Pathogenesis of bacterial meningitis: contributions by experimental models in rabbits

Rabbits models of bacterial meningitis have contributed substantially to our understanding of the disease, although the technical characteristics of these models only allow the study of specific aspects of the disease. Bacterial multiplication in the subarachnoidal space is not substantially influenced by host defense mechanisms, mainly because of the lack of sufficient amounts of specific antibodies and functional complement in infected CSF. The multiplying bacteria induce profound changes in the blood-brain barrier, an influx of serum proteins into the CSF and the invasion of polymorphonuclear leukocytes at the site of the infection. The presence of polymorphonuclear leukocytes in CSF not only appears to be of limited value in combating the infection, but also seems to produce deleterious effects on the central nervous system. Components of the leukocytes, such as unsaturated fatty acids, arachidonic metabolites and free oxygen radicals, may contribute to the profound hydrodynamic, structural and metabolic changes that are currently under study in experimental models of the disease. A better understanding of the pathophysiology of bacterial meningitis may allow us to design more effective therapeutic strategies and improve the outcome of this disease.

[Neither Descartes nor Freud? current pain models in psychosomatic medicine]

Models explaining chronic pain based on the mere presence or absence of peripheral somatic findings or which view pain of psychological origin when there is no somatic explanation, have their shortcomings. Current scientific knowledge calls for distinct pain concepts, which integrate neurobiological and neuropsychological aspects of pain processing.

Antitumor effect of SIRT1 inhibition in human HCC tumor models in vitro and in vivo

Sirtuins (SIRT1-7) are a highly conserved family of NAD(+)-dependent enzymes that control the activity of histone and nonhistone regulatory proteins. SIRT1 is purposed to promote longevity and to suppress the initiation of some cancers. Nevertheless, SIRT1 is reported to function as a tumor suppressor as well as an oncogenic protein. Our data show that compared with normal liver or surrounding tumor tissue, SIRT1 is strongly overexpressed in human hepatocellular carcinoma (HCC). In addition, human HCC cell lines (Hep3B, HepG2, HuH7, HLE, HLF, HepKK1, skHep1) were screened for the expression of the sirtuin family members and only SIRT1 was consistently overexpressed compared with normal hepatocytes. To determine its effect on HCC growth, SIRT1 activity was inhibited either with lentiviruses expressing short hairpin RNAs or with the small molecule inhibitor, cambinol. Knockdown or inhibition of SIRT1 activity had a cytostatic effect, characterized by an altered morphology, impaired proliferation, an increased expression of differentiation markers, and cellular senescence. In an orthotopic xenograft model, knockdown of SIRT1 resulted in 50% fewer animals developing tumors and cambinol treatment resulted in an overall lower tumor burden. Taken together, our data show that inhibition of SIRT1 in HCC cells impairs their proliferation in vitro and tumor formation in vivo. These data suggest that SIRT1 expression positively influences the growth of HCC and support further studies aimed to block its activity alone or in combination as a novel treatment strategy.

Replications of fundamental research models in ultra high dilutions 1994 and 2015 - update on a bibliometric study

INTRODUCTION This paper focuses exclusively on experimental models with ultra high dilutions (i.e. beyond 10(-23)) that have been submitted to replication scrutiny. It updates previous surveys, considers suggestions made by the research community and compares the state of replication in 1994 with that in 2015. METHODS Following literature research, biochemical, immunological, botanical, cell biological and zoological studies on ultra high dilutions (potencies) were included. Reports were grouped into initial studies, laboratory-internal, multicentre and external replications. Repetition could yield either comparable, or zero, or opposite results. The null-hypothesis was that test and control groups would not be distinguishable (zero effect). RESULTS A total of 126 studies were found. From these, 28 were initial studies. When all 98 replicative studies were considered, 70.4% (i.e. 69) reported a result comparable to that of the initial study, 20.4% (20) zero effect and 9.2% (9) an opposite result. Both for the studies until 1994 and the studies 1995-2015 the null-hypothesis (dominance of zero results) should be rejected. Furthermore, the odds of finding a comparable result are generally higher than of finding an opposite result. Although this is true for all three types of replication studies, the fraction of comparable studies diminishes from laboratory-internal (total 82.9%) to multicentre (total 75%) to external (total 48.3%), while the fraction of opposite results was 4.9%, 10.7% and 13.8%. Furthermore, it became obvious that the probability of an external replication producing comparable results is bigger for models that had already been further scrutinized by the initial researchers. CONCLUSIONS We found 28 experimental models which underwent replication. In total, 24 models were replicated with comparable results, 12 models with zero effect, and 6 models with opposite results. Five models were externally reproduced with comparable results. We encourage further replications of studies in order to learn more about the model systems used.

