Tridimensional Model Research Articles

17-β Estradiol up-regulates energy metabolic pathways, cellular proliferation and tumor invasiveness in ER+ breast cancer spheroids.

Several biological processes related to cancer malignancy are regulated by 17-β estradiol (E2) in ER+-breast cancer. To establish the role of E2 on the atypical cancer energy metabolism, a systematic study analyzing transcription factors, proteins, and fluxes associated with energy metabolism was undertaken in multicellular tumor spheroids (MCTS) from human ER+ MCF-7 breast cancer cells. At E2 physiological concentrations (10 and 100 nM for 24 h), both ERα and ERβ receptors, and their protein target pS2, increased by 0.6-3.5 times vs. non-treated MCTS, revealing an activated E2/ER axis. E2 also increased by 30-470% the content of several transcription factors associated to mitochondrial biogenesis and oxidative phosphorylation (OxPhos) (p53, PGC1-α) and glycolytic pathways (HIF1-α, c-MYC). Several OxPhos and glycolytic proteins (36-257%) as well as pathway fluxes (48-156%) significantly increased being OxPhos the principal ATP cellular supplier (>75%). As result of energy metabolism stimulation by E2, cancer cell migration and invasion processes and related proteins (SNAIL, FN, MM-9) contents augmented by 24-189% vs. non-treated MCTS. Celecoxib at 10 nM blocked OxPhos (60%) as well as MCTS growth, cell migration and invasiveness (>40%); whereas the glycolytic inhibitor iodoacetate (0.5 µM) and doxorubicin (70 nM) were innocuous. Our results show for the first time using a more physiological tridimensional cancer model, resembling the initial stages of solid tumors, that anti-mitochondrial therapy may be useful to deter hormone-dependent breast carcinomas.

Synthesis, characterization and evaluation of prenylated chalcones ethers as promising antileishmanial compounds.

Drug therapy for leishmaniasis remains a major challenge as currently available drugs have limited efficacy, induce serious side-effects and are not accessible to everyone. Thus, the discovery of affordable drugs is urgently needed. Chalcones present a great potential as bioactive agents due to simple structure and functionalization capacity. The antileishmanial activity of different natural and synthetic chalcones have been reported. Here we report the synthesis of twenty-five novel prenylated chalcones that displayed antiparasitic activity in Leishmania mexicana. All the chalcones were evaluated at 5µg/mL and eleven compounds exhibited a metabolic inhibition close to or exceeding 50%. Compounds 49, 30 and 55 were the three most active with IC50 values < 10μM. These chalcones also showed the highest selectivity index (SI) values. Interestingly 49 and 55 possessing a substituent at a meta position in the B ring suggests that the substitution pattern influences antileishmanial activity. Additionally, a tridimensional model of fumarate reductase of L. mexicana was obtained by homology modeling. Docking studies suggest that prenylated chalcones could modulate fumarate reductase activity by binding with good affinity to two binding sites that are critical for the target. In conclusion, the novel prenylated chalcones could be considered as promising antileishmanial agents.

High Performance Composites Based on Highly Filled Glass Fiber-Reinforced Polybenzoxazine for Post Application

Glass fiber post based on the new polymeric material, polybenzoxazine, is prepared and the effects of glass fiber contents on mechanical and thermal properties are evaluated. The mechanical response to externally applied loads of tooth restored with glass fiber-reinforced polybenzoxazine composite posts is also simulated by finite element analysis of a tridimensional model and compared with the response to that of a natural tooth. The reinforcing of glass fiber can help improve the mechanical and thermal properties of the polybenzoxazine influenced by the interfacial adhesion between the glass fiber and polybenzoxazine matrix, except for the relatively high mechanical property of the glass fiber. The mechanical data, i.e., elastic modulus under flexure load or flexural modulus by three-point bending test of the glass fiber-reinforced polybenzoxazine composites are agreed with the elastic modulus of dentin and then used in the finite element model. The restoration using the glass fiber-reinforced polybenzoxazine composite post provided the maximum von Mises equivalent stress at the cervical third area of the endodontically treated tooth model as similarly observed in the natural tooth. In addition, the maximum von Mises equivalent stress of the tooth restored with the glass fiber-reinforced polybenzoxazine composite post is also quietly like that of the natural tooth. The finding of this work provided the essential properties of the glass fiber-reinforced polybenzoxazine composite for dental restorations and appliances.

