Fentanyl Structure as a Scaffold for Opioid/Non-Opioid Multitarget Analgesics

One of the strategies in the search for safe and effective analgesic drugs is the design of multitarget analgesics. Such compounds are intended to have high affinity and activity at more than one molecular target involved in pain modulation. In the present contribution we summarize the attempts in which fentanyl or its substructures were used as a μ-opioid receptor pharmacophoric fragment and a scaffold to which fragments related to non-opioid receptors were attached. The non-opioid ‘second’ targets included proteins as diverse as imidazoline I₂ binding sites, CB₁ cannabinoid receptor, NK₁ tachykinin receptor, D₂ dopamine receptor, cyclooxygenases, fatty acid amide hydrolase and monoacylglycerol lipase and σ₁ receptor. Reviewing the individual attempts, we outline the chemistry, the obtained pharmacological properties and structure-activity relationships. Finally, we discuss the possible directions for future work.     

Causes and Effects of Uncontrolled Water Inrush into a Decommissioned Mine Shaft

Central Europe experienced catastrophic rainfalls and flooding in 2010. This paper discusses a decommissioned shaft that was flooded by surface water, which led to displacement of shaft backfill and an inrush of large amounts of water into an underground pumping station. The weather conditions for the period preceding the inrush, the hydrogeological conditions, the quantity of water that entered the mine dewatering systems, and the underground hydraulic connections are all described. Uncontrolled inflow of water as a cause of backfill saturation and the hazard for active underground infrastructure were analysed. A need to rebuild damaged infrastructure was identified. The case study highlights the need to improve underground mine closure requirements to ensure safe conditions above ground, particularly in densely populated areas.     

Estimation of heat transfer coefficient of forced-air cooling and its experimental validation in controlled processing of forgings

Estimation of the cooling efficiency of an accelerated air for the needs of cooling of die forgings is presented. Temperature dependence of heat transfer coefficient (HTC) was calculated for different cooling conditions varied by airflow velocity, covering the range from 18 to 48?m/s. Time–temperature measurements performed on a full-scale semi-industrial cooling line provided similarity to conditions typical of industrial conveyor, which gives the results utilitarian significance in design of controlled processing (of steel forged products). Acquired HTC values, ranging from 164.7 to 298?W/m²?·?K, were validated in numerical simulation of cooling complex-shape forgings and subject to experimental verification, indicating perfect agreement with physical measurements.     

Training neural networks on high-dimensional data using random projection

Pattern Analysis and Applications - Training deep neural networks (DNNs) on high-dimensional data with no spatial structure poses a major computational problem. It implies a network architecture...     

A Stochastic Petri Net-Based Model of the Involvement of Interleukin 18 in Atherosclerosis

Interleukin 18 (IL-18) is a proinflammatory and proatherogenic cytokine with pleiotropic properties, which is involved in T and NK cell maturation and the synthesis of other inflammatory cytokines and cell adhesion molecules. It plays a significant role in orchestrating the cytokine cascade, accelerates atherosclerosis and influences plaque vulnerability. To investigate the influence of IL-18 cytokine on atherosclerosis development, a stochastic Petri net model was built and then analyzed. First, MCT-sets and t-clusters were generated, then knockout and simulation-based analysis was conducted. The application of systems approach that was used in this research enabled an in-depth analysis of the studied phenomenon. Our results gave us better insight into the studied phenomenon and allow revealing that activation of macrophages by the classical pathway and IL-18-MyD88 signaling axis is crucial for the modeled process.     

In Silico Study on Tumor-Size-Dependent Thermal Profiles inside an Anthropomorphic Female Breast Phantom Subjected to Multi-Dipole Antenna Array

