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The scale and the course of antibody production in patients with SARS-CoV-2 is highly variable. Factors involved in the immune regulation during the infection may play a major role in the antibody response. We investigated the relationship between the inflammatory markers of the kynurenine pathway and the concentration of antibodies against SARS-CoV-2 in infected patients 8 - 11 days after admission.The study included 72 SARS-CoV-2 - positive inpatients hospitalized between August 2020 and April 2021. The plasma concentrations of tryptophan, kynurenine, anti-SARS-CoV-2 antibodies and the leucocyte count were measured 8 - 11 days after admission. The kynurenine/tryptophan ratio (KYN/TRP ratio) was calculated. Tertiles based on the values for tryptophan, kynurenine, KYN/TRP ratio and the leucocytes were generated.Statistically significant correlations were observed between anti-SARS-CoV-2 antibodies and tryptophan, kynurenine, KYN/TRP ratio and the leucocytes (p-values 0.001-0.007). The high kynurenine and KYN/TRP ratio tertiles showed significantly lower antibody titers compared to the low tertiles (p-values 0.017 and 0.001). The low tryptophan and leucocytes tertiles showed significantly lower antibody titers compared to the high tertiles (p-values 0.001 and 0.008).Patients with higher activation levels of the kynurenine pathway tended to develop lower anti-SARS-CoV-2 antibody titers.

International audience; Pulsed field ablation (PFA), a non-thermal ablative modality, may show different effects on the myocardial tissue compared to thermal ablation. Thus, this study aimed to compare the left atrial (LA) structural and mechanical characteristics after PFA vs. thermal ablation.Cardiac magnetic resonance was performed pre-ablation, acutely (

The paper deals with the optimal parameter tuning for the elastic net problem. This process is formulated as an optimization problem over a Pareto set. The Pareto set is associated with a convex multi-objective optimization problem, and, based on the scalarization theorem, we give a parametrical representation of it. Thus, the problem becomes a bilevel optimization with a unique response of the follower (strong Stackelberg game). Then, we apply this strategy to the parameter tuning for the elastic net problem. We propose a new algorithm called Ensalg to compute the optimal regularization path of the elastic net w.r.t. the sparsity-inducing term in the objective. In contrast to existing algorithms, our method can also deal with the so-called “many-at-a-time” case, where more than one variable becomes zero at the same time and/or changes from zero. In examples involving real-world data, we demonstrate the effectiveness of the algorithm.

Tantalum doped rutile nanorods were hydrothermally grown on FTO substrates using a new seeding approach. This approach allows the incorporation of high concentrations of up to 4.8 at% tantalum as active doping and results in a significant enhancement of photoelectrochemical water splitting rate (1.8 mA/cm2 at a potential of +1.5 V vs RHE) which corresponds to ca. 1% photocurrent conversion efficiency under AM 1.5, 100 mW/cm2 simulated sunlight irradiation.

Pulmonary vein (PV) stenosis is an important potential complication of PV isolation using thermal modalities such as radiofrequency ablation (RFA). Pulsed field ablation (PFA) is an alternative energy that causes nonthermal myocardial cell death.The purpose of this study was to compare the effect of PFA vs RFA on the incidence and severity of PV narrowing or stenosis.Data were analyzed from 4 paroxysmal atrial fibrillation ablation trials using either PFA or RFA; because of absent CT scans or poor computed tomography scan quality, 73 of 153 patients (47.7%) were excluded. Baseline and 3-month cardiac computed tomography scans were reconstructed into 3-dimensional images, and the long and short axes of the PV ostia were quantitatively and qualitatively assessed in a randomized blinded manner by 2 physicians.A total of 299 PVs from 80 patients after either PFA (n = 37) or RFA (n = 43) were enrolled. PV ostial diameters decreased significantly less with PFA than with RFA (% change; long axis: 0.9% ± 8.5% vs -11.9% ± 16.3%; P.001 and short axis: 3.4% ± 12.7% vs -12.9% ± 18.5%; P.001). After a combined quantitative/qualitative analysis, mild (30%-49%), moderate (50%-69%), or severe (70%-100%) PV narrowing was observed, respectively, in 9.0% (15 of 166), 1.8% (3 of 166), and 1.2% (2 of 166) of PVs in the RFA cohort but in none of the PVs after PFA (P.001). Overall, PV narrowing/stenosis was present in 0% and 0% vs 12.0% and 32.5% of PVs and patients who underwent PFA and RFA, respectively.This study indicates that unlike after RFA, the incidence and severity of PV narrowing/stenosis after PV isolation is virtually eliminated with PFA.

