Use of an in silico knowledge discovery approach to determine mechanistic studies of silver nanoparticles-induced toxicity from in vitro to in vivo

Background Silver nanoparticles (AgNPs) are considered a double-edged sword that demonstrates beneficial and harmful effects depending on their dimensions and surface coating types. However, mechanistic understanding of the size- and coating-dependent effects of AgNPs in vitro and in vivo remains elusive. We adopted an in silico decision tree-based knowledge-discovery-in-databases process to prioritize the factors affecting the toxic potential of AgNPs, which included exposure dose, cell type and AgNP type (i.e., size and surface coating), and exposure time. This approach also contributed to effective knowledge integration between cell-based phenomenological observations and in vitro/in vivo mechanistic explorations. Results The consolidated cell viability assessment results were used to create a tree model for generalizing cytotoxic behavior of the four AgNP types: SCS, LCS, SAS, and LAS. The model ranked the toxicity-related parameters in the following order of importance: exposure dose > cell type > particle size > exposure time ≥ surface coating. Mechanistically, larger AgNPs appeared to provoke greater levels of autophagy in vitro, which occurred during the earlier phase of both subcytotoxic and cytotoxic exposures. Furthermore, apoptosis rather than necrosis majorly accounted for compromised cell survival over the above dosage range. Intriguingly, exposure to non-cytotoxic doses of AgNPs induced G2/M cell cycle arrest and senescence instead. At the organismal level, SCS following a single intraperitoneal injection was found more toxic to BALB/c mice as compared to SAS. Both particles could be deposited in various target organs (e.g., spleen, liver, and kidneys). Morphological observation, along with serum biochemical and histological analyses, indicated that AgNPs could produce pancreatic toxicity, apart from leading to hepatic inflammation. Conclusions Our integrated in vitro, in silico, and in vivo study revealed that AgNPs exerted toxicity in dose-, cell/organ type- and particle type-dependent manners. More importantly, a single injection of lethal-dose AgNPs (i.e., SCS and SAS) could incur severe damage to pancreas and raise blood glucose levels at the early phase of exposure.

Application of a tungsten apron for occupational radiation exposure in nursing care of children with neuroblastoma during 131I-meta-iodo-benzyl-guanidine therapy

The use of effective shielding materials against radiation is important among medical staff in nuclear medicine. Hence, the current study investigated the shielding effects of a commercially available tungsten apron using gamma ray measuring instruments. Further, the occupational radiation exposure of nurses during 131I-meta-iodo-benzyl-guanidine (131I-MIBG) therapy for children with high-risk neuroblastoma was evaluated. Attachable tungsten shields in commercial tungsten aprons were set on a surface-ray source with 131I, which emit gamma rays. The mean shielding rate value was 0.1 ± 0.006 for 131I. The shielding effects of tungsten and lead aprons were evaluated using a scintillation detector. The shielding effect rates of lead and tungsten aprons against 131I was 6.3% ± 0.3% and 42.1% ± 0.2% at 50 cm; 6.1% ± 0.5% and 43.3% ± 0.3% at 1 m; and 6.4% ± 0.9% and 42.6% ± 0.6% at 2 m, respectively. Next, we assessed the occupational radiation exposure during 131I-MIBG therapy (administration dose: 666 MBq/kg, median age: 4 years). The total occupational radiation exposure dose per patient care per 131I-MIBG therapy session among nurses was 0.12 ± 0.07 mSv. The average daily radiation exposure dose per patient care among nurses was 0.03 ± 0.03 mSv. Tungsten aprons had efficient shielding effects against gamma rays and would be beneficial to reduce radiation exposures per patient care per 131I-MIBG therapy session.

Patient exposure dose in interventional cardiology per clinical and technical complexity levels. Part 1: results of the VERIDIC project

Background Patients can be exposed to high skin doses during complex interventional cardiology (IC) procedures. Purpose To identify which clinical and technical parameters affect patient exposure and peak skin dose (PSD) and to establish dose reference levels (DRL) per clinical complexity level in IC procedures. Material and Methods Validation and Estimation of Radiation skin Dose in Interventional Cardiology (VERIDIC) project analyzed prospectively collected patient data from eight European countries and 12 hospitals where percutaneous coronary intervention (PCI), chronic total occlusion PCI (CTO), and transcatheter aortic valve implantation (TAVI) procedures were performed. A total of 62 clinical complexity parameters and 31 technical parameters were collected, univariate regressions were performed to identify those parameters affecting patient exposure and define DRL accordingly. Results Patient exposure as well as clinical and technical parameters were collected for a total of 534 PCI, 219 CTO, and 209 TAVI. For PCI procedures, body mass index (BMI), number of stents ≥2, and total stent length >28 mm were the most prominent clinical parameters, which increased the PSD value. For CTO, these were total stent length >57 mm, BMI, and previous anterograde or retrograde technique that failed in the same session. For TAVI, these were male sex, BMI, and number of diseased vessels. DRL values for Kerma-area product ( PKA), air kerma at patient entrance reference point ( Ka,r), fluoroscopy time (FT), and PSD were stratified, respectively, for 14 clinical parameters in PCI, 10 in CTO, and four in TAVI. Conclusion Prior knowledge of the key factors influencing the PSD will help optimize patient radiation protection in IC.