Evaluation of marginal bone loss in implant supported over-dentures

Aim: The purpose of the present research was to assess the marginal bone loss due to stresses encountered in implant supported over-dentures. Methodology: Tridimensional models were built from the images of a computerized tomography of a mandible and 3D laser digitalization of implants, abutments, mucosa, and complete denture. The geometric models of implants and abutments were mounted at the canine region to build reference model 1 - absence of bone resorption. To build the test models the mandible geometric solid was modified to simulate 2-mm vertical bone loss surrounding the implants (model 2) and resorption of the distal ridge (model 3). Finite elements models were generated, and a 100 N static load was applied at the first molar region of each model to compare the von Mises stress distributions in selected points. Results: Von Mises stresses increased on the bone surrounding implants and on the prosthetic components in the model with 2-mm vertical bone loss. The combination of 2-mm vertical bone loss and resorption of the distal ridge did not increase the stresses compared with the model with only bone loss surrounding implants.

Predictive biophysical models of bivalve larvae dispersal in Scotland

In Scotland, bivalves are widely distributed. However, their larvae dispersion is still largely unknown and difficult to assess in situ. And, while Mytilus spp. dominate shellfish production, it is mostly dependent on natural spat recruitment from wild populations. Understanding the larval distribution pattern would safeguard natural resources while also ensuring sustainable farming practises. The feasibility of a model that simulates biophysical interactions between larval behaviour and ocean motions was investigated. We employed an unstructured tri-dimensional hydrodynamic model (finite volume coastal ocean model) to drive a particle tracking model, where prediction of larval movement and dispersal at defined locations might aid in population monitoring and spat recruitment. Our findings reveal a strong link between larval distribution and meteorological factors such as wind forces and currents velocity. The model, also, depicts a fast and considerable larval movement, resulting in a substantial mix of plankton and bivalve larvae, forming a large connection between the southern and northern regions of Scotland’s West coast. This enables us to forecast the breeding grounds of any area of interest, potentially charting connectivity between cultivated and wild populations. These results have significant implications for the dynamics of ecologically and economically important species, such as population growth and loss, harvesting and agricultural management in the context of climate change, and sustainable shellfish fisheries management. Furthermore, the observations on Scottish water flow suggest that tracking particles with similar behaviour to bivalve larvae, such as other pelagic larval stages of keystone species and potential pathogens such as sea lice, may have policy and farming implications, as well as disease control amid global warming issues.

Identification of atrial fibrillation drivers by means of concentric ring electrodes

Background and objectiveThe prevalence of atrial fibrillation (AF) has tripled in the last 50 years due to population aging. High-frequency (DFdriver) activated atrial regions lead the activation of the rest of the atria, disrupting the propagation wavefront. Fourier based spectral analysis of body surface potential maps have been proposed for DFdriver identification, although these approaches present serious drawbacks due to their limited spectral resolution for short AF epochs and the blurring effect of the volume conductor. Laplacian signals (BC-ECG) from bipolar concentric ring electrodes (CRE) have been shown to outperform the spatial resolution achieved with conventional unipolar recordings. Our aimed was to determine the best DFdriver estimator in endocardial electrograms and to assess the BC-ECG capacity of CRE to quantify AF activity non-invasively. Methods31 AF episodes were simulated using realistic tridimensional models of the atria electrical activity and torso. Periodogram and autoregressive (AR) spectral estimators were computed and the percentile (P90th, P95th and P98th) to impose on the dominant frequencies (DFs) across whole atria to define the best DFdriver estimator evaluated. The identification of DFdriver on DFs from BC-ECG and unipolar surface signals with conventional disc electrodes was compared. ResultsThe best DFdriver estimator was P95th and AR order 100. BC-ECG signals allowed better detection of AF activity than unipolar signals, with a significantly greater percentage of electrode locations in which DFdriver was identified (p-value 0.0095). ConclusionsThe use of BC-ECG signals for body surface Laplacian potential mapping with CRE could be helpful for better AF diagnosis, prognosis and ablation procedures than those with conventional disk electrodes.

