Level Of Resolution Research Articles

DNA choreography: correlating mobility and organization of DNA across different resolutions from loops to chromosomes

The dynamics of DNA in the cell nucleus plays a role in cellular processes and fates but the interplay of DNA mobility with the hierarchical levels of DNA organization is still underexplored. Here, we made use of DNA replication to directly label genomic DNA in an unbiased genome-wide manner. This was followed by live-cell time-lapse microscopy of the labeled DNA combining imaging at different resolutions levels simultaneously and allowing one to trace DNA motion across organization levels within the same cells. Quantification of the labeled DNA segments at different microscopic resolution levels revealed sizes comparable to the ones reported for DNA loops using 3D super-resolution microscopy, topologically associated domains (TAD) using 3D widefield microscopy, and also entire chromosomes. By employing advanced chromatin tracking and image registration, we discovered that DNA exhibited higher mobility at the individual loop level compared to the TAD level and even less at the chromosome level. Additionally, our findings indicate that chromatin movement, regardless of the resolution, slowed down during the S phase of the cell cycle compared to the G1/G2 phases. Furthermore, we found that a fraction of DNA loops and TADs exhibited directed movement with the majority depicting constrained movement. Our data also indicated spatial mobility differences with DNA loops and TADs at the nuclear periphery and the nuclear interior exhibiting lower velocity and radius of gyration than the intermediate locations. On the basis of these insights, we propose that there is a link between DNA mobility and its organizational structure including spatial distribution, which impacts cellular processes.

The Role of Emotional Intelligence in Leadership Effectiveness and Organisational Behavior

Objectives: The primary objective of this study is to investigate the significance of emotional intelligence (EI) in relation to leadership efficacy and organizational conduct. Specifically, the study aims to explore the constituent elements of emotional intelligence, their influence on leadership behavior, and their correlation with organizational behavior. Additionally, the study seeks to examine the impact of emotional intelligence on fostering a favorable organizational climate, improving communication, facilitating decision-making, resolving conflicts, and promoting employee engagement. Methods: This study employs a quantitative research methodology, utilizing a self-administered survey instrument. The sample consists of 60 participants holding managerial positions in various organizations. Statistical methodologies such as explanatory diagrams and correlation analysis are used to analyze the data and investigate the relationships between emotional intelligence, managerial competence, organizational behavior, and employee satisfaction. Results: The results of the study highlight a positive association between emotional intelligence and managerial competence, organizational behavior, and employee satisfaction. The findings suggest that higher levels of emotional intelligence are correlated with more effective leadership, improved organizational climate, better communication, enhanced decision-making, conflict resolution, and higher levels of employee engagement. Conclusion: In conclusion, this study emphasizes the importance of emotional intelligence in leadership effectiveness and organizational behavior. The findings underscore the positive impact of emotional intelligence on various aspects of organizational conduct and employee satisfaction. Additionally, the study suggests avenues for future research, including longitudinal inquiries, intercultural variances, exploring intervening and moderating factors, developing interventions, and conducting comparative assessments.

Direct investigations of interactions between nucleolins and aptamers on pancreatic cancer and normal cells by atomic force microscopy

Nucleolin is overexpressed on the surface of pancreatic cancer cells and are regarded as the remarkable therapeutic target. Aptamers are capable of binding the external domain of nucleolin on the cell surface with high affinity and specificity. But nucleolin has not been localized on pancreatic cancer cells at very high spatial resolution, and the interactions between nucleolin and aptamers have not been investigated at very high force resolution level. In this work, nucleolin was localized on pancreatic cancer and normal cells by aptamers (9FU-AS1411-NH2, AS1411-NH2 and CRONH2) in Single Molecule Recognition Imaging mode of Atomic Force Microscopy. There are plenty of nucleolin on the surfaces of pancreatic cancer cells (area percentage about 5 %), while there are little nucleolin on the surfaces of normal cells. The interactions between three types of aptamers and nucleolins on the surfaces of pancreatic cancer cells were investigated by Single Molecule Force Spectroscopy. The unbinding forces of nucleolins-(9FU-AS1411-NH2) are larger than nucleolins-(AS1411-NH2). The dissociation activation energy on nucleolin-(9FU-AS1411-NH2) is higher than nucleolin-(AS1411-NH2), which indicates that the former complex is more stable and harder to dissociate than the later complex. There are no unbinding forces between nucleolin and CRONH2. All these demonstrate that nucleolin was localized on pancreatic cancer and normal cells at single molecule level quantitatively, and the interactions (unbinding forces and kinetics) between nucleolin and aptamers were studied at picoNewton level. The approaches and results of this work will pave new ways in the investigations of nucleolin and aptamers, and will also be useful in the studies on other proteins and their corresponding aptamers.