Electromagnetic hyperthermia as a potent adjuvant for conventional cancer therapies can be considered valuable in modern oncology, as its task is to thermally destroy cancer cells exposed to high-frequency electromagnetic fields. Hyperthermia treatment planning based on computer in silico simulations has the potential to improve the localized heating of breast tissues through the use of the phased-array dipole applicators. Herein, we intended to improve our understanding of temperature estimation in an anatomically accurate female breast phantom embedded with a tumor, particularly when it is exposed to an eight-element dipole antenna matrix surrounding the breast tissues. The Maxwell equations coupled with the modified Pennes’ bioheat equation was solved in the modelled breast tissues using the finite-difference time-domain (FDTD) engine. The microwave (MW) applicators around the object were modelled with shortened half-wavelength dipole antennas operating at the same 1 GHz frequency, but with different input power and phases for the dipole sources. The total input power of an eight-dipole antenna matrix was set at 8 W so that the temperature in the breast tumor did not exceed 42 °C. Finding the optimal setting for each dipole antenna from the matrix was our primary objective. Such a procedure should form the basis of any successful hyperthermia treatment planning. We applied the algorithm of multi for multi-objective optimization for the power and phases for the dipole sources in terms of maximizing the specific absorption rate (SAR) parameter inside the breast tumor while minimizing this parameter in the healthy tissues. Electro-thermal simulations were performed for tumors of different radii to confirm the reliable operation of the given optimization procedure. In the next step, thermal profiles for tumors of various sizes were calculated for the optimal parameters of dipole sources. The computed results showed that larger tumors heated better than smaller tumors; however, the procedure worked well regardless of the tumor size. This verifies the effectiveness of the applied optimization method, regardless of the various stages of breast tumor development.     

Optimization of reinforcement layout of scissor‐type bridge using differential evolution algorithm

Scissors mechanisms are commonly used in safety engineering during the construction of temporary structures, owing to their inherent advantages of foldability, transformability, and reusability. We effectively utilized these scissors mechanism features to develop a lightweight, deployable emergency Mobile Bridge (MB) based on optimization, and control of the folding structure. Here, we discuss the problems of optimal reinforcement layout for the MB by formulating and solving three optimization problems, namely: (a) the load capacity maximization problem, (b) the weight minimization problem, and (c) coupling the load capacity maximization problem and the weight minimization problem. The potential benefits resulting from the application of reinforcement were evaluated using a combination of finite element analysis and an optimization algorithm based on the differential evolution method. The results demonstrate the significant positive influence of the additional reinforcing members. In particular, the limit load was increased by over 10 times, while the weight was decreased to approximately half. The proposed methodology enabled the development of a substantially improved version of the MB characterized by a higher load capacity and lower weight in comparison to the initial bridge design.     

Gas‐phase removal of indoor volatile organic compounds and airborne microorganisms over mono‐ and bimetal‐modified (Pt,Cu, Ag) titanium(IV) oxide nanocomposites

The photocatalytic deactivation of volatile organic compounds and mold fungi using TiO₂ modified with mono‐ and bimetallic (Pt, Cu, Ag) particles is reported in this study. The mono‐ and bimetal‐modified (Pt, Cu, Ag) titanium(IV) oxide photocatalysts were prepared by chemical reduction method and characterized using XRD, XPS, DR/UV‐Vis, BET, and TEM analysis. The effect of incident light, type and content of mono‐ and bimetallic nanoparticles deposited on titanium(IV) oxide was studied. Photocatalytic activity of as‐prepared nanocomposites was examined in the gas phase using LEDs array. High photocatalytic activity of Ag/Pt‐TiO₂ and Cu/Pt‐TiO₂ in the reaction of toluene degradation resulted from improved efficiency of interfacial charge transfer process, which was consistent with the fluorescence quenching effect revealed by photoluminescence (PL) emission spectra. The photocatalytic deactivation of Penicillium chrysogenum, a pathogenic fungi present in the indoor environment, especially in a damp or water‐damaged building using mono‐ and bimetal‐modified (Pt, Cu, Ag) titanium(IV) oxide was evaluated for the first time. TiO₂ modified with mono‐ and bimetallic NPs of Ag/Pt, Cu, and Ag deposited on TiO₂ exhibited improved fungicidal activity under LEDs illumination than pure TiO₂.     

Efficiency optimisation of the thermal energy storage unit in the form of the ceiling panel for summer conditions

The thermal energy storage unit in the form of the ceiling panel made of the gypsum‐microencapsulated phase change material composite with internal U‐shaped channels was optimised applying previously developed 1D‐3D numerical simulator. Calculations were carried out for variable inlet velocities of air, different properties of the composite expressed by enthalpy‐temperature curves, and summer climatic conditions in Central Poland (Warsaw). Optimal working temperature ranges of the composite were determined. Moreover, studies showed that for Central Poland, composites with wide ranges of the working temperature are preferred due to significant daily variations of ambient temperature during the whole summer.