The aim of this paper is to determine the optimal indoor comfort conditions for residential houses in two European countries through a thorough statistical analysis. Information from residential indoor environmental conditions, occupants’ feedback and European standards are utilized. This analysis aims to understand and determine the optimal environmental conditions in indoor spaces based on occupants’ satisfaction. The experimental results illustrate that the proposed analysis and its results can be the basis for the optimal indoor environmental conditions determination. A comfortable indoor environment was found to be when the indoor temperature is from 21.5 oC to 23.4 oC and humidity is from 43.5% to 46%. The visual comfort was estimated as neutral from 93 to 124 lux.

It is well known that optimal control problems with L1-control costs produce sparse solutions, i.e., the optimal control is zero on whole intervals. In this paper, we study a general class of convex linear-quadratic optimal control problems with a sparsity functional that promotes a so-called group sparsity structure of the optimal controls. In this case, the components of the control function take the value of zero on parts of the time interval, simultaneously. These problems are both theoretically interesting and practically relevant. After obtaining results about the structure of the optimal controls, we derive stability estimates for the solution of the problem w.r.t. perturbations and L2-regularization. These results are consequently applied to prove convergence of the Euler discretization. Finally, the usefulness of our approach is demonstrated by solving an illustrative example using a semismooth Newton method.

Tyrosine-kinase inhibitors (TKIs) have revolutionized cancer therapy in recent years. Although more targeted than conventional chemotherapy, TKIs exhibit substantial cardiotoxicity, often manifesting as hypertension or heart failure. Here, we assessed myocyte intrinsic cardiotoxic effects of the TKI sorafenib and investigated underlying alterations of myocyte calcium homeostasis. We found that sorafenib reversibly decreased developed force in auxotonically contracting human myocardia (3 µM: −25 ± 4%, 10 µM: −29 ± 7%, 30 µM: −43 ± 12%, p

RNA molecules play important and diverse regulatory roles in the cell. Inspired by this natural versatility, RNA devices are increasingly important for many synthetic biology applications, e.g. optimizing engineered metabolic pathways, gene therapeutics or building up complex logical units. A major advantage of RNA is the possibility of de novo design of RNA-based sensing domains via an in vitro selection process (SELEX). Here, we describe development of a novel ciprofloxacin-responsive riboswitch by in vitro selection and next-generation sequencing-guided cellular screening. The riboswitch recognizes the small molecule drug ciprofloxacin with a KD in the low nanomolar range and adopts a pseudoknot fold stabilized by ligand binding. It efficiently interferes with gene expression both in lower and higher eukaryotes. By controlling an auxotrophy marker and a resistance gene, respectively, we demonstrate efficient, scalable and programmable control of cellular survival in yeast. The applied strategy for the development of the ciprofloxacin riboswitch is easily transferrable to any small molecule target of choice and will thus broaden the spectrum of RNA regulators considerably.

We implement a prototype for an application of automatic optical material testing in the manufacturing of glass panels. Based on a nonlinear optimal control approach, we present a numerical method for optimal control at run time. The algorithm will be demonstrated and tested with the help of an illustrative example where it turns out that the optimal control is of bang-bang or bang-zero-bang type, depending on the state constraints.

