Rearing effect of biofloc on antioxidant and antimicrobial transcriptional response in Litopenaeus stylirostris shrimp facing an experimental sub-lethal hydrogen peroxide stress

This study compares the antioxidant and antimicrobial transcriptional expression of blue shrimps reared according to two different systems, BioFloc Technology (BFT) and Clear sea Water (CW) and their differential responses when facing an experimental sublethal hydrogen peroxide stress. After 30 days of rearing, juvenile shrimps were exposed to H2O2 stress at a concentration of 30 ppm during 6 hours. The oxidative stress caused by H2O2 was examined in the digestive glands of the shrimp, in which antioxidant enzyme (AOE) and antimicrobial peptide (AMP) gene expression were analysed by quantitative real-time PCR. Results showed that rearing conditions did not affect the expression of genes encoding AOEs or AMPs. However, H2O2 stress induced a differential response in expression between shrimps from the two rearing treatments (BFT and CW). Comparative analysis of the expression profiles indicates that catalase transcripts were significantly upregulated by H2O2 stress for BFT shrimps while no change was observed for CW shrimps. In contrast, H2O2 caused down-regulation of superoxide dismutase and glutathione transferase transcripts and of the three AMP transcripts studied (penaeidin 2 and 3, and crustin) for CW shrimps, while no effect was observed on BFT shrimp transcript levels. These results suggested that BFT shrimps maintained antioxidant and AMP responses after stress and therefore can effectively protect their cells against oxidative stress, while CW shrimp immune competence seems to decrease after stress.

The regulation of AMP-activated protein kinase by vascular endothelial growth factor

The function of the vascular endothelium is to maintain vascular homeostasis, by providing an anti-thrombotic, anti-inflammatory and vasodilatory interface between circulating blood and the vessel wall, meanwhile facilitating the selective passage of blood components such as signaling molecules and immune cells. Dysfunction of the vascular endothelium is implicated in a number of pathological states including atherosclerosis and hypertension, and is thought to precede atherogenesis by a number of years. Vascular endothelial growth factor A (VEGF) is a crucial mitogenic signaling molecule, not only essential for embryonic development, but also in the adult for regulating both physiological and pathological angiogenesis. Previous studies by our laboratory have demonstrated that VEGF-A activates AMP-activated protein kinase (AMPK), the downstream component of a signaling cascade important in the regulation of whole body and cellular energy status. Furthermore, studies in our laboratory have indicated that AMPK is essential for VEGF-A-stimulated vascular endothelial cell proliferation. AMPK activation typically stimulates anabolic processes and inhibits catabolic processes including cell proliferation, with the ultimate aim of redressing energy imbalance, and as such is an attractive therapeutic target for the treatment of obesity, metabolic syndromes, and type 2 diabetes. Metabolic diseases are associated with adverse cardiovascular outcomes and AMPK activation is reported to have beneficial effects on the vascular endothelium. The mechanism by which VEGF-A stimulates AMPK, and the functional consequences of VEGF-A-stimulated AMPK activation remain uncertain. The present study therefore aimed to identify the specific mechanism(s) by which VEGF-A regulates the activity of AMPK in endothelial cells, and how this might differ from the activation of AMPK by other agents. Furthermore, the role of AMPK in the pro-proliferative actions of VEGF-A was further examined. Human aortic and umbilical vein endothelial cells were therefore used as a model system to characterise the specific effect(s) of VEGF-A stimulation on AMPK activation. The present study reports that AMPK α1 containing AMPK complexes account for the vast majority of both basal and VEGF-A-stimulated AMPK activity. Furthermore, AMPK α1 is localized to the endoplasmic reticulum when sub-confluent, but translocated to the Golgi apparatus when cells are cultured to confluence. AMPK α2 appears to be associated with a structural cellular component, but neither α1 nor α2 complexes appear to translocate in response to VEGF-A stimulation. The present study confirms previous reports that when measured using the MTS cell proliferation assay, AMPK is required for VEGF-A-stimulated endothelial cell proliferation. However, parallel experiments measuring cell proliferation using the Real-Time Cell Analyzer xCELLigence system, do not agree with these previous reports, suggesting that AMPK may in fact be required for an aspect of mitochondrial metabolism which is enhanced by VEGF-A. Studies into the mitochondrial activity of endothelial cells have proved inconclusive at this time, but further studies into this are warranted. During previous studies in our laboratory, it was suggested that VEGF-A-stimulated AMPK activation may be mediated via the diacylglycerol (DAG)-sensitive transient receptor potential cation channel (TRPCs -3, -6 or -7) family of ion channels. The present study can neither confirm, nor exclude the expression of TRPCs in vascular endothelial cells, nor rule out their involvement in VEGF-A-stimulated AMPK activation; more specific investigative tools are required in order to characterise their involvement. Furthermore, nicotinic acid adenine dinucleotide phosphate (NAADP)-stimulated Ca2+ release from acidic intracellular organelles is not required for AMPK activation by VEGF-A. Despite what is known about the mechanisms by which AMPK is activated, far less is known concerning the downregulation of AMPK activity, as observed in human and animal models of metabolic disease. Phosphorylation of AMPK α1 Ser485 (α2 Ser491) has recently been characterised as a mechanism by which the activity of AMPK is negatively regulated. We report here for the first time that VEGF-A stimulates AMPK α1 Ser485 phosphorylation independently of the previously reported AMPK α1 Ser485 kinases Akt (protein kinase B) and ERK1/2 (extracellular signal-regulated kinase 1/2). Furthermore, inhibition of protein kinase C (PKC), the activity of which is reported to be elevated in metabolic disease, attenuates VEGF-A- and phorbol 12-myristate 13-acetate (PMA)-stimulated AMPK α1 Ser485 phosphorylation, and increases basal AMPK activity. In contrast to this, PKC activation reduces AMPK activity in human vascular endothelial cells. Attempts to identify the PKC isoform responsible for inhibiting AMPK activity suggest that it is one (or more) of the Ca2+-regulated DAG-sensitive isoforms of PKC, however cross regulation of PKC isoform expression has limited the present study. Furthermore, AMPK α1 Ser485 phosphorylation was inversely correlated with human muscle insulin sensitivity. As such, enhanced AMPK α1 Ser485 phosphorylation, potentially mediated by increased PKC activation may help explain some of the reduced AMPK activity observed in metabolic disease.