2D and 3D visualization of herbaceous plant–plant contact zones using high‐resolution X‐ray computed tomography (HRXCT)

Societal Impact StatementParasitic plants that deprive crops of water and nutrients are an increasingly concerning food security issue, affecting the livelihood of millions of subsistence, small‐ and mid‐scale farmers. An in‐depth understanding of parasite–host interactions is required to develop species‐specific and ecologically sustainable parasite management methods. The non‐invasive visualization of herbaceous contact zones, applicable to diverse parasite–host pathosystems presented in this study, brings methodological advance to the research of biotic interactions between crops and plant parasites belonging to the most devastating parasitic plant family (Orobanchaceae). This work also provides first insights into how the parasites' feeding organ displaces host tissue beyond the direct parasite–host interface.SummaryHigh‐resolution X‐ray computed tomography (HRXCT) enables sectioning‐free two‐dimensional imaging of biological structures and reconstruction of three‐dimensional objects. Although its application is common in many areas of biomedicine and despite its flexibility regarding resolution levels, the technology remains underutilized in the plant sciences. Here, we explored HRXCT for the study of parasitic plant–plant interactions by developing protocols to access soft‐tissue host–parasite contact zones at cell‐level resolution. We tested various sample preparation methods and contrast stains for their efficiency to improve the imaging of haustorium samples. In doing so, we achieved cellular resolution with the visible cellular organization of haustorial structures, especially of the vascular system. Fresh stained and dehydrated sample preparation of soft haustoria enables the highest spatial resolution with fine‐cellular discrimination of haustorium versus host cells. Application of cell‐level resolved HRXCT to five pathosystems: Alectra‐cowpea, Phelipanche‐tomato, Phtheirospermum‐tomato, Rhamphicarpa‐tomato, and Striga‐sorghum highlighted a life history‐specific organization and uncovered an as yet undescribed internal displacement of host tissue at parasite–host interfaces. Following image‐based training, our HRXCT approach could invoke AI‐based cell recognition for automated parasite cell–host cell differentiation. Superseding extensive microsectioning for 3D imaging, the newly established HRXCT protocol for 2D‐ and 3D‐visualization of herbaceous plant–plant contact zones and the first insights gained from it, is useful for mid‐throughput, comparative studies of parasitic plant–host interactions.

Revealing the complexity of meniscus microvasculature through 3D visualization and analysis

Three-dimensional information is essential for a proper understanding of the healing potential of the menisci and their overall role in the knee joint. However, to date, the study of meniscal vascularity has relied primarily on two-dimensional imaging techniques. Here we present a method to elucidate the intricate 3D meniscal vascular network, revealing its spatial arrangement, connectivity and density. A polymerizing contrast agent was injected into the femoral artery of human cadaver legs, and the meniscal microvasculature was examined using micro-computed tomography at different levels of detail and resolution. The 3D vascular network was quantitatively assessed in a zone-base analysis using parameters such as diameter, length, tortuosity, and branching patterns. The results of this study revealed distinct vascular patterns within the meniscus, with the highest vascular volume found in the outer perimeniscal zone. Variations in vascular parameters were found between the different circumferential and radial meniscal zones. Moreover, through state-of-the-art 3D visualization using micro-CT, this study highlighted the importance of spatial resolution in accurately characterizing the vascular network. These findings, both from this study and from future research using this technique, improve our understanding of microvascular distribution, which may lead to improved therapeutic strategies.

