A dynamical model for the basal ganglia-thalamo-cortical oscillatory activity and its implications in Parkinson’s disease

© 2020 The Authors. Published by Springer. This is an open access article available under a Creative Commons licence. The published version can be accessed at the following link on the publisher’s website: https://doi.org/10.1007/s11571-020-09653-y© 2020, The Author(s). We propose to investigate brain electrophysiological alterations associated with Parkinson’s disease through a novel adaptive dynamical model of the network of the basal ganglia, the cortex and the thalamus. The model uniquely unifies the influence of dopamine in the regulation of the activity of all basal ganglia nuclei, the self-organised neuronal interdependent activity of basal ganglia-thalamo-cortical circuits and the generation of subcortical background oscillations. Variations in the amount of dopamine produced in the neurons of the substantia nigra pars compacta are key both in the onset of Parkinson’s disease and in the basal ganglia action selection. We model these dopamine-induced relationships, and Parkinsonian states are interpreted as spontaneous emergent behaviours associated with different rhythms of oscillatory activity patterns of the basal ganglia-thalamo-cortical network. These results are significant because: (1) the neural populations are built upon single-neuron models that have been robustly designed to have eletrophysiologically-realistic responses, and (2) our model distinctively links changes in the oscillatory activity in subcortical structures, dopamine levels in the basal ganglia and pathological synchronisation neuronal patterns compatible with Parkinsonian states, this still remains an open problem and is crucial to better understand the progression of the disease.Published versio

Effect of nitrogen and potassium fertilizers on melon plant productivity

The objective of this investigation was to evaluate the effect of different doses of nitrogen and potassium fertilizers on some production parameters of melon plants. The experiment was carried out in San Roque, which is 24 km from the city of Concepción, Paraguay, at the coordinates 57°14´10.29´´ South and 23°19´12.05´´ West. The study design was the completely randomized block with three replications in a split plot scheme 4 x 4. The dose used in the main plot was of N (0, 50, 100 and 150 kg ha-1) and in the sub-plot, K (0, 95, 190 and 285 kg ha-1). A light harrow was carried out to prepare the soil, seedlings were produced in 1500 cm3 pots of 60-micron thickness and the transplant was carried out when the seedlings had between 4 and 6 true leaves at 30 days after planting. Urea with 45% N was used as the source of nitrogen and potassium chloride 60% was used as the source of potassium. Fertilisation was carried out in September 2017 on two occasions: at 15 and 30 days after transplanting. The spacing used was of 1.5 m between rows and 1.5 m between plants, giving a total of 4356 plants ha-1. Harvesting began 90 days after planting and was carried out three times as the fruits reached commercial ripeness. The variables that were measured were average fruit weight (AFW), total soluble solids (TSS), polar diameter (PD), equatorial diameter (ED), fruit weight per plant (FWP). The data of the evaluated variables were subjected to the analysis of variance using the Fisher test where significant differences were found in: AFW, TSS, PD, ED and FWP. Subsequently, the regression analysis was performed (AFW, TSS and PD) and response surface (ED and FWP). The dose combination that produced the best values for equatorial diameter and fruit weight per plant was 71.9495 kg ha-1 of N and 160.554 kg ha-1 of K, 77.5921 kg ha-1 of N and 147.369 kg ha-1 of K, respectively.&nbsp

Approximated stability analysis of bi-modal hybrid co-simulation scenarios

This is an accepted manuscript of an article published by Springer in: Cerone A., Roveri M. (eds) Software Engineering and Formal Methods. SEFM 2017. Lecture Notes in Computer Science, vol 10729, available online at: https://doi.org/10.1007/978-3-319-74781-1_24 The accepted version of the publication may differ from the final published version. For information on re-use, please refer to the publisher’s terms and conditions.Co-simulation is a technique to orchestrate multiple simulators in order to approximate the behavior of a coupled system as a whole. Simulators execute in a lockstep fashion, each exchanging inputs and output data points with the other simulators at pre-accorded times. In the context of systems with a physical and a cyber part, the communication frequency with which the simulators of each part communicate can have a negative impact in the accuracy of the global simulation results. In fact, the computed behavior can be qualitatively different, compared to the actual behavior of the original system, laying waste to potentially many hours of computation. It is therefore important to develop methods that answer whether a given communication frequency guarantees trustworthy co-simulation results. In this paper, we take a small step in that direction. We develop a technique to approximate the lowest frequency for which a particular set of simulation tools can exchange values in a co-simulation and obtain results that can be trusted.Published versio

Exploring pig trade patterns to inform the design of risk-based disease surveillance and control strategies

