Metabolite identification using automated comparison of high-resolution multistage mass spectral trees

Multistage mass spectrometry (MS(n)) generating so-called spectral trees is a powerful tool in the annotation and structural elucidation of metabolites and is increasingly used in the area of accurate mass LC/MS-based metabolomics to identify unknown, but biologically relevant, compounds. As a consequence, there is a growing need for computational tools specifically designed for the processing and interpretation of MS(n) data. Here, we present a novel approach to represent and calculate the similarity between high-resolution mass spectral fragmentation trees. This approach can be used to query multiple-stage mass spectra in MS spectral libraries. Additionally the method can be used to calculate structure-spectrum correlations and potentially deduce substructures from spectra of unknown compounds. The approach was tested using two different spectral libraries composed of either human or plant metabolites which currently contain 872 MS(n) spectra acquired from 549 metabolites using Orbitrap FTMS(n). For validation purposes, for 282 of these 549 metabolites, 765 additional replicate MS(n) spectra acquired with the same instrument were used. Both the dereplication and de novo identification functionalities of the comparison approach are discussed. This novel MS(n) spectral processing and comparison approach increases the probability to assign the correct identity to an experimentally obtained fragmentation tree. Ultimately, this tool may pave the way for constructing and populating large MS(n) spectral libraries that can be used for searching and matching experimental MS(n) spectra for annotation and structural elucidation of unknown metabolites detected in untargeted metabolomics studies.     

Numerical and experimental investigation on Ag+-Na+ field assisted ion-exchanged channel waveguides

The characteristics of Ag+ diffusion during field assisted fabrication of a channel waveguide in glass substrates are analyzed using a numerical model. Differences between the results of the author's original model and the other typically used models are discussed. Experimental conditions have been chosen to clearly demonstrate the essential features of Ag+ concentration contours, particularly near the mask edges. Metallic and dielectric masks have been used in the experiment, and the results are similar for both mask materials. The shapes of Ag+ concentration contours reveal the presence of a thin polarized layer under the mask and seem to be consistent with the results predicted by the proposed numerical model. Some modifications of the model are suggested for a better fit of the numerical to the experimental results.     

Radiation sterilized bone response to dynamic loading

Allogeneic bone grafts are used on a large scale in surgeries. To avoid the risk of infectious diseases, allografts should be radiation-sterilized. So far, no international consensus has been achieved regarding the optimal radiation dose. Many authors suggest that bone sterilization deteriorates bone mechanical properties. However, no data on the influence of ionizing radiation on bone dynamic mechanical properties are available. Bovine femurs from 2-year old animal were machine cut and irradiated with the doses 10, 15, 25, 35, 45 and 50 kGy. Dynamic mechanical analysis was performed at 1–10 Hz at the temperature range of 0–350 °C in 3-point bending configuration. No statistically significant differences in storage modulus were observed. However, there were significant decreased values of loss modulus between the samples irradiated with doses of 10 (↓14.3%), 15, 45 and 50 kGy (↓33.2%) and controls. It was stated that increased irradiation dose decreases the temperature where collagen denaturation process starts and increases the temperature where the collagen denaturation process finishes. It was shown that activation energy of denaturation process is significantly higher for the samples irradiated with the dose of 50 kGy (615 kJ/mol) in comparison with control samples and irradiation with other doses (100–135 kJ/mol).     

Van der Waals two-color infrared detection

Light:Science&Applications 11, 6 (2022) https://doi.org/10.1038/s41377-021-00694-4 Two-color infrared detection technology realizes target recognition in a comp...     

Insight into Cisplatin-Resistance Signaling of W1 Ovarian Cancer Cells Emerges mTOR and HSP27 as Targets for Sensitization Strategies

The microenvironment possesses a strong impact on the tumor chemoresistance when cells bind to components of the extracellular matrix. Here we elucidate the signaling pathways of cisplatin resistance in W1 ovarian cancer cells binding to collagen type 1 (COL1) and signaling interference with constitutive cisplatin resistance in W1CR cells to discover the targets for sensitization. Proteome kinase arrays and Western blots were used to identify the signaling components, their impact on cisplatin resistance was evaluated by inhibitory or knockdown approaches. W1 cell binding to COL1 upregulates integrin-associated signals via FAK/PRAS40/mTOR, confirmed by β1-integrin (ITGB1) knockdown. mTOR appears as key for resistance, its blockade reversed COL1 effects on W1 cell resistance completely. W1CR cells compensate ITGB1-knockdown by upregulation of discoidin domain receptor 1 (DDR1) as alternative COL1 sensor. COL1 binding via DDR1 activates the MAPK pathway, of which JNK1/2 appears critical for COL1-mediated resistance. JNK1/2 inhibition inverts COL1 effects in W1CR cells, whereas intrinsic cisplatin resistance remained unaffected. Remarkably, knockdown of HSP27, another downstream MAPK pathway component overcomes intrinsic resistance completely sensitizing W1CR cells to the level of W1 cells for cisplatin cytotoxicity. Our data confirm the independent regulation of matrix-induced and intrinsic chemoresistance in W1 ovarian cancer cells and offer novel targets for sensitization.     

