Sistema de autoconstrucción sismorresistente: características resistentes y proceso constructivo

The dwelling construction with soil, adobe or brick without call for technical advice is very typical in countries in process of development that are in areas of high seismic risk. To give an answer to the problem of earthquake building using these materials, providing simplicity of construction, we have worked for years in the use of the Integral Masonry System (IMS). The IMS is a system that, used combined with native materials, has earthquake resistant properties and its ease of implementation makes it suitable for self-build earthquake-resistant dwellings. This article describes the IMS, develops the constructive process applied to a type of two storey houses, and shows the seismic behaviour by means of the results obtained in the three test campaigns. The originality of the system lies in the use of a single type of prefabricated trusses, intertwined in the three spatial directions allowing create a dimensional mesh.<br><br>La autoconstrucción con tierra, adobe o ladrillo es muy habitual en los países en vías de desarrollo que están en zonas de alto riesgo sísmico. Ante la necesidad de dar respuesta al problema, aportando sencillez constructiva, hemos trabajado desde hace años en el empleo del Sistema de Albañilería Integral (SAI). El SAI es un sistema que, combinado con materiales autóctonos, aporta resistencia sísmica y su facilidad de ejecución lo hace adecuado para la autoconstrucción de viviendas antisísmicas. Este artículo describe el SAI, desarrolla el proceso constructivo aplicado a una vivienda tipo de dos alturas y muestra su comportamiento sismo-resistente mediante los resultados obtenidos en tres campañas de ensayos. La originalidad del sistema radica en el empleo de un solo tipo de armaduras prefabricadas en forma de cercha que se entrelazan entre si en las tres direcciones del espacio permitiendo crear una malla tridimensional

Classification of head impacts based on the spectral density of measurable kinematics

Traumatic brain injury can be caused by head impacts, but many brain injury risk estimation models are less accurate across the variety of impacts that patients may undergo. We investigated the spectral characteristics of different head impact types with kinematics classification. Data was analyzed from 3,262 head impacts from lab reconstruction, American football, mixed martial arts, and publicly available car crash data. A random forest classifier with spectral densities of linear acceleration and angular velocity was built to classify head impact types (e.g., football), reaching a median accuracy of 96% over 1,000 random partitions of training and test sets. To test the classifier on data from different measurement devices, another 271 lab-reconstructed impacts were obtained from 5 other instrumented mouthguards with the classifier reaching over 96% accuracy. The most important features in the classification included both low-frequency and high-frequency features, both linear acceleration features and angular velocity features. Different head impact types had different distributions of spectral densities in low-frequency and high-frequency ranges (e.g., the spectral densities of MMA impacts were higher in high-frequency range than in the low-frequency range). Finally, with the classifier, type-specific, nearest-neighbor regression models were built for 95th percentile maximum principal strain, 95th percentile maximum principal strain in corpus callosum, and cumulative strain damage (15th percentile). This showed a generally higher R2-value than baseline models. The classifier enables a better understanding of the impact kinematics in different sports, and it can be applied to evaluate the quality of impact-simulation systems and on-field data augmentation. Key words: traumatic brain injury, head impacts, classification, impact kinematicsComment: 16 pages, 5 figure

Multi-directional dynamic model for traumatic brain injury detection

Traumatic brain injury (TBI) is a complex injury that is hard to predict and diagnose, with many studies focused on associating head kinematics to brain injury risk. Recently, there has been a push towards using computationally expensive finite element (FE) models of the brain to create tissue deformation metrics of brain injury. Here, we developed a 3 degree-of-freedom lumped-parameter brain model, built based on the measured natural frequencies of a FE brain model simulated with live human impact data, to be used to rapidly estimate peak brain strains experienced during head rotational accelerations. On our dataset, the simplified model correlates with peak principal FE strain by an R2 of 0.80. Further, coronal and axial model displacement correlated with fiber-oriented peak strain in the corpus callosum with an R2 of 0.77. Using the maximum displacement predicted by our brain model, we propose an injury criteria and compare it against a number of existing rotational and translational kinematic injury metrics on a dataset of head kinematics from 27 clinically diagnosed injuries and 887 non-injuries. We found that our proposed metric performed comparably to peak angular acceleration, linear acceleration, and angular velocity in classifying injury and non-injury events. Metrics which separated time traces into their directional components had improved deviance to those which combined components into a single time trace magnitude. Our brain model can be used in future work as a computationally efficient alternative to FE models for classifying injuries over a wide range of loading conditions.Comment: 10 figures, 3 table

Predictive Factors of Kinematics in Traumatic Brain Injury from Head Impacts Based on Statistical Interpretation

