The Multifunctional Sactipeptide Ruminococcin C1 Displays Potent Antibacterial Activity In Vivo as Well as Other Beneficial Properties for Human Health

The world is on the verge of a major antibiotic crisis as the emergence of resistant bacteria is increasing, and very few novel molecules have been discovered since the 1960s. In this context, scientists have been exploring alternatives to conventional antibiotics, such as ribosomally synthesized and post-translationally modified peptides (RiPPs). Interestingly, the highly potent in vitro antibacterial activity and safety of ruminococcin C1, a recently discovered RiPP belonging to the sactipeptide subclass, has been demonstrated. The present results show that ruminococcin C1 is efficient at curing infection and at protecting challenged mice from Clostridium perfringens with a lower dose than the conventional antibiotic vancomycin. Moreover, antimicrobial peptide (AMP) is also effective against this pathogen in the complex microbial community of the gut environment, with a selective impact on a few bacterial genera, while maintaining a global homeostasis of the microbiome. In addition, ruminococcin C1 exhibits other biological activities that could be beneficial for human health, as well as other fields of applications. Overall, this study, by using an in vivo infection approach, confirms the antimicrobial clinical potential and highlights the multiple functional properties of ruminococcin C1, thus extending its therapeutic interest.     

X-ray Fluorescence Uptake Measurement of Functionalized Gold Nanoparticles in Tumor Cell Microsamples

Quantitative cellular in vitro nanoparticle uptake measurements are possible with a large number of different techniques, however, all have their respective restrictions. Here, we demonstrate the application of synchrotron-based X-ray fluorescence imaging (XFI) on prostate tumor cells, which have internalized differently functionalized gold nanoparticles. Total nanoparticle uptake on the order of a few hundred picograms could be conveniently observed with microsamples consisting of only a few hundreds of cells. A comparison with mass spectroscopy quantification is provided, experimental results are both supported and sensitivity limits of this XFI approach extrapolated by Monte-Carlo simulations, yielding a minimum detectable nanoparticle mass of just 5 pg. This study demonstrates the high sensitivity level of XFI, allowing non-destructive uptake measurements with very small microsamples within just seconds of irradiation time.     

Chronically Elevated Exogenous Glucose Elicits Antipodal Effects on the Proteome Signature of Differentiating Human iPSC-Derived Pancreatic Progenitors

The past decade revealed that cell identity changes, such as dedifferentiation or transdifferentiation, accompany the insulin-producing β-cell decay in most diabetes conditions. Mapping and controlling the mechanisms governing these processes is, thus, extremely valuable for managing the disease progression. Extracellular glucose is known to influence cell identity by impacting the redox balance. Here, we use global proteomics and pathway analysis to map the response of differentiating human pancreatic progenitors to chronically increased in vitro glucose levels. We show that exogenous high glucose levels impact different protein subsets in a concentration-dependent manner. In contrast, regardless of concentration, glucose elicits an antipodal effect on the proteome landscape, inducing both beneficial and detrimental changes in regard to achieving the desired islet cell fingerprint. Furthermore, we identified that only a subgroup of these effects and pathways are regulated by changes in redox balance. Our study highlights a complex effect of exogenous glucose on differentiating pancreas progenitors characterized by a distinct proteome signature.     

Temporal Hydrologic Alterations Coupled with Climate Variability and Drought for Transboundary River Basins

Climate change (CC) and drought episode impacts linked with anthropogenic pressure have become an increasing concern for policy makers and water resources managers. The current research presents a comprehensive methodology but simple approach for predicting the annual streamflow alteration based on drought indices and hydrological alteration indicators. This has been achieved depending on the evaluation of drought severity and CC impacts during the human intervention periods to separate the influence of climatic abnormality and measure the hydrologic deviations as a result of streamflow regulation configurations. As a representative case study, the Lesser Zab River Basin in northern Iraq has been chosen. In order to analyse the natural flow regime, 34 hydrological years of streamflow (1931–1965) prior to the main dam construction were assessed. The Indicators of Hydrologic Alteration (IHA) method has been applied to quantify the hydrological alterations of various flow characteristics. In addition, an easy approach for hydrological drought prediction in relatively small basins grounded on meteorological parameters during the early months of the hydrological year has been presented. The prediction was accomplished by implementing the one-dimensional drought examination and the reconnaissance drought index (RDI) for evaluating the severity of meteorological drought. The proposed methodology is founded on linear regression relations connecting the RDI of 3, 6, and 12 months and the streamflow drought index (SDI). The results are critical for circumstances where an early exploration of meteorological drought is obtainable. Outcomes assist water resources managers, engineers, policy makers and decision-makers responsible for mitigating the effects of CC.     

Computational Problem Solving in Spatial Substrates -- A Cognitive Systems Engineering Approach

The ability to perform spatial tasks is crucial for everyday life and of great importance to cognitive agents such as humans, animals, and autonomous robots. A common artificial intelligence approach to accomplish spatial tasks is to represent spatial configurations and tasks in form of detailed knowledge about various aspects of space and time. Suitable algorithms then use the representations to compute solutions to spatial problems. In comparison, natural embodied and situated agents often solve spatial tasks without detailed knowledge about geometric, topological, or mechanical laws; they directly relate actions to effects that are due to spatio-temporal affordances in their bodies and environments. Accordingly, we propose a paradigm that makes the spatio-temporal substrate an integral part of the engine that drives spatial problem solving. We argue that spatial and temporal structures in body and environment can substantially support (and even replace) reasoning effort in computational processes: physical manipulation and perception in spatial environments substitute formal computation. While the approach is well known – for example, we employ diagrams as spatial substrate for geometric problem solving and maps for wayfinding – the underlying principle has not been systematically investigated or formally analyzed as a paradigm of cognitive processing. Topology, distance, and orientation constraints are all integrated and interdependent in truly 2- or 3-dimensional space. Exploiting this fact may not only help overcome the need for acquiring detailed knowledge about the interrelationships between different aspects of space; it also can point to a way of avoiding exploding computational complexity that occurs when we deal with these aspects of space in complex real-world scenarios. Our approach employs affordance-based object-level problem solving to complement knowledge-level formal approaches. We will assess strengths and weaknesses of the new cognitive systems paradigm.     

