500 research outputs found
A feasibility analysis towards the simulation of hysteresis with spin-lattice dynamics
We use spin-lattice dynamics simulations to study the possibility of modeling
the magnetic hysteresis behavior of a ferromagnetic material. The temporal
evolution of the magnetic and mechanical degrees of freedom is obtained through
a set of two coupled Langevin equations. Hysteresis loops are calculated for
different angles between the external field and the magnetocrystalline
anisotropy axes. The influence of several relevant parameters is studied,
including the field frequency, magnetic damping, magnetic anisotropy (magnitude
and type), magnetic exchange, and system size. The role played by a moving
lattice is also discussed. For a perfect bulk ferromagnetic system we find
that, at low temperatures, the exchange and lattice dynamics barely affect the
loops, while the field frequency and magnetic damping have a large effect on
it. The influence of the anisotropy magnitude and symmetry are found to follow
the expected behavior. We show that a careful choice of simulation parameters
allows for an excellent agreement between the spin-lattice dynamics
measurements and the paradigmatic Stoner-Wohlfarth model. Furthermore, we
extend this analysis to intermediate and high temperatures for the perfect bulk
system and for spherical nanoparticles, with and without defects, reaching
values close to the Curie temperature. In this temperature range, we find that
lattice dynamics has a greater role on the magnetic behavior, especially in the
evolution of the defective samples. The present study opens the possibility for
more accurate inclusion of lattice defects and thermal effects in hysteresis
simulation
A case of systemic pseudohypoaldosteronism with a novel mutation in the SCNN1A gene
We report a neonatal case of systemic pseudohypoaldosteronism type 1 caused by a novel mutation in the SCNN1A gene (homozygous c.1052+2dupT in intron 3) in which the patient presented with life-threatening hyperkalemia, hyponatremia and metabolic acidosis. It remains uncertain if there is genotype-phenotype correlation, due to the rarity of the disease. This mutation, which to our best knowledge has not been described before, was associated with a very severe phenotype requiring aggressive therapy
Microarray in clinical practice – utility vs complexity. Mixed phenotype of duplication 15q11.2q13.1 and deletion 16p11.2
Introduction: There’s a consensus to perform chromosomal microarray
technique as first-tier clinical diagnostic test for individuals with developmental
disabilities. However, given the complexity of clinical presentations, often several
diagnostic methods are held before conducting microarray.
Method: We report the case of a 5 year-old boy referred to Medical Genetics due
to short stature, developmental disabilities and facial dysmorphic features.
He was born from eutocic delivery after an uneventful pregnancy. He had
psychomotor milestones delayed like sitting at 9 months and walking at 24
months, holding an immature broad-based gait. There was history of learning
difficulties from both parents, and the mother has also short stature.
On examination it was noted some facial dysmorphic features like high forehead,
conical canines and rarefaction of the distal portion of the eyebrows.
Due to the history of an episode of transient ataxia, and suspicion of an inherited
metabolic disorder, he had already performed various analytical and imaging
screenings, all normal.
Results: Chromosomal microarray analysis revealed two pathogenic Copy
Number Variants (CNV’s): 16p11.2 deletion and 15q11.2q13.1 duplication.
The 15q11q13 microduplication syndrome (OMIM # 608636) is a very rare clinical
entity with about 30 reported cases with maternal origin, and it is characterized by
neurobehavioral disorder, hypotonia, cognitive impairment, epilepsy and short
stature.
The 16p11.2 microdeletion syndrome (OMIM # 613444) is also a rare clinical
entity, with high penetrance, associated with obesity and developmental
disabilities.
Discussion: Despite the unquestionable utility of microarray, the correlation of
the CNV's with the phenotype is often difficult by the rarity of these new
microdeletion/duplication clinical entities. In this case the interpretation has
increased difficulty because of the simultaneous existence of two distinct clinical
entities. Segregation studies, which in the first step include parental analysis, are
essential for genetic counseling and determining the risk of recurrence but also
for a more accurate correlation genotype-phenotype
An automated fluorescence videomicroscopy assay for the detection of mitotic catastrophe
Mitotic catastrophe can be defined as a cell death mode that occurs during or shortly after a prolonged/aberrant mitosis, and can show apoptotic or necrotic features. However, conventional procedures for the detection of apoptosis or necrosis, including biochemical bulk assays and cytofluorometric techniques, cannot discriminate among pre-mitotic, mitotic and post-mitotic death, and hence are inappropriate to monitor mitotic catastrophe. To address this issue, we generated isogenic human colon carcinoma cell lines that differ in ploidy and p53 status, yet express similar amounts of fluorescent biosensors that allow for the visualization of chromatin (histone H2B coupled to green fluorescent protein (GFP)) and centrosomes (centrin coupled to the Discosoma striata red fluorescent protein (DsRed)). By combining high-resolution fluorescence videomicroscopy and automated image analysis, we established protocols and settings for the simultaneous assessment of ploidy, mitosis, centrosome number and cell death (which in our model system occurs mainly by apoptosis). Time-lapse videomicroscopy showed that this approach can be used for the high-throughput detection of mitotic catastrophe induced by three mechanistically distinct anti-mitotic agents (dimethylenastron (DIMEN), nocodazole (NDZ) and paclitaxel (PTX)), and – in this context – revealed an important role of p53 in the control of centrosome number