Brain tissue deformation resulting from head impacts is primarily caused by rotation and can lead to traumatic brain injury. To quantify brain injury risk based on measurements of kinematics on the head, finite element (FE) models and various brain injury criteria based on different factors of these kinematics have been developed, but the contribution of different kinematic factors has not been comprehensively analyzed across different types of head impacts in a data-driven manner. To better design brain injury criteria, the predictive power of rotational kinematics factors, which are different in 1) the derivative order (angular velocity, angular acceleration, angular jerk), 2) the direction and 3) the power (e.g., square-rooted, squared, cubic) of the angular velocity, were analyzed based on different datasets including laboratory impacts, American football, mixed martial arts (MMA), NHTSA automobile crashworthiness tests and NASCAR crash events. Ordinary least squares regressions were built from kinematics factors to the 95\% maximum principal strain (MPS95), and we compared zero-order correlation coefficients, structure coefficients, commonality analysis, and dominance analysis. The angular acceleration, the magnitude, and the first power factors showed the highest predictive power for the majority of impacts including laboratory impacts, American football impacts, with few exceptions (angular velocity for MMA and NASCAR impacts). The predictive power of rotational kinematics in three directions (x: posterior-to-anterior, y: left-to-right, z: superior-to-inferior) of kinematics varied with different sports and types of head impacts

Role of mitochondrial raft-like microdomains in the regulation of cell apoptosis

Lipid rafts are envisaged as lateral assemblies of specific lipids and proteins that dissociate and associate rapidly and form functional clusters in cell membranes. These structural platforms are not confined to the plasma membrane; indeed lipid microdomains are similarly formed at subcellular organelles, which include endoplasmic reticulum, Golgi and mitochondria, named raft-like microdomains. In addition, some components of raft-like microdomains are present within ER-mitochondria associated membranes. This review is focused on the role of mitochondrial raft-like microdomains in the regulation of cell apoptosis, since these microdomains may represent preferential sites where key reactions take place, regulating mitochondria hyperpolarization, fission-associated changes, megapore formation and release of apoptogenic factors. These structural platforms appear to modulate cytoplasmic pathways switching cell fate towards cell survival or death. Main insights on this issue derive from some pathological conditions in which alterations of microdomains structure or function can lead to severe alterations of cell activity and life span. In the light of the role played by raft-like microdomains to integrate apoptotic signals and in regulating mitochondrial dynamics, it is conceivable that these membrane structures may play a role in the mitochondrial alterations observed in some of the most common human neurodegenerative diseases, such as Amyotrophic lateral sclerosis, Huntington's chorea and prion-related diseases. These findings introduce an additional task for identifying new molecular target(s) of pharmacological agents in these pathologies

Alternative-NHEJ Is a Mechanistically Distinct Pathway of Mammalian Chromosome Break Repair

Characterizing the functional overlap and mutagenic potential of different pathways of chromosomal double-strand break (DSB) repair is important to understand how mutations arise during cancer development and treatment. To this end, we have compared the role of individual factors in three different pathways of mammalian DSB repair: alternative-nonhomologous end joining (alt-NHEJ), single-strand annealing (SSA), and homology directed repair (HDR/GC). Considering early steps of repair, we found that the DSB end-processing factors KU and CtIP affect all three pathways similarly, in that repair is suppressed by KU and promoted by CtIP. In contrast, both KU and CtIP appear dispensable for the absolute level of total-NHEJ between two tandem I-SceI–induced DSBs. During later steps of repair, we find that while the annealing and processing factors RAD52 and ERCC1 are important to promote SSA, both HDR/GC and alt-NHEJ are significantly less dependent upon these factors. As well, while disruption of RAD51 causes a decrease in HDR/GC and an increase in SSA, inhibition of this factor did not affect alt-NHEJ. These results suggest that the regulation of DSB end-processing via KU/CtIP is a common step during alt-NHEJ, SSA, and HDR/GC. However, at later steps of repair, alt-NHEJ is a mechanistically distinct pathway of DSB repair, and thus may play a unique role in mutagenesis during cancer development and therapy

ATM Limits Incorrect End Utilization during Non-Homologous End Joining of Multiple Chromosome Breaks

Chromosome rearrangements can form when incorrect ends are matched during end joining (EJ) repair of multiple chromosomal double-strand breaks (DSBs). We tested whether the ATM kinase limits chromosome rearrangements via suppressing incorrect end utilization during EJ repair of multiple DSBs. For this, we developed a system for monitoring EJ of two tandem DSBs that can be repaired using correct ends (Proximal-EJ) or incorrect ends (Distal-EJ, which causes loss of the DNA between the DSBs). In this system, two DSBs are induced in a chromosomal reporter by the meganuclease I-SceI. These DSBs are processed into non-cohesive ends by the exonuclease Trex2, which leads to the formation of I-SceI–resistant EJ products during both Proximal-EJ and Distal-EJ. Using this method, we find that genetic or chemical disruption of ATM causes a substantial increase in Distal-EJ, but not Proximal-EJ. We also find that the increase in Distal-EJ caused by ATM disruption is dependent on classical non-homologous end joining (c-NHEJ) factors, specifically DNA-PKcs, Xrcc4, and XLF. We present evidence that Nbs1-deficiency also causes elevated Distal-EJ, but not Proximal-EJ, to a similar degree as ATM-deficiency. In addition, to evaluate the roles of these factors on end processing, we examined Distal-EJ repair junctions. We found that ATM and Xrcc4 limit the length of deletions, whereas Nbs1 and DNA-PKcs promote short deletions. Thus, the regulation of end processing appears distinct from that of end utilization. In summary, we suggest that ATM is important to limit incorrect end utilization during c-NHEJ