Meshless track assimilation (MTA) of 3D PTV data

We propose a data assimilation algorithm to improve the resolution of 3D particle tracking velocimetry (PTV) data and, as a byproduct, it estimates the pressure field. The proposed method, called meshless tracking assimilation (MTA), does not rely on a mesh to compute derivatives. Instead, it exploits the analytical formulation of the obtained field to extract the gradients of the involved quantities in arbitrary points. MTA actively constraints PTV data points to satisfy the Navier–Stokes equations in both time and space at user-defined spatial locations. Three test cases are investigated. The first one is a synthetic dataset reconstructed from a direct numerical simulation and it serves to ensure that the method is properly implemented and working. The second one is the 2020 data assimilation challenge which gives a qualitative comparison with other data assimilation methods. Finally, MTA is used on a Tomographic PTV experiment of a Jet Flow with ReD≃3000 to ensure it can be implemented successfully on experimental data. The first and third test cases show a significant performance boost compared to the classic linear interpolation. This improvement allows for a higher level of structural resolution without sacrificing the temporal and spatial smoothness of the solution. The second test case generally aligns well with other state-of-the-art data assimilation techniques in terms of performance, but there are some noticeable differences.

Hydrodynamic characteristics of the microlayer under vapour bubbles on solid surfaces

This study investigates the hydrodynamic behaviour of the microlayer, a thin liquid film of a few micrometres thickness that forms beneath vapour bubbles during boiling under specific conditions. This microlayer serves as a rapid heat transfer medium through evaporation due to its low thermal resistance, making it a compelling subject for enhanced heat transfer research. We employ the geometric Volume-Of-Fluid (VOF) method for numerical simulations, allowing us to accurately replicate the growth of a vapour bubble on solid surfaces. The computational approach offers a level of detail and resolution that can compensate for certain aspects of microlayer behaviour absent in experimental methods. Our simulations reveal the complete spatial distribution of the microlayer and the profiles of the bubble interface near the meniscus front (the part of the interface near the solid). We compare the results with experimental data and conduct simulations with various bubble growth laws to explore how the microlayer responds to different growth scenarios. These findings lay the foundation for incorporating the microlayer’s contribution to overall boiling heat transfer in future models, potentially unlocking new avenues for enhanced heat transfer applications.

Zooming into lipid droplet biology through the lens of electron microscopy.

Electron microscopy (EM), in its various flavors, has significantly contributed to our understanding of lipid droplets (LD) as central organelles in cellular metabolism. For example, EM has illuminated that LDs, in contrast to all other cellular organelles, are uniquely enclosed by a single phospholipid monolayer, revealed the architecture of LD contact sites with different organelles, and provided near-atomic resolution maps of key enzymes that regulate neutral lipid biosynthesis and LD biogenesis. In this review, we first provide a brief history of pivotal findings in LD biology unveiled through the lens of an electron microscope. We describe the main EM techniques used in the context of LD research and discuss their current capabilities and limitations, thereby providing a foundation for utilizing suitable EM methodology to address LD-related questions with sufficient level of structural preservation, detail, and resolution. Finally, we highlight examples where EM has recently been and is expected to be instrumental in expanding the frontiers of LD biology.

Exploring the possibility of adding DGGS support to the S-100 Universal Hydrographic Data Model

reference systems. A DGGS is a spatial reference system consisting of multiple layers of grids with increasing resolution which partition the globe into polygon shaped cells of equal area. Individual cells can be easily identified and basic Geographic Information System (GIS) operations can be performed on data stored within the cells. Advantages of using DGGS for spatial data include the ability to integrate data layers of different data types in a statistically uniform way, the possibility to avoid distortions caused from projection, and the capability to scale analysis across multiple resolution levels. The benefits of using DGGS for hydrographic data, specifically Electronic Navigational Charts (ENC) are examined. The addition of DGGS to S-100 would provide a uniform gridding system for ENC cells, and would eliminate distortions in the Polar Regions caused when projecting rectangular cells based on latitude and longitude. The Open Geospatial Consortium (OGC) led a pilot project for which one of the participants developed a server that offers S-100 marine protected area data organized according to DGGS. Because of this success and the availability of open-source software for the implementation of DGGS, the BSH (German Federal Maritime and Hydrographic Agency) investigated the feasibility and possible benefits of using Discrete Global Grid Systems for S-100 data. The outcome was successful. However, it is recognized that DGGS as a standard is not yet advanced enough and the available software tools are inadequate for wide implementation. More investigation needs to be done, and additionally the best grid shape, orientation and aperture for a uniform grid for hydrographic data need to be determined. Overall, DGGS should be considered for future versions of S-100, the new universal hydrographic data model, because the benefits for ENCs and hydrographic data are clear and in the future, it is expected that DGGS will revolutionize GIS.

