BINA

The brain is likely the most complex organ, given the variety of functions it controls, the number of cells it comprises, and their corresponding connectivity and diversity. Identifying and studying neurons, the major building blocks of the brain, is a crucial milestone and is essential for understanding brain functionality in health and disease. Recent developments in machine learning have provided advanced abilities for classifying neurons, mainly according to their morphology. This paper aims to provide an explainable deep-learning framework to classify neurons based on their electrophysiological activity. Our analysis is performed on data provided by the Allen Cell Types database. The data contains a survey of biological features derived from single-cell recordings from mice. Neurons are classified into subtypes based on Cre mouse lines using an inherently interpretable locally sparse deep neural network model …

Analysis of an individual's immunoglobulin or T cell receptor gene repertoire can provide important insights into immune function. High-quality analysis of adaptive immune receptor repertoire sequencing data depends upon accurate and relatively complete germline sets, but current sets are known to be incomplete. Established processes for the review and systematic naming of receptor germline genes and alleles require specific evidence and data types, but the discovery landscape is rapidly changing. To exploit the potential of emerging data, and to provide the field with improved state-of-the-art germline sets, an intermediate approach is needed that will allow the rapid publication of consolidated sets derived from these emerging sources. These sets must use a consistent naming scheme and allow refinement and consolidation into genes as new information emerges. Name changes should be minimised, but …

Upscaling of kidney epithelial cells is crucial for renal regenerative medicine. Nonetheless, the adult kidney lacks a distinct stem cell hierarchy, limiting the ability to long-term propagate clonal populations of primary cells that retain renal identity. Toward this goal, we tested the paradigm of shifting the balance between differentiation and stemness in the kidney by introducing a single pluripotency factor, OCT4. Here we show that ectopic expression of OCT4 in human adult kidney epithelial cells (hKEpC) induces the cells to dedifferentiate, stably proliferate, and clonally emerge over many generations. Control hKEpC dedifferentiate, assume fibroblastic morphology, and completely lose clonogenic capacity. Analysis of gene expression and histone methylation patterns revealed that OCT4 represses the HNF1B gene module, which is critical for kidney epithelial differentiation, and concomitantly activates stemness …

Atopic dermatitis (AD) is associated with dysregulated type 1 IFN‒mediated responses, in parallel with the dominant type 2 inflammation. However, the pathophysiology of this dysregulation is largely unknown. Adenosine-to-inosine RNA editing plays a critical role in immune regulation by preventing double-stranded RNA recognition by MDA5 and IFN activation. We studied global adenosine-to-inosine editing in AD to elucidate the role played by altered editing in the pathophysiology of this disease. Analysis of three RNA-sequencing datasets of AD skin samples revealed reduced levels of adenosine-to-inosine RNA editing in AD. This reduction was seen globally throughout Alu repeats as well as in coding genes and in specific pre-mRNA loci expected to create long double-stranded RNA, the main substrate of MDA5 leading to type I IFN activation. Consistently, IFN signature genes were upregulated. In contrast …

Analysis of dynamic differential speckle patterns, scattered from human tissues illuminated by a laser beam, has been found by many researchers to be applicable for noncontact sensing of various biomedical parameters. The COVID-19 global pandemic brought the need for massive rapid-remote detection of a fever in closed public spaces. The existing non-contact temperature measurement methods have a significant tradeoff between the measurement distance and accuracy. This paper aims to prove the feasibility of an accurate temperature measurement system based on speckle patterns analysis, enabling the sensing of human temperature from an extended distance greater than allowed by the existing methods. In this study, we used speckle patterns analysis combined with artificial intelligence (AI) methods for human temperature extraction, starting with fever/no fever binary classification and continuing with …