RNA-engineered systems offer simple and versatile control over gene expression in many organisms. In particular, the design and implementation of riboswitches presents a unique opportunity to manipulate any reporter device in cis, executing tight temporal and spatial control at low metabolic costs. Assembled to higher order genetic circuits, such riboswitch-regulated devices may efficiently process logical operations. Here, we propose a hierarchical stochastic modeling approach to characterize an in silico repressor gate based on neomycin- and tetracycline-sensitive riboswitches. The model was calibrated on rich, transient in vivo single-cell data to account for cell-to-cell variability. To capture the effect of this variability on gate performance we employed the well-known ROC-analysis and derived a novel performance indicator for logic gates. Introduction of such a performance measure is necessary, since we aimed to assess the correct functionality of the gate at the single-cell level-a prerequisite for its further adaption to a genetic circuitry. Our results may be applied to other genetic devices to analyze their efficiency and ensure their correct performance in the light of cell-to-cell variability.

'Black' TiO2 -in the widest sense, TiO2 reduced by various treatments-has attracted tremendous scientific interest in recent years because of some outstanding properties; most remarkably in photocatalysis. While the material effects visible light absorption (the blacker, the better), black titania produced by high pressure hydrogenation was recently reported to show another highly interesting feature; noble-metal-free photocatalytic H2 generation. In a systematic investigation of high-temperature hydrogen treatments of anatase nanoparticles, TEM, XRD, EPR, XPS, and photoelectrochemistry are used to characterize different degrees of surface hydrogenation, surface termination, electrical conductivity, and structural defects in the differently treated materials. The materials' intrinsic activity for photocatalytic hydrogen evolution is coupled neither with their visible light absorption behavior nor the formation of amorphous material, but rather must be ascribed to optimized and specific defect formation (gray is better than black). This finding is further confirmed by using a mesoporous anatase matrix as a hydrogenation precursor, which, after conversion to the gray state, even further enhances the overall photocatalytic hydrogen evolution activity.

Latent variable graphical models are an extension of Gaussian graphical models that decompose the precision matrix into a sparse and a low-rank component. These models can be learned with theoretical guarantees from data via a semidefinite program. This program features two regularization terms, one for promoting sparsity and one for promoting a low rank. In practice, however, it is not straightforward to learn a good model since the model highly depends on the regularization parameters that control the relative weight of the loss function and the two regularization terms. Selecting good regularization parameters can be modeled as a bi-level optimization problem, where the upper level optimizes some form of generalization error and the lower level provides a description of the solution gamut. The solution gamut is the set of feasible solutions for all possible values of the regularization parameters. In practice, it is often not feasible to describe the solution gamut efficiently. Hence, algorithmic schemes for approximating solution gamuts have been devised. One such scheme is Benson's generic vector optimization algorithm that comes with approximation guarantees. So far Benson's algorithm has not been used in conjunction with semidefinite programs like the latent variable graphical Lasso. Here, we develop an adaptive variant of Benson's algorithm for the semidefinite case and show that it keeps the known approximation and run time guarantees. Furthermore, Benson's algorithm turns out to be practically more efficient for the latent variable graphical model than the existing solution gamut approximation scheme on a wide range of data sets.

A randomized controlled trial found that providing immunonutrition supplementation before surgery reduced the rate of postoperative complications and the length of hospital stays.

Riboswitch development for clinical, technological, and synthetic biology applications constantly seeks to optimize regulatory behavior. Here, we present a machine learning approach to improve the regulation of a tetracycline (tc)-dependent riboswitch device composed of two individual tc aptamers. We developed a bioinformatics model that combines random forest analysis with a convolutional neural network to predict the switching behavior of such tandem riboswitches. We found that both biophysical parameters and the hydrogen bond pattern influence regulation. Our new design pipeline led to significant improvement of the tc riboswitch device with a dynamic range extension from 8.5 to 40-fold. We are confident that our novel method not only results in an excellent tc-dependent riboswitch device but further holds great promise and potential for the optimization of other riboswitches.