Heavy black hole seed formation in high-z atomic cooling halos

Context. Halos with masses in excess of the atomic limit are believed to be ideal environments in which to form heavy black hole seeds with masses above 103 M⊙. In cases where the H2 fraction is suppressed, this is expected to lead to reduced fragmentation of the gas and the generation of a top-heavy initial mass function. In extreme cases this can result in the formation of massive black hole seeds. Resolving the initial fragmentation scale and the resulting protostellar masses has, until now, not been robustly tested. Aims. We run zoom-in simulations of atomically cooled halos in which the formation of H2 is suppressed to assess whether they can truly resist fragmentation at high densities and tilt the initial mass function towards a more top-heavy form and the formation of massive black hole seeds. Methods. Cosmological simulations were performed with the moving mesh code AREPO, using a primordial chemistry network until z ∼ 11. Three haloes with masses in excess of the atomic cooling mass were then selected for detailed examination via zoom-ins. A series of zoom-in simulations, with varying levels of maximum spatial resolution, captured the resulting fragmentation and formation of metal-free stars using the sink particle technique. The highest resolution simulations resolved densities up to 10−6 g cm−3 (1018 cm−3) and captured a further 100 yr of fragmentation behaviour at the centre of the halo. Lower resolution simulations were then used to model the future accretion behaviour of the sinks over longer timescales. Results. Our simulations show intense fragmentation in the central region of the halos, leading to a large number of near-solar mass protostars. Even in the presence of a super-critical Lyman-Werner radiation field (JLW > 105J21), H2 continues to form within the inner ∼2000 au of the halo. Despite the increased fragmentation, the halos produce a protostellar mass spectrum that peaks at higher masses relative to standard Population III star-forming halos. The most massive protostars have accretion rates of 10−3–10−1 M⊙ yr−1 after the first 100 years of evolution, while the total mass of the central region grows at 1 M⊙ yr−1. Lower resolution zoom-ins show that the total mass of the system continues to accrete at ∼1 M⊙ yr−1 for at least 104 yr, although how this mass is distributed amongst the rapidly growing number of protostars is unclear. However, assuming that a fraction of stars can continue to accrete rapidly, the formation of a sub-population of stars with masses in excess of 103 M⊙ is likely in these halos. In the most optimistic case, we predict the formation of heavy black hole seeds with masses in excess of 104 M⊙, assuming an accretion behaviour in line with expectations from super-competitive accretion and/or frequent mergers with secondary protostars.

Review of Luneburg Lens Antenna Designs Manufactured Using 3D Printing

Introduction. The interest in multibeam dielectric lens antenna arrays has been growing in recent years due to the development of millimeter-wave telecommunication and radar systems. Progress in the development of mobile communication systems based on adaptive beamforming technology is increasingly associated with multibeam systems based on lens antenna structures, providing an alternative to hard-to-implement and energy-consuming phased antenna arrays. In recent years, spherical and cylindrical Luneburg lens antennas implemented using additive manufacturing technology have attracted research attention. Despite their complexity of execution, these design exhibit excellent electromagnetic characteristics. This paper provides a review of Luneburg lens antennas manufactured using 3D printing, which can find application in 5G and 6G communication systems.Aim. To review achievements in the design of lens antenna structures manufactured using additive manufacturing.Materials and methods. Materials for analysis, comparison, and systematization were derived from various sources, including research articles, publications in proceedings of Russian and international conferences, and websites of manufacturers of lens antennas over the past 20 years. The material selection mechanism was based on the originality of the presented designs of printed Luneburg lens antennas.Results. A review of Luneburg lens antennas manufactured using 3D printing, which differ from each other in terms of mechanical strength, complexity of execution, and electrodynamic characteristics, was carried out. The results of a comparative analysis of the key characteristics of these antennas are presented, along with examples of their practical implementation.Conclusion. The disadvantage of Luneburg lens antennas has always been the complexity of their manufacture; however, additive manufacturing technologies open up new opportunities for their fast, high-quality, and automated production. Various 3D printing technologies can be used to create dielectric lens antennas, which differ in the resolution of printers, printing speed, and cost. Additive manufacturing methods are constantly developing, having reached the technological possibility of printing Luneburg lens for the sub-THz range with a high level of resolution and accuracy. In addition, 3D printers capable of printing multiple lenses simultaneously have also appeared.

