Miracle-dz/UniFAR-FTUs huggingface dataset:
New horizons in the ageing autonomic nervous system: orthostatic hypotension and supine hypertension

Abstract Blood pressure regulation is an automatic, moment-by-moment buffering of the blood pressure in response to physiological changes such as orthostasis, exercise and haemorrhage. This finely orchestrated reflex is called the baroreflex. It is a regulated arc of afferent, central and efferent arms. Multiple physiological changes occur with ageing that can disrupt this reflex, making blood pressure regulation less effective. In addition, multiple changes can occur with ageing-related diseases such as neurodegeneration, atherosclerosis, deconditioning and polypharmacy. These changes commonly result in orthostatic hypotension, hypertension or both, and are consistently associated with multiple adverse outcomes. In this article, we discuss the healthy baroreflex, and physiological and pathophysiological reasons for impaired baroreflex function in older people. We discuss why the common clinical manifestations of orthostatic hypotension and concomitant supine hypertension occur, and strategies for balancing these conflicting priorities. Finally, we discuss strategies for treating them, outlining our practice alongside consensus and expert guidance.
The use of combined quality management instruments to analyze the causes of non-conformities in the castings of the cover of the rail vehicle bearing housing

Abstract The most critical activities influencing the success of each company are continuous improvement of the quality of manufactured products and monitoring of the production process. Skillful use of available technologies and quality management tools allows for eliminating casting non-conformities and preventing their repetition in the future. The research aimed to analyze the types of defects occurring in castings, the location of their most frequent occurrence areas, and to identify the causes of defects in castings of bearing housings used in rail vehicles. The benefits of a combination of quality management tools for diagnosing material discontinuities in the analyzed castings are presented in this article.
National Competitiveness and Foreign Direct Investment in Emerging Europe

Abstract The paper evaluates the relationship between the indicators of competitiveness of national economies (real unit labour costs and Global Competitiveness Index) and the flow of FDI in Central and Eastern Europe (CEE) over the last two decades. Our results show that from 2000 to 2020, CEE economies had an average annual inflow of FDI of 3.9% of GDP, with significant variation across the region. We have found out that the relationship between the net inflow of FDI and the real unit labour costs was strongly negative, while the results on the link with the Global Competitiveness Index was less conclusive. In 2020, due to pandemic global flow of FDI, shrank by around 40%, while the net inflow of FDI to CEE countries declined on average by 15%. These trends and results of survey-based analyses from other studies suggest that CEE region, and especially the Western Balkans countries, may benefit from the nearshoring process in the future. To exploit that opportunity, they may need to put focus of their policies on efficiency-enhancing tax reforms (that would reduce the unit labour costs) and other structural reforms that would result in improvement of the stock and quality of their physical and human capital.
A non-interleaved bidirectional Janus metasurface with full-space scattering channels

Abstract Metasurfaces have attracted broad interest thanks to their unprecedented capacity for electromagnetic wavefront manipulation. The compact, ultrathin and multifunctional metasurface calls for novel design principles. Here, we propose and experimentally demonstrate a non-interleaved and non-segmented bidirectional Janus metasurface that encodes multiple functionalities in full-space scattering channels with different propagation directions and polarization in the microwave region. Specifically, by rotating and adjusting the elementary double-arrow-shaped structure within the same meta-atom, the independent phase control can be achieved in both cross-polarized transmission and co-polarized reflection components under oppositely directed incident waves. Our metasurface with broken mirror symmetry can fully exploit four independent information channels under opposite propagation directions. A series of proof-of-concept is constructed to validity of our methodology, and the simulations and experimental results further show that the proposed non-interleaved bidirectional metasurface can provide an attractive platform for various applications, ranging from structured light conversion, optical imaging, multifunctional optical information processing and others.
Measurable Chromatic Number of Spheres

We examine the measurable chromatic number of distance colorings on the surface of 2-dimensional spheres of varying radii, showing in particular that similar arguments to those used to raise lower bounds in the plane work for all but a countable set of radii. Furthermore, we show that measurable chromatic number as a function of the radius, or more generally the curvature, is not monotonic.
Backstepping Control for MPPT and UPF of a Three Phase Single Stage Grid Connected PV System

This paper presents a new control methodology of a three phase grid connected photovoltaic system without using the intermediary DC/DC converter. Based on the synchronized nonlinear model of the whole photovoltaic system, two controllers have been proposed for the three-phase inverter in order to ensure the operation of the PV system at the maximum power point with unity power factor and minimum grid disturbance. Grid synchronization has been ensured by a three-phase 2nd order PLL (Phase-Locked Loop). The stability of each controller is demonstrated by means of Lyapunov analysis and evaluated under changing atmospheric conditions using the Matlab/Simulink environment, the simulation results clearly demonstrate the performance provided by each controller.
The genomic basis of copper tolerance in Drosophila is shaped by a complex interplay of regulatory and environmental factors

