Inference of the Mass Composition of Cosmic Rays with Energies from 10^{18.5} to 10^{20} eV Using the Pierre Auger Observatory and Deep Learning.

We present measurements of the atmospheric depth of the shower maximum X_{max}, inferred for the first time on an event-by-event level using the surface detector of the Pierre Auger Observatory. Using deep learning, we were able to extend measurements of the X_{max} distributions up to energies of 100 EeV (10^{20}  eV), not yet revealed by current measurements, providing new insights into the mass composition of cosmic rays at extreme energies. Gaining a 10-fold increase in statistics compared to the fluorescence detector data, we find evidence that the rate of change of the average X_{max} with the logarithm of energy features three breaks at 6.

Anti-ceramide antibody and sphingosine-1-phosphate as potential biomarkers of unresectable non-small cell lung cancer.

Objectives: Spingosine-1-phosphate (S1P) and ceramides are bioactive sphingolipids that influence cancer cell fate. Anti-ceramide antibodies might inhibit the effects of ceramide. The aim of this study was to assess the potential role of circulating S1P and anti-ceramide antibody as biomarkers in non-small cell lung cancer (NSCLC).

Development of a Novel Human Serum Albumin-Based Tool for Effective Drug Discovery: The Investigation of Protein Quality and Immobilization.

The binding ability of human serum albumin (HSA) on active pharmaceutical ingredients (APIs) is one of the most important parameters in the early stages of drug discovery. In this study, an immobilized HSA-based tool was developed for the rapid and easy in vitro screening of API binding. The work explored the serious incompleteness in the identification of HSA used for in vitro screening published in the last five years.

Probe set selection for targeted spatial transcriptomics.

Targeted spatial transcriptomic methods capture the topology of cell types and states in tissues at single-cell and subcellular resolution by measuring the expression of a predefined set of genes. The selection of an optimal set of probed genes is crucial for capturing the spatial signals present in a tissue. This requires selecting the most informative, yet minimal, set of genes to profile (gene set selection) for which it is possible to build probes (probe design).

The neurobiology of parenting and infant-evoked aggression.

Parenting behavior comprises a variety of adult-infant and adult-adult interactions across multiple timescales. The state transition from nonparent to parent requires an extensive reorganization of individual priorities and physiology and is facilitated by combinatorial hormone action on specific cell types that are integrated throughout interconnected and brainwide neuronal circuits. In this review, we take a comprehensive approach to integrate historical and current literature on each of these topics across multiple species, with a focus on rodents.

Unveiling the regulatory network controlling natural transformation in lactococci.

Lactococcus lactis is a lactic acid bacterium of major importance for food fermentation and biotechnological applications. The ability to manipulate its genome quickly and easily through competence for DNA transformation would accelerate its general use as a platform for a variety of applications. Natural transformation in this species requires the activation of the master regulator ComX.

Piximi - An Images to Discovery web tool for bioimages and beyond.

Deep learning has greatly accelerated research in biological image analysis yet it often requires programming skills and specialized tool installation. Here we present Piximi, a modern, no-programming image analysis tool leveraging deep learning. Implemented as a web application at Piximi.

Harmonic Imaging of Stem Cells in Whole Blood at GHz Pixel Rate.

The pre-clinical validation of cell therapies requires monitoring the biodistribution of transplanted cells in tissues of host organisms. Real-time detection of these cells in the circulatory system and identification of their aggregation state is a crucial piece of information, but necessitates deep penetration and fast imaging with high selectivity, subcellular resolution, and high throughput. In this study, multiphoton-based in-flow detection of human stem cells in whole, unfiltered blood is demonstrated in a microfluidic channel.

Fluorescence-Guided Laparoscopy after Oral Hypericin Administration for Staging of Locally Advanced Gastric Cancer-A Pilot Study.

(1) Laparoscopic staging is essential in gastric cancer (GC) to rule out peritoneal metastasis (PM). Hypericin, a plant-derived fluorescent compound, has been suggested to improve laparoscopic visualization of PM from GC. This prospective, single-arm, open-label clinical trial aimed to assess the feasibility and safety of oral hypericin administration as well as the suitability of fluorescence-guided laparoscopy (FGL) for improving the sensitivity and specificity of staging in GC patients (EudraCT-Number: 2015-005277-21; clinicaltrials.

SuperCUT, an unsupervised multimodal image registration with deep learning for biomedical microscopy.

Numerous imaging techniques are available for observing and interrogating biological samples, and several of them can be used consecutively to enable correlative analysis of different image modalities with varying resolutions and the inclusion of structural or molecular information. Achieving accurate registration of multimodal images is essential for the correlative analysis process, but it remains a challenging computer vision task with no widely accepted solution. Moreover, supervised registration methods require annotated data produced by experts, which is limited.

Stabilization of G-Quadruplex Structures of the SARS-CoV-2 Genome by TMPyP4, BRACO19, and PhenDC3.

The G-quadruplex is one of the non-canonical structures formed by nucleic acids, which can be formed by guanine-rich sequences. They became the focus of much research when they were found in several oncogene promoter regions and also in the telomeres. Later on, they were discovered in viruses as well.

Learning representations for image-based profiling of perturbations.

Measuring the phenotypic effect of treatments on cells through imaging assays is an efficient and powerful way of studying cell biology, and requires computational methods for transforming images into quantitative data. Here, we present an improved strategy for learning representations of treatment effects from high-throughput imaging, following a causal interpretation. We use weakly supervised learning for modeling associations between images and treatments, and show that it encodes both confounding factors and phenotypic features in the learned representation.

Escherichia coli CRISPR arrays from early life fecal samples preferentially target prophages.

