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Generating clean energy is necessary due to the increasing demand resulting from the development of human civilization and the global economy. The generation of clean energy is justified by the need to reduce the negative impact on the natural environment. Every action aimed at converting one form of energy into another carries consequences related to the efficiency of the transformation process and the physicochemical properties characterizing the systems of its utilization. Special attention should be paid to hydrogen, which is a fuel with high activity in terms of penetration through the structures of conventional construction materials, and there is a high probability of significant emissions of this fuel from its storage and transportation processes. This situation worsens the overall efficiency of the hydrogen utilization process but also necessitates the identification of the consequences of hydrogen emissions into the atmosphere. Therefore, a comprehensive assessment of energy conversion for the purposes of hydrogen production and storage in terms of environmental impact is necessary. The conducted analyses are presented in this article.

This article presents the results of experimental investigations on an advanced model of a polymer exchange membrane fuel cell (PEMFC) stack designed to serve as a charging unit for electric vehicle batteries or off-grid distributed power sources. The assembled 720 W PEMFC stack comprises two 360 W modules that can be electrically connected in series or parallel. A liquid cooling system for the PEMFC stack has also been constructed. The dependencies – voltage (U) versus current (I) and current (I) versus electrical power (P) – for single modules, as well as for the electrically connected two-module PEMFC stack, are determined. Additionally, the hydrogen utilization versus the electrical power (P) of the PEMFC stack is examined. The electrical efficiency of the PEMFC stack varies between 42% and 50%, depending on the electrical power. An adjustable DC/DC converter, operating in two modes (step-down or stepup), is proposed as a device to integrate a lithium-ion (Li-ion) battery pack with approximately 720 W PEMFC stack. The electrical architecture of the integrated system, comprising the PEMFC stack, DC/DC converter, and Li-ion battery pack, is investigated and discussed in this paper. It was found that the electrical efficiency of the proposed DC/DC converter varies depending on the electrical power, reaching a peak efficiency of 95%– 98%. The environmental benefit, in terms of reducing CO2 emissions when charging the battery, was also identified.

Isolation and cohesion are two key network features, often used to predict outcomes like mental health and deviance. More cohesive settings tend to have better outcomes, while isolates tend to fare worse than their more integrated peers. A common assumption of past work is that the effect of cohesion is universal, so that all actors get the same benefits of being in a socially cohesive environment. Here, we suggest that the effect of cohesion is universal only for specific types of outcomes. For other outcomes, experiencing the benefits of cohesion depends on an individual’s position in the network, such as whether or not an individual has any social ties. Network processes thus operate at both the individual and contextual level, and we employ hierarchical linear models to analyze these jointly to arrive at a full picture of how networks matter. We explore these ideas using the case of adolescents in schools (using Add Health data), focusing on the effect of isolation and cohesion on two outcomes, school attachment and academic engagement. We find that cohesion has a uniform effect in the case of engagement but not attachment. Only non-isolates experience stronger feelings of attachment as cohesion increases, while all students, both isolates and non-isolates, are more strongly engaged in high cohesion settings. Overall, the results show the importance of taking a systematic, multi-level approach, with important implications for studies of health and deviance.

The purpose of this experiment was a selection of scab resistant apple cultivars suitable for juice production. Special attention was paid to cloudy juices. During three successive seasons, apple cultivars were processed into juices using laboratory method of juice extraction. Considering the possibility of both clear and cloudy juice production, apples were pressed with and without mash enzymation. The parameters investigated were: pressing yield, titratable acidity, soluble solids, juice density, and juices’ sensory characteristics. Average values indicate that all the cultivars fulfilled the requirements of the Code of Practice of the European Fruit Juice Association concerning investigated chemical components, however, in single years, there were some deviations that should be taken into consideration offering single cultivar juices. Considering a low yield of juice without mash enzymation (below 70%), cultivars ‘Renora’ and ‘Retina’ are not recommended for cloudy juice production. Sensory quality of juices, irrespectively if cloudy or clear, depended mostly on taste acceptability and in fact on soluble solids to acidity ratio. Juices with the ratio above 17 were usually scored higher concerning the taste than those with lower values. An example of exception was ‘Free Redstar’ which is highly astringent. Considering the efficiency of pressing and soluble solids content several investigated cultivars were highly suitable for concentrated apple juice production. Especially valuable may be considered ‘Regine’, ‘Rebella’, ‘Sawa’, and ‘Topaz’ and can be recommended for planting in industrial orchards, which became of special interest in recent years.