Background Escalation in industrialization and anthropogenic activity have resulted in an increase of pollutants released into the environment. Of these pollutants, heavy metals such as copper are particularly concerning due to their bio-accumulative nature. Due to its highly heterogeneous distribution and its dual nature as an essential micronutrient and toxic element, the genetic basis of copper tolerance is likely shaped by a complex interplay of genetic and environmental factors. Results In this study, we utilized the natural variation present in multiple populations of Drosophila melanogaster collected across Europe to screen for variation in copper tolerance. We found that latitude and the degree of urbanization at the collection sites, rather than any other combination of environmental factors, were linked to copper tolerance. While previously identified copper-related genes were not differentially expressed in tolerant vs. sensitive strains, genes involved in metabolism, reproduction, and protease induction contributed to the differential stress response. Additionally, the greatest transcriptomic and physiological responses to copper toxicity were seen in the midgut, where we found that preservation of gut acidity is strongly linked to greater tolerance. Finally, we identified transposable element insertions likely to play a role in copper stress response. Conclusions Overall, by combining genome-wide approaches with environmental association analysis, and functional analysis of candidate genes, our study provides a unique perspective on the genetic and environmental factors that shape copper tolerance in natural D. melanogaster populations and identifies new genes, transposable elements, and physiological traits involved in this complex phenotype.
Genome-wide single cell annotation of the human protein-coding genes

An important quest for the life science community is to deliver a complete annotation of the human building-blocks of life, the genes and the proteins. Here, we report on a genome-wide effort to annotate all protein-coding genes based on single cell transcriptomics data representing all major tissues and organs in the human body, integrated with data from bulk transcriptomics and antibody-based tissue profiling. Altogether, 25 tissues have been analyzed with single cell transcriptomics resulting in genome-wide expression in 444 single cell types using a strategy involving pooling data from individual cells to obtain genome-wide expression profiles of individual cell type. We introduce a new genome-wide classification tool based on clustering of similar expression profiles across single cell types, which can be visualized using dimensional reduction maps (UMAP). The clustering classification is integrated with a new “tau” score classification for all protein-coding genes, resulting in a measure of single cell specificity across all cell types for all individual genes. The analysis has allowed us to annotate all human protein-coding genes with regards to function and spatial distribution across individual cell types across all major tissues and organs in the human body. A new version of the open access Human Protein Atlas (www.proteinatlas.org) has been launched to enable researchers to explore the new genome-wide annotation on an individual gene level.
Novel genetic modules encoding high‐level antibiotic‐free protein expression in probiotic lactobacilli

Lactobacilli are ubiquitous in nature, often beneficially associated with animals as commensals and probiotics, and are extensively used in food fermentation. Due to this close-knit association, there is considerable interest to engineer them for healthcare applications in both humans and animals, for which high-performance and versatile genetic parts are greatly desired. For the first time, we describe two genetic modules in Lactiplantibacillus plantarum that achieve high-level gene expression using plasmids that can be retained without antibiotics, bacteriocins or genomic manipulations. These include (i) a promoter, PtlpA, from a phylogenetically distant bacterium, Salmonella typhimurium, that drives up to 5-fold higher level of gene expression compared to previously reported promoters and (ii) multiple toxin-antitoxin systems as a self-contained and easy-to-implement plasmid retention strategy that facilitates the engineering of tunable transient Genetically Modified Organisms. These modules and the fundamental factors underlying their functionality that are described in this work will greatly contribute to expanding the genetic programmability of lactobacilli for healthcare applications.
Quantitative multiplexed imaging of chromatin ultrastructure with Decode-PAINT

Super-resolution chromatin imaging techniques are emerging as powerful tools for spatial genomics. However, it remains challenging to visualize the genome on the order of tens of nanometers, a scale that can reveal rich structural detail about the nuclear organization. Here we introduce Decode-PAINT, a multiplexed in situ method, which leverages rapid diffraction-limited pre-decoding and DNA-PAINT (DNA points accumulation for imaging nanoscale topography). Decode-PAINT visualizes multiple discrete genomic regions at a resolution close to the nucleosome scale with a simple and easy-to-implement optical setup, reduces total imaging time by omitting multiple rounds of single-molecule recording, and enables the interrogation of the ultrastructure of the targets with <12 nm lateral and <20 nm axial resolution. We showcase the ability of our approach to perform multiplexed, high-resolution profiling of chromatin structure by performing targeted imaging of nine regions of active and inactive X chromosomes in individual cells. In short, Decode-PAINT accelerates in situ structural genomics.
Bayesian models for event-related potentials time-series and electrode correlations estimation