An understanding of the patterns of animal contact networks provides essential information for the design of risk-based animal disease surveillance and control strategies. This study characterises pig movements throughout England and Wales between 2009 and 2013 with a view to characterising spatial and temporal patterns, network topology and trade communities. Data were extracted from the Animal and Plant Health Agency (APHA)’s RADAR (Rapid Analysis and Detection of Animal-related Risks) database, and analysed using descriptive and network approaches. A total of 61,937,855 pigs were moved through 872,493 movements of batches in England and Wales during the 5-year study period. Results show that the network exhibited scale-free and small-world topologies, indicating the potential for diseases to quickly spread within the pig industry. The findings also provide suggestions for how risk-based surveillance strategies could be optimised in the country by taking account of highly connected holdings, geographical regions and time periods with the greatest number of movements and pigs moved, as these are likely to be at higher risk for disease introduction. This study is also the first attempt to identify trade communities in the country, information which could be used to facilitate the pig trade and maintain disease-free status across the country in the event of an outbreak

How Gaussian competition leads to lumpy or uniform species distributions

A central model in theoretical ecology considers the competition of a range of species for a broad spectrum of resources. Recent studies have shown that essentially two different outcomes are possible. Either the species surviving competition are more or less uniformly distributed over the resource spectrum, or their distribution is 'lumped' (or 'clumped'), consisting of clusters of species with similar resource use that are separated by gaps in resource space. Which of these outcomes will occur crucially depends on the competition kernel, which reflects the shape of the resource utilization pattern of the competing species. Most models considered in the literature assume a Gaussian competition kernel. This is unfortunate, since predictions based on such a Gaussian assumption are not robust. In fact, Gaussian kernels are a border case scenario, and slight deviations from this function can lead to either uniform or lumped species distributions. Here we illustrate the non-robustness of the Gaussian assumption by simulating different implementations of the standard competition model with constant carrying capacity. In this scenario, lumped species distributions can come about by secondary ecological or evolutionary mechanisms or by details of the numerical implementation of the model. We analyze the origin of this sensitivity and discuss it in the context of recent applications of the model.Comment: 11 pages, 3 figures, revised versio

Dynamics of DNA replication loops reveal temporal control of lagging-strand synthesis

In all organisms, the protein machinery responsible for the replication of DNA, the replisome, is faced with a directionality problem. The antiparallel nature of duplex DNA permits the leading-strand polymerase to advance in a continuous fashion, but forces the lagging-strand polymerase to synthesize in the opposite direction. By extending RNA primers, the lagging-strand polymerase restarts at short intervals and produces Okazaki fragments. At least in prokaryotic systems, this directionality problem is solved by the formation of a loop in the lagging strand of the replication fork to reorient the lagging-strand DNA polymerase so that it advances in parallel with the leading-strand polymerase. The replication loop grows and shrinks during each cycle of Okazaki fragment synthesis. Here we use single-molecule techniques to visualize, in real time, the formation and release of replication loops by individual replisomes of bacteriophage T7 supporting coordinated DNA replication. Analysis of the distributions of loop sizes and lag times between loops reveals that initiation of primer synthesis and the completion of an Okazaki fragment each serve as a trigger for loop release. The presence of two triggers may represent a fail-safe mechanism ensuring the timely reset of the replisome after the synthesis of every Okazaki fragment.

Doxorubicin plus lurbinectedin in patients with advanced endometrial cancer: Results from an expanded phase i study

Objective: Second-line treatment of endometrial cancer is an unmet medical need. We conducted a phase I study evaluating lurbinectedin and doxorubicin intravenously every 3 weeks in patients with solid tumors. The aim of this study was to characterise the efficacy and safety of lurbinectedin and doxorubicin for patients with endometrial cancer. Methods: Thirty-four patients were treated: 15 patients in the escalation phase (doxorubicin 50 mg/m2 and lurbinectedin 3.0-5.0 mg) and 19 patients in the expansion cohort (doxorubicin 40 mg/m2 and lurbinectedin 2.0 mg/m2). All histological subtypes were eligible and patients had received one to two prior lines of chemotherapy for advanced disease. Antitumor activity was evaluated every two cycles according to the Response Evaluation Criteria in Solid Tumors version 1.1. Adverse events were graded according to the National Cancer Institute-Common Terminology Criteria for Adverse Events version 4. Results: Median age (range) was 65 (51-78) years. Eastern Cooperative Oncology Group performance status was up to 1 in 97% of patients. In the escalation phase, 4 (26.7%) of 15 patients had confirmed response: two complete and two partial responses (95% CI 7.8% to 55.1%). Median duration of response was 19.5 months. Median progression-free survival was 7.3 (2.5 to 10.1) months. In the expansion cohort, confirmed partial response was reported in 8 (42.1%) of 19 patients (95% CI 20.3% to 66.5%). Median duration of response was 7.5 (6.4 to not reached) months, median progression-free survival was 7.7 (2.0 to 16.7) months and median overall survival was 14.2 (4.5 to not reached) months. Fatigue (26.3% of patients), and transient and reversible myelosuppression (neutropenia, 78.9%; febrile neutropenia, 21.1%; thrombocytopenia, 15.8%) were the main grade 3 and higher toxicities in the expanded cohort. Conclusions: In patients with recurrent advanced endometrial cancer treated with doxorubicin and lurbinectedin, response rates (42%) and duration of response (7.5 months) were favorable. Further evaluation of doxorubicin and lurbinectedin is warranted in this patient population

