The ability of microorganisms to generate resistance outcompetes with the generation of new and efficient antibiotics; therefore, it is critical to develop novel antibiotic agents and treatments to ...control bacterial infections. An alternative to this worldwide problem is the use of nanomaterials with antimicrobial properties. Silver nanoparticles (AgNPs) have been extensively studied due to their antimicrobial effect in different organisms. In this work, the synergistic antimicrobial effect of AgNPs and conventional antibiotics was assessed in Gram-positive and Gram-negative bacteria. AgNPs minimal inhibitory concentration was 10-12 μg mL-1 in all bacterial strains tested, regardless of their different susceptibility against antibiotics. Interestingly, a synergistic antimicrobial effect was observed when combining AgNPs and kanamycin according to the fractional inhibitory concentration index, FICI: <0.5), an additive effect by combining AgNPs and chloramphenicol (FICI: 0.5 to 1), whereas no effect was found with AgNPs and β-lactam antibiotics combinations. Flow cytometry and TEM analysis showed that sublethal concentrations of AgNPs (6-7 μg mL-1) altered the bacterial membrane potential and caused ultrastructural damage, increasing the cell membrane permeability. No chemical interactions between AgNPs and antibiotics were detected. We propose an experimental supported mechanism of action by which combinatorial effect of antimicrobials drives synergy depending on their specific target, facilitated by membrane alterations generated by AgNPs. Our results provide a deeper understanding about the synergistic mechanism of AgNPs and antibiotics, aiming to combat antimicrobial infections efficiently, especially those by multi-drug resistant microorganisms, in order to mitigate the current crisis due to antibiotic resistance.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Lipophilic efficiency (LipE) is an important metric that has been increasingly applied in drug discovery medicinal chemistry lead optimization programs. In this Perspective, using literature drug ...discovery examples, we discuss the concept of rigorously applying LipE to guide medicinal chemistry lead optimization toward drug candidates with potential for superior in vivo efficacy and safety, especially when guided by physiochemical property-based optimization (PPBO). Also highlighted are examples of small structural modifications such as addition of single atoms, small functional groups, and cyclization that produce large increases in LipE. Understanding the factors that may contribute to LipE changes through analysis of ligand–protein crystal structures and using structure-based drug design (SBDD) to increase LipE by design is also discussed. Herein we advocate for use of LipE analysis coupled with PPBO and SBDD as an efficient mechanism for drug design.
Neural Manifolds for the Control of Movement Gallego, Juan A.; Perich, Matthew G.; Miller, Lee E. ...
Neuron (Cambridge, Mass.),
06/2017, Letnik:
94, Številka:
5
Journal Article
Recenzirano
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The analysis of neural dynamics in several brain cortices has consistently uncovered low-dimensional manifolds that capture a significant fraction of neural variability. These neural manifolds are ...spanned by specific patterns of correlated neural activity, the “neural modes.” We discuss a model for neural control of movement in which the time-dependent activation of these neural modes is the generator of motor behavior. This manifold-based view of motor cortex may lead to a better understanding of how the brain controls movement.
Firing patterns of neurons seen individually are mere Plato-like shadows of underlying brain activity, unlikely to yield real insight. Gallego et al. argue that studies of neural population activity will better illuminate how the brain makes plans and generates movements.
Long-term learning of language, mathematics, and motor skills likely requires cortical plasticity, but behavior often requires much faster changes, sometimes even after single errors. Here, we ...propose one neural mechanism to rapidly develop new motor output without altering the functional connectivity within or between cortical areas. We tested cortico-cortical models relating the activity of hundreds of neurons in the premotor (PMd) and primary motor (M1) cortices throughout adaptation to reaching movement perturbations. We found a signature of learning in the “output-null” subspace of PMd with respect to M1 reflecting the ability of premotor cortex to alter preparatory activity without directly influencing M1. The output-null subspace planning activity evolved with adaptation, yet the “output-potent” mapping that captures information sent to M1 was preserved. Our results illustrate a population-level cortical mechanism to progressively adjust the output from one brain area to its downstream structures that could be exploited for rapid behavioral adaptation.
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•Macaque monkeys rapidly adapted to reaching movement perturbations•Functional connectivity within motor and premotor cortex was unchanged•The “output-null” activity within PMd held a signature of force-field learning•There was no corresponding change accompanying visuomotor rotation learning
Behavioral adaptation occurs rapidly, even after single errors. Perich et al. propose that the premotor cortex can exploit an “output-null” subspace to learn to adjust its output to downstream regions in response to behavioral errors.
Animals readily execute learned behaviors in a consistent manner over long periods of time, and yet no equally stable neural correlate has been demonstrated. How does the cortex achieve this stable ...control? Using the sensorimotor system as a model of cortical processing, we investigated the hypothesis that the dynamics of neural latent activity, which captures the dominant co-variation patterns within the neural population, must be preserved across time. We recorded from populations of neurons in premotor, primary motor and somatosensory cortices as monkeys performed a reaching task, for up to 2 years. Intriguingly, despite a steady turnover in the recorded neurons, the low-dimensional latent dynamics remained stable. The stability allowed reliable decoding of behavioral features for the entire timespan, while fixed decoders based directly on the recorded neural activity degraded substantially. We posit that stable latent cortical dynamics within the manifold are the fundamental building blocks underlying consistent behavioral execution.