A Tri-dimensional Equilibrium-based stochastic optimal dispatching model for a novel virtual power plant incorporating carbon Capture, Power-to-Gas and electric vehicle aggregator

This study proposes a novel structure of carbon-to-power-based virtual power plant (C2P-VPP) considering the flexible demand response and electric vehicle-to-grid aggregators (EVA). C2P is integrated by gas-power plant carbon capture (GPPCC), carbon storage devices (CS), and power-to-gas (P2G). Then, to balance the multiple objectives of the dispatching cost, the carbon emission and the output fluctuation, a tri-dimensional coordinated optimal dispatching model is construct from the perspective of the energy impossibility triangle problem. And the robust optimization theory is applied to characterize the uncertainty of wind power plant (WPP) and photovoltaic power generation (PV). Thirdly, to solve the above multi-objective model, an improved fuzzy equilibrium coordination-based-model solution algorithm is proposed. The algorithm integrates the fuzzy satisfaction theory, the multi-objective input income table, the entropy weight method into the complete information static game model. Finally, the CIGRE medium voltage distribution system is chosen for case study, the results show: (1) GPPCC could capture and store CO2 in carbon storage devices, and P2G could convert the CO2 into CH4 for conventional gas turbines (CGT) providing flexible power output. Compared with the scenario only with CS or P2G, when they are both introduced, the carbon emissions reduced by 7.75 % and 3.82 %, the dispatching cost reduced by 2.90 % and 7.77 %, and the output fluctuation reduced by 10.03 % and 2.80 %. (2) When robust coefficient Г is from 0.85 to 0.95, the decision-maker is the risk preference type and willing to bear risk to pursue excess benefit. (3) Sensitivity analysis shows when the rated capacity ratio of CGT, GPPCC and P2G is from 8:4:1 to 2:2:1, the dispatching scheme are optimal. When the capacity ratio of WPP, PV and EVA is from 20:1 to 10:1, the objective value changes significantly, and the optimal equilibrium scheme could be established when the capacity ratio is higher than 10:1. Therefore, the proposed optimal dispatching model could provide an effective tools for decision makers to achieve the optimal dispatching schemes.

Modeling of the electron beam induced current signal in nanowires with an axial p-n junction

A tridimensional mathematical model to calculate the electron beam induced current (EBIC) of an axial p-n nanowire junction is proposed. The effect of the electron beam and junction parameters on the distribution of charge carriers and on the collected EBIC current is reported. We demonstrate that the diffusion of charge carriers within the wire is strongly influenced by the electrical state of its lateral surface which is characterized by a parameter called surface recombination velocity (v r). When the surface recombination is weak (i.e. low v r value), the diffusion of charge carriers occurs in one dimension (1D) along the wire axis, and, in this case, the use of bulk EBIC models to extract the diffusion length (L) of charge carriers is justified. However, when the surface effects are strong (i.e. high v r values), the diffusion happens in three dimensions (3D). In this case, the EBIC profiles depend on v r value and two distinct cases can be defined. If the L is larger than the nanowire radius (r a), the EBIC profiles show a strong dependency with this parameter. This gives evidence that the recombination of generated carriers on the surface through v r is the dominant process. In this situation, a decrease of two orders of magnitude in the EBIC profiles computed with a high and a low v r value is observed in neutral regions of the junction. For the case of L smaller than r a the dependency of the EBIC profiles on the v r is weak, and the prevalent recombination mechanism is the bulk recombination process.