Time-resolved x-ray emission/absorption spectroscopy (Tr-XES/XAS) is an informative experimental tool sensitive to electronic dynamics in materials, widely exploited in diverse research fields. Typically, Tr-XES/XAS requires x-ray pulses with both a narrow bandwidth and subpicosecond pulse duration, a combination that in principle finds its optimum with Fourier transform-limited pulses. In this work, we explore an alternative experimental approach, capable of simultaneously retrieving information about unoccupied (XAS) and occupied (XES) states from the stochastic fluctuations of broadband extreme ultraviolet pulses of a free electron laser. We used this method, in combination with singular-value decomposition and Tikhonov regularization procedures, to determine the XAS/XES response from a crystalline silicon sample at the L 2, 3 edge, with an energy resolution of a few tens of meV. Finally, we combined this …

We explore the effects of various receiver coil dimensions and configurations on power transfer efficiency and cost of operation, using advanced simulation tools. We demonstrate that the spatial distribution of the magnetic field leads to a nonmonotonic dependence of the coupling coefficient on coil size. Thus, an optimal coil size, where the coupling coefficient peaks, should be regarded a crucial design parameter which affects the entire system performances. The incorporation of our findings into a multi-objective optimization algorithm is also discussed.

Interferometers are highly sensitive to phase differences and are utilized in numerous schemes. Of special interest is the quantum SU (1, 1) interferometer which is able to improve the sensitivity of classical interferometers. We theoretically develop and experimentally demonstrate a temporal SU (1, 1) interferometer based on two time lenses in a 4 f configuration. This temporal SU (1, 1) interferometer has a high temporal resolution, imposes interference on both time and spectral domains, and is sensitive to the phase derivative which is important for detecting ultrafast phase changes. Therefore, this interferometer can be utilized for temporal mode encoding, imaging, and studying the ultrafast temporal structure of quantum light.

Since the times of Holtsmark (1911), statistics of fields in random environments have been widely studied, for example in astrophysics, active matter, and line-shape broadening. The power-law decay of the two-body interaction, of the form , and assuming spatial uniformity of the medium particles exerting the forces, imply that the fields are fat-tailed distributed, and in general are described by stable L\'evy distributions. With this widely used framework, the variance of the field diverges, which is non-physical, due to finite size cutoffs. We find a complementary statistical law to the L\'evy-Holtsmark distribution describing the large fields in the problem, which is related to the finite size of the tracer particle. We discover bi-scaling, with a sharp statistical transition of the force moments taking place when the order of the moment is , where is the dimension. The high-order moments, including the variance, are described by the framework presented in this paper, which is expected to hold for many systems. The new scaling solution found here is non-normalized similar to infinite invariant densities found in dynamical systems.

We show that a system using down conversion of x-ray photons into optical photons together with the concept of quantum imaging with undetected photons can provide nanoscale resolution even for radiation sensitive samples.

Time-resolved x-ray emission/absorption spectroscopy (Tr-XES/XAS) is an informative experimental tool sensitive to electronic dynamics in materials, widely exploited in diverse research fields. Typically, Tr-XES/XAS requires x-ray pulses with both a narrow bandwidth and subpicosecond pulse duration, a combination that in principle finds its optimum with Fourier transform-limited pulses. In this work, we explore an alternative experimental approach, capable of simultaneously retrieving information about unoccupied (XAS) and occupied (XES) states from the stochastic fluctuations of broadband extreme ultraviolet pulses of a free electron laser. We used this method, in combination with singular-value decomposition and Tikhonov regularization procedures, to determine the XAS/XES response from a crystalline silicon sample at the L2, 3 edge, with an energy resolution of a few tens of meV. Finally, we combined this spectroscopic method with a pump-probe approach to measure structural and electronic dynamics of a silicon membrane. Tr-XAS/XES data obtained after photoexcitation with an optical laser pulse at 390 nm allowed us to observe perturbations of the band structure, which are compatible with the formation of the predicted precursor state of a nonthermal solid-liquid phase transition associated with a bond softening phenomenon.