Recent developments on Bayesian inference and prediction for effects on event-related potentials (ERPs) stem from a wide variety of methods, including machine learning, multilevel models, and others. However, few of these approaches make use of clear estimates of the ERP voltage across time and across space (scalp). In the present article, via an iterative process, we propose Gaussian random walk (GRW) models that can estimate voltage uncertainty across time and also provide correlation matrices across electrodes. We apply these models to real ERP data from a P3b paradigm as an example. We discuss results in terms of past and current literature of both ERP estimation and electroencephalography analysis in general.
Single Cell Transcriptomics identifies a WNT7A-FZD5 Signaling Axis that maintains Fallopian Tube Stem Cells in Patient-derived Organoids

Despite its significance to reproduction, fertility, sexually transmitted infections and various pathologies, the fallopian tube (FT) is relatively understudied. Strong evidence points to the FT as the tissue-of-origin of high grade serous ovarian cancer (HGSOC), the most fatal gynaecological malignancy. HGSOC precursor lesions arise specifically in the distal FT (fimbria) which is reported to be enriched in stem-like cells. Investigation of the role of FT stem cells in health and disease has been hampered by a lack of characterization of FT stem cells and lack of models that recapitulate stem cell renewal and differentiation in vitro. Using optimized organoid culture conditions to address these limitations, we found that FT stem cell renewal is highly dependent on WNT/β-catenin signaling and engineered endogenous WNT/β-catenin signaling reporter organoids to biomark, isolate and characterize putative FT stem cells. Using functional approaches as well as bulk and single cell transcriptomic analyses, we show that an endogenous hormonally-regulated WNT7A-FZD5 signaling axis is critical for self-renewal of human FT stem cells, and that WNT/β-catenin pathway-activated FT cells form a distinct transcriptomic cluster of cells enriched in ECM remodelling and integrin signaling pathways. In addition, we find that the WNT7A-FZD5 signaling axis is dispensable for mouse oviduct regeneration. Overall, we provide a deep characterization of FT stem cells and their molecular requirements for self-renewal, paving the way for mechanistic work investigating the role of stem cells in FT health and disease. GRAPHICAL ABSTRACT
Helicobacter chronic stage inflammation undergoes fluctuations that are altered in tlpA mutants

Helicobacter pylori colonizes half of the world’s population and is responsible for a significant disease burden by causing gastritis, peptic ulcers, and gastric cancer. The development of host inflammation drives these diseases, but there are still open questions in the field about how H. pylori controls this process. We characterized H. pylori inflammation using an eight month mouse infection time course and comparison of wild type and a previously identified mutant lacking the TlpA chemoreceptor that causes elevated inflammation. Our work shows that H. pylori chronic stage corpus inflammation undergoes surprising fluctuations, with changes in Th17 and eosinophil numbers. The H. pylori tlpA mutant changed the inflammation temporal characteristics, resulting in different inflammation from wild type at some time points. tlpA mutants have equivalent total and gland colonization at late stage infections. During early infection, in contrast, they show elevated gland and total colonization compared to WT. Our results suggest the chronic inflammation setting is dynamic, and may be influenced by colonization properties of early infection. Importance Helicobacter pylori established chronic infection in half of the world’s population. This infection initiates during childhood, and leads to later life gastric diseases including gastritis, peptic ulcers, and gastric cancer. These diseases are driven by host inflammation, with more severe inflammation leading to more severe disease. It is not fully understood how H. pylori controls inflammation. In this work, we used an H. pylori mouse infection model and characterized inflammation and colonization of wild-type H. pylori and a mutant that was known to cause elevated inflammation. We found that inflammation in the chronic stage undergoes surprising fluctuations, with related changes in Th17 numbers. H. pylori tlpA mutants caused offset inflammation dynamics, suggesting that H. pylori infection underlies this dynamism. Although there were not colonization dynamics at the time of inflammation fluctuations, there were differences between WT and tlpA mutant colonization at early time points. Our results suggest the chronic inflammation setting is more dynamic than previously thought and may be influenced by colonization properties of early infection.
Distinct hyperactive RAS/MAPK alleles converge on common GABAergic interneuron core programs

RAS/MAPK gene dysfunction underlies various cancers and neurocognitive disorders. While the role of RAS/MAPK genes have been well studied in cancer, less is known about their function during neurodevelopment. There are many genes that work in concert to regulate RAS/MAPK signaling, suggesting that if common brain phenotypes could be discovered they could have a broad impact on the many other disorders caused by distinct RAS/MAPK genes. We assessed the cellular and molecular consequences of hyperactivating the RAS/MAPK pathway using two distinct genes in a cell type previously implicated in RAS/MAPK-mediated cognitive changes, cortical GABAergic interneurons. We uncovered some GABAergic core programs that are commonly altered in each of the mutants. Notably, hyperactive RAS/MAPK mutants bias developing cortical interneurons towards those that are somatostatin+. The increase in somatostatin+ interneurons could also be induced by elevated neural activity and we show the core RAS/MAPK signaling pathway is one mechanism by which this occurs. Overall, these findings present new insights into how different RAS/MAPK mutations can converge on GABAergic interneurons, which may be important for other RAS/MAPK genes/disorders.
Global Protein-Turnover Quantification in Escherichia coli Reveals Cytoplasmic Recycling under Nitrogen Limitation