Effects of source space resolution, randomization and averaging in focal EEG source localization: Estimation of forward and inverse errors

In this article, we study randomized multiresolution forward modeling and source localization in electroencephalography (EEG). Our goal is to determine numerically the effects of variable source space resolution on both forward modeling and source localization perspectives and to examine how it affects the detection of the sources at different depths inside the brain. Our concentration is in the main principles of multiresolution methods: random source space generation and the reconstruction obtained via averaging over multiple maximum a posteriori (MAP) estimations obtained at a finite set of different sub source spaces, and their suggested enhancement in distinguishability of weak components. The motivation of averaging is to reduce the discretization and optimization error and marginalize other variable factors. Due to the unguided randomized source space generation, multiple samples of the same size source spaces are needed. For this very reason, a large number of source spaces of multiple source counts are used to obtain statistically feasible results in this paper. This study verifies the described postulates of the multiresolution technique by showing averaging to be crucial in order to obtain a robust projection to a lower resolution, where the lead field matrix is overdetermined. From the viewpoint of source localization, the multiresolution approach was found to improve the reconstruction accuracy obtained with each resolution level below the highest and observed to be necessary to achieve an accuracy comparable to that of forward modeling.

Network of large pedigrees reveals social practices of Avar communities.

From AD 567-568, at the onset of the Avar period, populations from the Eurasian Steppe settled in the Carpathian Basin for approximately 250 years1. Extensive sampling for archaeogenomics (424 individuals) and isotopes, combined with archaeological, anthropological and historical contextualization of four Avar-period cemeteries, allowed for a detailed description of the genomic structure of these communities and their kinship and social practices. We present a set of large pedigrees, reconstructed using ancient DNA, spanning nine generations and comprising around 300 individuals. We uncover a strict patrilineal kinship system, in which patrilocality and female exogamy were the norm and multiple reproductive partnering and levirate unions were common. The absence of consanguinity indicates that this society maintained a detailed memory of ancestry over generations. These kinship practices correspond with previous evidence from historical sources and anthropological research on Eurasian Steppe societies2. Network analyses of identity-by-descent DNA connections suggest that social cohesion between communities was maintained via female exogamy. Finally, despite the absence of major ancestry shifts, the level of resolution of our analyses allowed us to detect genetic discontinuity caused by the replacement of a community at one of the sites. This was paralleled with changes in the archaeological record and was probably a result of local political realignment.

Genome structural dynamics: insights from Gaussian network analysis of Hi-C data.

Characterization of the spatiotemporal properties of the chromatin is essential to gaining insights into the physical bases of gene co-expression, transcriptional regulation and epigenetic modifications. The Gaussian network model (GNM) has proven in recent work to serve as a useful tool for modeling chromatin structural dynamics, using as input high-throughput chromosome conformation capture data. We focus here on the exploration of the collective dynamics of chromosomal structures at hierarchical levels of resolution, from single gene loci to topologically associating domains or entire chromosomes. The GNM permits us to identify long-range interactions between gene loci, shedding light on the role of cross-correlations between distal regions of the chromosomes in regulating gene expression. Notably, GNM analysis performed across diverse cell lines highlights the conservation of the global/cooperative movements of the chromatin across different types of cells. Variations driven by localized couplings between genomic loci, on the other hand, underlie cell differentiation, underscoring the significance of the four-dimensional properties of the genome in defining cellular identity. Finally, we demonstrate the close relation between the cell type-dependent mobility profiles of gene loci and their gene expression patterns, providing a clear demonstration of the role of chromosomal 4D features in defining cell-specific differential expression of genes.