The four-dimensional nucleome (4DN) consortium studies the architecture of the genome and the nucleus in space and time. We summarize progress by the consortium and highlight the development of technologies for (1) mapping genome folding and identifying roles of nuclear components and bodies, proteins, and RNA, (2) characterizing nuclear organization with time or single-cell resolution, and (3) imaging of nuclear organization. With these tools, the consortium has provided over 2,000 public datasets. Integrative computational models based on these data are starting to reveal connections between genome structure and function. We then present a forward-looking perspective and outline current aims to (1) delineate dynamics of nuclear architecture at different timescales, from minutes to weeks as cells differentiate, in populations and in single cells, (2) characterize cis-determinants and trans-modulators of …

The electrochemical response of ethereal solutions containing magnesium organohaloaluminate complexes has drawn great interest in recent decades owing to their relevance to rechargeable magnesium batteries, as demonstrated with solutions containing complexes formed by reacting R2Mg and AlCl2R moieties in ethers like tetrahydrofuran (THF). However, most of previous reports focused on battery related performances, and less on the structure of the active species. Herein, we focus on (1) identifying electroactive species and (2) correlating the electrochemical properties of their solutions to the preparation modes: either through reactions of their precursors in THF, or by dissolving isolated crystallized products in the ether solvent. Specifically, we explore the products of the reaction of the Grignard reagent t-BuMgCl with AlCl3 (1:1) in THF, and how their presence in solutions affect their electrochemical …

We study ergodic properties of one-dimensional Brownian motion with resetting. Using generic classes of statistics of times between resets, we find respectively for thin/fat tailed distributions, the normalized/non-normalised invariant density of this process. The former case corresponds to known results in the resetting literature and the latter to infinite ergodic theory. Two types of ergodic transitions are found in this system. The first is when the mean waiting time between resets diverges, when standard ergodic theory switches to infinite ergodic theory. The second is when the mean of the square root of time between resets diverges and the properties of the invariant density are drastically modified. We then find a fractional integral equation describing the density of particles. This finite time tool is particularly useful close to the ergodic transition where convergence to asymptotic limits is logarithmically slow. Our study implies rich ergodic behaviors for this non-equilibrium process which should hold far beyond the case of Brownian motion analyzed here.

In quantum mechanics, a quantum system is irreversibly collapsed by a projective measurement. Hence, delicately probing the time evolution of a quantum system holds the key to understanding curious phenomena. Here we experimentally explore an anomalous time evolution, where, illustratively, a particle disappears from a box and emerges in a different box, with a certain moment in which it can be found in neither of them. In this experiment, we directly probe this curious time evolution of a single photon by measuring up to triple-operator sequential weak values using a novel probeless scheme. The naive interpretation provided by single-operator weak values seems to imply the “disappearance” and “re-appearance” of a photon as theoretically predicted. However, double- and triple-operator sequential weak values, representing temporal correlations between the aforementioned values, show that spatial …

Accessing the low-energy non-equilibrium dynamics of materials with simultaneous spatial and temporal resolutions has been a bold frontier of electron microscopy in recent years. One of the main challenges is the ability to retrieve extremely weak signals while simultaneously disentangling amplitude and phase information. Here, we present an algorithm-based microscopy approach that uses light-induced electron modulation to demonstrate the coherent amplification effect in electron imaging of optical near-fields. We provide a simultaneous time-, space-, and phase-resolved measurement in a micro-drum made from a hexagonal boron nitride membrane, visualizing the sub-cycle spatio-temporal dynamics of 2D polariton wavepackets therein. The phase-resolved measurement reveals vortex-anti-vortex singularities on the polariton wavefronts, together with an intriguing phenomenon of a traveling wave mimicking the amplitude profile of a standing wave. Our experiments show a 20-fold coherent amplification of the near-field signal compared to conventional electron near-field imaging, resolving peak field intensities of ~W/cm2 (field amplitude of few kV/m). As a result, our work opens a path toward spatio-temporal electron microscopy of biological specimens and quantum materials - exciting yet sensitive samples, which are currently difficult to investigate.

