Developing a Macroscopic Mechanistic Model for Low Molecular Weight Diffusion through Polymers in the Rubbery State

Raman microspectroscopy was used to determine the Fickian diffusivity of two families of low molecular weight molecules through amorphous polystyrene in the rubbery state. Different effects of the temperature on diffusivity for each of the families suggested that molecular mobility is controlled by both the volume and flexibility of the diffusing substance when the movement of polymer chains can generate stress induced deformation of molecules. The diffusing molecules were represented as Newtonian spring-bead systems, which allowed us to quantify their flexibility, in function of the vibration frequency of their bonds by reconstructing their theoretical spectra. Results showed that the use of molecular descriptors that take into account flexibility rather than the most stable conformation of the diffusing molecules may improve the description of the diffusion behavior caused by variations in shape and size of the free volumes of the polymeric matrix in the rubbery state

M2I-1 disrupts the in vivo interaction between CDC20 and MAD2 and increases the sensitivities of cancer cell lines to anti-mitotic drugs via MCL-1s

Background Drugs such as taxanes, epothilones, and vinca alkaloids are widely used in the treatment of breast, ovarian, and lung cancers but come with major side effects such as neuropathy and loss of neutrophils and as single agents have a lack of efficacy. M2I-1 (MAD2 inhibitor-1) has been shown to disrupt the CDC20-MAD2 interaction, and consequently, the assembly of the mitotic checkpoint complex (MCC). Results We report here that M2I-1 can significantly increase the sensitivity of several cancer cell lines to anti-mitotic drugs, with cell death occurring after a prolonged mitotic arrest. In the presence of nocodazole or taxol combined with M2I-1 cell death is triggered by the premature degradation of Cyclin B1, the perturbation of the microtubule network, and an increase in the level of the pro-apoptotic protein MCL-1s combined with a marginal increase in the level of NOXA. The elevated level of MCL-1s and the marginally increased NOXA antagonized the increased level of MCL-1, a pro-survival protein of the Bcl-2 family. Conclusion Our results provide some important molecular mechanisms for understanding the relationship between the mitotic checkpoint and programmed cell death and demonstrate that M2I-1 exhibits antitumor activity in the presence of current anti-mitotic drugs such as taxol and nocodazole and has the potential to be developed as an anticancer agent

Estimating the mass of galactic components using machine learning algorithms

The estimation of the bulge and disk massses, the main baryonic components of a galaxy, can be performed using various approaches, but their implementation tend to be challenging as they often rely on strong assumptions about either the baryon dynamics or the dark matter model. In this work, we present an alternative method for predicting the masses of galactic components, including the disk, bulge, stellar and total mass, using a set of machine learning algorithms: KNN-neighbours (KNN), Linear Regression (LR), Random Forest (RF) and Neural Network (NN). The rest-frame absolute magnitudes in the ugriz-photometric system were selected as input features, and the training was performed using a sample of spiral galaxies hosting a bulge from Guo's mock catalogue \citep{Guo-Catalog} derived from the Millennium simulation. In general, all the algorithms provide good predictions for the galaxy's mass components ranging from $10^9\,M_\odot$ to $10^{11}\,M_\odot$, corresponding to the central region of the training mass domain; however, the NN give rise to the most precise predictions in comparison to other methods. Additionally, to test the performance of the NN architecture, we used a sample of observed galaxies from the SDSS survey whose mass components are known. We found that the NN can predict the luminous masses of disk-dominant galaxies within the same range of magnitudes that for the synthetic sample up to a $99\%$ level of confidence, while mass components of galaxies hosting larger bulges are well predicted up to $95\%$ level of confidence. The NN algorithm can also bring up scaling relations between masses of different components and magnitudes.Comment: 13 pages, 5 figures and 1 table. Comments are welcom

Differential hypertrophic effects of cardiotrophin-1 on adult cardiomyocytes from normotensive and spontaneously hypertensive rats