A Distributed O(1)-Approximation Algorithm for the Uniform Facility Location Problem

We investigate a metric facility location problem in a distributed setting. In this problem, we assume that each point is a client as well as a potential location for a facility and that the opening costs for the facilities and the demands of the clients are uniform. The goal is to open a subset of the input points as facilities such that the accumulated cost for the whole point set, consisting of the opening costs for the facilities and the connection costs for the clients, is minimized. We present a randomized distributed algorithm that computes in expectation an ${\mathcal {O}}(1)$ -approximate solution to the metric facility location problem described above. Our algorithm works in a synchronous message passing model, where each point is an autonomous computational entity that has its own local memory and that communicates with the other entities by message passing. We assume that each entity knows the distance to all the other entities, but does not know any of the other pairwise distances. Our algorithm uses three rounds of all-to-all communication with message sizes bounded to $\mathcal{O}(\log(n))$ bits, where n is the number of input points. We extend our distributed algorithm to constant powers of metric spaces. For a metric exponent ?≥1, we obtain a randomized ${\mathcal {O}}(1)$ -approximation algorithm that uses three rounds of all-to-all communication with message sizes bounded to $\mathcal{O}(\log(n))$ bits.     

Unmanned Ground Vehicle Navigation in Coordinate-Free and Localization-Free Wireless Sensor and Actuator Networks

We present a set of algorithms for the navigation of Unmanned Ground Vehicles (UGVs) towards a set of pre-identified target nodes in coordinate-free and localization-free wireless sensor and actuator networks. The UGVs are equipped with a set of wireless listeners that provide sensing information about the potential field generated by the network of actuators. Two main navigation scenarios are considered: single-UGV, single-destination navigation and multi-UGV, multi-destination navigation. For the single-UGV, single-destination case, we present both centralized and distributed navigation algorithms. Both algorithms share a similar two-phase concept. In the first phase, the system assigns level numbers to individual nodes based on their hop distance from the target nodes. In the second phase, the UGV uses the potential field created by the network of actuators to move towards the target nodes, requiring cooperation between triplets of actuator nodes and the UGV. The hop distance to the target nodes is used to control the main moving direction while the potential field, which can be measured by listeners on the UGV, is used to determine the UGV’s movement. For the multi-UGV, multi-destination case, we present a decentralized allocation algorithm such that multiple UGVs avoid converging to the same destination. After each UGV determines its destination, the proposed navigation scheme is applied. The presented algorithms do not attempt to localize UGVs or sensor nodes and are therefore suitable for operating in GPS-free/denied environments. We also present a study of the communication complexity of the algorithms as well as simulation examples that verify the proposed algorithms and compare their performances.     

Ordering Partial Partitions for Image Segmentation and Filtering: Merging,Creating and Inflating Blocks

The refinement order on partitions corresponds to the operation of merging blocks in a partition, which is relevant to image segmentation and filtering methods. Its mathematical extension to partial partitions, that we call standard order, involves several operations, not only merging, but also creating new blocks or inflating existing ones, which are equally relevant to image segmentation and filtering techniques. These three operations correspond to three basic partial orders on partial partitions, the merging, inclusion and inflating orders. There are three possible combinations of these three basic orders, one of them is the standard order, the other two are the merging-inflating and inclusion-inflating orders. We study these orders in detail, giving in particular their minimal and maximal elements, covering relations and height functions. We interpret hierarchies of partitions and partial partitions in terms of an adjunction between (partial) partitions (possibly with connected blocks) and scalars. This gives a lattice-theoretical interpretation of edge saliency, hence a typology for the edges in partial partitions. The use of hierarchies in image filtering, in particular with component trees, is also discussed. Finally, we briefly mention further orders on partial partitions that can be useful for image segmentation.     

Characterization of Maximum Likelihood Solutions to Image Reconstruction in Photon Emission Tomography

For photon emission tomography, the maximum likelihood (ML) estimator for image reconstruction is generally solution to a nonlinear equation involving the vector of measured data. No explicit closed-form solution is known in general for such a nonlinear ML equation, and numerical resolution is usually implemented, with a very popular iterative method formed by the expectation-maximization algorithm. The numerical character of such resolutions usually makes it difficult to obtain a general characterization of the performance of the ML solution. We show that the nonlinear ML equation can be replaced by an equivalent system of two dual linear equations nonlinearly coupled. This formulation allows us to exhibit explicit (to some extent) forms for the solutions to the ML equation, in general conditions corresponding to the various possible configurations of the imaging system, and to characterize their performance with expressions for the mean-squared error, bias and Cramér-Rao bound. The approach especially applies to characterize the ML solutions obtained numerically, and offers a theoretical framework to contribute to better appreciation of the capabilities of ML reconstruction in photon emission tomography.