This study presents a noise-robust closed-loop control strategy for wake flows employing model predictive control. The proposed control framework involves the autonomous offline selection of ...hyperparameters, eliminating the need for user interaction. To this purpose, Bayesian optimization maximizes the control performance, adapting to external disturbances, plant model inaccuracies and actuation constraints. The noise robustness of the control is achieved through sensor data smoothing based on local polynomial regression. The plant model can be identified through either theoretical formulation or using existing data-driven techniques. In this work we leverage the latter approach, which requires minimal user intervention. The self-tuned control strategy is applied to the control of the wake of the fluidic pinball, with the plant model based solely on aerodynamic force measurements. The closed-loop actuation results in two distinct control mechanisms: boat tailing for drag reduction and stagnation point control for lift stabilization. The control strategy proves to be highly effective even in realistic noise scenarios, despite relying on a plant model based on a reduced number of sensors.
Due to the emergence of antimicrobial resistance, new alternative therapies are needed. Silver was used to treat bacterial infections since antiquity due to its known antimicrobial properties. Here, ...we aimed to evaluate the in vitro activity of colloidal silver (CS) against multidrug-resistant (MDR) Gram-negative and Gram-positive bacteria. A total of 270 strains (
(
= 45),
(
= 25),
(
= 79),
(
= 58),
(
= 34),
(
= 14), and
(
= 15)) were used. The minimal inhibitory concentration (MIC) of CS was determined for all strains by using microdilution assay, and time-kill curve assays of representative reference and MDR strains of these bacteria were performed. Membrane permeation and bacterial reactive oxygen species (ROS) production were determined in presence of CS. CS MIC
was 4-8 mg/L for all strains. CS was bactericidal, during 24 h, at 1× and 2× MIC against Gram-negative bacteria, and at 2× MIC against Gram-positive bacteria, and it did not affect their membrane permeabilization. Furthermore, we found that CS significantly increased the ROS production in Gram-negative with respect to Gram-positive bacteria at 24 h of incubation. Altogether, these results suggest that CS could be an effective treatment for infections caused by MDR Gram-negative and Gram-positive bacteria.
The objective of this study was to evaluate the in vitro and in vivo efficacy of clavulanic acid (C/A) in combination with tazobactam against clinical strains of carbapenem-resistant
Acinetobacter ...baumannii
. The MIC of 24 clinical strains of
A. baumannii
was determined, and a checkerboard assay and time-kill curve analysis were performed in selected strains to determine the synergy between C/A and tazobactam. The efficacy of C/A in monotherapy and in combination with tazobactam was evaluated in vitro in cell culture experiments and in a murine peritoneal sepsis model. The C/A and C/A plus tazobactam MIC
50
were 128 and <1 mg/L, respectively. The checkerboard assay showed that tazobactam (4 and 8 mg/L) demonstrated synergy with C/A against
A. baumannii
Ab40, an OXA-24 producer strain, and Ab293, a lacking OXA β-lactamase strain. The time-kill curve assay showed both bactericidal and synergistic effects against Ab40 and Ab293, with C/A 1xMIC and tazobactam (4 and 8 mg/L) at 24 h. In the murine peritoneal sepsis model with Ab293 strain, the combination of C/A and tazobactam reduced bacterial loads in tissues and blood by 2 and 4 log
10
CFU/g or mL compared with C/A alone. Combining C/A with tazobactam could be considered as a potential alternative strategy to treat
A. baumannii
in some cases, and future work with more strains is needed to confirm this possibility.
Nonparametric estimators of a regression function with circular response and
R
d
-valued predictor are considered in this work. Local polynomial estimators are proposed and studied. Expressions for ...the asymptotic conditional bias and variance of these estimators are derived, and some guidelines to select asymptotically optimal local bandwidth matrices are also provided. The finite sample behavior of the proposed estimators is assessed through simulations, and their performance is also illustrated with a real data set.
In oceanography, modeling wave fields requires the use of statistical tools capable of handling the circular nature of the data measurements. An important issue in ocean wave analysis is the study of ...height and direction waves, being direction values recorded as angles or, equivalently, as points on a unit circle. Hence, reconstruction of a wave direction field on the sea surface can be approached by the use of a linear–circular regression model, viewing wave directions as a realization of a circular spatial process whose trend should be estimated. In this paper, we consider a spatial regression model with a circular response and several real-valued predictors. Nonparametric estimators of the circular trend surface are proposed, accounting for the (unknown) spatial correlation. Some asymptotic results about these estimators as well as some guidelines for their practical implementation are also given. The performance of the proposed estimators is investigated in a simulation study. An application to wave directions in the Adriatic Sea is provided for illustration.
The problem of assessing a parametric regression model in the presence of spatial correlation is addressed in this work. For that purpose, a goodness-of-fit test based on a
L
2
-distance comparing a ...parametric and nonparametric regression estimators is proposed. Asymptotic properties of the test statistic, both under the null hypothesis and under local alternatives, are derived. Additionally, a bootstrap procedure is designed to calibrate the test in practice. Finite sample performance of the test is analyzed through a simulation study, and its applicability is illustrated using a real data example.