Current Adaptive Immune Receptor Repertoire sequencing (AIRR-seq) using short-read sequencing strategies resolve expressed Ab transcripts with limited resolution of the C region. In this article, we present the near-full-length AIRR-seq (FLAIRR-seq) method that uses targeted amplification by 5′ RACE, combined with single-molecule, real-time sequencing to generate highly accurate (99.99%) human Ab H chain transcripts. FLAIRR-seq was benchmarked by comparing H chain V (IGHV), D (IGHD), and J (IGHJ) gene usage, complementarity-determining region 3 length, and somatic hypermutation to matched datasets generated with standard 5′ RACE AIRR-seq using short-read sequencing and full-length isoform sequencing. Together, these data demonstrate robust FLAIRR-seq performance using RNA samples derived from PBMCs, purified B cells, and whole blood, which recapitulated results generated by …

SignificanceWide-field measurements of time-resolved fluorescence anisotropy (TR-FA) provide pixel-by-pixel information about the rotational mobility of fluorophores, reflecting changes in the local microviscosity and other factors influencing the fluorophore’s diffusional motion. These features offer promising potential in many research fields, including cellular imaging and biochemical sensing, as demonstrated by previous works. Nevertheless, θ imaging is still rarely investigated in general and in carbon dots (CDs) in particular.AimTo extend existing frequency domain (FD) fluorescence lifetime (FLT) imaging microscopy (FLIM) to FD TR-FA imaging (TR-FAIM), which produces visual maps of the FLT and θ, together with the steady-state images of fluorescence intensity (FI) and FA (r).

A steerable parametric loudspeaker array is known for its directivity and narrow beam width. However, it often suffers from the grating lobes due to periodic array distributions. Here we propose the array configuration of hyperuniform disorder, which is short-range random while correlated at large scales, as a promising alternative distribution of acoustic antennas in phased arrays. Angle-resolved measurements reveal that the proposed array suppresses grating lobes and maintains a minimal radiation region in the vicinity of the main lobe for the primary frequency waves. These distinctive emission features benefit the secondary frequency wave in canceling the grating lobes regardless of the frequencies of the primary waves. Besides, the hyperuniform disordered array is duplicatable, which facilitates extra-large array design without any additional computational efforts.

Kaposi’s sarcoma-associated herpesvirus (KSHV), formally designated the human herpesvirus 8 (HHV-8), is the causative agent of Kaposi’s sarcoma (KS), primary effusion lymphoma (PEL), and plasmablastic variant of multicentric Castleman’s disease (MCD). KSHV also has been linked to another pathological condition with many features in common with MCD, named KSHV inflammatory cytokine syndrome (KICS) and with a number of other rare lymphoproliferative conditions. KSHV infection is highly prevalent in sub-Saharan Africa and among some Amerindian and Melanesian populations, and diffuse in the Mediterranean area and in parts of South America. KSHV is less prevalent in Northern Europe, North America, and most of Asia. KSHV is transmitted via nonsexual routes during childhood in regions with intermediate and high seroprevalence, and mainly via sexual contact during adulthood in countries …

This work describes a novel concept for unifying Superconducting Magnetic Energy Storage (SMES) and an inductive-type Fault Current Limiter (FCL). A single superconducting coil is used both as an energy source for the operation of the SMES and as the field source for saturating the magnetic cores in the FCL. A possible geometry model for the implementation of this concept is suggested and a test case in an 11 kV, 10 MVA network is described for a fully, and 50% charged SMES states. Results show that the Saturated Cores FCL exhibits low insertion impedance and high limiting ratio in both scenarios. The unified SMES-FCL device saves major resources by making the superconducting coil a dual-purpose source, thus opening the door for an easier and efficient implementation of SMES and FCL technologies.