Populations of cortical neurons flexibly perform different functions; for the primary motor cortex (M1) this means a rich repertoire of motor behaviors. We investigate the flexibility of M1 movement ...control by analyzing neural population activity during a variety of skilled wrist and reach-to-grasp tasks. We compare across tasks the neural modes that capture dominant neural covariance patterns during each task. While each task requires different patterns of muscle and single unit activity, we find unexpected similarities at the neural population level: the structure and activity of the neural modes is largely preserved across tasks. Furthermore, we find two sets of neural modes with task-independent activity that capture, respectively, generic temporal features of the set of tasks and a task-independent mapping onto muscle activity. This system of flexibly combined, well-preserved neural modes may underlie the ability of M1 to learn and generate a wide-ranging behavioral repertoire.
Summary
In wheat (Triticum aestivum L) and other cereals, the number of ears per unit area is one of the main yield‐determining components. An automatic evaluation of this parameter may contribute to ...the advance of wheat phenotyping and monitoring. There is no standard protocol for wheat ear counting in the field, and moreover it is time consuming. An automatic ear‐counting system is proposed using machine learning techniques based on RGB (red, green, blue) images acquired from an unmanned aerial vehicle (UAV). Evaluation was performed on a set of 12 winter wheat cultivars with three nitrogen treatments during the 2017–2018 crop season. The automatic system uses a frequency filter, segmentation and feature extraction, with different classification techniques, to discriminate wheat ears in micro‐plot images. The relationship between the image‐based manual counting and the algorithm counting exhibited high levels of accuracy and efficiency. In addition, manual ear counting was conducted in the field for secondary validation. The correlations between the automatic and the manual in‐situ ear counting with grain yield were also compared. Correlations between the automatic ear counting and grain yield were stronger than those between manual in‐situ counting and GY, particularly for the lower nitrogen treatment. Methodological requirements and limitations are discussed.
Significance Statement
Ear density (ears m–2) is one of the main agronomical yield components of wheat. This study represents a novel contribution to the field of RGB image processing for plant phenotyping using unmanned aerial vehicle (UAV) platforms. By combining high‐resolution RGB imagery with an automatic ear classification and counting system, we have shown that it is possible to assess ear density with high precision from an aerial platform. This is the first published study successfully deploying this approach.
Institutions, Human Capital, and Development Acemoglu, Daron; Gallego, Francisco A; Robinson, James A
Annual review of economics,
01/2014, Letnik:
6, Številka:
1
Journal Article
Recenzirano
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In this article, we revisit the relationship among institutions, human capital, and development. We argue that empirical models that treat institutions and human capital as exogenous are ...misspecified, both because of the usual omitted variable bias problems and because of differential measurement error in these variables, and that this misspecification is at the root of the very large returns of human capital, about four to five times greater than that implied by micro (Mincerian) estimates, found in the previous literature. Using cross-country and cross-regional regressions, we show that when we focus on historically determined differences in human capital and control for the effect of institutions, the impact of institutions on long-run development is robust, whereas the estimates of the effect of human capital are much diminished and become consistent with micro estimates. Using historical and cross-country regression evidence, we also show that there is no support for the view that differences in the human capital endowments of early European colonists have been a major factor in the subsequent institutional development of former colonies.
•Solar energy use has increased considerably in the last decade.•One of the main challenges identified by the U.S. National Academy of Engineering is to make solar energy economical.•Advanced control ...techniques can be useful to improve the performance of solar systems.•This paper presents a procedure to optimize the operation of trough solar plants.
One of the most important challenges in the use of solar energy is to make it economical. This can be done by reducing investment and operating costs and by increasing solar plants performance. This paper presents a three-layer hierarchical control strategy to optimize the operation of solar trough plants. The first layer deals with the operational planning of the solar plant and it computes the electrical power to be produced and delivered. The second layer computes the optimal set-point for the solar plant, aiming at producing the electrical power provided by the first layer and optimizing the economic profit. The third layer addresses the problem of tracking the set-point calculated by the second layer. A model of the Plataforma Solar de Almería (PSA) solar trough plant is used to illustrate the proposed algorithm. Simulations show that important increments in electricity production are obtained by using the proposed control scheme.
The number of ears per unit ground area (ear density) is one of the main agronomic yield components in determining grain yield in wheat. A fast evaluation of this attribute may contribute to ...monitoring the efficiency of crop management practices, to an early prediction of grain yield or as a phenotyping trait in breeding programs. Currently the number of ears is counted manually, which is time consuming. Moreover, there is no single standardized protocol for counting the ears. An automatic ear-counting algorithm is proposed to estimate ear density under field conditions based on zenithal color digital images taken from above the crop in natural light conditions. Field trials were carried out at two sites in Spain during the 2014/2015 crop season on a set of 24 varieties of durum wheat with two growing conditions per site. The algorithm for counting uses three steps: (1) a Laplacian frequency filter chosen to remove low and high frequency elements appearing in an image, (2) a Median filter to reduce high noise still present around the ears and (3) segmentation using
to segment local peaks and determine the ear count within the image.
The results demonstrate high success rate (higher than 90%) between the algorithm counts and the manual (image-based) ear counts, and precision, with a low standard deviation (around 5%). The relationships between algorithm ear counts and grain yield was also significant and greater than the correlation with manual (field-based) ear counts. In this approach, results demonstrate that automatic ear counting performed on data captured around anthesis correlated better with grain yield than with images captured at later stages when the low performance of ear counting at late grain filling stages was associated with the loss of contrast between canopy and ears.
Developing robust, low-cost and efficient field methods to assess wheat ear density, as a major agronomic component of yield, is highly relevant for phenotyping efforts towards increases in grain yield. Although the phenological stage of measurements is important, the robust image analysis algorithm presented here appears to be amenable from aerial or other automated platforms.
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