We analyze the implicit Euler discretization for a class of convex linear-quadratic optimal control problems with control appearing linearly. Constraints are defined by lower and upper bounds for the controls, and the cost functional may depend on a regularization parameterźź. Without any structural assumption on the optimal control we prove convergence of orderź1 w.r.t. the mesh size for the discrete optimal values. Under the additional assumption that the optimal control is of bang-bang type and the switching function satisfies a growth condition around their zeros we show that the solutions are calm functions of perturbation and regularization parameters. By applying this result to the implicit Euler discretization we improve existing error estimates for discretizations based on the explicit Euler method. Numerical experiments confirm the theoretical findings and demonstrate the usefulness of implicit methods and regularization in case of bang-bang controls.

Over the past five years a number of different synthesis approaches has been reported to obtain so-called ‘black’ titania. One of the outstanding features of the material is that certain synthesis processes lead to the formation of an intrinsic co-catalytic center and thus enable noble-metal free photocatalytic H2-generation. In the present work, using TiO2 nanotube layers, we compare three common ‘blackening’ approaches, namely i) the original high-pressure hydrogenation (HPT-H2), ii) a classic high temperature reduction in Ar, and iii) an electrochemical (cathodic) reduction. We demonstrate that except for high pressure hydrogenation also cathodic reduction leads to an activation of TiO2 - that is, it exhibits noble-metal-free photocatalytic H2 generation. Moreover, we show that a combination of cathodic reduction/high pressure hydrogenation leads to a synergistic effect, that is, a significant enhancement of the combined co-catalytic activity.

During the past years customized gene network design has become of tremendous interest among various disciplines in life science. The identification of artificial genetic elements sensitive to internal or external stimuli constitutes the foundation for the design and realization of conditional gene expression systems. Typically, strategies involving selection or screening steps are employed alongside approaches focusing on rational design to select for the desired functionality of a given element. Here we present a fluorescence-based in vivo screening approach that combines an initial in vitro selection with subsequent extensive screening steps and a final rational design to identify RNA based regulators in baker's yeast. These artificial RNA regulators, termed synthetic riboswitches, are derived from RNA aptamers. Our method allows for the separation of aptamers featuring the potential to be transformed into a riboswitch from those inherently unable to confer control over gene expression. The system may be applied to virtually all existing aptamer-ligand pairs and as such presents a powerful means to enhance the setup of switchable genetic circuits.

Objectives The purpose of this study was to assess the feasibility of pulmonary vein (PV) isolation using low-intensity collimated ultrasound. Background Contemporary approaches to PV isolation are limited by the technical complexity of mapping and ablation. We describe a novel approach to left atrial anatomic rendering and PV isolation that aims to overcome some of these limitations by using low-intensity collimated ultrasound (LICU) system, which allows for near real-time geometry creation and automated ablation in a porcine model. Methods Twenty swine were anesthetized, and the LICU ablation catheter was placed in the left atrium via percutaneous transseptal access. Ultrasound M-mode–based anatomies of the inferior PVs were successfully created, and ablation was performed under automatic robotic control along a user-defined lesion path. One animal was excluded because of device failure. Results All target PVs in the 19 remaining animals were isolated acutely, requiring a mean of 1.6 applications. Ten animals were sacrificed acutely, and the remaining 9 survived for 35 ± 11 days. Of these 9, 1 animal was excluded from analysis because the index lasso position could not be reliably recreated. PVs in 5 of 8 animals remained isolated at sacrifice. Of the 77 total histological sections, 62 lesions (80.5%) were noted to be transmural. Lesions were homogeneous and characterized by coagulative necrosis and fibrous tissue. The mean myocardial thickness was 2.66 ± 1.80 mm, and the mean lesion depth was 4.28 ± 1.97 mm. No extra cardiac or collateral lesions were noted. Conclusions This study demonstrates the safety and efficacy of a novel noncontact ultrasound mapping and ablation system to produce continuous transmural lesions that can isolate PVs in a porcine model.

