale magnetic force actuators (m-Torquer), which deliver torque force under rotating magnetic fields to activate pre-encoded Piezo1 ion channels on target neurons, our system enables wireless and STN-specific DBS without implants, addressing key unmet challenges in the DBS field. In both late- and early-stage PD mice, MMG-DBS significantly improved locomotor activity and motor balance by 2-fold compared to untreated PD mice. Moreover, MMG-DBS enabled sustained therapeutic effects. This approach provides a non-invasive and implant-free DBS with cellular targeting capability for the effective treatment of Parkinsonian symptoms.

Enabling Visual Object Detection With Object Sounds via Visual Modality Recalling Memory.

When humans hear the sound of an object, they recall associated visual information and integrate the sound with recalled visual modality to detect the object. In this article, we present a novel sound-based object detector that mimics this process. We design a visual modality recalling (VMR) memory to recall information of a visual modality based on an audio modal input (i.e., sound). To achieve this goal, we propose a VMR loss and an audio-visual association loss to guide the VMR memory to memorize visual modal information by establishing associations between audio and visual modalities. With the visual modal information recalled through the VMR memory along with the original audio input, we perform audio-visual integration. In this step, we introduce an integrated feature contrastive loss that allows the integrated feature to be embedded as if it were encoded using both audio and visual modal inputs. This guidance enables our sound-based object detector to effectively perform visual object detection even when only sound is provided. We believe that our work is a cornerstone study that offers a new perspective to conventional object detection studies that solely rely on the visual modality. Comprehensive experimental results demonstrate the effectiveness of the proposed method with the VMR memory.

Information processing in the dorsal pathway: from "where" to "what we do with it".

Visual processing in the brain has been understood as the ventral and dorsal pathways processing "what" and "where" information, respectively. Mocz et al. (Mocz V, Vaziri-Pashkam M, Chun M, Xu Y. J Cogn Neurosci 34: 2406-2435, 2022), however, report that the two pathways code object features in a parallel manner. These results support that information processing in the dorsal pathway is not strictly limited to "where" and that the two pathways work in parallel to process task-relevant information ("what we do with it").

Hydrogel Magnetomechanical Actuator Nanoparticles for Wireless Remote Control of Mechanosignaling In Vivo.

As a new enabling nanotechnology tool for wireless, target-specific, and long-distance stimulation of mechanoreceptors in vivo, here we present a hydrogel magnetomechanical actuator (h-MMA) nanoparticle. To allow both deep-tissue penetration of input signals and efficient force generation, h-MMA integrates a two-step transduction mechanism that converts magnetic anisotropic energy to thermal energy within its magnetic core (i.e., Zn0.4Fe2.6O4 nanoparticle cluster) and then to mechanical energy to induce the surrounding polymer (i.e., pNiPMAm) shell contraction, finally delivering forces to activate targeted mechanoreceptors. We show that h-MMAs enable on-demand modulation of Notch signaling in both fluorescence reporter cell lines and a xenograft mouse model, demonstrating its utility as a powerful in vivo perturbation approach for mechanobiology interrogation in a minimally invasive and untethered manner.

Stereoscopic Vision Recalling Memory for Monocular 3D Object Detection.

Monocular 3D object detection has drawn increasing attention in various human-related applications, such as autonomous vehicles, due to its cost-effective property. On the other hand, a monocular image alone inherently contains insufficient information to infer the 3D information. In this paper, we propose a new monocular 3D object detector that can recall the stereoscopic visual information about an object, given a left-view monocular image. Here, we devise a location embedding module to handle each object by being aware of its location. Next, given the object appearance of the left-view monocular image, we devise Monocular-to-Stereoscopic (M2S) memory that can recall the object appearance of the right-view and depth information. For this purpose, we introduce a stereoscopic vision memorizing loss that guides the M2S memory to store the stereoscopic visual information. Furthermore, we propose a binocular vision association loss to guide the M2S memory that can associate the information of the left-right view about the object when estimating the depth. As a result, our monocular 3D object detector with the M2S memory can effectively exploit the recalled stereoscopic visual information in the inference phase. The comprehensive experimental results on two public datasets, KITTI 3D Object Detection Benchmark and Waymo Open Dataset, demonstrate the effectiveness of the proposed method. We claim that our method is a step-forward method that follows the behaviors of humans that can recall the stereoscopic visual information even when one eye is closed.

Molecular Decrowding by Tissue Expansion Allows Precise Determination of the Spatial Distribution of Synaptic Proteins at a Nanometer Scale by exTEM.