Essential Factors for Incompatible DNA End Joining at Chromosomal DNA Double Strand Breaks In Vivo

Non-homologous end joining (NHEJ) is a major pathway for the repair of DNA double strand break (DSBs) with incompatible DNA ends, which are often generated by ionizing irradiation. In vitro reconstitution studies have indicated that NHEJ of incompatible DNA ends requires not only the core steps of synapsis and ligation, employing KU80/DNA-PKcs and LIG4, but also additional DNA end processing steps, such as DNA end resection by Artemis and gap-filling by POLλ and POLμ. It seems that DNA end processing steps are important for joining of incompatible DNA ends rather than compatible ends. Despite the fact that DNA end processing is important for incompatible DNA end joining in vitro, the role of DNA processing in NHEJ of incompatible DSBs in vivo has not yet been demonstrated. Here we investigated the in vivo roles of proteins implicated in each step of NHEJ using an assay in which NHEJ of incompatible DNA ends on chromosomal DNA can be assessed in living human cells. siRNA- or inhibitor-mediated impairment of factors in each NHEJ step resulted in a reduction in joining efficiency. Strikingly, stronger effects were observed when DNA end resection and ligation protein functions were impaired. Disruption of synapsis by KU80 and DNA-PKcs impairment, or the disruption of gap filling by POLλ and POLμ depletion, resulted in higher levels of microhomology-mediated joining. The present study indicates that DNA end resection and ligation factors are critical for the efficient joining of incompatible ends in vivo, further emphasizing the importance of synapsis and gap-filling factors in preventing illegitimate joining

Ku Regulates the Non-Homologous End Joining Pathway Choice of DNA Double-Strand Break Repair in Human Somatic Cells

The repair of DNA double-strand breaks (DSBs) is critical for the maintenance of genomic integrity and viability for all organisms. Mammals have evolved at least two genetically discrete ways to mediate DNA DSB repair: homologous recombination (HR) and non-homologous end joining (NHEJ). In mammalian cells, most DSBs are preferentially repaired by NHEJ. Recent work has demonstrated that NHEJ consists of at least two sub-pathways—the main Ku heterodimer-dependent or “classic” NHEJ (C-NHEJ) pathway and an “alternative” NHEJ (A-NHEJ) pathway, which usually generates microhomology-mediated signatures at repair junctions. In our study, recombinant adeno-associated virus knockout vectors were utilized to construct a series of isogenic human somatic cell lines deficient in the core C-NHEJ factors (Ku, DNA-PKcs, XLF, and LIGIV), and the resulting cell lines were characterized for their ability to carry out DNA DSB repair. The absence of DNA-PKcs, XLF, or LIGIV resulted in cell lines that were profoundly impaired in DNA DSB repair activity. Unexpectedly, Ku86-null cells showed wild-type levels of DNA DSB repair activity that was dominated by microhomology joining events indicative of A-NHEJ. Importantly, A-NHEJ DNA DSB repair activity could also be efficiently de-repressed in LIGIV-null and DNA-PKcs-null cells by subsequently reducing the level of Ku70. These studies demonstrate that in human cells C-NHEJ is the major DNA DSB repair pathway and they show that Ku is the critical C-NHEJ factor that regulates DNA NHEJ DSB pathway choice

Changes in circulating microRNA levels can be identified as early as day 8 of pregnancy in cattle

<div><p>Poor reproductive performance remains a major issue in the dairy industry, with low conception rates having a significant impact on milk production through extended calving intervals. A major limiting factor is the lack of reliable methods for early pregnancy diagnosis. Identification of animals within a herd that fail to conceive within 3 weeks after insemination would allow early re-insemination and shorten calving intervals. In a previous study, we found an increase in plasma miR-26a levels in Day 16-pregnant relative to non-pregnant heifers, however changes in miRNA levels that early during pregnancy were very small which likely prevented the identification of robust biomarkers. In this study, we extended our analyses to a wider interval during pregnancy (Days 8 to 60, n = 11 heifers) with the rationale that this may facilitate the identification of additional early pregnancy miRNA biomarkers. Using small RNA sequencing we identified a total of 77 miRNAs that were differentially expressed on Day 60 relative to Day 0 of pregnancy. We selected 14 miRNAs for validation by RT-qPCR and confirmed significant differences in the expression of let-7f, let-7c, miR-30c, miR-101, miR-26a, miR-205 and miR-143 between Days 0 and 60. RT-qPCR profiling throughout Days 0, 8, 16 and 60 of pregnancy showed a distinct increase in circulating levels of miR-26a (3.1-fold, P = 0.046) as early as Day 8 of pregnancy. In summary, in contrast to earlier stages of pregnancy (≤ Day 24), marked differences in the levels of multiple miRNAs can be detected in circulation by Day 60 in cattle. Retrospective analyses showed miR-26a levels to be increased in circulation as early as Day 8, sooner than previously reported in any species, suggesting a biological role for this miRNA in the very early events of pregnancy.</p></div