The current, fast market changes require enterprises to dynamically adapt the way they conduct their business. This poses many challenges for information technology. Market requirements for immediate response to business changes became the basis of the idea of a real-time information processing (RTE) company. RTE provides real-time information to employees and business partners. Integrated IT systems supporting management constitute a common platform – the foundation of a real-time enterprise. The aim of the article is to present the basic problems of building an IT system that is the basis of a real-time information processing (RTE) company. It is a summary of our work on this type of system. The article justifies the thesis about the need to build a system for the RTE's requirements and the conditions of its implementation. Such a system is designed to provide employees and business partners with the information they need in real time. The use of integrated systems such as ERP, CRM, SCM, and so on provides the ability to implement the main business processes of a real-time enterprise. The article presents both literature analysis and the characteristics of own work on designing IT systems for RTE. Particular attention was paid to the analysis of success factors (determinants) in system design and the use of MUST methodology (MUST is a Danish acronym for theories of and methods for design activities). The final part of the article presents a proposal for further work on IT systems for RTE in the context of existing trends such as DARQ technology (Distributed Ledger, Artificial Intelligence, Extended Reality, Quantum computing).

The article aims to present the methodology of estimating the atmospheric water exchange components in the lake. In the absence of direct precipitation and evaporation measurements, these water balance elements need to be estimated. However, the inadequate selection of precipitation and evaporation estimation methods causes the incorrect determination of the hydrological function of the lake and the effect it has on the formation of river drainage. Determination of the evaporation from the lake’s surface was based on the Davidov formula, which considered the monthly average surface temperature of a given lake. The saturated water vapour pressure under the lake’s monthly mean surface water temperature (TWP) was calculated according to ISO 13788 standard. The interpolation method, which is the inverse-distance deterministic method (IDW), was used to calculate precipitation reaching the lake surface. The calculations were made for three hydrological years diverse in terms of humidity and thermal conditions. The methodology for estimating the components of atmospheric water exchange was presented on a small river-lake system of the upper Gościcina River catchment, an example of a postglacial lake district area. The lake elements of this system are lobelia lakes, poorly known in terms of water circulation. At the beginning of the twenty-first century, unjustified activities regarding assessing the water circulation conditions in this river-lake system led to changes in water relations, causing environmental, financial and social losses.

Aim/purpose – The purpose of the research is to verify the Capital Asset Pricing Model (CAPM) in the Polish capital market based on a conventional and downside risk approach.

The intensification of environmental protection measures is being implemented in all economic and industrial activities. The goal of reducing harmful emissions from various types of combustion engines used in different applications is being pursued dynamically. The introduced changes concern the values of harmful emission limits and the methods of measuring or assessing their emissions. There are solutions for propulsion systems, such as turbine engines used on ships, where there is a need for constant monitoring of operational and environmental parameters during the operation of the vessels. Continuous measurement of harmful emission values contained in exhaust gases during the operation of these systems allows for an assessment of their impact on the environment. However, due to the costs of measuring equipment and limitations associated with its use, alternative methods are being sought to evaluate pollution emissions resulting from the operation of turbine engines. One possibility is to assess the emission characteristics of the propulsion system in emission tests under conditions of its actual operation. Based on this, by introducing basic mathematical tools, it is possible to determine the values of emissions of individual pollutants during the propulsion system operation in actual conditions. These actions are presented in this paper.