CRISPR-Cas systems are defense mechanisms against phages and other nucleic acids that invade bacteria and archaea. In Escherichia coli, it is generally accepted that CRISPR-Cas systems are inactive in laboratory conditions due to a transcriptional repressor. In natural isolates, it has been shown that CRISPR arrays remain stable over the years and that most spacer targets (protospacers) remain unknown.

Demonstrating Agreement between Radio and Fluorescence Measurements of the Depth of Maximum of Extensive Air Showers at the Pierre Auger Observatory.

We show, for the first time, radio measurements of the depth of shower maximum (X_{max}) of air showers induced by cosmic rays that are compared to measurements of the established fluorescence method at the same location. Using measurements at the Pierre Auger Observatory we show full compatibility between our radio and the previously published fluorescence dataset, and between a subset of air showers observed simultaneously with both radio and fluorescence techniques, a measurement setup unique to the Pierre Auger Observatory. Furthermore, we show radio X_{max} resolution as a function of energy and demonstrate the ability to make competitive high-resolution X_{max} measurements with even a sparse radio array.

Advantages of Induced Circular Dichroism Spectroscopy for Qualitative and Quantitative Analysis of Solution-Phase Cyclodextrin Host-Guest Complexes.

The presence of a chiral or chirally perturbed chromophore in the molecule under investigation is a fundamental requirement for the appearance of a circular dichroism (CD) spectrum. For native and for most of the substituted cyclodextrins, this condition is not applicable, because although chiral, cyclodextrins lack a chromophore group and therefore have no characteristic CD spectra over 220 nm. The reason this method can be used is that if the guest molecule has a chromophore group and this is in the right proximity to the cyclodextrin, it becomes chirally perturbed.

Central Ring Puckering Enhances the Stokes Shift of Xanthene Dyes.

Small-molecule dyes are generally designed based on well-understood electronic effects. However, steric hindrance can promote excited-state geometric relaxation, increasing the difference between the positions of absorption and emission bands (the Stokes shift). Accordingly, we hypothesized that sterically induced central ring puckering in xanthene dyes could be used to systematically increase their Stokes shift.

Role of the kisspeptin-KISS1R axis in the pathogenesis of chronic kidney disease and uremic cardiomyopathy.

The prevalence of chronic kidney disease (CKD) is increasing globally, especially in elderly patients. Uremic cardiomyopathy is a common cardiovascular complication of CKD, characterized by left ventricular hypertrophy (LVH), diastolic dysfunction, and fibrosis. Kisspeptins and their receptor, KISS1R, exert a pivotal influence on kidney pathophysiology and modulate age-related pathologies across various organ systems.

Machine learning-based analysis of cancer cell-derived vesicular proteins revealed significant tumor-specificity and predictive potential of extracellular vesicles for cell invasion and proliferation - A meta-analysis.

Background: Although interest in the role of extracellular vesicles (EV) in oncology is growing, not all potential aspects have been investigated. In this meta-analysis, data regarding (i) the EV proteome and (ii) the invasion and proliferation capacity of the NCI-60 tumor cell lines (60 cell lines from nine different tumor types) were analyzed using machine learning methods.

Methods: On the basis of the entire proteome or the proteins shared by all EV samples, 60 cell lines were classified into the nine tumor types using multiple logistic regression.

RuX: A Novel, Flexible, and Sensitive Mifepristone-Induced Transcriptional Regulation System.

Inducible gene regulation methods are indispensable in diverse biological applications, yet many of them have severe limitations in their applicability. These include inducer toxicity, a limited variety of organisms the given system can be used in, and side effects of the induction method. In this study, a novel inducible system, the , was created using a mutant ligand-binding domain of the glucocorticoid receptor (CS1/CD), used together with various genetic elements such as the Gal4 DNA-binding domain or Cre recombinase.

Neuregulin-1β Improves Uremic Cardiomyopathy and Renal Dysfunction in Rats.

Chronic kidney disease is a global health problem affecting 10% to 12% of the population. Uremic cardiomyopathy is often characterized by left ventricular hypertrophy, fibrosis, and diastolic dysfunction. Dysregulation of neuregulin-1β signaling in the heart is a known contributor to heart failure.

Structure preserving adversarial generation of labeled training samples for single-cell segmentation.

We introduce a generative data augmentation strategy to improve the accuracy of instance segmentation of microscopy data for complex tissue structures. Our pipeline uses regular and conditional generative adversarial networks (GANs) for image-to-image translation to construct synthetic microscopy images along with their corresponding masks to simulate the distribution and shape of the objects and their appearance. The synthetic samples are then used for training an instance segmentation network (for example, StarDist or Cellpose).

Image-based and machine learning-guided multiplexed serology test for SARS-CoV-2.

We present a miniaturized immunofluorescence assay (mini-IFA) for measuring antibody response in patient blood samples. The method utilizes machine learning-guided image analysis and enables simultaneous measurement of immunoglobulin M (IgM), IgA, and IgG responses against different viral antigens in an automated and high-throughput manner. The assay relies on antigens expressed through transfection, enabling use at a low biosafety level and fast adaptation to emerging pathogens.

The kisspeptin-1 receptor antagonist peptide-234 aggravates uremic cardiomyopathy in a rat model.

Uremic cardiomyopathy is characterized by diastolic dysfunction, left ventricular hypertrophy (LVH), and fibrosis. Dysregulation of the kisspeptin receptor (KISS1R)-mediated pathways are associated with the development of fibrosis in cancerous diseases. Here, we investigated the effects of the KISS1R antagonist peptide-234 (P234) on the development of uremic cardiomyopathy.