Acousto-optic modulation of optical reflection properties in fiber Bragg gratings and the application in fiber lasers

This thesis aims to investigate the interaction of acoustic waves and fiber Bragg gratings (FBGs) in standard and suspended-core fibers (SCFs), to evaluate the influence of the fiber, grating and modulator design on the increase of the modulation efficiency, bandwidth and frequency. Initially, the frequency response and the resonant acoustic modes of a low frequency acousto-optic modulator (f < 1.2 MHz) are numerically investigated by using the finite element method. Later, the interaction of longitudinal acoustic waves and FBGs in SCFs is also numerically investigated. The fiber geometric parameters are varied and the strain and grating properties are simulated by means of the finite element method and the transfer matrix method. The study indicates that the air holes composing the SCF cause a significant reduction of the amount of silica in the fiber cross section increasing acousto-optic interaction in the core. Experimental modulation of the reflectivity of FBGs inscribed in two distinct SCFs indicates evidences of this increased interaction. Besides, a method to acoustically induce a dynamic phase-shift in a chirped FBG employing an optimized design of modulator is shown. Afterwards, a combination of this modulator and a FBG inscribed in a three air holes SCF is applied to mode-lock an ytterbium doped fiber laser. To improve the modulator design for future applications, two other distinct devices are investigated to increase the acousto-optic interaction, bandwidth and frequency (f > 10 MHz). A high reflectivity modulation has been achieved for a modulator based on a tapered fiber. Moreover, an increased modulated bandwidth (320 pm) has been obtained for a modulator based on interaction of a radial long period grating (RLPG) and a FBG inscribed in a standard fiber. In summary, the results show a considerable reduction of the grating/fiber length and the modulator size, indicating possibilities for compact and faster acousto-optic fiber devices. Additionally, the increased interaction efficiency, modulated bandwidth and frequency can be useful to shorten the pulse width of future all-fiber mode-locked fiber lasers, as well, to other photonic devices which require the control of the light in optical fibers by electrically tunable acoustic waves.