In the last two decades, fractional calculus has become a subject of great interest in various areas of physics, biology, economics and other sciences. The idea of such a generalization was mentioned by Leibniz and L’Hospital. Fractional calculus has been found to be a very useful tool for modeling linear systems. In this paper, a method for computation of a set of a minimal positive realization of a given transfer function of linear fractional continuous-time descriptor systems has been presented. The proposed method is based on digraph theory. Also, two cases of a possible input-output digraph structure are investigated and discussed. It should be noted that a digraph mask is introduced and used for the first time to solve a minimal positive realization problem. For the presented method, an algorithm was also constructed. The proposed solution allows minimal digraph construction for any one-dimensional fractional positive system. The proposed method is discussed and illustrated in detail with some numerical examples.

The assessment of the physicochemical parameters of fuels is particularly important in energy generation processes implemented using combustion processes. The calorific value of the fuels used is important in these processes. The calorific value of fuel is the basic parameter from which the mass of fuel necessary to generate a certain amount of energy results. Calorimeters are used to determine the calorific value of fuels. The subject of analyzes is the conceptual design of the calorimeter for gaseous fuel testing. A special element in the construction of the calorimeter is the combustion chamber. In its initial part, the gaseous fuel oxidation process is carried out, and in the final part, the required parameters are measured. In order to obtain high accuracy in the measurement of selected thermodynamic parameters, it is necessary to ensure homogeneity of the exhaust gases flowing in the measurement space. For this purpose, the construction of the combustion chamber was developed and simulation tests aimed at homogenization of exhaust gases in the chamber measuring space were carried out. An example of the construction and the tests carried out are provided in this article.

Lobelia lakes are valuable elements of the natural environment. They are characterised by low trophy, mainly in-forest location and a high transparency of water. However, similarly to other surface waters, they are subjected to increasing anthropogenic pressures, a good indicator of which is the level of surfactants, also called surface-active agents (SAAs). The aim of the study was to evaluate the intensity of anthropogenic pressures in 13 selected lobelia lakes and 14 streams in the catchments of these lakes in Northern Poland, based on SAA concentrations in the waters of these water bodies. We collected one water sample from each of these water bodies and determined the concentrations of cationic, anionic and non-ionic SAAs. We then compared the results with data concerning the ways in which these catchments and water bodies are used. While ionic (cationic and anionic) SAAs were found to be present in all the 27 samples (with concentrations ranging from 0.05 to 0.51 mg dm−3), non-ionic SAAs were identified in 17 of 27 samples (from 0.00 to 2.43 mg dm−3) with three samples largely exceeding the maximum concentration values reported by other authors. We concluded that SAAs are a real threat to the aquatic geoecosystems of lobelia lakes and that the pressures of tourism and leisure have the greatest impact.

Intensive and expansive human activity greatly accelerates the natural process of lake evolution. It is assumed that an increase in the rate of lake fertilization (often termed “eutrophication”) is the most common and most serious anthropogenic disturbance occurring in these aquatic geoecosystems. Lobelia lakes, one of the most valuable water bodies, are particularly exposed to this type of pressure. The article presents the trophic state of 13 lobelia lakes, located close to the Tricity area, in the northeastern part of the Kashubian Lakeland, which are not legally protected. These lakes represent different geoecosystems determining the rate of their natural evolution, and are subjected to various forms of anthropopressure (numerous summerhouses, fishing, waterside leisure and recreation). The trophic status of these lakes was assessed on the basis of the Carlson-type indices. The evaluation indicated that six of these lakes were in borderline mesotrophic-eutrophic state, and seven represented a significantly advanced eutrophic state.

In recent years elastic optical networks have been perceived as a prospective choice for future optical networks due to better adjustment and utilization of optical resources than is the case with traditional wavelength division multiplexing networks. In the paper we investigate the elastic architecture as the communication network for distributed data centers. We address the problems of optimization of routing and spectrum assignment for large-scale computing systems based on an elastic optical architecture; particularly, we concentrate on anycast user to data center traffic optimization. We assume that computational resources of data centers are limited. For this offline problems we formulate the integer linear programming model and propose a few heuristics, including a meta-heuristic algorithm based on a tabu search method. We report computational results, presenting the quality of approximate solutions and efficiency of the proposed heuristics, and we also analyze and compare some data center allocation scenarios.