Potential and limitations of LiDAR altimetry in archaeological survey. Copper Age and Bronze Age settlements in southern Iberia

Potential and limitations of LiDAR altimetry in archaeological survey. Copper Age and Bronze Age settlements in southern Iberia

Estimating the maize above-ground biomass by constructing the tridimensional concept model based on UAV-based digital and multi-spectral images

Above-ground biomass (AGB) is an important basis for the formation of crop yield. The accurate estimation of maize AGB based on unmanned aerial vehicle (UAV) images is important for superior varieties selection, field management and maize yield prediction. The previous studies mainly focused on constructing empirical models of AGB by using spectral vegetation indices (VIs), plant height (PH), texture, and is lacked of universality. We conducted the field experiments of maize breeding materials for three years, and obtained UAV digital and multi-spectral images. Considering that the maize AGB before tasseling stage was composed of stem and leaf, we constructed a tridimensional concept model to predict maize AGB coordinated by integrating leaf area index (LAI) and PH, in order to improve the accuracy and universality of UAV data on monitoring maize AGB at multiple growth stages. Firstly, the maize PH was estimated based on the maize canopy height model constructed using the UAV digital images. Secondly, the maize LAI was estimated based on UAV multi-spectrum images and the modified Beer-Lambert law. Finally, the tridimensional concept model of maize AGB was constructed by integrating PH and LAI, and compared with the AGB regression model based on the normalized difference vegetation index (NDVI). The results showed that the maize PH could be estimated well, and the R ², RMSE and rRMSE of the measured and estimated PH were 0.87, 11.17 cm and 16.04% respectively. The LAI could be estimated effectively, and the R ², RMSE, and rRMSE of the sample set were 0.78, 0.49 and 30% respectively. Compared with the maize AGB estimation model based on NDVI ( R ² = 0.79, RMSE = 41.95 g/m², rRMSE = 31.79%), the tridimensional concept model could better estimate the maize AGB ( R ² = 0.82, RMSE = 38.53 g/m², rRMSE = 29.19%). Testing the tridimensional concept model by stand-alone data of 2019 and 2021 years, the accuracy of the AGB estimation model based on the tridimensional concept was much higher than that of the NDVI model. In conclusion，the tridimensional concept model of maize AGB proposed in this study effectively improved the accuracy, stability and universality, which could provide a reference for the estimation of maize AGB by UAV technology at plot scale of the breeding materials.

A Micro-Immunotherapy Sequential Medicine MIM-seq Displays Immunomodulatory Effects on Human Macrophages and Anti-Tumor Properties towards In Vitro 2D and 3D Models of Colon Carcinoma and in an In Vivo Subcutaneous Xenograft Colon Carcinoma Model

In this study, the immunomodulatory effects of a sequential micro-immunotherapy medicine, referred as MIM-seq, were appraised in human primary M1 and M2 macrophages, in which the secretion of pro-inflammatory cytokines, such as interleukin (IL)-1β, IL-6, IL-12, IL-23, and tumor necrosis factor (TNF)-alpha, was inhibited. In addition, the potential anti-proliferative effects of MIM-seq on tumor cells was assessed in three models of colorectal cancer (CRC): an in vitro two-dimensions (2D) model of HCT-116 cells, an in vitro tri-dimensional (3D) model of spheroids, and an in vivo model of subcutaneous xenografted mice. In these models, MIM-seq displayed anti-proliferative effects when compared with the vehicle. In vivo, the tumor growth was slightly reduced in MIM-seq-treated animals. Moreover, MIM-seq could slightly reduce the growth of our spheroid models, especially under serum-deprivation. When MIM-seq was combined with two well-known anti-cancerogenic agents, either resveratrol or etoposide, MIM-seq could even further reduce the spheroid’s volume, pointing up the need to further assess whether MIM-seq could be beneficial for CRC patients as an adjuvant therapy. Altogether, these data suggest that MIM-seq could have anti-tumor properties against CRC and an immunomodulatory effect towards the mediators of inflammation, whose systemic dysregulation is considered to be a poor prognosis for patients.