TEST-ANALYSIS MODEL CORRELATION AND CALIBRATION OF A MULTI-COMPONENT PLASTIC PART

The goal of this project is to learn the necessary steps to create a finite element model, which can accurately predict the dynamic response of a Kohler Engines Heavy Duty Air Cleaner (HDAC). This air cleaner is composed of three glass reinforced plastic components and two air filters. Several uncertainties arose in the finite element (FE) model due to the HDAC’s component material properties and assembly conditions. To help understand and mitigate these uncertainties, analytical and experimental modal models were created concurrently to perform a model correlation and calibration. Over the course of the project simple and practical methods were found for future FE model creation. Similarly, an experimental method for the optimal acquisition of experimental modal data was arrived upon. After the model correlation and calibration was performed a validation experiment was used to confirm the FE models predictive capabilities.

Investigations of Cloud Microphysical Response to Mixing Using Digital Holography

Cloud edge mixing plays an important role in the life cycle and development of clouds. Entrainment of subsaturated air affects the cloud at the microscale, altering the number density and size distribution of its droplets. The resulting effect is determined by two timescales: the time required for the mixing event to complete, and the time required for the droplets to adjust to their new environment. If mixing is rapid, evaporation of droplets is uniform and said to be homogeneous in nature. In contrast, slow mixing (compared to the adjustment timescale) results in the droplets adjusting to the transient state of the mixture, producing an inhomogeneous result. Studying this process in real clouds involves the use of airborne optical instruments capable of measuring clouds at the `single particle' level. Single particle resolution allows for direct measurement of the droplet size distribution. This is in contrast to other `bulk' methods (i.e. hot-wire probes, lidar, radar) which measure a higher order moment of the distribution and require assumptions about the distribution shape to compute a size distribution. The sampling strategy of current optical instruments requires them to integrate over a path tens to hundreds of meters to form a single size distribution. This is much larger than typical mixing scales (which can extend down to the order of centimeters), resulting in difficulties resolving mixing signatures. The Holodec is an optical particle instrument that uses digital holography to record discrete, local volumes of droplets. This method allows for statistically significant size distributions to be calculated for centimeter scale volumes, allowing for full resolution at the scales important to the mixing process. The hologram also records the three dimensional position of all particles within the volume, allowing for the spatial structure of the cloud volume to be studied. Both of these features represent a new and unique view into the mixing problem. In this dissertation, holographic data recorded during two different field projects is analyzed to study the mixing structure of cumulus clouds. Using Holodec data, it is shown that mixing at cloud top can produce regions of clear but humid air that can subside down along the edge of the cloud as a narrow shell, or advect down shear as a `humid halo'. This air is then entrained into the cloud at lower levels, producing mixing that appears to be very inhomogeneous. This inhomogeneous-like mixing is shown to be well correlated with regions containing elevated concentrations of large droplets. This is used to argue in favor of the hypothesis that dilution can lead to enhanced droplet growth rates. I also make observations on the microscale spatial structure of observed cloud volumes recorded by the Holodec.

SIMULATING LARGE DEFORMATION OF INTRANEURAL GANGLION CYST USING FINITE ELEMENT METHOD

Intraneural Ganglion Cyst is disorder observed in the nerve injury, it is still unknown and very difficult to predict its propagation in the human body so many times it is referred as an unsolved history. The treatments for this disorder are to remove the cystic substance from the nerve by a surgery. However these treatments may result in neuropathic pain and recurrence of the cyst. The articular theory proposed by Spinner et al., (Spinner et al. 2003) considers the neurological deficit in Common Peroneal Nerve (CPN) branch of the sciatic nerve and adds that in addition to the treatment, ligation of articular branch results into foolproof eradication of the deficit. Mechanical modeling of the affected nerve cross section will reinforce the articular theory (Spinner et al. 2003). As the cyst propagates, it compresses the neighboring fascicles and the nerve cross section appears like a signet ring. Hence, in order to mechanically model the affected nerve cross section; computational methods capable of modeling excessively large deformations are required. Traditional FEM produces distorted elements while modeling such deformations, resulting into inaccuracies and premature termination of the analysis. The methods described in research report have the capability to simulate large deformation. The results obtained from this research shows significant deformation as compared to the deformation observed in the conventional finite element models. The report elaborates the neurological deficit followed by detail explanation of the Smoothed Particle Hydrodynamic approach. Finally, the results show the large deformation in stages and also the successful implementation of the SPH method for the large deformation of the biological organ like the Intra-neural ganglion cyst.