Resuspension in lakes affects the quality of lake water. It is possible to model this process and visualize its outcomes using GIS tools. An assessment of the size of the zone of sediment resuspension was made for two lakes located in Northern Poland threatened by rapid eutrophication. For each of the lakes, four simulations using two methods for determining the effective wind length (F) (Model 1 and Model 2) and two methods for determining the wind wavelength (Lw) (Model A and Model B) were performed. The analysis, taking into account the morphometry of the studied lakes and anemometric conditions, indicated that the differentiator is the applied simulation method of calculating the wavelength caused by the wind. The analysis is theoretical in nature and the results need to be verified in the field..

The generalized Darken method was applied to simulate the diffusion between γ-Ni| γ’-Ni3Al and γ’-Ni3Al|β-NiAl interfaces. The results of calculations were compared with the experimental concentration’s profiles of nickel, aluminum and hafnium in aluminide and hafnium doped aluminide coatings deposited by the CVD and PVD methods on pure nickel. The method deals with the Wagner’s integral diffusion coefficients and thermodynamic data - activities of components. The experimental results agree with the simulated ones.

Study aim: The aim of this study was to evaluate the relationship between basic somatic features (body mass and height) and body mass loss in physically inactive young women and men exposed to thermal stress in a dry sauna.

The generalized Darken method allows a quantitative description of diffusion mass transport in multi-phase materials. The method characterizes the diffusion zone by phase volume fractions. The results of the calculations are compared with experimental concentration’s profiles of nickel, zirconium and aluminum in zirconium doped aluminide coatings deposited on pure nickel by the PVD and CVD methods.

Image sequences, in particular digital video sequences, are characterised by the features which result in their high potential as measurement data. However, as early as at the stage of visual assessment of digital film images, originating, in particular, from amateur cameras, occurrence of some deformations may be observed, which may highly influence the results of measurements performed using these images; such deformations differ from deformations occurred in the case of static photographic images. It results both, by the method of image recording, using an electronic shutter and interlaced or progressive scanning, as well as the method of file recording and compression. It is worth to notice the systematic nature of such deformations, which highly depend on mutual motions of a camera and recorded objects. The objective of presented research works was to develop the mathematical description of image deformations, as a function of motion parameters. This would allow for adaptation of the camera calibration process to the demands of sequential imaging, as well as for modification of algorithms of measurements using self-calibration, and, as a result, minimisation of deformations. Another objective was to analyse the influence of deformations, typical for digital film images, on the results of measurements performed using these images, by means of series of experiments, which were based on multiple calibration of static and a moving camera, also with the use of a spatial test field. The first part was made by developing formulas based on some geometric relations, using some simplifications. On the stage of experimental research a certain degree of compatibility of experimental results and theoretical assumptions were confirmed.

In the years 2009-2010 limnological research was carried out on 13 lobelia lakes of the Tricity metropolitan area. These lakes, of unique value not only on the scale of the country, are undergoing degradation due to increasing anthropogenic pressure. Grade of degradation of these lakes, depends on geoecosystem type, which they are representing. Geoecosystem type of the lake, defines the rate of natural eutrophication of reservoir. In this article types of geoecosystems of analysed lobelia lakes where defined in accordance with the guidelines of Bajkiewicz-Grabowska (1981, 1983, 1985, 1987, 2002). The obtained results indicate that only one of the analysed lakes (Zawiat Lake) is likely to retain a low trophic level. Four lakes (Głębokie, Kamień, Borowo, Techlinko) represent geoecosystems with a moderate rate of natural eutrophication. The remaining of the analysed lobelia lakes are threatened with fast water eutrophication, which is demonstrated by a high catchment vulnerability to activate areal load, and a low resistance of the lakes (resulting from their natural properties) to external supply. The obtained results correspond to field measurements and make it possible to indicate actions aimed at protecting the group of the analysed lobelia lakes.