Cardiotrophin-1 (CT-1) produces longitudinal elongation of neonatal cardiomyocytes, but its effects in adult cardiomyocytes are not known. Recent observations indicate that CT-1 may be involved in pressure overload left ventricular hypertrophy (LVH). We investigated whether the hypertrophic effects of CT-1 are different in cardiomyocytes isolated from adult normotensive and spontaneously hypertensive rats (SHR). Hypertrophy was evaluated by planimetry and confocal microscopy, contractile proteins were quantified by Western blotting and real-time RT-PCR, and intracellular pathways were analyzed with specific chemical inhibitors. CT-1 increased c-fos and ANP expression (p<0.01) and cell area (p<0.01) in cardiomyocytes from both rat strains. In Wistar cells, CT-1 augmented cell length (p<0.01) but did not modify either the transverse diameter or cell depth. In SHR cells, CT-1 increased cell length (p<0.05), cell width (p<0.01) and cell depth, augmented the expression of myosin light chain-2v (MLC-2v) and skeletal alpha-actin (p<0.01) and enhanced MLC-2v phosphorylation (p<0.01). The blockade of gp130 or LIFR abolished CT-1-induced growth in the two cell types. All distinct effects observed in cardiomyocytes from SHR were mediated by STAT3. Baseline angiotensinogen expression was higher in SHR cells, and CT-1 induced a 1.7-fold and 3.2-fold increase of angiotensinogen mRNA in cardiomyocytes from Wistar rats and SHR respectively. In addition, AT1 blockade inhibited the specific effects of CT-1 in SHR cells. Finally, ex vivo determinations revealed that adult SHR exhibited enhanced myocardial CT-1 (mRNA and protein, p<0.01), increased cell width (p<0.01) and concentric LVH compared with pre-hypertensive SHR. These findings reveal a specific cell-broadening effect of CT-1 in cardiomyocytes from adult SHR and suggest that the hypertensive phenotype of these cells may influence the hypertrophic effects of CT-1, probably by means of an exaggerated induction of angiotensinogen expression. We suggest that CT-1 might facilitate LVH in genetic hypertension through a cross-talk with the renin-angiotensin system

Evolution of public hospitals expenditure by healthcare area in the Spanish National Health System: the determinants to pay attention to

Background: In Spain, hospital expenditure represents the biggest share of overall public healthcare expenditure, the most important welfare system directly run by the Autonomous Communities (ACs). Since 2001, public healthcare expenditure has increased well above the GDP growth, and public hospital expenditure increased at an even faster rate. This paper aims at assessing the evolution of need-adjusted public hospital expenditure at healthcare area level (HCA) and its association with utilisation and ''price'' factors, identifying the relative contribution of ACs, as the main locus of health policy decisions. Methods: Ecological study on public hospital expenditure incurred in 198 (HCAs) in 16 Spanish ACs, between 2003 and 2015. Aggregated and annual log-log multilevel models, considering ACs as a cluster, were modelled using administrative data. HCA expenditure was analysed according to differences in population need, utilization and price factors. Standardised coefficients were also estimated, as well as the variance partition coefficients. Results: Between 2003 and 2015, over 59 million hospital episodes were produced in Spain for an overall expenditure of (sic) 384, 200 million. Need-adjusted public hospital expenditure, at HCA level, was mainly associated to medical and surgical hospitalizations (standardized coefficients 0.32 and 0.28, respectively). The ACs explained 42% of the variance not explained by HCA utilization and ''price'' factors. Conclusions: Utilization, rather than ''price'' factors, may be explaining the difference in need-adjusted public hospital expenditure at HCA level in Spain. ACs, third-payers in the fully devolved Spanish National Health System, are responsible for a great deal of the variation in hospital expenditure

Exploración posturográfica de pacientes simuladores

Introduction: An aphysiological pattern in computerized dynamic posturography (CDP) may be produced by numerous causes. We analyze the results obtained in this test by a group of malingering patients. Patients and method: This study analyzes a particular group of 7 malingerers, ie patients simulating a false and unreal equilibrium disorder, without any a priori awareness of the gain expected from a pathological report. The condition can only be identified with the very complex postural disorder known as “continuous imbalance.” We analyze the results of the dynamic posturography test following the diagnostic criteria described by other authors. Results: Of the criteria analyzed, we found Cevette’s to be the most frequently positive for our study group. Conclusions: The wide diversity in the criteria used makes it necessary to apply them together, assuming a high level of suspicion and great care in the diagnostic process

Microelectronic cmos implementation of a machine learning technique for sensor calibration

An integrated machine-learning based adaptive circuit for sensor calibration implemented in standard 0.18μm CMOS technology with 1.8V power supply is presented in this paper. In addition to linearizing the device response, the proposed system is also capable to correct offset and gain errors. The building blocks conforming the adaptive system are designed and experimentally characterized to generate numerical high-level models which are used to verify the proper performance of each analog block within a defined multilayer perceptron architecture. The network weights, obtained from the learning phase, are stored in a microcontroller EEPROM memory, and then loaded into each of the registers of the proposed integrated prototype. In order to verify the proposed system performance, the non-linear characteristic of a thermistor is compensated as an application example, achieving a relative error er below 3% within an input span of 130°C, which is almost 6 times less than the uncorrected response. The power consumption of the whole system is 1.4mW and it has an active area of 0.86mm 2 . The digital programmability of the network weights provides flexibility when a sensor change is required