Construction and validation of a low-cost system for indoor air quality measurements in livestock facilities

In recent years, there has been an increase in demand for food of ani-mal origin. The number of intensive production systems such as pig and poultry farming has been increasing more and more and exerting great impacts on the environment, due to a large amount of particulate material and gaseous pollutants that are generated within these facilities. Thus, low-cost devices emerge as a cheap alternative that provides farmers with information on indoor air quality in its facilities. However, it is important that these devices make precise and accu-rate measurements, providing reliable concentration readings. Therefore, the ob-jective of this study is the construction and validation of a low-cost system capa-ble of measuring, storing and sending, via the mobile network, the concentrations of hydrogen sulfide, ammonia, carbon dioxide, PM2.5, PM10, temperature, and relative humidity. Preliminary inter-comparison tests showed that the built sys-tem had a reliable behavior in relation to all variables, even though the CO2 sen-sor was the one with the highest determination coefficient. The built device is able to provide continuous monitoring of atmospheric pollutants concentrations, at low cost and with simple handling.This study was supported by the Fundação para a Ciência e Tecnologia (FCT, Portugal) and FEDER under the PT2020 Program through financial support to CIMO (UID/AGR/00690/2013) and by the bilateral project established between the Polytechnic Institute of Bragança (Portugal) and the Federal University of Technology – Paraná (Brazil).info:eu-repo/semantics/publishedVersio

Urban Heat Island and Vulnerable Population. The Case of Madrid

The Urban Heat Island effect shows the differences among temperatures in urban areas and the surrounding rural ones. Previous studies have demonstrated that temperature differences could be up to 8 °C during the hottest periods of summer in Madrid , and that it varies according to the urban structure. Associated to this effect, the impact of temperature increase over dwelling indoor thermal comfort seems to double cooling energy demand . In Madrid, fuel poor households already suffering from inadequate indoor temperatures can face important overheating problems and, as a consequence, relevant health problems could become more frequent and stronger. This poses an increment in mortality rates in risk groups that should be evaluated. This research is aimed at establishing the geospatial connection between the urban heat island and the most vulnerable population living in the city of Madrid. Hence, those areas most in need for an urban intervention can be detected and prioritized

The effect of seasoning with herbs on the nutritional, safety and sensory properties of reduced-sodium fermented Cobrançosa cv. table olives

This study aimed at evaluating the effectiveness of seasoning Cobrancosa table olives in a brine with aromatic ingredients, in order to mask the bitter taste given by KCl when added to reduced-sodium fermentation brines. Olives were fermented in two different salt combinations: Brine A, containing 8% NaCl and, Brine B, a reduced-sodium brine, containing 4% NaCl + 4% KCl. After the fermentation the olives were immersed in seasoning brines with NaCl (2%) and the aromatic herbs (thyme, oregano and calamintha), garlic and lemon. At the end of the fermentation and two weeks after seasoning, the physicochemical, nutritional, organoleptic, and microbiological parameters, were determined. The olives fermented in the reduced-sodium brines had half the sodium concentration, higher potassium and calcium content, a lower caloric level, but were considered, by a sensorial panel, more bitter than olives fermented in NaCl brine. Seasoned table olives, previously fermented in Brine A and Brine B, had no significant differences in the amounts of protein (1.23% or 1.11%), carbohydrates (1.0% or 0.66%), fat (20.0% or 20.5%) and dietary fiber (3.4% or 3.6%). Regarding mineral contents, the sodium-reduced fermented olives, presented one third of sodium, seven times more potassium and three times more calcium than the traditional olives fermented in 8% NaCl. Additionally, according to the panelists' evaluation, seasoning the olives fermented in 4% NaCl + 4% KCl, resulted in a decrease in bitterness and an improvement in the overall evaluation and flavor. Escherichia coli and Salmonella were not found in the olives produced.info:eu-repo/semantics/publishedVersio