Over the last decade, supercell simulations and observations with ever-increasing resolution have provided new insights into the vortex-scale processes of tornado formation. This article incorporates these and other recent findings into the existing three-step model by adding an additional fourth stage. The goal is to provide an updated and clear picture of the physical processes occurring during tornadogenesis. Specifically, we emphasize the importance of the low-level wind shear and mesocyclone for tornado potential, the organization and interaction of relatively small-scale pretornadic vertical vorticity maxima, and the transition to a tornado-characteristic flow. Based on these insights, guiding research questions are formulated for the decade ahead. SIGNIFICANCE STATEMENT: This article provides a nontechnical overview of how tornadoes form. Sequentially, the most important processes include the initial creation of rotating updrafts, the development of disorganized patches of rotation at the surface, the organization of these patches into a more defined, symmetric vortex, and the final transition into a fully developed tornado in which air turns abruptly upward very near the surface. Based on this proposed conceptual model, guiding research questions are formulated for the decade ahead. KEYWORDS: Tornadogenesis; Severe storms; Tornadoes; Radars/Radar observations; Supercells, 1. How does a tornado form? This is perhaps one of the most elementary yet enduring questions in meteorology. Even though severe-storm research has focused on this problem for over [...]

The issue of measuring and determining the calorific value of fuels is related to thermodynamic analysis of the effects of the combustion process aimed at determining the amount of heat transferred to the environment. Currently, there are several methods for determining the calorific value of fuels and their methodology is related to the type of fuel being analyzed. These methods are quite complicated and require the use of specialized measuring equipment. The energy demand of modern civilization along with the need to protect the natural environment prompts the search for new ways to generate energy directed at sources other than conventional fossil fuels. Technologies related to the use of biogas, synthesis gas obtained in biomass or waste gasification processes are being introduced. The use of these fuels in industrial processes of generating heat and electricity requires caloric stability of the fuel. The caloric stability of the fuel is necessary to ensure the stability of thermal energy conversion processes that translate directly into the set values of generated electricity using electric machines. One way to assess the energy quality of a fuel is to measure its calorific value. There are several methods for determining the calorific value of a fuel, but they all require special measurement conditions. The article presents the author’s concept of a calorimeter dedicated to the analysis of the calorific value of gaseous fuels.

The allergic reactions to fruits are lesser known among food sensitivities. The most common fruits belonging to the Rosaceae family that might cause allergic reactions are apples, pears and peaches. However, little is known about the potential allergic reactions caused by another member of the Rosaceae, the cherry. The aim of this study was to assess the risk of any allergic reaction or food hypersensitivity resulting from topical application and chronic oral administration of cherry fruits. The cherry fruits ‘Sabina’ cv. were produced in the orchard in Dąbrowice according to the principles of integrated (IFP) and organic (OR) productions. Fruits of ‘Debreceni Bötermö’ cv. were produced in Dąbrowice (IFP), and in the orchard in Nowy Dwór (OR). The experiments were performed on 65 outbred young, adult, white albinotic guinea pigs (Dankin Hartley). Three procedures were applied: I. Guinea-Pig Maximization Test (GPMT); II. Chronic administration of fruits and III. Skin prick (Dreborg) test. The skin reactions based on GPMT or Dreborg tests revealed no differences between the two cherry cultivars ‘Sabina’ and ‘Debreceni’ obtained from integrated or organic production. Similarly, it was not observed of any effect of cultivars of cherries nor the type of fruits production on the guinea pig skin reaction as a result of chronic feeding with fruits.

The increasing transport needs of societies are prompting manufacturers and inventors to seek new ways to satisfy them which are closely related to the development of new transport systems and means of transport. The current level of technological and social systems imposes limits on the implementation of new concepts which combine the advantages of existing systems currently functioning as separate entities. Combining the advantages of rail transport with the characteristics of air transport gave rise to the concept of a new transport system called Hyperloop, whose main purpose is to create a transport network combining the advantages of air and rail transport with low operating costs. The project assumes a pipeline structure and a transport capsule that moves inside its channels. To obtain high-velocity capsules, it is assumed that the pressure in the pipeline will be reduced, which will reduce in turn the losses resulting from the resistance of the moving capsule. Most means of transport in current use involve motion in open space. The proposed Hyperloop system involves different problems concerning the movement of the capsule as a means of transport within the confined space of the pipeline. These problems require specific analysis of conditions inside the system which depend on the velocity and shape of the capsule. These issues can be addressed using currently available numerical tools. An attempt to assess the phenomena associated with the flow of the capsule, using an important factor found in the pipeline space, was undertaken in the analyses conducted here. The study involved determination of the force acting on the nose of the capsule, an important component of its resistance to movement. The results and analyses were used to evaluate the differences in energy demand between two compared structures. On the basis of these results, conclusions were drawn regarding the directions for further modifications of the shape of the capsule aimed at reducing the energy demand necessary for its propulsion.