Holistic health record for Hidradenitis suppurativa patients

Hidradenitis suppurativa (HS) is a recurrent inflammatory skin disease with a complex etiopathogenesis whose treatment poses a challenge in the clinical practice. Here, we present a novel integrated pipeline produced by the European consortium BATMAN (Biomolecular Analysis for Tailored Medicine in Acne iNversa) aimed at investigating the molecular pathways involved in HS by developing new diagnosis algorithms and building cellular models to pave the way for personalized treatments. The objectives of our european Consortium are the following: (1) identify genetic variants and alterations in biological pathways associated with HS susceptibility, severity and response to treatment; (2) design in vitro two-dimensional epithelial cell and tri-dimensional skin models to unravel the HS molecular mechanisms; and (3) produce holistic health records HHR to complement medical observations by developing a smartphone application to monitor patients remotely. Dermatologists, geneticists, immunologists, molecular cell biologists, and computer science experts constitute the BATMAN consortium. Using a highly integrated approach, the BATMAN international team will identify novel biomarkers for HS diagnosis and generate new biological and technological tools to be used by the clinical community to assess HS severity, choose the most suitable therapy and follow the outcome.

Developing a Valid and Reliable Cross-cultural Measure of Coparenting Conflict between Divorced Parents: The Portuguese Version of the Acrimony Scale.

Coparenting conflict is predictive of parents’ and children’s adjustment to divorce. An accurate assessment of postdivorce acrimonious coparenting relationships is critical for research, clinical, forensic, and public policy purposes. The Acrimony Scale (AS) is a measure commonly used to assess coparenting conflict. We translated and cross-culturally adapted the AS to the Portuguese context, testing its reliability and validity. Using a web-based survey, data were collected from a community and convenience sample of 196 unrelated divorced parents, assessing sociodemographic characteristics, coparenting conflict, and divorce adjustment. The study consisted of two phases: (1) forward-backward translation and cultural adaptation and (2) psychometric properties analyses: construct and criterion-related validity and internal consistency reliability. The 25-item AS was successfully translated and cross-culturally adapted to the Portuguese language. Principal component analyses (PCA) suggested a three-factor structure solution of 22-items, explaining 57.5% of the variance. Confirmatory factor analysis (CFA) showed the goodness of fit of this tridimensional model. The results also demonstrated acceptable convergent and good discriminant validity and high internal reliability. Scores on the AS suggested good known-groups validity and high discriminative power with 86.7% classification accuracy. The area under the ROC curve was 0.91, establishing a very good predictive value of the scale. We suggest that the AS is a reliable multidimensional measure to assess coparenting conflict after divorce and may be useful, namely, in the psychological assessment of child custody and evaluation of the effectiveness of coparenting conflict-based interventions. We discussed future research and practical implications.

3D In Vitro Models: Novel Insights into Idiopathic Pulmonary Fibrosis Pathophysiology and Drug Screening.

Idiopathic pulmonary fibrosis (IPF) is a progressive and often lethal interstitial lung disease of unknown aetiology. IPF is characterised by myofibroblast activation, tissue stiffening, and alveolar epithelium injury. As current IPF treatments fail to halt disease progression or induce regeneration, there is a pressing need for the development of novel therapeutic targets. In this regard, tri-dimensional (3D) models have rapidly emerged as powerful platforms for disease modelling, drug screening and discovery. In this review, we will touch on how 3D in vitro models such as hydrogels, precision-cut lung slices, and, more recently, lung organoids and lung-on-chip devices have been generated and/or modified to reveal distinct cellular and molecular signalling pathways activated during fibrotic processes. Markedly, we will address how these platforms could provide a better understanding of fibrosis pathophysiology and uncover effective treatment strategies for IPF patients.

