A Mobility Determination Method for Parallel Platforms Based on the Lie Algebra of SE(3) and Its Subspaces

This contribution presents a screw theory-based method for determining the mobility of fully parallel platforms. The method is based on the application of three stages. The first stage involves the application of the intersection of subalgebras of Lie algebra, se(3), of the special Euclidean group, SE(3), associated with the legs of the platform. The second stage analyzes the possibility of the legs of the platform generating a sum or direct sum of two subalgebras of the Lie algebra, se(3). The last stage, if necessary, considers the possibility of the kinematic pairs of the legs satisfying certain velocity conditions; these conditions reduce the platform’s mobility analysis to one that can be solved using one of the two previous stages. Several examples are illustrated

Pharmacological Interventions to Ameliorate Neuropathological Symptoms in a Mouse Model of Lafora Disease

14 páginas; 9 figuras.Lafora disease (LD, OMIM 254780) is a rare fatal neurodegenerative disorder that usually occurs during childhood with generalized tonic-clonic seizures, myoclonus, absences, drop attacks or visual seizures. Unfortunately, at present, available treatments are only palliatives and no curative drugs are available yet. The hallmark of the disease is the accumulation of insoluble polyglucosan inclusions, called Lafora bodies (LBs), within the neurons but also in heart, muscle and liver cells. Mouse models lacking functional EPM2A or EPM2B genes (the two major loci related to the disease) recapitulate the Lafora disease phenotype: they accumulate polyglucosan inclusions, show signs of neurodegeneration and have a dysregulation of protein clearance and endoplasmic reticulum stress response. In this study, we have subjected a mouse model of LD (Epm2b-/-) to different pharmacological interventions aimed to alleviate protein clearance and endoplasmic reticulum stress. We have used two chemical chaperones, trehalose and 4-phenylbutyric acid. In addition, we have used metformin, an activator of AMP-activated protein kinase (AMPK), as it has a recognized neuroprotective role in other neurodegenerative diseases. Here, we show that treatment with 4-phenylbutyric acid or metformin decreases the accumulation of Lafora bodies and polyubiquitin protein aggregates in the brain of treated animals. 4-Phenylbutyric acid and metformin also diminish neurodegeneration (measured in terms of neuronal loss and reactive gliosis) and ameliorate neuropsychological tests of Epm2b-/- mice. As these compounds have good safety records and are already approved for clinical uses on different neurological pathologies, we think that the translation of our results to the clinical practice could be straightforward.This work was supported by grants from the Spanish Ministry of Education and Science SAF2011-27442, Fundació La Marato de TV3 (ref. 100130) and an ACCI2012 action from CIBERER. A.B. holds a postdoctoral fellowship from the Program “Junta para la Ampliación de Estudios” (JAE-Doc) co-funded by the European Social Fund (ESF).Peer reviewe

Artificial intelligence-based software (AID-FOREST) for tree detection: A new framework for fast and accurate forest inventorying using LiDAR point clouds