The problem of turbine microjet engine operation is related to flight conditions of unmanned aircraft. These flights are often performed at low altitudes, where, in autumn and winter conditions, the air can be characterized by high humidity and low temperature. Such operating conditions may cause freezing the turbine engine inlet. In particular, this problem may be related to microengines, which most often are not equipped with a de-icing installation. Frosting of the inlet violates the air flow conditions at the engine inlet and may cause unstable operation and even outages, which eventually may lead to a loss of aircraft’s stability and breakdown. Therefore, an attempt was made to evaluate the changes in operational parameters of the turbine microjet engine under conditions leading to the freezing of the inlet. The engine test was performed in stationary conditions and the analysis of the obtained results are presented in this article.

The last decade in Poland has been a period of intense expansion of the public roads network. During this period a spectacular increase in the number of vehicles and traffic intensities has been noticed. Considering this, organising and carrying out maintenance work is increasingly important. The paper provides a brief analysis of currently used maintenance models in Europe and Poland and their characteristics which determine the safety of both road users and workers carrying out roadworks. The historical change in the approach towards the quality of road maintenance, the evolution of the economic model and a description of how the expectations and preferences of drivers have changed are included in the paper. In addition, the paper presents specific road maintenance standards and suggestions for maintenance and road works. The summary of the paper gives a recommendation for future development directions and suggests which features of road maintenance models and standards improve safety to the highest degree, particularly in the context of the further development of the road network.

The issue of exhaust gas emission generated by turbine engines described in ICAO Annex 16 of the International Civil Aviation Convention includes a number of procedures and requirements. Their implementation is aimed at determining the value of the engine’s environmental parameters and comparing them to the values specified in the norms. The turbine engine exhaust gas emission test procedures are defined as stationary and the operating parameters values are set according to the LTO test. The engine load setting values refer to engine operating parameters that occur when the plane is in the vicinity of airports. Such a procedure is dedicated to civilian passenger and transport aircraft. The operating conditions of a multirole fighter aircraft vary considerably from passenger aircraft and the variability of their flight characteristics requires a special approach in assessing its environmental impact. This article attempts to evaluate the exhaust gas emissions generated by the turbine engine in a multirole fighter flight using the parameters recorded by the onboard flight recorder.

The introduction of new emission limits for exhaust emissions of ship engines contributes to the development of new powertrain solutions. New solutions in the simplest approach concern the reduction of the concentration of sulfur in motor fuels. Typically, the aforementioned fuels have a lower value of viscosity which causes a number of supply system problems. It is becoming more and more common to use fuel cells in engine rooms of various types of marine vessels. Unlike conventional systems that use internal combustion engines, these systems have zero exhaust emissions. Hydrogen, methanol, methane and other substances may be used as a fuel in fuel cells. However, so far the best operating parameters are manifested by cells powered by hydrogen, which is associated with difficulties in obtaining and storing this fuel. Therefore, the use of turbine engines allows the obtaining of large operating and environmental advantages. The paper presents a comparison of the ecological parameters of turbine and piston engines.

The article presents the results of studies conducted in the area adjacent to the airport located in Poznan, to determine the impact of aircraft landing operation on the concentration of particulate matter. Measurements were carried out using Engine Exhaust Particle Sizer Spectrometer 3090, enabling the measurement of the particle size distribution. The research allowed to determine the nature of the emitted particles and adds to the evaluation of impact on air quality. The tests were carried out during four aircraft landing operations. In each of the four cases total concentration of particulates number before landing (reference level) and during the landing of the aircraft was measured. In addition, the size distribution of reference level particles and its change after the landing operation was measured. Based on the conducted research, it was found that landing aircrafts have a significant impact on the concentration of particulate matter in the area adjacent to the airport. A single landing operation causes an substantially increase of the value of particle number concentration.