Protein turnover is critical for proteostasis, but turnover quantification is challenging, and even in well-studied E. coli, proteome-wide measurements remain scarce. Here, we quantify the degradation rates of ∼3.2k E. coli proteins under 12 conditions by combining heavy isotope labeling with complement reporter ion quantification and find that cytoplasmic proteins are recycled when nitrogen is limited. We use knockout experiments to assign substrates to the known cytoplasmic ATP-dependent proteases. Surprisingly, none of these proteases are responsible for the observed cytoplasmic protein degradation in nitrogen limitation, suggesting that a major proteolysis pathway in E. coli remains to be discovered. Lastly, we show that protein degradation rates are generally independent of cell division rates. Thus, we introduce broadly applicable technology for protein turnover measurements and provide a rich resource for protein half-lives and protease substrates in E. coli, complementary to genomics data, that will allow researchers to decipher the control of proteostasis.
Soil microbiota and herbivory drive the assembly of plant-associated microbial communities through different mechanisms

Plant-associated microbial communities are key to shaping many aspects of plant biology. In this study, we tested whether soil microbial communities and herbivory influence the microbial community of tomato plants and whether their influence in different plant compartments is driven by microbial spillover between compartments or whether plants are involved in mediating this effect. We grew our plants in soils hosting three different microbial communities and covered (or not) the soil surface to prevent (or allow) passive microbial spillover between compartments, and we exposed them (or not) to herbivory by Manduca sexta. The results showed that the soil-driven effect on aboveground compartments was consistently detected regardless of soil coverage, whereas soil cover influenced the herbivore-driven effect on belowground microbiota. Together, our results suggest that the soil microbiota influences aboveground plant and insect microbial communities via changes in plant metabolism and physiology or by sharing microorganisms via xylem sap. In contrast, herbivores influence the belowground plant microbiota via a combination of microbial spillover and changes in plant metabolism. These results demonstrate the important role of plants in linking aboveground and belowground microbiota, and can foster further research on soil microbiota manipulation for sustainable pest management.
Water salinity does not affect acute thermal tolerance (CTmax) in zebrafish (Danio rerio)

Tolerance against acute warming is an essential trait that can determine how organisms cope during heatwaves, yet the mechanisms underlying it remain elusive. Water salinity has previously been shown to modulate thermal tolerance and may therefore provide clues towards these limiting mechanisms. Here we tested whether short (2 hours) and long (10 days) term exposure to different water salinities (0-5 ppt) affected acute thermal tolerance in zebrafish (N=269). We found that water salinity did not affect the thermal tolerance of zebrafish at either time point, indicating that salinity does not affect the mechanism limiting acute thermal tolerance limits in zebrafish. We did, however, observe unexpected behaviour during the CTmax test in a subset of fish in the highest salinity treatment after 10 days (3 ppt), indicating some form of salinity-driven disturbance during warming.
ASM-3D: An attentional search model fashioned after what and where/how pathways for target search in 3D environment

We propose a biologically inspired attentional search model for target search in a 3D environment, which has two separate channels for object classification, analogous to the “what” pathway in the human visual system, and for prediction of the next location of the camera, analogous to the “where” pathway. We generated 3D Cluttered Cube datasets that consist of an image on one vertical face, and clutter images on the other faces. The camera goes around each cube on a circular orbit centered on the cube and determines the identity of the image and the face on which it is located. The images pasted on the cube faces were drawn from three: MNIST handwriting digit, QuickDraw, and RGB MNIST handwriting digit datasets. The attentional input of 3 concentric cropped windows resembling the high-resolution central fovea and low-resolution periphery of the retina, flows through a Classifier Network and a Camera Motion Network. The Classifier Network classifies the current view into one of the classes or clutter. The Camera Motion Network predicts the camera’s next position on the orbit (varying the azimuthal angle or ‘θ’). Here the camera performs one of three actions: move right, move left, or don’t move. The Camera-Position Network adds the camera’s current θ information into the higher features level of the Classifier Network and the Camera Motion Network. The Camera Motion Network is trained using Q-learning where the reward is 1 if the classifier network gives the correct classification, otherwise 0. Total loss is computed by adding the mean square loss of temporal difference and cross entropy loss. Then the total loss is backpropagated using Adam optimizer. Results on two grayscale image datasets and one RGB image dataset show that the proposed model is successfully able to discover the desired search pattern to find the target face on the cube, and also classify the target face accurately.