Particle swarm intelligence tunning of fuzzy geometric protoforms for price patterns recognition and stock trading

A novel approach for detecting patterns in price time series is shown. The proposed system for identifying consolidation phases is based on fuzzy geometric protoforms and classification trees. Promising results of the empirical studies prove that the suggested fuzzy geometric protoforms are very useful for identifying patterns in graphical visualizations of data. Moreover, the architecture of the system enables successful incorporation of genetic optimization what enables capturing various data sets structure and unstable conditions on financial markets.     

Comparison of Metabolite Concentrations in the Left Dorsolateral Prefrontal Cortex,the Left Frontal White Matter,and the Left Hippocampus in Patients in Stable Schizophrenia Treated with Antipsychotics with or without Antidepressants. 1H-NMR Spectroscopy Study

Managing affective, negative, and cognitive symptoms remains the most difficult therapeutic problem in stable phase of schizophrenia. Efforts include administration of antidepressants. Drugs effects on brain metabolic parameters can be evaluated by means of proton nuclear magnetic resonance (¹H-NMR) spectroscopy. We compared spectroscopic parameters in the left prefrontal cortex (DLPFC), the left frontal white matter (WM) and the left hippocampus and assessed the relationship between treatment and the spectroscopic parameters in both groups. We recruited 25 patients diagnosed with schizophrenia (DSM-IV-TR), with dominant negative symptoms and in stable clinical condition, who were treated with antipsychotic and antidepressive medication for minimum of three months. A group of 25 patients with schizophrenia, who were taking antipsychotic drugs but not antidepressants, was matched. We compared metabolic parameters (N-acetylaspartate (NAA), myo-inositol (mI), glutamatergic parameters (Glx), choline (Cho), and creatine (Cr)) between the two groups. All patients were also assessed with the Positive and Negative Syndrome Scale (PANSS) and the Calgary Depression Scale for Schizophrenia (CDSS). In patients receiving antidepressants we observed significantly higher NAA/Cr and NAA/Cho ratios within the DLPFC, as well as significantly higher mI/Cr within the frontal WM. Moreover, we noted significantly lower values of parameters associated with the glutamatergic transmission—Glx/Cr and Glx/Cho in the hippocampus. Doses of antipsychotic drugs in the group treated with antidepressants were also significantly lower in the patients showing similar severity of psychopathology.     

Properties of Hemp–Flax Composites for Use in the Building Industry

This article presents the results of research concerning lightweight composites produced on the basis of lime, cement, and clay binders, with the addition of perlite, hemp shives, and flax straw. Tests of physical and mechanical properties of composites were performed and their basic characteristics were determined, i.e. absorptivity, density, thermal conductivity coefficient, and compressive and flexural strength. The study was conducted to determine the use of hemp and flax composites to fill the frames of a wooden house. The results prove that the composites have low thermal conductivity, apparent density, and low strength properties compared with conventional building materials.     

Digital Holographic Microscopy with extended field of view using tool for generic image stitching

This paper describes in detail the processing path leading to successful phase images stitching in digital holographic microscope for the extension of the field of view. It applies FIJI Grid/Collection Stitching Plugin, which is a general tool for images stitching, non‐specific for phase images. The FIJI plugin is extensively supported by aberration and phase offset correction. Comparative analysis of different aberration correction methods and data processing strategies is presented, together with the critical analysis of their applicability. The proposed processing path provides good background for statistical phase analysis of cell cultures and digital phase pathology.     

Size Effects of Hardness and Strain Rate Sensitivity in Amorphous Silicon Measured by Nanoindentation

Metallurgical and Materials Transactions A - In this work, dynamic mechanical properties of amorphous silicon and scale effects were investigated by the means of nanoindentation. An amorphous...