LipiDex 2 Integrates MSn Tree-Based Fragmentation Methods and Quality Control Modules to Improve Discovery Lipidomics.

As lipidomics experiments increase in scale and complexity, data processing tools must support workflows for new liquid chromatography-mass spectrometry (LC-MS) methods while simultaneously supporting quality controls to maximize the confidence in lipid identifications. LipiDex 2 improves lipidomics data processing algorithms from LipiDex 1 and introduces new tools for spectral matching and peak annotation functions, with improvements in speed and user-friendliness. In silico spectral library generation now supports tandem mass spectral (MSn) tree-based fragmentation methods, and the LipiDex 2 workflow fully integrates the fragmentation logic into the data processing steps to enable lipid identification at the appropriate level of structural resolution. Finally, LipiDex 2 features new modules for automated quality control checks that also allow users to visualize data quality in a data dashboard user interface.

Estimation of pop-up satellite archival tag initial surface position: applications for eastern Bering Sea crab research

BackgroundClimate change is reshaping Bering Sea crab distributions and recent population declines have elevated the urgency in understanding spatial dynamics in relation to management boundaries. While pop-up satellite archival tags (PSATs) can provide fishery-independent movement information, a high level of spatial resolution is needed to evaluate small-scale (i.e., 10 s of km) movements of crabs. Because PSATs drift at the surface prior to acquisition of a satellite-estimated location (via Argos), the accuracy of pop-up location (i.e., animal terminal position) estimates depends on the ability to accurately estimate drift error. We deployed PSATs (n = 36) on fixed-position moorings in Bristol Bay and Marmot Bay, Alaska to validate a new method to estimate tag pop-up location and an associated error ellipse that uses in situ drift data from surfaced tags to estimate drift error. Estimated pop-up location was compared to the location of tag surfacing (i.e., the tag’s fixed position) and to an alternative estimate (i.e., an early satellite-estimated location). Additional tags were deployed on mature male red king crab (Paralithodes camtschaticus) in Bristol Bay during 2020 (n = 84) and 2021 (n = 90) to compare estimates of tag drift error and crab displacement derived using the method.ResultsFor red king crab tags with pop-up location estimates in 2020 (n = 79) and 2021 (n = 46), mean drift error was 9% and 44% of mean crab displacement, respectively. For fixed-position PSATs with pop-up location estimates (n = 27), mean distance between the estimated pop-up location and the tag’s fixed position was 2.0 km, representing a mean improvement in accuracy of 51% over alternative estimates. Corresponding error ellipse estimates either encompassed the tag’s fixed position (n = 11) or their boundaries were a mean distance of 1.3 km (n = 16) from the fixed position.ConclusionsOur method improves pop-up location estimates for PSAT-tagged animals and is particularly well suited for crabs and other slow-moving benthic marine species. The improved estimates enhance PSAT utility for addressing management and ecological questions that require a fine spatial resolution, such as movement near management boundaries or defining essential habitat for important life history events.

A priori parameter estimation of space SAR operating in the sliding spotlight scan mode and in the terrain observation mode by progressive scans

In the detailed mode of operation of the synthetic aperture radar (SAR), an improved level of geometric resolution of the terrain in a small frame is achieved. If, however, the frame length exceeds the size of the bottom trace in the azimuthal direction, then it is necessary to use a sliding spotlight operation mode (SSL), in which antenna pattern is scanned in the swath along the azimuth angle. To increase the width of the swath, ScanSAR mode is used. In the traditional implementation of this mode, image serration occurs. This effect can be eliminated by using terrain observation by progressive scans mode (TOPS)). In this mode, when shooting a frame, the antenna pattern runs quickly and alternately through all the specified partial swath bands. Despite the presence of a large number of publications in domestic and foreign literature devoted to the analysis of the main parameters of SAR operating in SSL and TOPS modes, there is a need to clarify calculation methods and increase the number of system parameters issued by them, which generally determine the basic appearance of the equipment. The purpose of the work is to clarify and detail the presentation of the methodology for a priori estimation of an increased number of parameters describing the main system characteristics of space SAR operating in SSL and TOPS. The paper develops and describes in detail a methodology with an exhaustive list of calculation ratios for a priori estimation of parameters describing the main system characteristics of space SAR operating in SSL and TOPS. Based on it, algorithms and software modules have been developed that allow you to perform calculations and display the results in a visual graphical form. Examples of computer calculations of 12 system parameters dependencies on the angle of sight of space radars operating in these two modes are given. The application of the developed methodology makes it possible to quickly perform an a priori assessment of a variety of basic system parameters of space radars operating in SSL and TOPS modes, which facilitates the selection of the most acceptable basic appearance of the equipment for practical implementation.

