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In this study, carried out using computational methods, the organisation of the lipid/water interface of bilayers composed of galactolipids with both α-linolenoyl acyl chains is analysed and compared in three different lyotropic liquid-crystalline phases. These systems include the monogalactosyldiglyceride (MGDG) and digalactosyldiglyceride (DGDG) bilayers in the lamellar phase, the MGDG double bilayer during stalk phase formation and the inverse hexagonal MGDG phase. For each system, lipid-water and direct and water-mediated lipid-lipid interactions between the lipids of one bilayer leaflet and those of two apposing leaflets at the onset of new phase (stalk) formation, are identified. A network of interactions between DGDG molecules and its topological properties are derived and compared to those for the MGDG bilayer.

Vemurafenib and dabrafenib are BRAF kinase inhibitors (BRAFi) used for the treatment of patients with melanoma carrying the V600E BRAF mutation. However, melanoma cells develop resistance to both drugs when used as monotherapy. Therefore, mechanisms of drug resistance are investigated, and new molecular targets are sought that could completely inhibit melanoma progression. Since receptor-interacting protein kinase (RIPK4) probably functions as an oncogene in melanoma and its structure is similar to the BRAF protein, we analyzed the impact of vemurafenib and dabrafenib on RIPK4 in melanomas. The in silico study confirmed the high similarity of BRAF kinase domains to the RIPK4 protein at both the sequence and structural levels and suggests that BRAFi could directly bind to RIPK4 even more strongly than to ATP. Furthermore, BRAFi inhibited ERK1/2 activity and lowered RIPK4 protein levels in BRAF-mutated melanoma cells (A375 and WM266.4), while in wild-type BRAF cells (BLM and LoVo), both inhibitors decreased the level of RIPK4 and enhanced ERK1/2 activity. The phosphorylation of phosphatidylethanolamine binding protein 1 (PEBP1)—a suppressor of the BRAF/MEK/ERK pathway—via RIPK4 observed in pancreatic cancer did not occur in melanoma. Neither downregulation nor upregulation of RIPK4 in BRAF- mutated cells affected PEBP1 levels or the BRAF/MEK/ERK pathway. The downregulation of RIPK4 inhibited cell proliferation and the FAK/AKT pathway, and increased BRAFi efficiency in WM266.4 cells. However, the silencing of RIPK4 did not induce apoptosis or necroptosis. Our study suggests that RIPK4 may be an off-target for BRAF inhibitors.

Xanthones are tricyclic compounds of natural or synthetic origin exhibiting a broad spectrum of therapeutic activities. Three synthetic xanthone derivatives (KS1, KS2, and KS3) with properties typical for nonsteroidal anti-inflammatory drugs (NSAID) were objects of the presented model study. NSAIDs are in common use however; several of them exhibit gastric toxicity predominantly resulting from their direct interactions with the outermost lipid layer of the gastric mucosa that impair its hydrophobic barrier property. Among the studied xanthones, gastric toxicity of only KS2 has been determined in previous pharmacological studies, and it is low. In this study, carried out using X-ray diffraction and computer simulation, a palmitoyloleoylphosphatidylcholine-cholesterol bilayer (POPC-Chol) was used as a model of a hydrophobic layer of lipids protecting gastric mucosa as POPC and Chol are the main lipids in human mucus. X-ray diffraction data were used to validate the computer model. The aim of the study was to assess potential gastric toxicity of the xanthones by analysing their atomic level interactions with lipids, ions, and water in the lipid bilayer and their effect on the bilayer physicochemical properties. The results show that xanthones have small effect on the bilayer properties except for its rigidity whereas their interactions with water, ions, and lipids depend on their protonation state and for a given state, are similar for all the xanthones. As gastric toxicity of KS2 is low, based on MD simulations one can predict that toxicity of KS1 and KS3 is also low.

This review summarises high resolution studies on the interface of lamellar lipid bilayers composed of the most typical lipid molecules which constitute the lipid matrix of biomembranes. The presented results were obtained predominantly by computer modelling methods. Whenever possible, the results were compared with experimental results obtained for similar systems. The first and main section of the review is concerned with the bilayer–water interface and is divided into four subsections. The first describes the simplest case, where the interface consists only of lipid head groups and water molecules and focuses on interactions between the lipid heads and water molecules; the second describes the interface containing also mono- and divalent ions and concentrates on lipid-ion interactions; the third describes direct inter-lipid interactions. These three subsections are followed by a discussion on the network of direct and indirect inter-lipid interactions at the bilayer interface. The second section summarises recent computer simulation studies on the interactions of antibacterial membrane active compounds with various models of the bacterial outer membrane. This article is part of a Special Issue entitled: Biosimulations edited by Ilpo Vattulainen and Tomasz Rog.