ADVANCED COMPUTATIONAL MODELING OF THE INTERNAL STRUCTURE OF SMART WIND-TURBINE BLADES

Implementation of stable aeroelastic models with the ability to capture the complex features of Multi concept smartblades is a prime step in reducing the uncertainties that come along with blade dynamics. The numerical simulations of fluid structure interaction can thus be used to test a realistic scenarios comprising of full-scale blades at a reasonably low computational cost. A code which was a combination of two advanced numerical models was designed and was run with the help of paralell HPC supercomputer platform. The first model was based on a variation of dimensional reduction technique proposed by Hodges and Yu. This model was the one to record the structural response of heterogenous composite blades. This technique reduces the geometrical complexities of the heterogenous blade section into a stiffness matrix for an equivalent beam. This derived equivalent 1-D strain energy matrix is similar to the actual 3-D strain energy matrix in an asymptotic sense. As this 1-D matrix helps in accurately modeling the blade structure as a 1-D finite element problem, this substantially redues the computational effort and subsequently the computational cost that are required to model the structural dynamics at each step. Second model comprises of implementation of the Blade Element Momentum Theory. In this approach we map all the velocities and the forces with the help of orthogonal matrices that help in capturing the large deformations and the effects of rotations in calculating the aerodynamic forces. This ultimately helps us to take into account the complex flexo torsional deformations. In this thesis we have succesfully tested these computayinal tools developed by MTU’s research team lead by for the aero elastic analysis of wind-turbine blades. The validation in this thesis is majorly based on several experiments done on NREL-5MW blade, as this is widely accepted as a benchmark blade in the wind industry. Along with the use of this innovative model the internal blade structure was also changed to add up to the existing benefits of the already advanced numerical models.

Hazard Mitigation Element Quality in Coastal Comprehensive Plans in a State with Strong Requirements for Hazard Mitigation Plan Elements

This dissertation examines the quality of hazard mitigation elements in a coastal, hazard prone state. I answer two questions. First, in a state with a strong mandate for hazard mitigation elements in comprehensive plans, does plan quality differ among county governments? Second, if such variation exists, what drives this variation? My research focuses primarily on Florida’s 35 coastal counties, which are all at risk for hurricane and flood hazards, and all fall under Florida’s mandate to have a comprehensive plan that includes a hazard mitigation element. Research methods included document review to rate the hazard mitigation elements of all 35 coastal county plans and subsequent analysis against demographic and hazard history factors. Following this, I conducted an electronic, nationwide survey of planning professionals and academics, informed by interviews of planning leaders in Florida counties. I found that hazard mitigation element quality varied widely among the 35 Florida coastal counties, but were close to a normal distribution. No plans were of exceptionally high quality. Overall, historical hazard effects did not correlate with hazard mitigation element quality, but some demographic variables that are associated with urban populations did. The variance in hazard mitigation element quality indicates that while state law may mandate, and even prescribe, hazard mitigation in local comprehensive plans, not all plans will result in equal, or even adequate, protection for people. Furthermore, the mixed correlations with demographic variables representing social and disaster vulnerability shows that, at least at the county level, vulnerability to hazards does not have a strong effect on hazard mitigation element quality. From a theory perspective, my research is significant because it compares assumptions about vulnerability based on hazard history and demographics to plan quality. The only vulnerability-related variables that appeared to correlate, and at that mildly so, with hazard mitigation element quality, were those typically representing more urban areas. In terms of the theory of Neo-Institutionalism and theories related to learning organizations, my research shows that planning departments appear to have set norms and rules of operating that preclude both significant public involvement and learning from prior hazard events.

Barrier Island Response to Sea Level Rise in North Carolina

The state of North Carolina is home to some of the most spectacular barrier islands in the world. These features are constantly shifting, impacted by waves, tides, and wind. Studies of the Outer Banks, North Carolina have resulted in varied results, but a detailed analysis of the barrier system as a whole is lacking. Using historic topographic surveys (T-sheets) from the 19th, the positions of various barrier segments were analyzed in relation to modern imagery. Changes in area, width, and center line locations were evaluated over the past 150 years. In total, 74 percent of modern transects have decreased in area. Total reductions in size were 130 km2 for the study period. Mean centerlines as a function of migration showed that 53 percent of segments were demonstrating directional movement away from the ocean. The average movement towards the bay between modern and historic centerlines was 8 meters. Thusly, barrier islands in North Carolina are demonstrating both decreases in total area and directional movement inland in response to sea level rise.