Hyper-dimensional Visualization of Cultural Heritage: A Novel Multi-analytical Approach on 3D Pomological Models in the Collection of the University of Milan

Digital close-range photogrammetry allows us to acquire high-fidelity tridimensional models useful to document cultural heritage objects with an impressive level of detail. In addition, this technique carries a strong analytical potentiality, able to gain improved knowledge of cultural objects and their preservation conditions. This project is focused on a comprehensive diagnostic survey using 3D multispectral modeling, high-resolution digital radiography, pulsed thermography, XRF, FT-IR, and FORS spectroscopies to document and characterize from a conservative point of view the poly-material objects that belong to the “Garnier Valletti” pomological collection—a unique collection from both scientific and artistic points of view. The analytical integration of imaging techniques, 3D modeling, and spectroscopic techniques provides information from the surface, sub-surface, and innermost layers of the object, respectively, capturing both accurate morphometric, spectral, and compositional data. The article presents the results obtained on typical poly-material and multilayered objects of this collection for which the combination of the considered techniques provided important data to the technical knowledge of the realization highlighting a particular predictive ability from a conservative point of view.

Cortical Volume in the Right Cingulate Cortex Mediates the Increase of Self-Control From Young Adult to Middle-Aged.

A high self-control capacity is related to better environmental adaptability and happy and healthy life. Neuroimaging studies have elucidated that the anterior cingulate, the prefrontal cortex, and the orbitofrontal cortex are involved in self-control. However, few studies integrated all three measurements, namely, age, human brain, and self-control, into a single quantitative model and examined whether self-control ability increased or decreased with age. In this study, we collected 65 participants’ data including structural MRI and Tangney’s Self-Control Scale to explore age dependence of cortical volume (CV) and self-control from young adult to middle-aged, as well as whether a non-linear association in the tridimensional model of age-brain-self-control was necessary to explain all the data in this study. We showed that self-control increased with age, but CV decreased with age. In a linear model, our mediation analyses revealed that CV in the right cingulate cortex mediated the increase of self-control; we also constructed a general non-linear model of age-brain-behavior and proved that the inverted development of human brain morphology and self-control abilities happened when morphology decays with age at a relatively smaller rate. Our study indicated that healthy aging in terms of increasing self-control is achievable, and our quantitative linear model of self-control laid theoretical foundations for studies on non-linear associations in age-brain-behavior.

CHILDREN MIGRATION AND THE EMPTY NEST PARENTS: INVESTIGATING THE IMPACT OF SOCIAL, PSYCHOLOGICAL AND THE ECONOMIC WELL-BEING OF THE ELDERLY LEFT BEHIND IN RAWALPINDI PAKISTAN

Pakistan is encountering a massive adult migration that is affecting its social fabric in various aspects. The present study has been carved out in context of the adult migration impacts on the elderly left behind in Pakistan. Particularly, the study examines the social, psychological, and economic reciprocity of the elderly left behind owing to their adult (children) outmigration. It has focused to explore the prevalence of social, psychological, and economic well-being of the elderly left behind, to find out the dynamics of the social, psychological, and economic well-being of elderly left behind by demographic variables e.g., gender, residence, etc. To identify the interrelation of the social, economic, and psychological well-being of the elderly left behind in District Rawalpindi, and considering this, to propose a Tridimensional Model of the well-being of elderly left behind and to suggest some measures to improve the social, psychological and economic wellbeing of elderly left behind. The tri-dimensional model of well-being employed the quantitative research design in order to map out the adult migration impact on parents. The study has been conducted in the Rawalpindi district of Punjab Pakistan. The researcher used the self-administered questionnaire and collected the data from the targeted elderly left behind through the multistage sampling technique. The sample size of the study was 400 elderly left behind from the different areas of Rawalpindi. The study concludes through its findings that its findings there is higher reciprocity between social well-being and psychological well-being, economic and social well-being has a strong association, but economic and psychological well-being has not been found significant. The study suggests there is a dire need to devise policies for the well-being of the increasing elderly population. Keywords: Social well-being, psychological well-being, Economic Well Being. Migration.