Internet of Things (IoT) is becoming the new driver for semiconductor industry and the largest electronic market ever seen. The number of IoT nodes is already many times larger than the human population and is continuously growing. It is thus mandatory that IoT nodes become self-supplying with energy harvested from environment since periodic exchange of batteries in such a huge number of units (often located in inaccessible places e.g. industrial environment or elements of constructions) is impractical and soon will be simply impossible. Photovoltaic generators may easily harvest energy where light is available, but the IoT nodes often work in dark, hidden locations where the only available energy sources are heat losses. There, ThermoElectric Generators (TEGs) could be the best candidate, if not that if we speak of exploiting heat losses it often means very low temperature differences. This means conditions where TEGs power production drops down dramatically. In this paper we put forward a new idea of TEG's pulse operation that boosts the power production up to X2.7. This extends the domain of applicability of TEGs to lower temperature differences, where conventional TEGs are out of the game. Next, we show that the improvement X2.7 maintains also at larger temperature differences that presents obvious advantages.

Biomembranes are omnipresent in the living world. Each cell is bounded by a cell (plasma) membrane. Also, sub-cellular structures (organelles and nucleus) are enclosed in internal membranes (Fig. 1). Biomembranes are thin lamellar structures of an enormous number of molecules of several chemical types, among them proteins, peptides, phospholipids, glycolipids, sterols, terpenoids.

Lipid and water molecules comprising the bilayer form an integral entity owing to only weak physical interactions. At the bilayer interface, these interactions chiefly involve hydrogen bonding and charge pairing. Lipid head groups make hydrogen bonds (H-bonds) predominantly with water, whereas interlipid H-bonds and charge pairs are less numerous. Both interlipid H-bonding and charge pairing depend on the distance and relative orientation of the interacting head groups. In this computational paper, correlations are analysed between the orientation of the lipid head group and the number of interlipid interactions at the interface of a bilayer made of galactolipids, forming direct interlipid H-bonds, and of phosphatidylcholines forming interlipid charge pairs. The correlations are not strong, however, in both bilayers they show a similar trend.

Interactions among lipid head groups at the bilayer/water interface do, to a large extent, determine membrane properties. In this study graph theory is employed to objectively describe and compare the pattern of the interactions at the interfaces of computer models of 128- and 512-lipid monogalactolipid (MGDG) and phosphatidylcholine (DOPC) bilayers. Both MGDG and DOPC have polar head groups but of different chemical structures so at the bilayer interfaces they participate in different types of interaction. Nevertheless, at both interfaces these interactions and the lipid molecules they link make networks. In graph theory, a network of interconnected objects (nodes) is described by well-defined quantities which define its topology and can be used to assess inner properties of the network, its strength and density, etc. In this study, several topological properties of the networks in the DOPC and MGDG bilayers are determined. A comparison of these properties indicates that the topologies of both networks differ significantly but are stable during the simulation time. The networks in the MGDG bilayers are more extended, branched, stable, and stronger than those in the DOPC bilayers. This is consistent with the smaller surface area per lipid and higher rigidity of the MGDG than the DOPC bilayers as well as the tendency of MGDG to form an inverse hexagonal phase in water. The scale of the systems is an important factor when assessing the properties of the network; the system scaling is more evident in the DOPC bilayers where several quantities increase directly proportional to the increasing size of the system than in the MGDG bilayers where this is rarely the case.

Monogalactosylodiacylglycerol (MGDG) is the main lipid component of thylakoid membranes. In water, MGDG molecules pack preferentially in the hexagonal HII phase, which consists of water-filled lipid cylinders arranged in a hexagonal lattice. The HII phase can also form in the thylakoid membrane where it plays a key role in the photoprotection of the photosynthetic apparatus. In this study an all-atom computer model of the 16-cylinder MGDG HII phase was generated in a 3-μs molecular dynamics simulation and mathematical tools were developed to analyse its structural properties. The model-predicted values of the basic structural parameters, namely hexagonal spacing, circular and effective radii of the water channel, surface area/MGDG, and order parameters for the MGDG acyl chains, were compared with the experimental data available in the literature to validate the model. A stable computer model of the MGDG HII phase and the tools developed may serve further numerical experiments and investigations into the role of this phase in biological processes.

The aim of this paper is to compare two methods of measurement of travel times along road sections in the city. Comparison is made by using a traffic simulator that records travel times of simulated vehicles using two algorithms. Those algorithms generalize two approaches in measuring travelling time: by tracking selected vehicles and by identifying vehicles at the ends of road sections. The former method is a well-known Floating Car Data (FCD) technique, the latter refers to usage of sensors installed in road infrastructure like RFID readers or video cameras which are used in license plate recognition systems. It is shown that even small fraction of FCD-enabled vehicles gives reasonable estimations, but in case the technology used for vehicle identification at crossroads guarantees correctness greater than 50% then the second method gives much realiable results.