Tantalum doped rutile nanorods were hydrothermally grown on FTO substrates using a new seeding approach. This approach allows the incorporation of high concentrations of up to 4.8 at% tantalum as active doping and results in a significant enhancement of the photoelectrochemical water splitting rate (1.8 mA cm

The high-pressure hydrogenation of commercially available anatase or anatase/rutile TiO2 powder can create a photocatalyst for H2 evolution that is highly effective and stable without the need for any additional co-catalyst. This activation effect cannot be observed for rutile; however, for anatase/rutile mixtures, a strong synergistic effect can be found (similar to results commonly observed for noble-metal-decorated TiO2). EPR and PL measurements indicated the intrinsic co-catalytic activation of anatase TiO2 to be due to specific defect centers formed during hydrogenation. These active centers can be observed specifically for high-pressure hydrogenation; other common reduction treatments do not result in this effect.

Summary We analyze a class of linear-quadratic optimal control problems with an additional L1-control cost depending on a parameter β. To deal with this nonsmooth problem, we use an augmentation approach known from linear programming in which the number of control variables is doubled. It is shown that if the optimal control for a given is bang-zero-bang and the switching function has a stable structure, the solutions are Lipschitz continuous functions of the parameter β. We also show that in this case the optimal controls for β * and a with | β − β * | sufficiently small coincide except on a set of measure . Finally, we use the augmentation approach to derive error estimates for Euler discretizations. Copyright © 2014 John Wiley & Sons, Ltd.

The Front Cover shows the classic hydrothermal equipment needed to synthesise TiO(2) nanostructures versus the simple room temperature, “test tube” approach described in the article on the synthesis of titanium dioxide ‘hedgehog’ nanowires (SEM picture). These different morphologies were then grown on conductive substrates and tested for their photoelectric properties. More information can be found in the Communication by C. Schneider et al. on page 817 in Issue 7, 2019 (DOI: 10.1002/open.201900013).[Image: see text]

'Black' TiO

Over the past five years a number of different synthesis approaches has been reported to obtain so-called 'black' titania. One of the outstanding features of the material is that certain synthesis processes lead to the formation of an intrinsic co-catalytic center and thus enable noble-metal free photocatalytic H

Although ductal carcinoma in situ (DCIS) does not require axillary evaluation, controversy exists regarding the use of sentinel lymph node biopsy (SLNB) in patients with DCIS diagnosed by core needle biopsy (CNB). Advocates of concomitant SLNB and lumpectomy cite the low morbidity of SLNB, the high rate of invasive ductal carcinoma in resected specimens, and the positive nodes found in 1 to 2 per cent of patients with resected DCIS despite finding no invasive component. Opponents of this practice cite the complication risk and the improbability of clinically significant axillary recurrence. We therefore proposed to determine our rate of invasive cancer in DCIS diagnosed by CNB and to determine whether SLNB at first operation would decrease return to the operating room. We retrospectively reviewed patients diagnosed with DCIS by CNB from 2003 to 2008. Standard clinicopathological data were collected and analyzed. In 110 patients, the prevalence of invasive cancer on final resection pathology was 13.6 per cent (15 of 110). Of those patients with invasive cancer, 93 per cent (14 of 15) had high-grade DCIS ( P = 0.077) by CNB. Seventeen per cent (14 of 82) of patients with high-grade DCIS had invasive cancer. Of 34 patients with SLNB, three (9%) had positive nodes. Fifteen patients required re-excision to obtain negative margins, including 13 patients with invasive cancer. Five patients (4.5%) were spared additional operative intervention by initially performing SLNB. We suggest using concomitant SLNB when a high clinical suspicion of invasive cancer exists, in the presence of a palpable mass, or when mastectomy precludes future SLNB. Intraoperative margin assessment is needed to avoid return to the operating room.