Changes on temperature patterns, on a local scale, are perceived by individuals as the most direct indicators of global warming and climate change. As a specific example, for an Atlantic climate ...location, spring and fall seasons should present a mild transition between winter and summer, and summer and winter, respectively. By observing daily temperature curves along time, being each curve attached to a certain calendar day, a regression model for these variables (temperature curve as covariate and calendar day as response) would be useful for modeling their relation for a certain period. In addition, temperature changes could be assessed by prediction and observation comparisons in the long run. Such a model is presented and studied in this work, considering a nonparametric Nadaraya–Watson-type estimator for functional covariate and circular response. The asymptotic bias and variance of this estimator, as well as its asymptotic distribution are derived. Its finite sample performance is evaluated in a simulation study and the proposal is applied to investigate a real-data set concerning temperature curves.
The excessive use of piperacillin/tazobactam (P/T) has promoted the emergence of P/T-resistant Enterobacterales. We reported that in Escherichia coli, P/T contributes to the development of ...extended-spectrum resistance to β-lactam/β-lactamase inhibitor (BL/BLI) (ESRI) in isolates that are P/T susceptible but have low-level resistance to BL/BLI. Currently, the detection of P/T resistance relying on conventional methods is time-consuming. To overcome this issue, we developed a cost-effective test based on MALDI-MS technology, called MALDIpiptaz, which aims to detect P/T resistance and ESRI developers in E. coli.
We used automated Clover MS Data Analysis software to analyse the protein profile spectra obtained by MALDI-MS from a collection of 248 E. coli isolates (91 P/T-resistant, 81 ESRI developers and 76 P/T-susceptible). This software allowed to preprocess all the spectra to build different peak matrices that were analysed by machine learning algorithms.
We demonstrated that MALDIpiptaz can efficiently and rapidly (15 min) discriminate between P/T-resistant, ESRI developer and P/T-susceptible isolates and allowed the correct classification between ESRI developers from their isogenic resistance to P/T.
The combination of excellent performance and cost-effectiveness are all desirable attributes, allowing the MALDIpiptaz test to be a useful tool for the rapid determination of P/T resistance in clinically relevant E. coli isolates.
This study aimed to evaluate the potential of tamoxifen and N-desmethyltamoxifen metabolites as therapeutic agents against multidrug-resistant
and
using a repurposing approach to shorten the time ...required to obtain a new effective treatment against multidrug-resistant bacterial infections. Characterisation and virulence studies were conducted on
(colistin-susceptible C1-7-LE and colistin-resistant MCR-1+) and
(tigecycline-susceptible Ab#9 and tigecycline-resistant Ab#186) strains. The efficacy of the metabolite mix (33.3% each) and N-desmethyltamoxifen in combination with colistimethate sodium (CMS) or tigecycline was evaluated in experimental models in mice. In the pneumonia model, N-desmethyltamoxifen exhibited significant efficacy against Ab#9 and both
strains, especially
MCR-1+ (-2.86 log
CFU/g lungs, -5.88 log
CFU/mL blood, and -50% mortality), and against the Ab#186 strain when combined with CMS (-2.27 log
CFU/g lungs, -2.73 log
CFU/mL blood, and -40% mortality) or tigecycline (-3.27 log
CFU/g lungs, -4.95 log
CFU/mL blood, and -50% mortality). Moreover, the metabolite mix in combination with both antibiotics decreased the bacterial concentrations in the lungs and blood for both
strains. In the sepsis model, the significant efficacy of the metabolite mix was restricted to the colistin-susceptible
C1-7-LE strain (-3.32 log
CFU/g lung, -6.06 log
CFU/mL blood, and -79% mortality). N-desmethyltamoxifen could be a new therapeutic option in combination with CMS or tigecycline for combating multidrug-resistant GNB, specifically
.
In 2019, the biggest listeriosis outbreak by
(Lm) in the South of Spain was reported, resulting in the death of three patients from 207 confirmed cases. One strain, belonging to clonal complex 388 ...(Lm CC388), has been isolated. We aimed to determine the Lm CC388 virulence in comparison with other highly virulent clones such as Lm CC1 and Lm CC4, in vitro and in vivo. Four
strains (Lm CC388, Lm CC1, Lm CC4 and ATCC 19115) were used. Attachment to human lung epithelial cells (A549 cells) by these strains was characterized by adherence and invasion assays. Their cytotoxicities to A549 cells were evaluated by determining the cells viability. Their hemolysis activity was determined also. A murine intravenous infection model using these was performed to determine the concentration of bacteria in tissues and blood. Lm CC388 interaction with A549 cells is non-significantly higher than that of ATCC 19115 and Lm CC1, and lower than that of Lm CC4. Lm CC388 cytotoxicity is higher than that of ATCC 19115 and Lm CC1, and lower than that of Lm CC4. Moreover, Lm CC388 hemolysis activity is lower than that of the Lm CC4 strain, and higher than that of Lm CC1. Finally, in the murine intravenous infection model by Lm CC388, higher bacterial loads in tissues and at similar levels of Lm CC4 were observed. Although a lower rate of mortality of patients during the listeriosis outbreak in Spain in 2019 has been reported, the Lm CC388 strain has shown a greater or similar pathogenicity level in vitro and in an animal model, like Lm CC1 and Lm CC4.
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