Forest inventories are essential to accurately estimate different dendrometric and forest stand parameters. However, classical forest inventories are time consuming, slow to conduct, sometimes inaccurate and costly. To address this problem, an efficient alternative approach has been sought and designed that will make this type of field work cheaper, faster, more accurate, and easier to complete. The implementation of this concept has required the development of a specifically designed software called "Artificial Intelligence for Digital Forest (AID-FOREST)", which is able to process point clouds obtained via mobile terrestrial laser scanning (MTLS) and then, to provide an array of multiple useful and accurate dendrometric and forest stand parameters. Singular characteristics of this approach are: No data pre-processing is required either pre-treatment of forest stand; fully automatic process once launched; no limitations by the size of the point cloud file and fast computations.To validate AID-FOREST, results provided by this software were compared against the obtained from in-situ classical forest inventories. To guaranty the soundness and generality of the comparison, different tree spe-cies, plot sizes, and tree densities were measured and analysed. A total of 76 plots (10,887 trees) were selected to conduct both a classic forest inventory reference method and a MTLS (ZEB-HORIZON, Geoslam, ltd.) scanning to obtain point clouds for AID-FOREST processing, known as the MTLS-AIDFOREST method. Thus, we compared the data collected by both methods estimating the average number of trees and diameter at breast height (DBH) for each plot. Moreover, 71 additional individual trees were scanned with MTLS and processed by AID-FOREST and were then felled and divided into logs measuring 1 m in length. This allowed us to accurately measure the DBH, total height, and total volume of the stems.When we compared the results obtained with each methodology, the mean detectability was 97% and ranged from 81.3 to 100%, with a bias (underestimation by MTLS-AIDFOREST method) in the number of trees per plot of 2.8% and a relative root-mean-square error (RMSE) of 9.2%. Species, plot size, and tree density did not significantly affect detectability. However, this parameter was significantly affected by the ecosystem visual complexity index (EVCI). The average DBH per plot was underestimated (but was not significantly different from 0) by the MTLS-AIDFOREST, with the average bias for pooled data being 1.8% with a RMSE of 7.5%. Similarly, there was no statistically significant differences between the two distribution functions of the DBH at the 95.0% confidence level.Regarding the individual tree parameters, MTLS-AIDFOREST underestimated DBH by 0.16 % (RMSE = 5.2 %) and overestimated the stem volume (Vt) by 1.37 % (RMSE = 14.3 %, although the BIAS was not statistically significantly different from 0). However, the MTLS-AIDFOREST method overestimated the total height (Ht) of the trees by a mean 1.33 m (5.1 %; relative RMSE = 11.5 %), because of the different height concepts measured by both methodological approaches. Finally, AID-FOREST required 30 to 66 min per ha-1 to fully automatically process the point cloud data from the *.las file corresponding to a given hectare plot. Thus, applying our MTLS-AIDFOREST methodology to make full forest inventories, required a 57.3 % of the time required to perform classical plot forest inventories (excluding the data postprocessing time in the latter case). A free trial of AID -FOREST can be requested at [email protected]

18F-FDG metabolism in a rat model of chronic infarction: a 17-sector semiquantitative analysis

Strategies to establish the functional benefit of cell therapy in cardiac regeneration and the potential mechanism are needed. Aims: Development of a semi-quantitative method for non invasive assessment of cardiac viability and function in a rat model of myocardial infarction (MI) based on the use of microPET. Animals, methods: Ten rats were subjected to myocardial imaging 2, 7, 14, 30, 60 and 90 days after left coronary artery ligation. Intravenous 18F-fluoro-2-deoxy-2-D-glucose (18F-FDG) was administered and regional 18F activity concentrations per unit area were measured in 17 regions of interest (ROIs) drawn on cardiac polar maps. By comparing the differences in 18F uptake between baseline and each of the follow up time points, parametric polar maps of statistical significance (PPMSS) were calculated. Left ventricular ejection fraction (LVEF) was blindly assessed echocardiographically. All animals were sacrificed for histopathological analysis after 90 days. Results: The diagnostic quality of 18F-FDG microPET images was excellent. PPMSS demonstrated a statistically significant decrease in 18F concentrations as early as 48 hours after MI in 4 of the 17 ROIs (segments 7, 13, 16 and 17; p <0.05) that persisted throughout the study. Semi-quantitative analysis of 18F-FDG uptake correlated with echocardiographic decrease in LVEF (p <0.001). Conclusion: The use of PPMSS based on 18F-FDG-microPET provides valuable semi-quantitative information of heart glucose metabolism allowing for non-invasive follow up thus representing a useful strategy for assessment of novel therapies in cardiac regeneration

Heterogeneity of melanoma cell responses to sleep apnea-derived plasma exosomes and to intermittent hypoxia