To understand how the molecular machinery of synapses works, it is essential to determine an inventory of synaptic proteins at a subsynaptic resolution. Nevertheless, synaptic proteins are difficult to localize because of the low expression levels and limited access to immunostaining epitopes. Here, we report on the exTEM (epitope-exposed by expansion-transmission electron microscopy) method that enables the imaging of synaptic proteins in situ. This method combines TEM with nanoscale resolution and expandable tissue-hydrogel hybrids for enhanced immunolabeling with better epitope accessibility via molecular decrowding, allowing successful probing of the distribution of various synapse-organizing proteins. We propose that exTEM can be employed for studying the mechanisms underlying the regulation of synaptic architecture and function by providing nanoscale molecular distribution of synaptic proteins in situ. We also envision that exTEM is widely applicable for investigating protein nanostructures located in densely packed environments by immunostaining of commercially available antibodies at nanometer resolution.

Magnetogenetics with Piezo1 Mechanosensitive Ion Channel for CRISPR Gene Editing.

Regulation of genetic activity in single cells and tissues is pivotal to determine key cellular functions in current biomedicine, yet the conventional biochemical activators lack spatiotemporal precision due to the diffusion-mediated slow kinetics and nonselectivity. Here, we describe a magnetogenetic method for target-specific activation of a clustered regularly interspaced short palindromic repeats (CRISPR) system for the regulation of intracellular proteins. We used magnetomechanical force generated by the magnetic nanostructure to activate pre-encoded Piezo1, the mechanosensitive ion channel, on the target cell. The activated Piezo1 further triggers the intracellular Ca2+ signaling pathway, inducing the pre-encoded genes to express genes of interest (GOIs), which is Cas9 protein for the CRISPR regulation of the target proteins. We demonstrated that this magnetogenetic CRISPR system successfully edits the target genome for both in vitro and pseudo-in vivo environments, providing a versatile magnetic platform for remote gene editing of animals with various size scales.

Quantitative analysis of trace N2, Ar in O2 using glow discharge optical emission spectroscopy.

A trace level of N2 and Ar gases in O2 ambience were quantitatively analyzed for the first time by glow discharge optical emission spectroscopy. Microplasma was generated in a compact gas cell by a metal (Au) electrode pair of 1 mm diameter and ∼1 mm separation with the driving voltage of ∼0.9 kV and the current of ∼5 mA in ∼60 Torr. 358 and 813 nm optical emission bands were used for N2 and Ar detection, respectively. A spectroscopy fiber bundle having a circular input cross section of ∼700 µm in diameter and an output of 100 µm in width and 3 mm in height was employed to promote the signal collection efficiency while preserving high spectral resolution. As a result, the detection sensitivities <1 ppm (3 - σ) were attained for both N2 and Ar within 10 s. The detection accuracy was also promoted by correcting the N2 and Ar band signal intensities using the neighboring O emission band intensities, which led to detection errors <2% (3 - σ) for both N2 and Ar.

Characteristics and clinical outcomes of patients with nonsmoking small cell lung cancer in Korea.

BACKGROUND: The aim of this study was to investigate the characteristics and clinical outcomes of patients with nonsmoking small cell lung cancer (SCLC) using a nationwide registry in Korea. METHODS: The Korean Association for Lung Cancer developed a registry in cooperation with the Korean Central Cancer Registry (KCCR) and surveyed approximately 10% of recorded lung cancer cases. RESULTS: From 2014 to 2016, the KCCR registered 1,043 patients newly diagnosed with SCLC among a total of 8,110 lung cancer patients. In subgroup analysis, Kaplan meier survival analysis showed that the overall survival (OS) was significantly shorter in the nonsmoking subgroup than the ever-smoking subgroup of SCLC patients with extensive disease (6.99 vs. 9.68 months; P = 0.016). Among SCLC patients with limited disease, OS was also shorter in the nonsmoking subgroup, without statistical significance (19.4 vs. 23.5 months; P = 0.247). In a multivariate analysis using a Cox regression model, never smoking was not associated with shorter OS, but older age, extensive stage, poor performance status (Eastern Cooperative Oncology Group grade ≥ 2), male sex, no prophylactic cranial irradiation, and no active treatment (chemotherapy and/or radiotherapy) were associated with poor prognosis. CONCLUSION: This evaluation of an unbiased nationwide survey dataset revealed that a significant proportion of Korean SCLC patients were never-smokers. No history of smoking appeared to be a significant prognostic factor according to the univariate analysis but was confirmed to be statistically insignificant through a multivariate analysis of the total population. Reasons for a poor prognosis may include the possibility that a high rate of the elderly population is composed of nonsmokers who did not receive active treatment.

Magnetothermally Activated Nanometer-level Modular Functional Group Grafting of Nanoparticles.

