Scientists have established a connection between environmental exposure to toxins like β-
N
-methylamino-
l
-alanine (BMAA) and a heightened risk of neurodegenerative disorders. BMAA is a byproduct ...from certain strains of cyanobacteria that are present in ecosystems worldwide and is renowned for its bioaccumulation and biomagnification in seafood. The sensitivity, selectivity, and reproducibility of the current analytical techniques are insufficient to support efforts regarding food safety and environment monitoring adequately. This work outlines the
in vitro
selection of BMAA-specific DNA aptamers
via
the systematic evolution of ligands through exponential enrichment (SELEX). Screening and characterization of the full-length aptamers was achieved using the SYBR Green (SG) fluorescence displacement assay. Aptamers BMAA_159 and BMAA_165 showed the highest binding affinities, with dissociation constants (
K
d
) of 2.2 ± 0.1 μM and 0.32 0.02 μM, respectively. After truncation, the binding affinity was confirmed using a BMAA-conjugated fluorescence assay. The
K
d
values for BMAA_159_min and BMAA_165_min were 6 ± 1 μM and 0.63 ± 0.02 μM, respectively. Alterations in the amino proton region studied using solution nuclear magnetic resonance (NMR) provided further evidence of aptamer-target binding. Additionally, circular dichroism (CD) spectroscopy revealed that BMAA_165_min forms hybrid G-quadruplex (G4) structures. Finally, BMAA_165_min was used in the development of an electrochemical aptamer-based (EAB) sensor that accomplished sensitive and selective detection of BMAA with a limit of detection (LOD) of 1.13 ± 0.02 pM.
Scientists have established a connection between environmental exposure to toxins like β-
N
-methylamino-
l
-alanine (BMAA) and a heightened risk of neurodegenerative disorders.
Rafael Cansinos Assens no es únicamente un escritor menor entre dos generaciones: la primera, que representa el estilo clásico del siglo diecinueve, y la segunda que es la nueva ola del lenguaje ...literario. No se trata ni de un escritor tradicional en su más amplio sentido, ni de un novelista representativo de la bohemia. Así, la crítica general olvida la importante aportación que Cansinos ofrece a la siguiente novelística del siglo veinte, no sólo en el aspecto técnico sino también en la estructura global, en la argumentación, el lirismo y el simbolismo. Cuando estudiamos en detalle su conjunto de novela corta observamos muchos de estos aspectos. En otras palabras, la sociedad está cambiando, y filósofos como Nietzsche son una poderosa influencia en la vida, como categoría artística. La presencia del “yo” en la novela moderna, como una voz reflexiva, como una construcción del ser, es uno de los pasos sustanciales que podemos intuir en su narrativa.
Abstract
Radiomics is an emerging technique for the quantification of imaging data that has recently shown great promise for deeper phenotyping of cardiovascular disease. Thus far, the technique has ...been mostly applied in single-centre studies. However, one of the main difficulties in multi-centre imaging studies is the inherent variability of image characteristics due to centre differences. In this paper, a comprehensive analysis of radiomics variability under several image- and feature-based normalisation techniques was conducted using a multi-centre cardiovascular magnetic resonance dataset. 218 subjects divided into healthy (n = 112) and hypertrophic cardiomyopathy (n = 106, HCM) groups from five different centres were considered. First and second order texture radiomic features were extracted from three regions of interest, namely the left and right ventricular cavities and the left ventricular myocardium. Two methods were used to assess features’ variability. First, feature distributions were compared across centres to obtain a distribution similarity index. Second, two classification tasks were proposed to assess: (1) the amount of centre-related information encoded in normalised features (centre identification) and (2) the generalisation ability for a classification model when trained on these features (healthy versus HCM classification). The results showed that the feature-based harmonisation technique ComBat is able to remove the variability introduced by centre information from radiomic features, at the expense of slightly degrading classification performance. Piecewise linear histogram matching normalisation gave features with greater generalisation ability for classification ( balanced accuracy in between 0.78 ± 0.08 and 0.79 ± 0.09). Models trained with features from images without normalisation showed the worst performance overall ( balanced accuracy in between 0.45 ± 0.28 and 0.60 ± 0.22). In conclusion, centre-related information removal did not imply good generalisation ability for classification.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
We attempted to identify cellular mechanisms as an approach to screen chemicals for the potential to cause developmental neurotoxicity. We examine, in SH-SY5Y cells, whether apoptosis and oxidative ...stress via reactive oxygen species (ROS) generation, caspase 3/7 activation, gene expression (Bax, Bcl-2, Casp-3, BNIP3, p53 and Nrf2) alterations and necrosis by release of cytosolic adenylate kinase (AK), underlie direct effects of the pyrethroids cyfluthrin and alpha-cypermethrin. We also determined transcriptional alterations of genes (TUBB3, NEFL, NEFH, GAP43, CAMK2A, CAMK2B, WNT3A, WNT5A, WNT7A, SYN1 and PIK3C3) linked to neuronal development and maturation. Our results indicate that cyfluthrin and alpha-cypermethrin have the ability to elicit concentration-dependent increases in AK release, cellular ROS production, caspase 3/7 activity and gene expression of apoptosis and oxidative stress mediators. Both pyrethroids caused changes in mRNA expression of key target genes linked to neuronal development. These changes might reflect in a subsequent neuronal dysfunction. Our study shows that SH-SY5Y cell line is a valuable in vitro model for predicting development neurotoxicity. Our research provides evidence that cyfluthrin and alpha-cypermethrin have the potential to act as developmental neurotoxic compounds. Additional information is needed to improve the utility of this in vitro model and/or better understand its predictive capability.