The article presents a study on emission measurements in passenger cars in tests conducted under real traffic conditions – Real Driving Emissions using a Portable Emission Measurement System type of equipment. A special feature of the outlined RDE tests is that they were performed in Polish road conditions, and thus their parameters may differ from their counterparts adopted in most European Union countries. Based on the findings vehicle emission conformity factors were developed, characterized as the fractional increase (or decrease) of traffic emissions during the homologation test or under normal operation conditions in relation to the emission limit standards (for chosen emission class) of the vehicle. Conducted research and the calculated conformity factors allowed for the environmental impact assessment of the vehicles of various emission classes, while also allowing early actions to restrict the emissions of selected components in passenger vehicles. The methods and measures used can also be applied to other types of vehicles (e.g. heavy duty or off-road vehicles) or vehicles powered by other fuels.

BackgroundEmerging data suggest that metastasis is a spectrum of disease burden rather than a binary state, and local therapies, such as radiation, might improve outcomes in oligometastasis. However, current definitions of oligometastasis are solely numerical.ObjectiveTo characterize the somatic mutational landscape across the disease spectrum of metastatic castration-sensitive prostate cancer (mCSPC) to elucidate a biological definition of oligometastatic CSPC.Design, setting, and participantsThis was a retrospective study of men with mCSPC who underwent clinical-grade sequencing of their tumors (269 primary tumor, 25 metastatic sites). Patients were classified as having biochemically recurrent (ie, micrometastatic), metachronous oligometastatic (≤5 lesions), metachronous polymetastatic (>5 lesions), or de novo metastatic (metastasis at diagnosis) disease.Outcome measurements and statistical analysisWe measured the frequency of driver mutations across metastatic classifications and the genomic associations with radiographic progression-free survival (rPFS) and time to castrate-resistant prostate cancer (CRPC).Results and limitationsThe frequency of driver mutations in TP53 (p =  0.01), WNT (p =  0.08), and cell cycle (p =  0.04) genes increased across the mCSPC spectrum. TP53 mutation was associated with shorter rPFS (26.7 vs 48.6 mo; p =  0.002), and time to CRPC (95.6 vs 155.8 mo; p =  0.02) in men with oligometastasis, and identified men with polymetastasis with better rPFS (TP53 wild-type, 42.7 mo; TP53 mutated, 18.5 mo; p =  0.01). Mutations in TP53 (incidence rate ratio [IRR] 1.45; p =  0.004) and DNA double-strand break repair (IRR 1.61; p

Abstract Background Spontaneous cessation of growth is a frequent finding in uterine fibroids. Increasing evidence suggests an important role of cellular senescence in this growth control. Deciphering the underlying mechanisms of growth control that can be expected not only to shed light on the biology of the tumors but also to identify novel therapeutic targets. Methods We have analyzed uterine leiomyomas and matching normal tissue for the expression of p14Arf and used explants to see if reducing the MDM2 activity using the small-molecule inhibitor nutlin-3 can induce p53 and activate genes involved in senescence and/or apoptosis. For these studies quantitative real-time RT-PCR, Western blots, and immunohistochemistry were used. Statistical analyses were performed using the student's t test. Results An in depth analysis of 52 fibroids along with matching myometrium from 31 patients revealed in almost all cases a higher expression of p14Arf in the tumors than in the matching normal tissue. In tissue explants, treatment with the MDM2 inhibitor nutlin-3 induced apoptosis as well as senescence as revealed by a dose-dependent increase of the expression of BAX as well as of p21, respectively. Simultaneously, the expression of the proliferation marker Ki-67 drastically decreased. Western-blot analysis identified an increase of the p53 level as the most likely reason for the increased activity of its downstream markers BAX and p21. Because as a rule fibroids express much higher levels of p14Arf, a major negative regulator of MDM2, than matching myometrium it was then analyzed if fibroids are more sensitive against nutlin-3 treatment than matching myometrium. We were able to show that in most fibroids analyzed a higher sensibility than that of matching myometrium was noted with a corresponding increase of the p53 immunopositivity of the fibroid samples compared to those from myometrium. Conclusions The results show that uterine fibroids represent a cell population of advanced cellular age compared to matching myometrium. Moreover, the data point to members of the p53-network as to potential novel therapeutic targets for the treatment of uterine fibroids.

