Cerebral Creatine Deficiency Syndromes

Introduction: Creatine deficiency syndromes are a recently described group of diseases characterized by inborn errors of creatine metabolism. Clinical features include a spectrum of neurodevelopment disorders of diverse severity. They are characterized by low levels of cerebral creatine caused by different pathogenic mutations concerning the genes coding for creatine synthesis enzymes [arginine: glicyne amidinotransferase (AGAT, EC 2.1.4.1) and guanidinoacetate methyltansferase (GAMT, EC 2.1.1.2)], AGAT and GAMT, respectively, or its transporter (CT1 deficiency), SLC6A8. Enzymatic deficiencies are transmitted as autosomal recessive traits, whereas the transporter deficit is X-linked. Objectives: To characterize the clinical and laboratorial presentation, diagnosis and treatment of cerebral creatine deficiency patients, followed in Hospital Pediátrico Carmona da Mota. The awareness of these inborn errors of metabolism as neurological disorders, namely of neurodevelopment, among the medical community is a secondary aim of the present work. Methods and Material: Retrospective analysis of the clinical files of patients followed in our Hospital and diagnosed with cerebral creatine deficiency syndrome. Results: Twelve patients belonging to seven different families were diagnosed with creatine deficiency syndromes. Five presented GAMT deficiency and seven CT1 deficiency. Present ages are 2 to 38 years old. The most common clinical presentations were: global development delay in seven patients (two with epilepsy), and speech delay in two patients. Only one patient had communication and social interaction dysfunction. In all, global development delay in the range of intellectual delay was identified. The pathognomonic pattern of cerebral creatine deficiency in the brain image was demonstrated in eight patients. Pathogenic mutations in GAMT or SLC6A8 genes were identified in all cases. Conclusions: The suspicion of cerebral creatine depletion must be considered in all children presenting unexplained global psychomotor development delay. Pre-symptomatic therapy has shown promising results, especially in GAMT deficiency patients. The high rate of asymptomatic carriers of GAMT mutations in our population makes this disorder eligible to neonatal screening in Portugal

Evaluation of policy based admission control mechanisms in NGN

The 3GPP consortium proposed in the release 7 of the IP Multimedia Subsystem (IMS) a Diameter interface for the resource admission communication process replacing the previous COPS solution. Although both academic and industry communities have deeply debate the advantages and disadvantages of each protocol, its impact in NGN may have not been thoroughly quantified. This paper compares both protocols in terms of messages exchanged between network entities, and of bandwidth requirements during the admission control process. Based on general network operator environment characteristics, we present several exploitation scenarios where it is analyzed the scalability and adequacy of each protocol

Considering the stiffness of the forming tools in the numerical analysis of the ironing process

Ironing can occur in cylindrical cup drawing whenever the thickness of the drawn flange is larger than the gap between the punch and the die. This is particularly relevant for materials that present r-values lower than 1.0, such as the aluminium alloys, since they tend to present more thickening of the flange. The aim of this study is to evaluate numerically the impact of the elastic deformation of the forming tools on the final cup geometry, i.e., the earing profile and the evolution of thickness along the circumferential direction, at different heights. Different contact conditions are also analysed since they strongly affect both the thickness strain and the earing profile. The process conditions considered are the ones from EXACT, the ESAFORM Benchmark 2021, enabling the comparison with experimental results. Considering the deformation of the forming tools mainly impacts the ironing stage, enabling predicting wall thickness values larger than the gap between the punch and the die.The authors gratefully acknowledge the financial support of the Portuguese Foundation for Science and Technology (FCT) under projects with reference 2022.08459.PTDC, UIDB/00285/2020 and LA/P/0112/2020

Unified platform for M2M Telco Providers

Although many environments are powered by M2M solutions, users do not have a simple way to gather their collective knowledge and program devices’ behaviour. Also, Telco providers still lack proper components for enabling integrated services over their networks. We present the final architecture of the APOLLO project, which delivers a enhanced M2M platform encompassing sensors, management and applications platform for a major Telco provider. APOLLO builds on top of ETSI M2M specifications and rich service execution environments providing easy orchestration of services to end-users

GTO : A toolkit to unify pipelines in genomic and proteomic research

Next-generation sequencing triggered the production of a massive volume of publicly available data and the development of new specialised tools. These tools are dispersed over different frameworks, making the management and analyses of the data a challenging task. Additionally, new targeted tools are needed, given the dynamics and specificities of the field. We present GTO, a comprehensive toolkit designed to unify pipelines in genomic and proteomic research, which combines specialised tools for analysis, simulation, compression, development, visualisation, and transformation of the data. This toolkit combines novel tools with a modular architecture, being an excellent platform for experimental scientists, as well as a useful resource for teaching bioinformatics enquiry to students in life sciences. GTO is implemented in C language and is available, under the MIT license, at https://bioinformatics.ua.pt/gto. (C) 2020 The Authors. Published by Elsevier B.V.Peer reviewe

Remapping algorithms: application to trimming operations in sheet metal forming

Most of sheet metal forming processes comprise intermediate trimming operations to remove superfluous material. These operations are required for subsequent forming operations. On the other hand, the springback is strongly influenced by the trimming operations that change the part stiffness and the stress field. From the numerical point of view, this involves the geometrical trimming of the finite element mesh and subsequent remapping of the state variables. This study presents a remapping method based on Dual Kriging interpolation, specifically developed for hexahedral finite elements, which has been implemented in DD3TRIM in-house code. Its performance is compared with the one of the Incremental Volumetric Remapping method, using the split-ring test to highlight their advantages and limitations. The numerical simulation of the forming processes is performed with DD3IMP finite element solver.The authors gratefully acknowledge the financial support of the Portuguese Foundation for Science and Technology (FCT) under the projects with reference UID/EMS/00285/2013, PTDC/EMS-TEC/0702/2014 (POCI-01-0145-FEDER-016779) and PTDC/EMS-TEC/6400/2014 (POCI-01-0145-FEDER-016876) by UE/FEDER through the program COMPETE2020. The first author is also grateful to the FCT for the Postdoctoral grant SFRH/BPD/101334/2014.info:eu-repo/semantics/publishedVersio