Electrochemical Immunosensing of Cortisol in an Automated Microfluidic System Towards Point-of-Care Applications

This dissertation describes the development of a label-free, electrochemical immunosensing platform integrated into a low-cost microfluidic system for the sensitive, selective and accurate detection of cortisol, a steroid hormone co-related with many physiological disorders. Abnormal levels of cortisol is indicative of conditions such as Cushing’s syndrome, Addison’s disease, adrenal insufficiencies and more recently post-traumatic stress disorder (PTSD). Electrochemical detection of immuno-complex formation is utilized for the sensitive detection of Cortisol using Anti-Cortisol antibodies immobilized on sensing electrodes. Electrochemical detection techniques such as cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS) have been utilized for the characterization and sensing of the label-free detection of Cortisol. The utilization of nanomaterial’s as the immobilizing matrix for Anti-cortisol antibodies that leads to improved sensor response has been explored. A hybrid nano-composite of Polyanaline-Ag/AgO film has been fabricated onto Au substrate using electrophoretic deposition for the preparation of electrochemical immunosening of cortisol. Using a conventional 3-electrode electrochemical cell, a linear sensing range of 1pM to 1µM at a sensitivity of 66µA/M and detection limit of 0.64pg/mL has been demonstrated for detection of cortisol. Alternately, a self-assembled monolayer (SAM) of dithiobis(succinimidylpropionte) (DTSP) has been fabricated for the modification of sensing electrode to immobilize with Anti-Cortisol antibodies. To increase the sensitivity at lower detection limit and to develop a point-of-care sensing platform, the DTSP-SAM has been fabricated on micromachined interdigitated microelectrodes (µIDE). Detection of cortisol is demonstrated at a sensitivity of 20.7µA/M and detection limit of 10pg/mL for a linear sensing range of 10pM to 200nM using the µIDE’s. A simple, low-cost microfluidic system is designed using low-temperature co-fired ceramics (LTCC) technology for the integration of the electrochemical cortisol immunosensor and automation of the immunoassay. For the first time, the non-specific adsorption of analyte on LTCC has been characterized for microfluidic applications. The design, fabrication technique and fluidic characterization of the immunoassay are presented. The DTSP-SAM based electrochemical immunosensor on µIDE is integrated into the LTCC microfluidic system and cortisol detection is achieved in the microfluidic system in a fully automated assay. The fully automated microfluidic immunosensor hold great promise for accurate, sensitive detection of cortisol in point-of-care applications.

Operant and Respondent Procedures to Establish Social Stimuli as Reinforcers in Children with Autism

According to the DSM-IV- TR (American Psychiatric Association, 2000), one of the core deficits in autism is in the impairment of social interaction. Some have suggested that underlying these deficits is the reality that individuals with autism do not find social stimuli to be as reinforcing as other types of stimuli (Dawson, 2008). An interesting and growing body of literature supports the notion that symptoms in autism may be caused by a general reduction in social motivation (Chevallier et al., 2012). A review of the literature suggests that social orienting and social motivation are low in individuals with autism, and including social motivation as a target for therapeutic intervention should be pursued (Helt et al., 2008). Through our understanding of learning processes, researchers in behavior analysis and related fields have been able to use conditioning procedures to change the function of neutral or ineffective stimuli, including tokens (Ayllon & Azrin, 1968), facial expressions (Gewirtz & Pelaez-Nogueras, 1992) and praise (Dozier et al., 2012). The current study aimed to use operant and respondent procedures to condition social stimuli that were empirically shown to not be reinforcing prior to conditioning. Further, this study aimed to compare the two procedures in their effectiveness to condition social stimuli to function as reinforcers, and in their maintenance of effects over time. Using a multiple-baseline, multi-element design, one social stimulus was conditioned under each procedure to compare the different response rates following conditioning. Finally, the study sought to determine if conditioning social stimuli to function as reinforcers had any effect on the social functioning of young children with autism. Six children diagnosed with autism between the ages of 18 months and 3 years participated. Results show that the respondent procedure (pairing) resulted in more robust and enduring effects than the operant procedure (Sd procedure). Results of a social communication assessment (ESCS, Mundy et al., 2003) before and after conditioning demonstrate gains in all areas of social communication, particularly in the areas of initiating and responding to joint attention.

