After the oil crisis in the 70s energy regulation codes were implemented, but a great portion of existing dwellings have not been retrofitted to current requirements. To face this issue several ...actions were taken in the European Union (EU), among these, the implementation of Energy Performance Certificates (EPC), which include a Recommendation List of Measures (RLMs) to retrofit buildings. Some concerns exist about the lack of confidence on these recommendations. The main objective of this study is to analyze the usefulness of the EPC, answering if it is possible to deliver a realistic financial assessment about renovation strategies using these tools. The study is based on three indicators: Consumption, energy saving variations and profitability. The study is based on a renovation project case study, where simulations and Life Cycle Cost Assessment (LCCA) were performed, in order to identify the different results that EPC’s and an energy efficiency assessment could lead to. The results show important differences in all the concepts evaluated.
Non-coding RNAs play a pivotal role in a number of diseases promoting an aberrant sequestration of nuclear RNA-binding proteins. In the particular case of myotonic dystrophy type 1 (DM1), a ...multisystemic autosomal dominant disease, the formation of large non-coding CUG repeats set up long-tract hairpins able to bind muscleblind-like proteins (MBNL), which trigger the deregulation of several splicing events such as cardiac troponin T (cTNT) and insulin receptor's, among others. Evidence suggests that conformational changes in RNA are determinant for the recognition and binding of splicing proteins, molecular modeling simulations can attempt to shed light on the structural diversity of CUG repeats and to understand their pathogenic mechanisms. Molecular dynamics (MD) are widely used to obtain accurate results at atomistic level, despite being very time consuming, and they contrast with fast but simplified coarse-grained methods such as Elastic Network Model (ENM). In this paper, we assess the application of ENM (traditionally applied on proteins) for studying the conformational space of CUG repeats and compare it to conventional and accelerated MD conformational sampling. Overall, the results provided here reveal that ANM can provide useful insights into dynamic rCUG structures at a global level, and that their dynamics depend on both backbone and nucleobase fluctuations. On the other hand, ANM fail to describe local U-U dynamics of the rCUG system, which require more computationally expensive methods such as MD. Given that several limitations are inherent to both methods, we discuss here the usefulness of the current theoretical approaches for studying highly dynamic RNA systems such as CUG trinucleotide repeat overexpansions.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
One way to characterize the seismicity in a given zone is through the study of the conditional intensity function of the ETAS model (Epidemic Type Aftershock Sequence) which represents the average ...number of seismic events greater than given magnitude. Being Chile one of the most seismic country in the world, it is very important to predict where the seismic events will happen with more frequency. In this work we propose a parallel neural network based on the Convolutional Network (CNN) and the Long Short Term Memory (LSTM) network, called Multi-Culumn ConvLSTM, using the accumulated crustal velocity and the intensity data as input for predicting the daily mean number of seismic events in Chile with magnitude greater than a given value. For the application, the central zone of Chile between the regions of Coquimbo and Araucanía, in the period from 2010 to 2017 was considered. At the spatial level, each region was partitioned considering a 20×20 dimension grid, while at the temporal level, input data from the last 20 days were used to predict the mean number of seismic events for the following day. The experiments showed that the Multi-column ConvLSTM network obtained the best results in the test set with an average coefficient of determination of 0.81.
Abstract
Cytokines such as IL-6, TNF-α and IL-1β trigger inflammatory cascades which may play a role in the pathogenesis of chronic kidney disease (CKD)-associated cachexia. CKD was induced by 5/6 ...nephrectomy in mice. We studied energy homeostasis in
Il1β
−/−
/CKD,
Il6
−/−
/
CKD and
Tnf
α
−/−
/
CKD mice and compared with wild type (WT)/CKD controls. Parameters of cachexia phenotype were completely normalized in
Il1β
−/−
/CKD mice but were only partially rescued in
Il6
−/−
/
CKD and
Tnf
α
−/−
/
CKD mice. We tested the effects of anakinra, an IL-1 receptor antagonist, on CKD-associated cachexia. WT/CKD mice were treated with anakinra (2.5 mg/kg/day, IP) or saline for 6 weeks and compared with WT/Sham controls. Anakinra normalized food intake and weight gain, fat and lean mass content, metabolic rate and muscle function, and also attenuated molecular perturbations of energy homeostasis in adipose tissue and muscle in WT/CKD mice. Anakinra decreased serum and muscle expression of IL-6, TNF-α and IL-1β in WT/CKD mice. Anakinra attenuated browning of white adipose tissue in WT/CKD mice. Moreover, anakinra normalized gastrocnemius weight and fiber size as well as attenuated muscle fat infiltration in WT/CKD mice. This was accompanied by correcting the increased muscle wasting signaling pathways while promoting the decreased myogenesis process in gastrocnemius of WT/CKD mice. We performed qPCR analysis for the top 20 differentially expressed muscle genes previously identified via RNAseq analysis in WT/CKD mice versus controls. Importantly, 17 differentially expressed muscle genes were attenuated in anakinra treated WT/CKD mice. In conclusion, IL-1 receptor antagonism may represent a novel targeted treatment for adipose tissue browning and muscle wasting in CKD.
