Solving large multiple-depot multiple-vehicle-type bus scheduling problems in practice

We consider the multiple-depot multiple-vehicle-type scheduling problem (MDVSP) which arises in public transport bus companies and aims to assign buses to cover a given set of timetabled trips with consideration of practical requirements, such as multiple depots and vehicle types as well as depot capacities. An optimal schedule is characterized by minimal fleet size and minimal operational costs including costs for empty movements and waiting time. It is well-known that the MDVSP is NP-hard.Although progress has recently been made in solving large practical MDVSP to optimality with time-space network models, current optimization technology sets limits to the model size that can be solved. In order to approach very large practical instances we propose a two-phase method which produces close to optimal solutions. This modeling approach enables us to solve real-world problem instances with thousands of scheduled trips by direct application of standard optimization software. Furthermore, we introduce the concept of depot groups for the case that a bus may return in the evening into another depot than where it started in the morning.     

Exploratory spatio-temporal visualization: an analytical review

Current software tools for visualization of spatio-temporal data, on the one hand, utilize the opportunities provided by modern computer technologies, on the other hand, incorporate the legacy from the conventional cartography. We have considered existing visualization-based techniques for exploratory analysis of spatio-temporal data from two perspectives: (1) what types of spatio-temporal data they are applicable to; (2) what exploratory tasks they can potentially support.The technique investigation has been based on an operational typology of spatio-temporal data and analytical tasks we specially devised for this purpose. The result of the study is a structured inventory of existing exploratory techniques related to the types of data and tasks they are appropriate for. This result is potentially helpful for data analysts—users of geovisualization tools: it provides guidelines for selection of proper exploratory techniques depending on the characteristics of data to analyze and the goals of analysis. At the same time the inventory as well as the suggested typology of tasks could be useful for tool designers and developers of various domain-specific geovisualization applications. The designers can, on the one hand, see what task types are insufficiently supported by the existing tools and direct their creative activities towards filling the gaps, on the other hand, use the techniques described as basic elements for building new, more sophisticated ones. The application developers can, on the one hand, use the task and data typology in the analysis of potential user needs, on the other hand, appropriately select and combine existing tools in order to satisfy these needs.     

Assessment of oxygen levels in convenience‐style muscle‐based sous vide products through optical means and impact on shelf‐life stability

An optical oxygen analyser was used in two small‐scale industrial trials to non‐destructively assess the quality of packaged convenience foods and packaging process. Beef lasagne packed under 70% vacuum and cooked under standard sous vide conditions was monitored for residual oxygen, using disposable sensors incorporated in each pack and a benchtop optical oxygen analyser. High levels of residual oxygen close to ambient were determined in the majority of packs after packaging, as opposed to anticipated levels of 4–5%. Residual oxygen was monitored over product shelf‐life (4 weeks at +4–10°C) along with measurement of microbial growth and lipid oxidation in food by conventional destructive methods. Oxygen levels in packs went down to almost zero between weeks 2 and 3 indicating deterioration of packaged product. Correlation between oxygen profiles and the rate of microbial growth and lipid oxidation was established. The optical oxygen sensor system was shown to provide valuable information about performance of the packaging process, product storage conditions and food quality in a convenient and cost‐efficient fashion and non‐destructively. Copyright © 2004 John Wiley & Sons, Ltd.     

The Cytoskeletal Protein Zyxin Inhibits Retinoic Acid Signaling by Destabilizing the Maternal mRNA of the RXRγ Nuclear Receptor

Zyxin is an LIM-domain-containing protein that regulates the assembly of F-actin filaments in cell contacts. Additionally, as a result of mechanical stress, Zyxin can enter nuclei and regulate gene expression. Previously, we found that Zyxin could affect mRNA stability of the maternally derived stemness factors of Pou5f3 family in Xenopus laevis embryos through binding to Y-box factor1. In the present work, we demonstrate that Zyxin can also affect mRNA stability of the maternally derived retinoid receptor Rxrγ through the same mechanism. Moreover, we confirmed the functional link between Zyxin and Rxrγ-dependent gene expression. As a result, Zyxin appears to play an essential role in the regulation of the retinoic acid signal pathway during early embryonic development. Besides, our research indicates that the mechanism based on the mRNA destabilization by Zyxin may take part in the control of the expression of a fairly wide range of maternal genes.     