Development of a Coupling Model for Fluid-Structure Interaction using the Mesh-free Finite Element Method and the Lattice Boltzmann Method

In the presented thesis work, the meshfree method with distance fields was coupled with the lattice Boltzmann method to obtain solutions of fluid-structure interaction problems. The thesis work involved development and implementation of numerical algorithms, data structure, and software. Numerical and computational properties of the coupling algorithm combining the meshfree method with distance fields and the lattice Boltzmann method were investigated. Convergence and accuracy of the methodology was validated by analytical solutions. The research was focused on fluid-structure interaction solutions in complex, mesh-resistant domains as both the lattice Boltzmann method and the meshfree method with distance fields are particularly adept in these situations. Furthermore, the fluid solution provided by the lattice Boltzmann method is massively scalable, allowing extensive use of cutting edge parallel computing resources to accelerate this phase of the solution process. The meshfree method with distance fields allows for exact satisfaction of boundary conditions making it possible to exactly capture the effects of the fluid field on the solid structure.

Progress in understanding of the molecular basis underlying functional diversification of cyclic di-nucleotide turnover proteins

Cyclic di-GMP was the first cyclic di-nucleotide second messenger described, presaging the discovery of additional cyclic di-nucleotide messengers in bacteria and eukaryotes. The GGDEF diguanylate cyclase (DGC) and EAL and HD-GYP phosphodiesterase (PDE) domains conduct the turnover of cyclic di-GMP. These three unrelated domains belong to superfamilies that exhibit significant variations in function, to include both enzymatically active and inactive members with a subset involved in synthesis and degradation of other cyclic di-nucleotides. Here we summarize current knowledge of sequence and structural varitions that underpin the functional diversification of cyclic di-GMP turnover proteins. Moreover, we highlight that superfamily diversification is not restricted to cyclic di-GMP signaling domains, as particular DHH/DHHA1 domain and HD domain proteins have been shown to act as cyclic di-AMP phosphodiesterases. We conclude with a consideration of the current limitations that such diversity of action places on bioinformatic prediction of the roles of GGDEF, EAL and HD-GYP domain proteins.

Modelling and studies of the spectral response of some optoelectronic components

Solar radiation takes in today's world, an increasing importance. Different devices are used to carry out spectral and integrated measurements of solar radiation. Thus the sensors can be divided into the fallow types: Calorimetric, Thermomechanical, Thermoelectric and Photoelectric. The first three categories are based on components converting the radiation to temperature (or heat) and then into electrical quantity. On the other hand, the photoelectric sensors are based on semiconductor or optoelectronic elements that when irradiated change their impedance or generate a measurable electric signal. The response function of the sensor element depends not only on the intensity of the radiation but also on its wavelengths. The radiation sensors most widely used fit in the first categories, but thanks to the reduction in manufacturing costs and to the increased integration of electronic systems, the use of the photoelectric-type sensors became more interesting. In this work we present a study of the behavior of different optoelectronic sensor elements. It is intended to verify the static response of the elements to the incident radiation. We study the optoelectronic elements using mathematical models that best fit their response as a function of wavelength. As an input to the model, the solar radiation values are generated with a radiative transfer model. We present a modeling of the spectral response sensors of other types in order to compare the behavior of optoelectronic elements with other sensors currently in use.

A finite element framework for the interplay between delamination and buckling of rubber-like bi-material systems and stretchable electronics

In this study, a finite element (FE) framework for the analysis of the interplay between buckling and delamination of thin layers bonded to soft substrates is proposed. The current framework incorporates the following modeling features: (i) geometrically nonlinear solid shell elements, (ii) geometrically nonlinear cohesive interface elements, and (iii) hyperelastic material constitutive response for the bodies that compose the system. A fully implicit Newton–Raphson solution strategy is adopted to deal with the complex simultaneous presence of geometrical and material nonlinearities through the derivation of the consistent FE formulation. Applications to a rubber-like bi-material system under finite bending and to patterned stiff islands resting on soft substrate for stretchable solar cells subjected to tensile loading are proposed. The results obtained are in good agreement with benchmark results available in the literature, confirming the accuracy and the capabilities of the proposed numerical method for the analysis of complex three-dimensional fracture mechanics problems under finite deformations.