Obstructive sleep apnea (OSA) is associated with increased cutaneous melanoma incidence and adverse outcomes. Exosomes are secreted by most cells, and play a role in OSA-associated tumor progression and metastasis. We aimed to study the effects of plasma exosomes from OSA patients before and after adherent treatment with continuous positive airway pressure (CPAP) on melanoma cells lines, and also to identify exosomal miRNAs from melanoma cells exposed to intermittent hypoxia (IH) or normoxia. Plasma-derived exosomes were isolated from moderate-to-severe OSA patients before (V1) and after (V2) adherent CPAP treatment for one year. Exosomes were co-incubated with three3 different melanoma cell lines (CRL 1424; CRL 1619; CRL 1675) that are characterized by genotypes involving different mutations in BRAF, STK11, CDKN2A, and PTEN genes to assess the effect of exosomes on cell proliferation and migration, as well as on pAMK activity in the presence or absence of a chemical activator. Subsequently, CRL-1424 and CRL-1675 cells were exposed to intermittent hypoxia (IH) and normoxia, and exosomal miRNAs were identified followed by GO and KEG pathways and gene networks. The exosomes from these IH-exposed melanoma cells were also administered to THP1 macrophages to examine changes in M1 and M2 polarity markers. Plasma exosomes from V1 increased CRL-1424 melanoma cell proliferation and migration compared to V2, but not the other two cell lines. Exposure to CRL-1424 exosomes reduced pAMPK/tAMPK in V1 compared to V2, and treatment with AMPK activator reversed the effects. Unique exosomal miRNAs profiles were identified for CRL-1424 and CRL-1675 in IH compared to normoxia, with six miRNAs being regulated and several KEGG pathways were identified. Two M1 markers (CXCL10 and IL6) were significantly increased in monocytes when treated with exosomes from IH-exposed CRL-1424 and CRL-1625 cells. Our findings suggest that exosomes from untreated OSA patients increase CRL-1424 melanoma malignant properties, an effect that is not observed in two other melanoma cell lines. Exosomal cargo from CRL-1424 cells showed a unique miRNA signature compared to CRL-1675 cells after IH exposures, suggesting that melanoma cells are differentially susceptible to IH, even if they retain similar effects on immune cell polarity. It is postulated that mutations in STK-11 gene encoding for the serine/threonine kinase family that acts as a tumor suppressor may underlie susceptibility to IH-induced metabolic dysfunction, as illustrated by CRL-1424 cells. © 2021 by the authors. Licensee MDPI, Basel, Switzerland

Importance of a deficiency in S-adenosyl-L-methionine synthesis in the pathogenesis of liver injury

One of the features of liver cirrhosis is an abnormal metabolism of methionine--a characteristic that was described more than a half a century ago. Thus, after an oral load of methionine, the rate of clearance of this amino acid from the blood is markedly impaired in cirrhotic patients compared with that in control subjects. Almost 15 y ago we observed that the failure to metabolize methionine in cirrhosis was due to an abnormally low activity of the enzyme methionine adenosyltransferase (EC 2.5.1.6). This enzyme converts methionine, in the presence of ATP, to S-adenosyl-L-methionine (SAMe), the main biological methyl donor. Since then, it has been suspected that a deficiency in hepatic SAMe may contribute to the pathogenesis of the liver in cirrhosis. The studies reviewed here are consistent with this hypothesis