Abstract Background Constraint-based approaches facilitate the prediction of cellular metabolic capabilities, based, in turn on predictions of the repertoire of enzymes encoded in the genome. Recently, genome annotations have been used to reconstruct genome scale metabolic reaction networks for numerous species, including Homo sapiens, which allow simulations that provide valuable insights into topics, including predictions of gene essentiality of pathogens, interpretation of genetic polymorphism in metabolic disease syndromes and suggestions for novel approaches to microbial metabolic engineering. These constraint-based simulations are being integrated with the functional genomics portals, an activity that requires efficient implementation of the constraint-based simulations in the web-based environment. Results Here, we present Acorn, an open source (GNU GPL) grid computing system for constraint-based simulations of genome scale metabolic reaction networks within an interactive web environment. The grid-based architecture allows efficient execution of computationally intensive, iterative protocols such as Flux Variability Analysis, which can be readily scaled up as the numbers of models (and users) increase. The web interface uses AJAX, which facilitates efficient model browsing and other search functions, and intuitive implementation of appropriate simulation conditions. Research groups can install Acorn locally and create user accounts. Users can also import models in the familiar SBML format and link reaction formulas to major functional genomics portals of choice. Selected models and simulation results can be shared between different users and made publically available. Users can construct pathway map layouts and import them into the server using a desktop editor integrated within the system. Pathway maps are then used to visualise numerical results within the web environment. To illustrate these features we have deployed Acorn and created a web server allowing constraint based simulations of the genome scale metabolic reaction networks of E. coli, S. cerevisiae and M. tuberculosis. Conclusions Acorn is a free software package, which can be installed by research groups to create a web based environment for computer simulations of genome scale metabolic reaction networks. It facilitates shared access to models and creation of publicly available constraint based modelling resources.

Abstract Background Our study was part of the large European project ISAFRUIT aiming to reveal the biological explanations for the epidemiologically well-established health effects of fruits. The objective was to identify effects of apple and apple product consumption on the composition of the cecal microbial community in rats, as well as on a number of cecal parameters, which may be influenced by a changed microbiota. Results Principal Component Analysis (PCA) of cecal microbiota profiles obtained by PCR-DGGE targeting bacterial 16S rRNA genes showed an effect of whole apples in a long-term feeding study (14 weeks), while no effects of apple juice, purée or pomace on microbial composition in cecum were observed. Administration of either 0.33 or 3.3% apple pectin in the diet resulted in considerable changes in the DGGE profiles. A 2-fold increase in the activity of beta-glucuronidase was observed in animals fed with pectin (7% in the diet) for four weeks, as compared to control animals (P < 0.01). Additionally, the level of butyrate measured in these pectin-fed animal was more than double of the corresponding level in control animals (P < 0.01). Sequencing revealed that DGGE bands, which were suppressed in pectin-fed rats, represented Gram-negative anaerobic rods belonging to the phylum Bacteroidetes, whereas bands that became more prominent represented mainly Gram-positive anaerobic rods belonging to the phylum Firmicutes, and specific species belonging to the Clostridium Cluster XIVa. Quantitative real-time PCR confirmed a lower amount of given Bacteroidetes species in the pectin-fed rats as well as in the apple-fed rats in the four-week study (P < 0.05). Additionally, a more than four-fold increase in the amount of Clostridium coccoides (belonging to Cluster XIVa), as well as of genes encoding butyryl-coenzyme A CoA transferase, which is involved in butyrate production, was detected by quantitative PCR in fecal samples from the pectin-fed animals. Conclusions Our findings show that consumption of apple pectin (7% in the diet) increases the population of butyrate- and β-glucuronidase producing Clostridiales, and decreases the population of specific species within the Bacteroidetes group in the rat gut. Similar changes were not caused by consumption of whole apples, apple juice, purée or pomace.