Evaluation of monolithic crystal detector with dual-ended readout utilizing multiplexing method

Objective. Monolithic crystal detectors are increasingly being applied in positron emission tomography (PET) devices owing to their excellent depth-of-interaction (DOI) resolution capabilities and high detection efficiency. In this study, we constructed and evaluated a dual-ended readout monolithic crystal detector based on a multiplexing method. Approach. We employed two 12 × 12 silicon photomultiplier (SiPM) arrays for readout, and the signals from the 12 × 12 array were merged into 12 X and 12 Y channels using channel multiplexing. In 2D reconstruction, three methods based on the centre of gravity (COG) were compared, and the concept of thresholds was introduced. Furthermore, a light convolutional neural network (CNN) was employed for testing. To enhance depth localization resolution, we proposed a method by utilizing the mutual information from both ends of the SiPMs. The source width and collimation effect were simulated using GEANT4, and the intrinsic spatial resolution was separated from the measured values. Main results. At an operational voltage of 29 V for the SiPM, an energy resolution of approximately 12.5 % was achieved. By subtracting a 0.8 % threshold from the total energy in every channel, a 2D spatial resolution of approximately 0.90 mm full width at half maximum (FWHM) can be obtained. Furthermore, a higher level of resolution, approximately 0.80 mm FWHM, was achieved using a CNN, with some alleviation of edge effects. With the proposed DOI method, a significant 1.36 mm FWHM average DOI resolution can be achieved. Additionally, it was found that polishing and black coating on the crystal surface yielded smaller edge effects compared to a rough surface with a black coating. Significance. The introduction of a threshold in COG method and a dual-ended readout scheme can lead to excellent spatial resolution for monolithic crystal detectors, which can help to develop PET systems with both high sensitivity and high spatial resolution.

Robotic Heller's cardiomyotomy for achalasia: early outcomes for a high-volume UK centre.

Heller's cardiomyotomy (HCM) is the gold standard treatment for achalasia. Laparoscopic HCM has been shown to be effective with low rates of symptom recurrence, though oesophageal mucosal perforation rates remain high. The aim of this prospective case series is to assess the short-term complication rates and perioperative outcomes for the first cohort of patients undergoing robotic-assisted HCM for achalasia in a single high-volume UK centre. Data were collected from a prospective cohort of patients who underwent robotic HCM at a single high-volume UK centre. Outcomes were assessed using the Eckhard score, which was calculated after their routine postoperative clinic appointments. Thirteen patients underwent robotic HCM during the study period; this is the second largest reported case series in the European literature. There were no intraoperative oesophageal perforations. Six patients were discharged as day cases, six patients were discharged on the first postoperative day and one patient's hospital stay was two nights. There was a single perioperative complication of urinary retention. All patients reported improvement of symptoms following their operation, and all had a postoperative Eckhard score of less than 3, indicating their achalasia was in remission. This cohort has demonstrated that robotic HCM has an exceptional safety profile and results in high levels of symptom resolution, even early in the learning curve. The robotic approach may be superior to laparoscopy as it allows more precise identification and dissection of the oesophageal muscle fibres, which likely reduces the risk of inadvertent mucosal damage or incomplete myotomy.

Tumor Microenvironment Landscapes Supporting EGFR-mutant NSCLC Are Modulated at the Single-cell Interaction Level by Unesbulin Treatment.

Targeting the TME is an attractive strategy for treatment of solid tumors. Here we revealed how EGFR-mutant landscapes are affected at the single-cell resolution level during Unesbulin treatment. This novel drug, by targeting cancer cells and their interactions with crucial TME components, could be envisioned for future therapeutic advancements.