Distributed models in P-Systems architectures to reduce computation time

Membrane systems are computational equivalent to Turing machines. However, their distributed and massively parallel nature obtains polynomial solutions opposite to traditional non-polynomial ones. At this point, it is very important to develop dedicated hardware and software implementations exploiting those two membrane systems features. Dealing with distributed implementations of P systems, the bottleneck communication problem has arisen. When the number of membranes grows up, the network gets congested. The purpose of distributed architectures is to reach a compromise between the massively parallel character of the system and the needed evolution step time to transit from one configuration of the system to the next one, solving the bottleneck communication problem. The goal of this paper is twofold. Firstly, to survey in a systematic and uniform way the main results regarding the way membranes can be placed on processors in order to get a software/hardware simulation of P-Systems in a distributed environment. Secondly, we improve some results about the membrane dissolution problem, prove that it is connected, and discuss the possibility of simulating this property in the distributed model. All this yields an improvement in the system parallelism implementation since it gets an increment of the parallelism of the external communication among processors. Proposed ideas improve previous architectures to tackle the communication bottleneck problem, such as reduction of the total time of an evolution step, increase of the number of membranes that could run on a processor and reduction of the number of processors.

Comparison of methods for downscaling runoff from regional climate models in Spanish basins

At present there is much literature that refers to the advantages and disadvantages of different methods of statistical and dynamical downscaling of climate variables projected by climate models. Less attention has been paid to other indirect variables, like runoff, which play a significant role in evaluating the impact of climate change on hydrological systems. Runoff presents a much greater bias in climate models than other climate variables, like temperature or precipitation. It is very important to identify the methods that minimize bias while downscaling runoff from the gridded results of climate models to the basin scale

The Analysis of Airline Business Models in the Development of Possible Future Business Options

Innovations in the current interconnected world of organizations have lead to a focus on business models as a fundamental statement of direction and identity. Although industry transformations generally emanate from technological changes, recent examples suggest they may also be due to the introduction of new business models. In the past, different types of airline business models could be clearly separated from each other. However, this has changed in recent years partly due to the concentration process and partly to reaction caused by competitive pressure. At least it can be concluded that in future the distinction of different business models will remain less clear. To advance the use of business models as a concept, it is essential to be able to compare and perform analyses to identify the business models that may have the highest potential. This can essentially contribute to understanding the synergies and incompatibilities in the case of two airlines that are going in for a merger. This is illustrated by the example of Swiss Air-Lufthansa merger analysis. The idea is to develop quantitative methods and tools for comparing and analyzing Aeronautical/Airline business models. The paper identifies available methods of comparing airline business models and lays the ground work for a quantitative model of comparing airline business models. This can be a useful tool for business model analysis when two airlines are merged

A review on probabilistic graphical models in evolutionary computation

Thanks to their inherent properties, probabilistic graphical models are one of the prime candidates for machine learning and decision making tasks especially in uncertain domains. Their capabilities, like representation, inference and learning, if used effectively, can greatly help to build intelligent systems that are able to act accordingly in different problem domains. Evolutionary algorithms is one such discipline that has employed probabilistic graphical models to improve the search for optimal solutions in complex problems. This paper shows how probabilistic graphical models have been used in evolutionary algorithms to improve their performance in solving complex problems. Specifically, we give a survey of probabilistic model building-based evolutionary algorithms, called estimation of distribution algorithms, and compare different methods for probabilistic modeling in these algorithms.

Comparasion of road traffic emission models in Madrid (Spain)

Many cities in Europe have difficulties to meet the air quality standards set by the European legislation, most particularly the annual mean Limit Value for NO2. Road transport is often the main source of air pollution in urban areas and therefore, there is an increasing need to estimate current and future traffic emissions as accurately as possible. As a consequence, a number of specific emission models and emission factors databases have been developed recently. They present important methodological differences and may result in largely diverging emission figures and thus may lead to alternative policy recommendations. This study compares two approaches to estimate road traffic emissions in Madrid (Spain): the COmputer Programme to calculate Emissions from Road Transport (COPERT4 v.8.1) and the Handbook Emission Factors for Road Transport (HBEFA v.3.1), representative of the ‘average-speed’ and ‘traffic situation’ model types respectively. The input information (e.g. fleet composition, vehicle kilometres travelled, traffic intensity, road type, etc.) was provided by the traffic model developed by the Madrid City Council along with observations from field campaigns. Hourly emissions were computed for nearly 15 000 road segments distributed in 9 management areas covering the Madrid city and surroundings. Total annual NOX emissions predicted by HBEFA were a 21% higher than those of COPERT. The discrepancies for NO2 were lower (13%) since resulting average NO2/NOX ratios are lower for HBEFA. The larger differences are related to diesel vehicle emissions under “stop & go” traffic conditions, very common in distributor/secondary roads of the Madrid metropolitan area. In order to understand the representativeness of these results, the resulting emissions were integrated in an urban scale inventory used to drive mesoscale air quality simulations with the Community Multiscale Air Quality (CMAQ) modelling system (1 km2 resolution). Modelled NO2 concentrations were compared with observations through a series of statistics. Although there are no remarkable differences between both model runs, the results suggest that HBEFA may overestimate traffic emissions. However, the results are strongly influenced by methodological issues and limitations of the traffic model. This study was useful to provide a first alternative estimate to the official emission inventory in Madrid and to identify the main features of the traffic model that should be improved to support the application of an emission system based on “real world” emission factors.