Levels and patterns of objectively assessed physical activity and compliance with different public health guidelines in university students

ArticleBackground Physical activity (PA) is associated with health enhancement. The aim of this study was to assess: 1) levels and patterns of PA in university students by using accelerometers; and 2) the percentage of fulfilment of PA recommendations for adults, according to different public health guidelines. Methods Observational cross-sectional study (Cuenca’s Adults Study) involving 296 (206 women) healthy Spanish university students aged 18–25 years old. Participants wore the ActiGraph GT1M accelerometer for seven consecutive days. Total PA, steps and time spent in sedentary time, light, moderate, vigorous, and moderate to vigorous PA (MVPA) was assessed, and the prevalence of sufficient PA was calculated according to various public health guidelines. Results No sex differences in total PA were found. University students were more sedentary during weekend days than weekdays (p<0.05). Only 30.3% of participants accumulated 30 min/day at least five days a week of MVPA. A total of 5.4% of students met the recommendation of 150 min/week of MVPA or 75 min/week of vigorous PA, in PA bouts of at least 10 min. using the same definition, but on five or more days a week, only 0.5% students were found to meet the recommendation. In addition, only 0.5% of students met the recommendation of 30 min/day of MVPA, at least five days a week and in bouts of at least 10 min. Finally, 28.1% of the students met the recommendation of 10,000 steps/day. Conclusions Our study shows a high incidence of sedentary time in university students. The number of students meeting PA recommendations significantly differed depending on the recommendation proposed. Specific strategies to promote PA in this population are necessary as well as an agreement as to which PA guidelines should be used.Fundación para la Investigación SanitariaMinistry of Health and Consumer AffairsInstituto de Salud Carlos IIIRed de Investigación en Actividades Preventivas y de Promoción de Salu

High-Linearity Self-Biased CMOS Current Buffer

A highly linear fully self-biased class AB current buffer designed in a standard 0.18 mu m CMOS process with 1.8 V power supply is presented in this paper. It is a simple structure that, with a static power consumption of 48 mu W, features an input resistance as low as 89 Omega, high accuracy in the input-output current ratio and total harmonic distortion (THD) figures lower than -60 dB at 30 mu A amplitude signal and 1 kHz frequency. Robustness was proved through Monte Carlo and corner simulations, and finally validated through experimental measurements, showing that the proposed configuration is a suitable choice for high performance low voltage low power applications

Loss of myocardial LIF receptor in experimental heart failure reduces cardiotrophin-1 cytoprotection. A role for neurohumoral agonists?

OBJECTIVES: Cardiomyocyte loss is involved in the transition from compensatory left ventricular hypertrophy (LVH) to heart failure (HF). Our aim was to investigate the status of the leukaemia inhibitory factor receptor (LIFR)/gp130 survival pathway and its cytoprotective activity in intact cardiac tissue and in cardiomyocytes obtained from adult spontaneously hypertensive rats (SHR) with LVH (non-failing SHR) and from aged SHR with overt HF (failing SHR). METHODS: Cardiac morphometry was assayed by planimetry in an image analysis system. mRNA and protein expression were quantified by real time RT-PCR and Western blotting. Receptors were localized by immunocytochemistry. Trypan blue staining, TUNEL, and MTT cell viability assays were employed to study the cytoprotective activity of cardiotrophin-1 (CT-1) in isolated caridomyocytes. RESULTS: Compared to non-failing SHR, failing SHR exhibited enhanced myocardial cell death (p<0.01) demonstrated by the increase in Bax/Bcl-2 ratio, caspase-3 activation and poly (ADP-ribose) polymerase (PARP) fragmentation. Failing SHR had a 7-fold diminished expression (p<0.01) of LIFR, no changes in gp130, and 1.6-fold increased myocardial expression (p<0.01) of CT-1. In cardiomyocytes isolated from non-failing SHR, recombinant CT-1 inhibited apoptotic and non-apoptotic cell death induced by angiotensin II or hydrogen peroxide. LIFR protein was entirely absent in cardiomyocytes isolated from failing SHR, which were resistant to the cytoprotective effects of CT-1. Finally, stimulation of non-failing SHR cardiomyocytes with angiotensin II, aldosterone, norepinephrine or endothelin-1 significantly decreased (p<0.01) LIFR expression. CONCLUSIONS: These data suggest that loss of CT-1-dependent survival mechanisms may contribute to the increase of cell death associated with HF in SHR. Neurohumoral activation may contribute to this alteration via suppression of LIFR