The main application of a DRGS is offering driver the best possible route while the vehicle is en route. The DRGS is aware of continuously changing traffic conditions and proposes the best route in terms of fuel savings, trip travel time, road tolls, and so on. The DRGS has to communicate with service providers and indirectly with data acquisition modules which aggregate and analyze data received from multiple sources such as sensors installed in the road infrastructure or coming from moving vehicles.

Biological processes are controlled automatically. Registration of signals and measuring their relative strength is hence a key problem. Receptors may be relatively simple or complex. The complexity is the direct response to ambiguity of signals. If there is however a common feature of diverse signals a construction of generic receptor mechanism is usually observed. Combinatorial technique is commonly used in biological systems to decrease the complexity in reception of highly ambiguous signals.

The recurrent 24 hours oscillations of biological activities which are generally called circadian rhythms are considered to be a mechanism allowing synchronisation of biological processes. The oscillations are generated by operation of special clock-like intra-cell devices comprising commonly transcription-translation processes as basis of measuring the time. The clock mechanism is controlled by two cooperating working out-of-phase negative feedback loops. Directly the oscillations are driven by steering signals changing the adjustment of feedback loops. They are created de novo in each cycle by complexation of synthesized proteins after their concentration reaches suitably high values. The complexes inhibit the protein synthesis in the own system while inducing it simultaneously in the cooperating one initiating in this way the next oscillation wave. The inhibition of protein synthesis is correlated with the degradation of already synthesizes molecules allowing the return to starting point of oscillation. The alignment of the proper phase of peripheral tissue cells clocks is maintained by the central brain clock � master clock.

A high percentage of people treated with a long-term nonsteroidal anti-inflammatory drug (NSAID) therapy suffer NSAID-induced gastrointestinal-tract-related side effects. A current hypothesis states that the side effects are related to the topical action of NSAID molecules on gastric mucus that lowers its resistance to luminal acid. The main lipids in human mucus are palmitoyloleoylphosphatidylcholine (POPC) and cholesterol (Chol). In this study, both X-ray diffraction and molecular dynamics (MD) simulation methods were employed to investigate the effects of selected NSAIDs in protonated and deprotonated states on the structural parameters of a POPC-Chol bilayer. The drugs were three commonly used NSAIDs with apparently different gastric toxicity: ketoprofen (KET), aspirin (ASP), and piroxicam (PXM). Both methods revealed that the effects of the NSAIDs on the POPC-Chol bilayer parameters were moderate and only slightly differentiated among the drugs. Much larger differences among the drugs were noticed in their interactions with interfacial water and Na(+) as well as with the polar groups of POPC and Chol, mainly via H-bonds. Of the three NSAIDs, KET interacted with POPC and water the most extensively, whereas ASP interacted with Chol and Na(+) more than did the other two. Interactions of PXM with POPC and Chol polar groups as well as with water and Na(+) were limited.

Capabilities of the devices installed in a smart home are often fully accessible only to qualified integrators. As the users become more interested in setting up their home automation devices by their own, there is a need to bridge the gap between the magnitude of possibilities offered by home automation devices and the limitations of the methods accessible to the user. This paper proposes an event-based language that allows defining of home automation control routines in a form of statements which are uncomplicated, easy to learn for intermediate users, while being easy to interpret by microcontrollers with low processing power that are widespread in home automation devices. All the complexity related to defining rules has been covered by the language that provides access to various capabilities of a smart home under self-explanatory function names. The mechanism that executes statements written in the proposed language has been successfully implemented on a hardware platform with 8-bit microcontroller. KNX standard has been used for communication with home automation devices in this research in examples and case studies. During the test the proposed solution proved to be reliable and efficient for purpose of writing and executing eventbased home automation control routines.

Structural studies of newly synthesized substituted spirans, derived from methyl- and tert-butylbenzenes, containing either 1,5-dioxepine or 1,5-dithiepine system are reported. Crystal structures of two representative compounds were determined by X-ray diffraction. One of spirans containing 1,5-benzodithiepine appears in two isomeric forms equivalent by inversion of both spirorings. Energy calculations were carried out to find the preferred conformations. For spiran with sulfur atoms, the minimum-energy conformation is virtually identical with that in the solid state, whereas for the 1,5-dioxepine system they are different.