Reinforced Concrete Building with IED Detonation: Test and Simulation
There is growing concern about the possibility of a suicide bomber being immolated when the army forces or the law enforcement agencies discover the place where they prepare their material or simply find themselves inside a building. To study the possible effects that these improvised explosive devices (IEDs) would have on the structures, eight tests were carried out with various configurations of IEDs with vest bombs inside a reinforced concrete (including walls and roof) building constructed ad hoc for these tests. These vests were made with different explosives (black powder, ANFO, AN/AL, PG2). For the characterization of these tests, a high-speed camera and pressure and acceleration sensors were used. The structure behaved surprisingly well, as it withstood all the first seven detonations without apparent structural damage. In the last detonation, located on the ground and with a significant explosive charge, the structural integrity of the roof and some of the walls was compromised. The simulation of the building was carried out with the LS-DYNA software with a Lagrangian formulation for the walls, using the LBE (based on CONWEP) module for the application of the charge. Despite the difficulty of this simulation, the results obtained, in terms of applied pressures and measured accelerations, are acceptable with differences of about 20%
Learning of the Object Oriented Paradigm Through Interactive Video-Games Development
The Object Orientation Paradigm (OOP) is more than Object Oriented languages. Learning the syntax of a language as C++ or Java is a relatively easy task compared with the understanding of the principles of OO Modeling and Design (OOD), which require a high ability of abstract reasoning. Moreover, it is not enough to teach the artifacts of Computer Aided Software Engineering (CASE) as the Unified Modeling Language (UML) if those principles are not properly understood. We wanted to engage the students in a motivating framework, so both the principles of OOD are properly acquired and put in practice with CASE and programming tools
Criteria to predict carriers of a novel SCN5A mutation in a large Portuguese family affected by the Brugada syndrome
Brugada syndrome (BrS) is a life-threatening arrhythmia disorder associated with autosomal-dominant mutations in the SCN5A gene. We aimed to characterize the diagnostic challenges and clinical manifestations of a novel SCN5A mutation associated with BrS.info:eu-repo/semantics/publishedVersio
The cdh1 c.1901c>t variant: A founder variant in the portuguese population with severe impact in mrna splicing
Hereditary diffuse gastric cancer (HDGC) caused by CDH1 variants predisposes to early-onset diffuse gastric (DGC) and lobular breast cancer (LBC). In Northern Portugal, the unusually high number of HDGC cases in unrelated families carrying the c.1901C>T variant (formerly known as p.A634V) suggested this as a CDH1-founder variant. We aimed to demonstrate that c.1901C>T is a bona fide truncating variant inducing cryptic splicing, to calculate the timing of a potential founder effect, and to characterize tumour spectrum and age of onset in carrying families. The impact in splicing was proven by using carriers’ RNA for PCR-cloning sequencing and allelic expression imbalance analysis with SNaPshot. Carriers and noncarriers were haplotyped for 12 polymorphic markers, and the decay of haplotype sharing (DHS) method was used to estimate the time to the most common ancestor of c.1901C>T. Clinical information from 58 carriers was collected and analysed. We validated the cryptic splice site within CDH1-exon 12, which was preferred over the canonical one in 100% of sequenced clones. Cryptic splicing induced an out-of-frame 37bp deletion in exon 12, premature truncation (p.Ala634ProfsTer7), and consequently RNA mediated decay. The haplotypes carrying the c.1901C>T variant were found to share a common ancestral estimated at 490 years (95% Confidence Interval 445–10,900). Among 58 carriers (27 males (M)–31 females (F); 13–83 years), DGC occurred in 11 (18.9%; 4M–7F; average age 33 ± 12) and LBC in 6 females (19.4%; average age 50 ± 8). Herein, we demonstrated that the c.1901C>T variant is a loss-of-function splice-site variant that underlies the first CDH1-founder effect in Portugal. Knowledge on this founder effect will drive genetic testing of this specific variant in HDGC families in this geographical region and allow intrafamilial penetrance analysis and better estimation of variant-associated tumour risks, disease age of onset, and spectrum.This research and its authors were funded by FEDER—Fundo Europeu de Desenvolvi-mento Regional funds through the COMPETE 2020—Operational Programme for Competitiveness and Internationalization (POCI), Portugal 2020, and by Portuguese funds through FCT—Fundação para a Ciência e a Tecnologia/Ministério da Ciência, Tecnologia e Inovação in the framework of the project “Institute for Research and Innovation in Health Sciences” (POCI-01-0145-FEDER-007274) and LEGOH (PTDC/BTM-TEC/6706/2020). This work was also financed by the projects NORTE-01-0145-FEDER-000003 (DOCnet)—supported by Norte Portugal Regional Programme (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF)—project POCI-01-0145-FEDER-016390 (CancelStem) and PTDC/BTM-TEC/30164/2017 (3DChroMe), funded by ERDF, POCI, and FCT
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