Bioengineered nanoparticles loaded-hydrogels to target TNF Alpha in inflammatory diseases

Rheumatoid Arthritis (RA) is an incurable autoimmune disease that promotes the chronic impairment of patientsâ mobility. For this reason, it is vital to develop therapies that target early inflammatory symptoms and act before permanent articular damage. The present study offers two novel therapies based in advanced drug delivery systems for RA treatment: encapsulated chondroitin sulfate modified poly(amidoamine) dendrimer nanoparticles (NPs) covalently bonded to monoclonal anti-TNF α antibody in both Tyramine-Gellan Gum and Tyramine-Gellan Gum/Silk Fibroin hydrogels. Using pro-inflammatory THP-1 (i.e., human monocytic cell line), the therapy was tested in an inflammation in vitro model under both static and dynamic conditions. Firstly, we demonstrated effective NP-antibody functionalization and TNF-α capture. Upon encapsulation, the NPs were released steadily over 21 days. Moreover, in static conditions, the approaches presented good anti-inflammatory activity over time, enabling the retainment of a high percentage of TNF α. To mimic the physiological conditions of the human body, the hydrogels were evaluated in a dual-chamber bioreactor. Dynamic in vitro studies showed absent cytotoxicity in THP-1 cells and a significant reduction of TNF-α in suspension over 14 days for both hydrogels. Thus, the developed approach showed potential for use as personalized medicine to obtain better therapeutic outcomes and decreased adverse effects.The authors thank the financial support provided under the Norte2020 project (NORTE-08-5369-FSE000044). D.C.F. acknowledges the Portuguese Foundation for Science and Technology (FCT) for her PhD scholarship (PD/BD/143081/2018) and F.R.M. for her contract under the Transitional Rule DL 57/2016 (CTTI-57/18-I3BS(5)). The FCT distinction attributed to J.M.O. under the Investigator FCT program (number IF/01285/2015) is also greatly acknowledged

Brief report: High frequency of biochemical markers for mitochondrial dysfunction in autism: no association with the mitochondrial aspartate/glutamate carrier SLC25A12 gene

In the present study we confirm the previously reported high frequency of biochemical markers of mitochondrial dysfunction, namely hyperlactacidemia and increased lactate/pyruvate ratio, in a significant fraction of 210 autistic patients. We further examine the involvement of the mitochondrial aspartate/glutamate carrier gene (SLC25A12) in mitochondrial dysfunction associated with autism. We found no evidence of association of the SLC25A12 gene with lactate and lactate/pyruvate distributions or with autism in 241 nuclear families with one affected individual. We conclude that while mitochondrial dysfunction may be one of the most common medical conditions associated with autism, variation at the SLC25A12 gene does not explain the high frequency of mitochondrial dysfunction markers and is not associated with autism in this sample of autistic patients

On the effect of the tension-compression ratio on forming of isotropic materials

It is generally believed that the choice of the yield criterion used to describe the plastic behaviour of isotropic metallic materials does not affect much the accuracy of the predictions of forming operations. For this reason, the von Mises yield criterion is widely used for modelling their plastic behaviour. However, according to the von Mises yield criterion, the ratio between the yield stresses in tension and compression is always 1.0. Nevertheless, materials can present same asymmetry, i.e. a strength differential (SD) effect. In this work, the yield criterion proposed by Cazacu et al. [1], is adopted to describe the mechanical behaviour of isotropic materials, with different levels of tension-compression asymmetry. Numerical simulations of the deep drawing of a cylindrical cup were performed considering these different virtual isotropic materials, in order to evaluate its impact on the thickness distribution and cup height. The analysis of the stress and strain paths, for material points initially located in the flange is performed, enabling the correlation between the thickness distributions predicted and the plastic strain ratios obtained analytically, using the yield function and the normality rule. The results show that even small changes in the tension-compression stress ratio can influence the strains distribution, in isotropic materials.The authors gratefully acknowledge the financial support of the projects POCI-01-0145-FEDER30592 (PTDC/EME-EME/30592/2017) and UIDB/00285/2020 financed by the Operational Program for Competitiveness and Internationalization, in its FEDER/FNR component, and the Portuguese Foundation of Science and Technology (FCT), in its State Budget component (OE)

An adaptive graph for volumetric mesh visualization

AbstractThis work presents an adaptive strategy in order to visualize volumetric data generated from numerical simulations of partial differential equations. The mesh is represented by a graph data structure. Moreover, the Autonomous Leaves Graph is extended to the three-dimensional case. This scheme intends to achieve better transversal cost than a treelike (e.g., bintree, quadtree and octree) space arrangement approach. Furthermore, this strategy intends to reduce the computational cost of constructing the discretization and the visualization of data. The total-ordering of the mesh volumes used in the discretization and the visualization processes is by the 3D Modified Hilbert space-filling Curve. To evaluate the performance, the strategy is applied on a Heat Conduction simulation problem using finite difference discretizations and the experimental results are discussed. Comparisons are made between numerical results obtained when using the Hilbert Curve and its modified version. In addition, experiments are shown when visualization is made from inside and outside the volume. The results expose the efficiency of using this strategy