1,2-di-O-acyl-3-O-β- d -galactopyranosyl- sn -glycerol (MGDG) is the main lipid component of thylakoid membranes of higher plants and algae. This monogalactolipid is thought of as a non-bilayer lipid but actually it can form both lamellar and nonlamellar phases. In this study, molecular dynamics (MD) simulations of the fully hydrated di-18:3 MGDG bilayer in the lamellar phase were carried out at 310 and 295 K for 200 and 450 ns, respectively, using the GROMACS 4 software package and OPLS-AA force field. At both temperatures, the lamellar phase of the systems was stable. The pure di-18:3 MGDG bilayer is the first step towards creating a computer model of the lipid matrix of the thylakoid membrane and the main aim of this study was to validate the computer model of di-18:3 MGDG in the bilayer and also to assess the properties of the bilayer. However, only a few of the predicted properties could be compared with those derived experimentally and in other MD simulations because of insufficient amount of such data. Thus, direct validation of the MGDG bilayer proved difficult. Therefore, in the validation process also an indirect approach was used, in which a computer model of the 1,2-dioleoyl- sn -glycero-3-phosphatidylcholine (DOPC) bilayer simulated at the same temperatures using the same force field as the MGDG bilayer was assessed. Successful validation of the DOPC bilayer parameterized in the OPLS-AA force field and similar properties of the MGDG molecules in the pure 18:3 MGDG and in binary 18:3 MGDG-PC bilayers indicate that the computer model of the MDGD molecule is faithful and the MGDG bilayer is representative on the time scales covered in these MD simulations.

With recent advances in microprocessor chip technology, wireless communication, and biomedical engineering it is possible to develop miniaturized ubiquitous health monitoring devices that are capable of recording physiological and movement signals during daily life activities. The aim of the research is to implement and test the prototype of health monitoring system. The system consists of the body central unit with Bluetooth module and wearable sensors: the custom-designed ECG sensor, the temperature sensor, the skin humidity sensor and accelerometers placed on the human body or integrated with clothes and a network gateway to forward data to a remote medical server. The system includes custom-designed transmission protocol and remote web-based graphical user interface for remote real time data analysis. Experimental results for a group of humans who performed various activities (eg. working, running, etc.) showed maximum 5% absolute error compared to certified medical devices. The results are promising and indicate that developed wireless wearable monitoring system faces challenges of multi-sensor human health monitoring during performing daily activities and opens new opportunities in developing novel healthcare services.

Lutein is present in the human retina and lens, where it plays a protective role. As lutein is associated with the lipid matrix of biomembranes, the role depends on its membrane location. Experimental studies predicted two orientations of lutein in a phosphatidylcholine (PC) bilayer: vertical and horizontal. Using a molecular dynamics simulation, we observed, in two different PC bilayers, both orientations of lutein, and in each bilayer, a single change from vertical to horizontal orientation or vice versa. Both orientations were stabilized by hydrogen bonding of lutein OH groups with mainly carbonyl but also phosphate oxygen atoms of PC.

This paper presents an assistive system for the visually impaired and blind people which helps them using public transport means. The proposed system uses mobile phones as a medium for passenger information system and GPS (Global Positioning System), GSM (Global System for Mobile Communications) and Bluetooth technologies for location and communication purposes. In the proposed system sound messages are given to the blind people via mobile phones which have dedicated software installed. This system has been implemented and tested in public transport in two pilot cities.

Staphylococcus aureus is a dangerous human pathogen. A number of the proteins secreted by this bacterium are implicated in its virulence, but many of the components of its secretome are poorly characterized. Strains of S. aureus can produce up to six homologous extracellular serine proteases grouped in a single spl operon. Although the SplA, SplB, and SplC proteases have been thoroughly characterized, the properties of the other three enzymes have not yet been investigated. Here, we describe the biochemical and structural characteristics of the SplD protease. The active enzyme was produced in an Escherichia coli recombinant system and purified to homogeneity. P1 substrate specificity was determined using a combinatorial library of synthetic peptide substrates showing exclusive preference for threonine, serine, leucine, isoleucine, alanine, and valine. To further determine the specificity of SplD, we used high-throughput synthetic peptide and cell surface protein display methods. The results not only confirmed SplD preference for a P1 residue, but also provided insight into the specificity of individual primed- and non-primed substrate-binding subsites. The analyses revealed a surprisingly narrow specificity of the protease, which recognized five consecutive residues (P4-P3-P2-P1-P1’) with a consensus motif of R-(Y/W)-(P/L)-(T/L/I/V)↓S. To understand the molecular basis of the strict substrate specificity, we crystallized the enzyme in two different conditions, and refined the structures at resolutions of 1.56 Å and 2.1 Å. Molecular modeling and mutagenesis studies allowed us to define a consensus model of substrate binding, and illustrated the molecular mechanism of protease specificity.