This study analyzed the effect of incorporating graphene nanoplatelets in the fiber-matrix interphase on the behavior of a multiscale composite laminate based on carbon fibers and epoxy resin ...subjected to contact loads. The selected loading mode was the contact between an elastic surface and a cylinder. The multiscale composite material used was a quasi-isotropic laminate with graphene nanoplatelets (GnPs) added at the fiber-matrix interface. The specimens were prepared with 0.0%, 0.1%, and 0.25% by-weight GnPs. Laminate beams were used according to the ASTM D7264 standard, and contact was studied in two configurations, applying the load at the edge of the laminate and in the other, in the plane of the test pieces. The normal strains in the contact region were determined experimentally using the interferometric Moiré technique. These results were compared with estimations using the Hertz contact theory and the finite element method (FEM). The normal strains in the contact area of specimens with fibers modified with 0.1% GnPs were lower than those with 0.25% or fibers without surface modification. Excellent agreement between the experimental results along lines in the contact zone with those estimated with the FEM. The normal strains in a direction perpendicular to the applied load obtained by the Hertz theory for the maximum deformation were slightly higher than those obtained by FEM. Except for those calculated for the normal strain in εy for the load in the direction of the thickness, although the distribution was very similar to those obtained by FEM as well as the experimental one.
This study evaluates the effect of recycled thermoplastic polyurethane (RTPU) on the Izod impact resistance of polypropylene (PP) compounds with 50% coconut fibers arranged randomly. The Izod impact ...resistance was compared to the performance of a commercial coupling agent (CCA) of maleic anhydride grafted PP copolymer (MAPP). The PP compounds were made with 0, 2.5, and 5% by weight of RTPU or CCA, and with 50% of short or long coconut fibers, in the form of plates molded by thermo-compression, where the plastic components were previously extruded in the form of filaments. The morphology of the resulting materials was studied by scanning electron microscopy (SEM). The functional groups and their possible interactions present were determined by Fourier transform infrared spectroscopy (FTIR). Furthermore, the interfacial shear strength between the polymeric matrix and the coconut fiber was determined. The results showed a higher Izod impact resistance and a higher adhesion between long coconut fiber and PP when they contain 5% RTPU. This is explained by the higher interfacial shear strength between them given by the chemical and/or physical interaction between functional groups such as the lignin of coconut fibers and the isocyanate groups of RTPU, which in turn determined the shortest critical length of coconut fiber. The impact resistance values ranged from 19.8 to 24.4 J/m for mixtures of PP with short coconut fibers and 39.9–71.7 J/m for PP with long coconut fibers.
Lignocellulosic fibers, such as henequen, sisal, coconut fiber (coir), jute, palm and bamboo, have been used as reinforcement materials for different thermosetting and thermoplastic resins because of ...their attractive physical and mechanical properties. Unlike the traditional engineering fibers, e.g. glass and carbon fibers, and mineral fillers, these lignocellulosic fibers are able to impart certain benefits such as low density, less machine wear, no health hazards, and a high degree of flexibility to the composite. The last attribute is especially true because these lignocellulosic fibers will bend rather than fracture, like glass fibers do, during processing of the composite. The mechanical properties and fracture behavior of a natural fiber reinforced polymer composite depend, not only on the properties of constituents, but also on the properties of the region surrounding the fiber, known as the interphase, where the stress transfer takes place. Moreover, the tailoring of the interphase by means of surface treatments, and carefully characterizing it, gives a better understanding of the performance of natural-fiber reinforced composites. The fracture toughness resulting from the use of natural fibers as reinforcing materials is quite different between ductile and brittle polymers, as well as between quasi-static and impact loading rates. The aim of this paper is to study the effect of the interphase properties, resulting from well controlled surface treatment of the natural fibers, on the behavior of a ductile polymer matrix composite under quasi-static loading using the essential work of fracture criteria. Specifically, the contribution of each of the different fiber-matrix interfacial adhesion levels towards the dissipation energy were analyzed and discussed. In the case of the plastic work βwp, there seems to be a synergy between the frictional and chemical interactions observed for both, low and high strain rates. The nonlinear mechanical behavior of the natural fiber under combined tensile-shear loads has also an effect on the fracture behavior of the composite. Additionally, different fiber surface treatments change the microstructural nature of the natural fiber, further affecting its behavior, particularly under high loading rates.