Accelerated Methods of Determining Wheat Genotypes Primary Resistance to Extreme Temperatures

Several morphological and functional mechanisms determine the resistance of plants to extreme temperatures. Depending on the specificity of mechanisms of action, we divided them into two groups: (1) the mechanisms that ensure the avoidance/reduction of the exposure dose; (2) functional mechanisms which increase plant resistance and ability to recover damages caused by stress through regulation metabolic and genes expression activity. We developed theoretical and practical methods to appreciate the contribution of parameters from both groups on the primary and adaptive resistance of different wheat genotypes. This problem became more complicated because some properties are epigenetically inherited and can influence genotypes’ primary (initial) resistance to stressors. The article describes results obtained by the accelerated determination of the initial resistance of wheat (Triticum aestivum L.) genotypes to temperature stress and the prospects for their implementation in the selection and development of methods for rational choosing wheat varieties for cultivation under specific environmental conditions.

Accessible, large-area, uniform dose photolithography using a moving light source

Photolithography is an essential microfabrication process in which ultraviolet (UV) light is projected through a mask to selectively expose and pattern a light-sensitive photoresist. Conventional photolithography devices are based on a stationary UV lamp and require carefully-designed optics to ensure that a uniform exposure dose is provided across the substrate being patterned. Access to such systems is typically limited to certain labs with domain-specific expertise and sufficient resources. The emergence of LED-based UV technologies has provided improved access to the necessary light sources, but issues with uniformity and limited exposure sizes still remain. In this work, we explore the use of a moving light source (MOLIS) for large-area lithography applications, in which the light source path speed, elevation, and movement pattern can be used to smooth out any spatial variations in source light intensity profiles, and deliver a defined and uniform cumulative UV exposure dose to a photoresist-coated substrate. By repurposing a 3D printer and UV-LED flashlight, we constructed an inexpensive MOLIS platform, simulated and verified the parameters needed to produce a uniform UV dose exposure, and demonstrate this approach for SU-8 microfabrication of features with dimensions relevant to many areas in biomedical engineering. The ready accessibility and inexpensive nature of this approach may be of considerable value to small laboratories interested in occasional and low-throughput prototype microfabrication applications.

Fiber-optic sensor for remote monitoring the γ-radiation of various powers

The necessity of improving the metrological characteristics and functional capabilities of the fiber-optic sensor for measurements at the large distances (more than 10 km) is substantiated. The new method for constructing a communication line with the fiber-optic sensor for controlling exposure dose in a large range of its variation (several orders of magnitude) in a remote mode is proposed. The functional capabilities of the sensor are determined; its connection setup and measurement limits are developed. The experimental results are presented.

Assessment of the photosensitizer efficacy after determination of threshold doses initiating erythrocyte hemolysis

Purpose: To find out a technique for determining the effectiveness of porphyrin-type photosensitizers with concentrations which cause hemolysis in erythrocytes (hemolysis threshold). The hemolysis threshold is found under the following conditions: irradiation in the Soret band with standard parameters – power density, exposure dose, irradiation time.Material and methods. Phototherapeutic device “AST” (LLC “Pankov-medical”) – average power 0.5 W, wavelength ≈ 405 nm. Rat blood erythrocytes. “Multiscan MS” device manufactured by Labsystems, Finland. Preparation “Dimegin”, hematoporphyrin derivative; preparation “Photoditazine” (LLC “VETA-GRAND”), chlorine E6 derivative.Results. On analyzing the results obtained after experimentation with the abovementioned two preparations, it was shown that the developed technique has a high efficacy. It was also shown that the studied photosensitizers are equally effective when irradiated in the Soret band.Conclusion. The developed technique is simple and easy to use. It helps to assess the efficacy of various photosensitizers thus, facilitating the selection of their necessary concentrations for managing different diseases.

Fabrication of Superconducting Nb–AlN–NbN Tunnel Junctions Using Electron-Beam Lithography

Mixers based on superconductor–insulator–superconductor (SIS) tunnel junctions are the best input devices at frequencies from 0.1 to 1.2 THz. This is explained by both the extremely high nonlinearity of such elements and their extremely low intrinsic noise. Submicron tunnel junctions are necessary to realize the ultimate parameters of SIS receivers, which are used as standard devices on both ground and space radio telescopes around the world. The technology for manufacturing submicron Nb–AlN–NbN tunnel junctions using electron-beam lithography was developed and optimized. This article presents the results on the selection of the exposure dose, development time, and plasma chemical etching parameters to obtain high-quality junctions (the ratio of the resistances below and above the gap Rj/Rn). The use of a negative-resist ma-N 2400 with lower sensitivity and better contrast in comparison with a negative-resist UVN 2300-0.5 improved the reproducibility of the structure fabrication process. Submicron (area from 2.0 to 0.2 µm2) Nb–AlN–NbN tunnel junctions with high current densities and quality parameters Rj/Rn > 15 were fabricated. The spread of parameters of submicron tunnel structures across the substrate and the reproducibility of the cycle-to-cycle process of tunnel structure fabrication were measured.

Relationship between surface free energy and development process (swelling and dissolution kinetics) of poly(4-hydroxystyrene) film in water and 2.38 wt% tetramethylammonium hydroxide aqueous solution

With the sharpening of optical images, the capability of resist materials has become a serious concern in lithography. The dissolution of a resist polymer is key to the realization of ultrafine patterning. However, the details of the dissolution of resist polymers remain unclarified. In this study, the relationships of surface free energy with swelling and dissolution kinetics were investigated using poly(4-hydroxystyrene) (PHS) film with triphenylsulfonium-nonaflate (TPS-nf). Developers were water and 2.38 wt% tetramethylammonium hydroxide (TMAH) aqueous solution. PHS and TPS-nf are a typical backbone polymer (a dissolution agent) and a typical acid generator of chemically amplified resists, respectively. The water intake and dissolution of PHS film with TPS-nf became fast with increasing UV exposure dose. It was found that the increase in the polar components (particularly, the hydrogen bonding component) and the decrease in the dispersion component of surface free energy underlie the fast water intake and dissolution.