Molecular Dynamics of CYFIP2 Protein and Its R87C Variant Related to Early Infantile Epileptic Encephalopathy

The CYFIP2 protein (cytoplasmic FMR1-interacting protein 2) is part of the WAVE regulatory complex (WRC). CYFIP2 was recently correlated to neurological disorders by the association of the R87C variant with early infantile epileptic encephalopathy (EIEE) patients. In this set of syndromes, the epileptic spasms and seizures since early childhood lead to impaired neurological development in children. Inside the WRC, the variant residue is at the CYFIP2 and WAVE1 protein interface. Thus, the hypothesis is that the R87C modification weakens this interaction, allowing the WRC complex’s constant activation. This work aimed to investigate the impacts of the mutation on the structure of the WRC complex through molecular dynamics simulation. For that, we constructed WRC models containing WAVE1-NCKAP1 proteins complexed with WT or R87C CYFIP2. Our simulations showed a flexibilization of the loop comprising residues 80–110 due to the loss of contacts between internal residues in the R87C CYFIP2 as well as the key role of residues R/C87, E624, and E689 in structural modification. These data could explain the mechanism by which the mutation impairs the stability and proper regulation of the WRC.     

Effects of Non-Opioid Analgesics on the Cell Membrane of Skin and Gastrointestinal Cancers

Skin and gastrointestinal cancer cells are the target of research by many scientists due to the increasing morbidity and mortality rates around the world. New indications for drugs used in various conditions are being discovered. Non-opioid analgesics are worth noting as very popular, widely available, relatively cheap medications. They also have the ability to modulate the membrane components of tumor cells. The aim of this review is to analyze the impact of diclofenac, ibuprofen, naproxen, acetylsalicylic acid and paracetamol on skin and gastrointestinal cancers cell membrane. These drugs may affect the membrane through topical application, at the in vitro and in vivo level after oral or parenteral administration. They can lead to up- or downregulated expression of receptors, transporters and other molecules associated with plasma membrane. Medications may also alter the lipid bilayer composition of membrane, resulting in changes in its integrity and fluidity. Described modulations can cause the visualization of cancer cells, enhanced response of the immune system and the initiation of cell death. The outcome of this is inhibition of progression or reduction of tumor mass and supports chemotherapy. In conclusion, non-opioid analgesics may be used in the future as adjunctive therapy for the treatment of these cancers.     

Cloning and Characterization of a Thermostable Endolysin of Bacteriophage TP-84 as a Potential Disinfectant and Biofilm-Removing Biological Agent

The obligatory step in the life cycle of a lytic bacteriophage is the release of its progeny particles from infected bacterial cells. The main barrier to overcome is the cell wall, composed of crosslinked peptidoglycan, which counteracts the pressure prevailing in the cytoplasm and protects the cell against osmotic lysis and mechanical damage. Bacteriophages have developed two strategies leading to the release of progeny particles: the inhibition of peptidoglycan synthesis and enzymatic cleavage by a bacteriophage-coded endolysin. In this study, we cloned and investigated the TP84_28 endolysin of the bacteriophage TP-84, which infects thermophilic Geobacillus stearothermophilus, determined the enzymatic characteristics, and initially evaluated the endolysin application as a non-invasive agent for disinfecting surfaces, including those exposed to high temperatures. Both the native and recombinant TP84_28 endolysins, obtained through the Escherichia coli T7-lac expression system, are highly thermostable and retain trace activity after incubation at 100 °C for 30 min. The proteins exhibit strong bacterial wall digestion activity up to 77.6 °C, decreasing to marginal activity at ambient temperatures. We assayed the lysis of various types of bacteria using TP84_28 endolysins: Gram-positive, Gram-negative, encapsulated, and pathogenic. Significant lytic activity was observed on the thermophilic and mesophilic Gram-positive bacteria and, to a lesser extent, on the thermophilic and mesophilic Gram-negative bacteria. The thermostable TP84_28 endolysin seems to be a promising mild agent for disinfecting surfaces exposed to high temperatures.     

The Role of Psychobiotics in Supporting the Treatment of Disturbances in the Functioning of the Nervous System—A Systematic Review

Stress and anxiety are common phenomena that contribute to many nervous system dysfunctions. More and more research has been focusing on the importance of the gut–brain axis in the course and treatment of many diseases, including nervous system disorders. This review aims to present current knowledge on the influence of psychobiotics on the gut–brain axis based on selected diseases, i.e., Alzheimer’s disease, Parkinson’s disease, depression, and autism spectrum disorders. Analyses of the available research results have shown that selected probiotic bacteria affect the gut–brain axis in healthy people and people with selected diseases. Furthermore, supplementation with probiotic bacteria can decrease depressive symptoms. There is no doubt that proper supplementation improves the well-being of patients. Therefore, it can be concluded that the intestinal microbiota play a relevant role in disorders of the nervous system. The microbiota–gut–brain axis may represent a new target in the prevention and treatment of neuropsychiatric disorders. However, this topic needs more research. Such research could help find effective treatments via the modulation of the intestinal microbiome.