Traveling-wave Phenomena in a Model of Autocrine Signaling Coupled with Dynamics of the MAPK Cascade

Recently we have revealed a minimal reaction subnetwork in the MAPK (mitogen-activated protein kinase) cascade that is responsible for the emergence of bistable and oscillatory behavior. Here we examine a possible mechanism that provides for the propagation of increased MAPK activity in cell populations by interconnecting the intracellular MAPK subnetwork with the ligand-receptor signaling machinery. Such approach allows for significant reduction of the dimensionality of the parameter space on one hand and the conservation of dynamical complexity of the system on the other hand. The coupled model predicts coexistence of one, two or three different stable steady states, or the coexistence of a stable steady state and periodic solution. We found two robust and physiologically relevant characteristics of the proposed model: (i) There is a very large region of coexistence of at least one stable steady state with non-zero MAPK activity and one steady state with zero MAPK activity in the parameter space. (ii) Spontaneous traveling front waves always switching originally inactive cells into ligand releasing cells emerge in adjacent cell populations, e. g. in healthy and injured tissues. Moreover, the formation of composite traveling front waves and spatial oscillatory patterns of MAPK activity are predicted and discussed.     

The influence of transition metals – Fe,Co, Cu on transformation of organic matters from Domanic rocks in hydrothermal catalytic system

Character of conversion of organic matter from Domanic rocks of Pervomaiskoye field (Tatarstan) of Semiluki horizon of upper Devonian deposits in the hydrothermal-catalytic system at temperature of 300?°C in carbon dioxide medium was studied with the application of complex of oil-soluble precursors of catalysts containing Fe, Co, and Cu. In presence of catalysts complex, content of organic extract increases, in which content of hydrocarbon fractions, saturated and aromatic hydrocarbons, increases 1.5 times, while resins content decreases by two times. As result of kerogen destruction in products of experiments, the content of asphaltenes and carbonaceous substances such as carbenes and carboides increase.     

An approach to torque and temperature thread by thread on tapping

During internal threading, small alterations in cutting parameters, tool geometry, or process characteristics produce considerable effects on torque and te     

Life-cycle assessment of hydrogen technologies with the focus on EU critical raw materials and end-of-life strategies

We present the results of a life-cycle assessment (LCA) for the manufacturing and end-of-life (EoL) phases of the following fuel-cell and hydrogen (FCH) technologies: alkaline water electrolyser (AWE), polymer-electrolyte-membrane water electrolyser (PEMWE), high-temperature (HT) and low-temperature (LT) polymer-electrolyte-membrane fuel cells (PEMFCs), together with the balance-of-plant components. New life-cycle inventories (LCIs), i.e., material inputs for the AWE, PEMWE and HT PEMFC are developed, whereas the existing LCI for the LT PEMFC is adopted from a previous EU-funded project. The LCA models for all four FCH technologies are created by modelling the manufacturing phase, followed by defining the EoL strategies and processes used and finally by assessing the effects of the EoL approach using environmental indicators. The effects are analysed with a stepwise approach, where the CML2001 assessment method is used to evaluate the environmental impacts. The results show that the environmental impacts of the manufacturing phase can be substantially reduced by using the proposed EoL strategies (i.e., recycled materials being used in the manufacturing phase and replacing some of the virgin materials). To point out the importance of critical materials (in this case, the platinum-group metals or PGMs) and their recycling strategies, further analyses were made. By comparing the EoL phase with and without the recycling of PGMs, an increase in the environmental impacts is observed, which is much greater in the case of both fuel-cell systems, because they contain a larger quantity of PGMs.     

Discovery of Affinity-Based Probes for Btk Occupancy Assays

Bruton's tyrosine kinase (Btk) is an attractive target for the treatment of a wide array of B-cell malignancies and autoimmune diseases. Small-molecule covalent irreversible Btk inhibitors targeting Cys481 have been developed for the treatment of such diseases. In clinical trials, probe molecules are required in occupancy studies to measure the level of engagement of the protein by these covalent irreversible inhibitors. The result of this pharmacodynamic (PD) activity provides guidance for appropriate dosage selection to optimize inhibition of the drug target and correlation of target inhibition with disease treatment efficacy. This information is crucial for successful evaluation of drug candidates in clinical trials. Based on the pyridine carboxamide scaffold of a novel solvent-accessible pocket (SAP) series of covalent irreversible Btk inhibitors, we successfully developed a potent and selective affinity-based biotinylated probe 12 (2-[(4-{4-[5-(1-{5-[(3aS,4S,6aR)-2-oxo-hexahydro-1H-thieno[3,4-d]imidazol-4-yl]pentanamido}-3,6,9,12-tetraoxapentadecan-15-amido)pentanoyl]piperazine-1-carbonyl}phenyl)amino]-6-[1-(prop-2-enoyl)piperidin-4-yl]pyridine-3-carboxamide). Compound 12 has been used in Btk occupancy assays for preclinical studies to determine the therapeutic efficacy of Btk inhibition in two mouse lupus models driven by TLR7 activation and type I interferon.     