•Neurotoxicity of pyrethroids cyfluthrin and alpha-cypermethrin in SH-SY5Y cells.•Both pyrethroids increase AK release, ROS production and caspase 3/7 activity.•Both pyrethroids increase gene expression of apoptosis and oxidative stress.•Both pyrethroids alter gene expression linked to neuronal development.•In vitro model SH-SY5Y cells is valuable for predicting development neurotoxicity.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The adaptive immune response requires interaction between T cells and APC to form a specialized structure termed the immune synapse (IS). Although the TCR is essential for IS organization, other ...factors such as chemokines participate in this process. In this study, we show that the chemokine CXCL12-mediated signaling contributes to correct IS organization and therefore influences T cell activation. CXCR4 downregulation or blockade on T cells caused defective actin polymerization at the contact site with APC, altered microtubule-organizing center polarization and the IS structure, and reduced T cell/APC contact duration. T cell activation was thus inhibited, as shown by reduced expression of CD25 and CD69 markers and of IL-2 mRNA levels. The results indicate that, through Gi and JAK1 and 2 kinases activation, CXCL12 signaling cooperates to build the IS and to maintain adhesive contacts between APC and T cells, required for continuous TCR signaling.
The aim of this paper is to obtain new inequalities involving some topological indices of a graph and characterize graphs extremal with respect to them. Our main results provide lower bounds on ...several indices involving just the minimum and the maximum degree of the graph
G
. This family of indices includes, among others, the Wiener index and several of its generalizations, the harmonic index and the general sum-connectivity index, and the geometric-arithmetic index. We also include some chemical applications of our results and some open problems.
The objective of this work is to elucidate the fate of quinolizidine alkaloids (QA) during the lupin protein extraction process assisted with ultrasound and the evaluation of the nutritional and ...functional properties of the protein fraction. Proximal characterization, concentration of anti-nutritional compounds, amino acid profile and protein solubility profile of flours from three lupin species were (
,
and
) assessed. The result showed a significant difference (
< 0.05) in protein concentration, fat, total alkaloids and particle size between the three species flours. Based on these parameters, the most different
species (
and
) were chosen to study the behavior of the protein fraction in terms of functionality, composition and resistance to thermal treatments. The results obtained for
described the ultrasound effect as beneficial for protein yield (14% more than control), QA reduction from bagasse (81% less than control) and protein isolate production (50% less than control). On the other hand,
was more resistant to the ultrasound effect with no significant difference between treatments (10 and 15 min) and control but with the lower toxicity and better amino acid score. These results will be useful to design processes to assist in the objective of meeting the future protein demand of the population.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Finite control set model predictive control techniques have been emerged as good alternatives in particularly for multilevel and multiphase power converters, for which switching vectors with multiple ...magnitudes/directions are available but the modulator or switching table design becomes complex. In this paper, a finite-control-set model predictive direct torque and power control (FCS-DTC-DPC) for grid-tied three-level neutral-point clamped back-to-back power converters in permanent-magnet synchronous generator wind turbine systems is presented and experimentally compared with its counterpart: switching table-based direct torque and power control (ST-DTC-DPC). Both methods have been implemented and verified at a lab-constructed setup with a fully FPGA-based real-time controller. Experimental results confirm that both achieve (equivalently) good control dynamics, whereas FCS-DTC-DPC outperforms ST-DTC-DPC in terms of steady-state control performances at similar switching frequencies but has a higher computational demanding and is more sensitive to system parameter variations.
To compute the hyperbolicity constant is an almost intractable problem, thus it is natural to try to bound it in terms of some parameters of the graph. Let G(g,c,n) be the set of graphs G with girth ...g(G)=g, circumference c(G)=c, and n vertices; and let H(g,c,m) be the set of graphs with girth g, circumference c, and m edges. In this work, we study the four following extremal problems on graphs: A(g,c,n)=min{δ(G)|G∈G(g,c,n)}, B(g,c,n)=max{δ(G)|G∈G(g,c,n)}, α(g,c,m)=min{δ(G)|∈H(g,c,m)} and β(g,c,m)=max{δ(G)|G∈H(g,c,m)}. In particular, we obtain bounds for A(g,c,n) and α(g,c,m), and we compute the precise value of B(g,c,n) and β(g,c,m) for all values of g, c, n and m.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Ex vivo confocal microscopy (EVCM) generates digitally colored purple-pink images similar to H&E without time-consuming tissue processing. It can be used during Mohs surgery for rapid detection of ...basal cell carcinoma (BCC); however, reading EVCM images requires specialized training. An automated approach using a deep learning algorithm for BCC detection in EVCM images can aid in diagnosis. A total of 40 BCCs and 28 negative (not-BCC) samples were collected at Memorial Sloan Kettering Cancer Center to create three training datasets: (i) EVCM image dataset (663 images), (ii) H&E image dataset (516 images), and (iii) a combination of the two datasets. A total of seven BCCs and four negative samples were collected to create an EVCM test dataset (107 images). The model trained with the EVCM dataset achieved 92% diagnostic accuracy, similar to the H&E model (93%). The area under the receiver operator characteristic curve was 0.94, 0.95, and 0.94 for EVCM-, H&E-, and combination-trained models, respectively. We developed an algorithm for automatic BCC detection in EVCM images (comparable accuracy to dermatologists). This approach could be used to assist with BCC detection during Mohs surgery. Furthermore, we found that a model trained with only H&E images (which are more available than EVCM images) can accurately detect BCC in EVCM images.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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