Nanoparticles with multifunctionality and high colloidal stability are essential for biomedical applications. However, their use is often hindered by the formation of thick coating shells and/or nanoparticle agglomeration. Herein, we report a single nanoparticle coating strategy to form 1 nm polymeric shells with a variety of chemical functional groups and surface charges. Under exposure to alternating magnetic field, nanosecond thermal energy pulses trigger a polymerization in the region only a few nanometers from the magnetic nanoparticle (MNP) surface. Modular coatings containing functional groups, according to the respective choice of monomers, are possible. In addition, the surface charge can be tuned from negative through neutral to positive. We adopted a coating method for use in biomedical targeting studies where obtaining compact nanoparticles with the desired surface charge is critical. A single MNP with a zwitterionic charge can provide excellent colloidal stability and cell-specific targeting.

Homogeneous Freezing of Water Using Microfluidics.

The homogeneous freezing of water is important in the formation of ice in clouds, but there remains a great deal of variability in the representation of the homogeneous freezing of water in the literature. The development of new instrumentation, such as droplet microfluidic platforms, may help to constrain our understanding of the kinetics of homogeneous freezing via the analysis of monodisperse, size-selected water droplets in temporally and spatially controlled environments. Here, we evaluate droplet freezing data obtained using the Lab-on-a-Chip Nucleation by Immersed Particle Instrument (LOC-NIPI), in which droplets are generated and frozen in continuous flow. This high-throughput method was used to analyse over 16,000 water droplets (86 µm diameter) across three experimental runs, generating data with high precision and reproducibility that has largely been unrepresented in the microfluidic literature. Using this data, a new LOC-NIPI parameterisation of the volume nucleation rate coefficient (JV(T)) was determined in the temperature region of -35.1 to -36.9 °C, covering a greater JV(T) compared to most other microfluidic techniques thanks to the number of droplets analysed. Comparison to recent theory suggests inconsistencies in the theoretical representation, further implying that microfluidics could be used to inform on changes to parameterisations. By applying classical nucleation theory (CNT) to our JV(T) data, we have gone a step further than other microfluidic homogeneous freezing examples by calculating the stacking-disordered ice-supercooled water interfacial energy, estimated to be 22.5 ± 0.7 mJ m-2, again finding inconsistencies when compared to theoretical predictions. Further, we briefly review and compile all available microfluidic homogeneous freezing data in the literature, finding that the LOC-NIPI and other microfluidically generated data compare well with commonly used non-microfluidic datasets, but have generally been obtained with greater ease and with higher numbers of monodisperse droplets.

Non-contact long-range magnetic stimulation of mechanosensitive ion channels in freely moving animals.

Among physical stimulation modalities, magnetism has clear advantages, such as deep penetration and untethered interventions in biological subjects. However, some of the working principles and effectiveness of existing magnetic neurostimulation approaches have been challenged, leaving questions to be answered. Here we introduce m-Torquer, a magnetic toolkit that mimics magnetoreception in nature. It comprises a nanoscale magnetic torque actuator and a circular magnet array, which deliver piconewton-scale forces to cells over a working range of ~70 cm. With m-Torquer, stimulation of neurons expressing bona fide mechanosensitive ion channel Piezo1 enables consistent and reproducible neuromodulation in freely moving mice. With its long working distance and cellular targeting capability, m-Torquer provides versatility in its use, which can range from single cells to in vivo systems, with the potential application in large animals such as primates.

Fast detection of SARS-CoV-2 RNA via the integration of plasmonic thermocycling and fluorescence detection in a portable device.

The diagnosis of severe acute respiratory syndrome 2 (SARS-CoV-2) infection by quantitative PCR with reverse transcription (RT-qPCR) typically involves bulky instrumentation in centralized laboratories and an assay time of 1-2 h. Here, we show that SARS-CoV-2 RNA can be detected in 17 min via a portable device integrating reverse transcription, fast thermocycling (via plasmonic heating through magneto-plasmonic nanoparticles) and in situ fluorescence detection following magnetic clearance of the nanoparticles. The device correctly classified all nasopharyngeal, oropharyngeal and sputum samples from 75 patients with COVID-19 and 75 healthy controls, with good concordance in fluorescence intensity with standard RT-qPCR (Pearson coefficients > 0.7 for the N1, N2 and RPP30 genes). Fast, portable and automated nucleic acid detection should facilitate testing at the point of care.

On-chip density-based sorting of supercooled droplets and frozen droplets in continuous flow.

The freezing of supercooled water to ice and the materials which catalyse this process are of fundamental interest to a wide range of fields. At present, our ability to control, predict or monitor ice formation processes is poor. The isolation and characterisation of frozen droplets from supercooled liquid droplets would provide a means of improving our understanding and control of these processes. Here, we have developed a microfluidic platform for the continuous flow separation of frozen from unfrozen picolitre droplets based on differences in their density, thus allowing the sorting of ice crystals and supercooled water droplets into different outlet channels with 94 ± 2% efficiency. This will, in future, facilitate downstream or off-chip processing of the frozen and unfrozen populations, which could include the analysis and characterisation of ice-active materials or the selection of droplets with a particular ice-nucleating activity.