Laplacian face blending

AbstractDesigning realistic tridimensional facial models is a challenging task, not only due to the effort and artistic abilities required but also because human visual perception is very tuned to the processing of facial features. For this reason, rather than creating face models from scratch, artists usually start from a scanned model of a real person. In this work, we present a novel method for blending human faces in order to create a new one. In a nutshell, our proposal uses Laplacian smoothing to segregate layers of details from one or more faces, which are then integrated into a base face with the help of an interactive and visual editor. In particular, our method supports blending multiple faces and multiple sub‐regions in those faces. Since our approach is intuitive and relatively easy to implement, it can be integrated into artistic pipelines aiming at designing human face models from preexisting ones.

Attenuated clinical and osteoclastic phenotypes of Paget\u2019s disease of bone linked to the p.Pro392Leu/SQSTM1 mutation by a rare variant in the DOCK6 gene

BackgroundWe identified two families with Paget's disease of bone (PDB) linked to the p.Pro392Leu mutation within the SQSTM1 gene displaying a possible digenism. This study aimed at identifying this second genetic variant cosegregating with the p.Pro392Leu mutation and at characterizing its impact on the clinical and cellular phenotypes of PDB.MethodsWhole exome sequencing was performed in one patient per family and two healthy controls. We compared clinical characteristics of PDB in 14 relatives from the two families. The osteoclastic phenotype was compared in in vitro differentiated osteoclasts from 31 participants carrying the DOCK6 and/or SQSTM1 variants. Tridimensional models of SQSTM1 and DOCK6 proteins were generated to evaluate the impact of these variants on their stability and flexibility. Statistical analyses were performed with Graphpad prism.ResultsWhole-exome sequencing allowed us to identify the p.Val45Ile missense variant in the DOCK6 gene in patients. In both families, the mean age at PDB diagnosis was delayed in pagetic patients carrier of the p.Val45Ile variant alone compared to those carrying the p.Pro392Leu mutation alone (67 vs. 44 years, P = 0.03). Although both p.Val45Ile and p.Pro392Leu variants gave rise to a pagetic phenotype of osteoclast versus healthy controls, the p.Val45Ile variant was found to attenuate the severity of the osteoclastic phenotype of PDB caused by the p.Pro392Leu mutation when both variants were present. The DOCK6 mRNA expression was higher in carriers of the p.Val45Ile variant than in pagetic patients without any mutations and healthy controls. Structural bioinformatics analyses suggested that the p.Pro392Leu mutation might rigidify the UBA domain and thus decrease its possible intramolecular interaction with a novel domain, the serum response factor–transcription factor (SRF-TF)-like domain, whereas the p.Val45Ile variant may decrease SRF-TF-like activity.ConclusionThe p.Val45Ile variant may attenuate the severity of the clinical phenotype of PDB in patient carriers of both variants. In vitro, the rare variant of the DOCK6 may have a modifier effect on the p.Pro392Leu mutation, possibly via its effect on the SRF-TF-like.

A numerical model capable of accurately simulating the punching shear behavior of a reinforced concrete slab

AbstractThe paper presents the tridimensional numeric model of an inner slab‐column connection of reinforced concrete, which was previously tested against the punching shear in the lab of the University of Brasília. The numerical analysis has been carried out by the finite element method, using the software ABAQUS. To evaluate the sensitivity of the main factors that influence the responses of the model, a parametric investigation was conducted as per the finite element mesh, mechanical properties of the concrete and plastic parameters of the assumed model for the concrete, named by concrete damaged plasticity model (CDPM). The results of the resistance capacity, displacements, strains, cracking pattern, and failure mode were compared with those obtained experimentally. From this comparison, it was concluded that the numerical model was able to reproduce the punching shear phenomenon with a high level of precision.