The mechanical characterization of plain foamed concrete (PFC) and fiber-reinforced foamed concrete (FRFC) with a density of 700 kg/m3 was performed with compression and tension tests. FRFC was ...reinforced with the natural fiber henequen (untreated or alkaline-treated) at volume fractions of 0.5%, 1% and 1.5%. Polypropylene fiber reinforcement was also used as a reference. For all FRFCs, the inclusion of the fibers enhanced the compressive and tensile strengths and plastic behavior, which was attributed to the increase of specimen integrity. Under compressive loading, after the peak strength, there was no considerable loss in strength and a plateau-like regime was observed. Under tensile loading, the fibers significantly increased the tensile strength of the FRFCs and prevented a sudden failure of the specimens, which was in contrast to the brittle behavior of the PFC. The tensile behavior enhancement was higher when treated henequen fibers were used, which was attributed to the increase in the fiber–matrix bond produced by the alkaline treatment. The microscopic characterization showed that the inclusion of fibers did not modify the air-void size and its distribution. Higher energy absorption was observed for FRFCs when compared to the PFC, which was attributed to the enhanced toughness and ductility by the fibers. The results presented herein warrant further research of FRFC with natural henequen fibers for engineering applications.
•The polygenic risk score for educational attainment (PRS-EA), rather than psychopathological PRS (schizophrenia or bipolar disorder), was associated with lower risk and a later onset of ...relapse.•These results could indicate that the biological mechanisms beyond the risk of suffering a psychotic episode and the mechanisms of its prognosis could be independent.•The combination of polygenic scores and clinical data are potentially useful predictors of relapse.
Little is known about genetic predisposition to relapse. Previous studies have linked cognitive and psychopathological (mainly schizophrenia and bipolar disorder) polygenic risk scores (PRS) with clinical manifestations of the disease. This study aims to explore the potential role of PRS from major mental disorders and cognition on schizophrenia relapse. 114 patients recruited in the 2EPs Project were included (56 patients who had not experienced relapse after 3 years of enrollment and 58 patients who relapsed during the 3-year follow-up). PRS for schizophrenia (PRS-SZ), bipolar disorder (PRS-BD), education attainment (PRS-EA) and cognitive performance (PRS-CP) were used to assess the genetic risk of schizophrenia relapse.Patients with higher PRS-EA, showed both a lower risk (OR=0.29, 95% CI 0.11–0.73) and a later onset of relapse (30.96± 1.74 vs. 23.12± 1.14 months, p=0.007. Our study provides evidence that the genetic burden of neurocognitive function is a potentially predictors of relapse that could be incorporated into future risk prediction models. Moreover, appropriate treatments for cognitive symptoms appear to be important for improving the long-term clinical outcome of relapse.
Spinocerebellar ataxia type 10 (SCA10) is caused by a pentanucleotide repeat expansion of r(AUUCU) within intron 9 of the ATXN10 pre-mRNA. The RNA causes disease by a gain-of-function mechanism in ...which it inactivates proteins involved in RNA biogenesis. Spectroscopic studies showed that r(AUUCU) repeats form a hairpin structure; however, there were no high-resolution structural models prior to this work. Herein, we report the first crystal structure of model r(AUUCU) repeats refined to 2.8 Å and analysis of the structure via molecular dynamics simulations. The r(AUUCU) tracts adopt an overall A-form geometry in which 3 × 3 nucleotide 5′UCU3′/3′UCU5′ internal loops are closed by AU pairs. Helical parameters of the refined structure as well as the corresponding electron density map on the crystallographic model reflect dynamic features of the internal loop. The computational analyses captured dynamic motion of the loop closing pairs, which can form single-stranded conformations with relatively low energies. Overall, the results presented here suggest the possibility for r(AUUCU) repeats to form metastable A-from structures, which can rearrange into single-stranded conformations and attract proteins such as heterogeneous nuclear ribonucleoprotein K (hnRNP K). The information presented here may aid in the rational design of therapeutics targeting this RNA.
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