Anisotropic Superparamagnetism of Monodispersive Cobalt-Platinum Nanocrystals

Based on the high-temperature organometallic route (Sun et al. Science 287, 1989 (2000)), we have synthesized powders containing CoPt_3 single crystals with mean diameters of 3.3(2) nm and 6.0(2) nm and small log-normal widths sigma=0.15(1). In the entire temperature range from 5 K to 400 K, the zero-field cooled susceptibility chi(T) displays significant deviations from ideal superparamagnetism. Approaching the Curie temperature of 450(10) K, the deviations arise from the (mean-field) type reduction of the ferromagnetic moments, while below the blocking temperature T_b, chi(T) is suppressed by the presence of energy barriers, the distributions of which scale with the particle volumes obtained from transmission electron microscopy (TEM). This indication for volume anisotropy is supported by scaling analyses of the shape of the magnetic absorption chi''(T,omega) which reveal distribution functions for the barriers being also consistent with the volume distributions observed by TEM. Above 200 K, the magnetization isotherms M(H,T) display Langevin behavior providing 2.5(1) mu_B per CoPt_3 in agreement with reports on bulk and thin film CoPt_3. The non-Langevin shape of the magnetization curves at lower temperatures is for the first time interpreted as anisotropic superparamagnetism by taking into account an anisotropy energy of the nanoparticles E_A(T). Using the magnitude and temperature variation of E_A(T), the mean energy barriers and 'unphysical' small switching times of the particles obtained from the analyses of chi''(T,omega) are explained. Below T_b hysteresis loops appear and are quantitatively described by a blocking model, which also ignores particle interactions, but takes the size distributions from TEM and the conventional field dependence of E_A into account.Comment: 12 pages with 10 figures and 1 table. Version accepted for publication in Phys. Rev. B . Two-column layou

S-Adenosylmethionine revisited: its essential role in the regulation of liver function

Dietary methionine is mainly metabolized in the liver where it is converted into S-adenosylmethionine (AdoMet), the main biologic methyl donor. This reaction is catalyzed by methionine adenosyltransferase I/III (MAT I/III), the product of MAT1A gene, which is exclusively expressed in this organ. It was first observed that serum methionine levels were elevated in experimental models of liver damage and in liver cirrhosis in human beings. Results of further studies showed that this pathological alteration was due to reduced MAT1A gene expression and MAT I/III enzyme inactivation associated with liver injury. Synthesis of AdoMet is essential to all cells in the organism, but it is in the liver where most of the methylation reactions take place. The central role played by AdoMet in cellular function, together with the observation that AdoMet administration reduces liver damage caused by different agents and improves survival of alcohol-dependent patients with cirrhosis, led us to propose that alterations in methionine metabolism could play a role in the onset of liver disease and not just be a consequence of it. In the present work, we review the recent findings that support this hypothesis and highlight the mechanisms behind the hepatoprotective role of AdoMet

Autologous intramyocardial injection of cultured skeletal muscle-derived stem cells in patients with non-acute myocardial infarction

AIM: Experimental animal studies suggest that the use of skeletal myoblast in patients with myocardial infarction may result in improved cardiac function. The aim of the study was to assess the feasibility and safety of this therapy in patients with myocardial infarction. METHODS AND RESULTS: Twelve patients with old myocardial infarction and ischaemic coronary artery disease underwent treatment with coronary artery bypass surgery and intramyocardial injection of autologous skeletal myoblasts obtained from a muscle biopsy of vastus lateralis and cultured with autologous serum for 3 weeks. Global and regional cardiac function was assessed by 2D and ABD echocardiogram. 18F-FDG and 13N-ammonia PET studies were used to determine perfusion and viability. Left ventricular ejection fraction (LVEF) improved from 35.5+/-2.3% before surgery to 53.5+/-4.98% at 3 months (P=0.002). Echocardiography revealed a marked improvement in regional contractility in those cardiac segments treated with skeletal myoblast (wall motion score index 2.64+/-0.13 at baseline vs 1.64+/-0.16 at 3 months P=0.0001). Quantitative 18F-FDG PET studies showed a significant (P=0.012) increased in cardiac viability in the infarct zone 3 months after surgery. No statistically significant differences were found in 13N-ammonia PET studies. Skeletal myoblast implant was not associated with an increase in adverse events. No cardiac arrhythmias were detected during early follow-up. CONCLUSIONS: In patients with old myocardial infarction, treatment with skeletal myoblast in conjunction with coronary artery bypass is safe and feasible and is associated with an increased global and regional left ventricular function,improvement in the viability of cardiac tissue in the infarct area and no induction of arrhythmias