Participatory design of a robot for demonstrating an epileptic seizure

ABSTRACT

We present the methodology and results of participatory design of a robot for presenting an epileptic seizure and a scenario of the educational workshop using this robot. Children with epilepsy encounter stigma and stereotypes and may receive inadequate aid when having an epileptic seizure. The goal of the larger project was to use the prototype device in a series of workshops for improving teachers' actions during an epileptic seizure and their attitudes towards epileptic students. In this paper, we show how various design goals for an educational robot were accomplished to fit the needs of all identified stakeholders, particularly people with epilepsy.

We used a co-design (participatory design) approach through a series of meetings participated by members of the association Polish Association for People Suffering from Epilepsy, students and faculty members of the biomedical engineering and robotics departments, teachers, psychologists and medical specialists (epileptologist, neurologist).

These meetings created an opportunity for a better understanding of the (functional and nonfunctional) requirements and resulting tradeoffs and led the participants to find appropriate solutions. Participation of people with epilepsy in the design process allowed them to deal with the potentially stereotyped representation of themselves. The prototype robot, therefore, combined goals of various stakeholders, such as an accurate presentation of an epileptic seizure, lightweight, ease of use and control, while preserving the dignity of people with epilepsy.

As a result of the co-designing process, an inexpensive robot was created and used in a series of 10 pilot workshops with 217 participants, mainly teachers of primary and middle schools. Teachers improved their understanding of epilepsy and suggested further improvements to the system.     

Photophoretic Levitation of Macroscopic Nanocardboard Plates

Scaling down miniature rotorcraft and flapping-wing flyers to sub-centimeter dimensions is challenging due to complex electronics requirements, manufacturing limitations, and the increase in viscous damping at low Reynolds numbers. Photophoresis, or light-driven fluid flow, was previously used to levitate solid particles without any moving parts, but only with sizes of 1–20 µm. Here, architected metamaterial plates with 50 nm thickness are leveraged to realize photophoretic levitation at the millimeter to centimeter scales. Instead of creating lift through conventional rotors or wings, the nanocardboard plates levitate due to light-induced thermal transpiration through microchannels within the plates, enabled by their extremely low mass and thermal conductivity. At atmospheric pressure, the plates hover above a solid substrate at heights of ≈0.5 mm by creating an air cushion beneath the plate. Moreover, at reduced pressures (10–200 Pa), the increased speed of thermal transpiration through the plate's channels creates an air jet that enables mid-air levitation and allows the plates to carry small payloads heavier than the plates themselves. The macroscopic metamaterial structures demonstrate the potential of this new mechanism of flight to realize nanotechnology-enabled flying vehicles without any moving parts in the Earth's upper atmosphere and at the surface of other planets.     

Some Molecular and Cellular Stress Mechanisms Associated with Neurodegenerative Diseases and Atherosclerosis

Chronic stress is a combination of nonspecific adaptive reactions of the body to the influence of various adverse stress factors which disrupt its homeostasis, and it is also a corresponding state of the organism’s nervous system (or the body in general). We hypothesized that chronic stress may be one of the causes occurence of several molecular and cellular types of stress. We analyzed literary sources and considered most of these types of stress in our review article. We examined genes and mutations of nuclear and mitochondrial genomes and also molecular variants which lead to various types of stress. The end result of chronic stress can be metabolic disturbance in humans and animals, leading to accumulation of reactive oxygen species (ROS), oxidative stress, energy deficiency in cells (due to a decrease in ATP synthesis) and mitochondrial dysfunction. These changes can last for the lifetime and lead to severe pathologies, including neurodegenerative diseases and atherosclerosis. The analysis of literature allowed us to conclude that under the influence of chronic stress, metabolism in the human body can be disrupted, mutations of the mitochondrial and nuclear genome and dysfunction of cells and their compartments can occur. As a result of these processes, oxidative, genotoxic, and cellular stress can occur. Therefore, chronic stress can be one of the causes forthe occurrence and development of neurodegenerative diseases and atherosclerosis. In particular, chronic stress can play a large role in the occurrence and development of oxidative, genotoxic, and cellular types of stress.