Search

Chromosomal structural rearrangements consist of anomalies in genomic architecture that may or may not be associated with genetic material gain and loss. Evaluating the precise breakpoint is crucial from a diagnostic point of view, highlighting possible gene disruption and addressing to appropriate genotype–phenotype association. Structural rearrangements can either occur randomly within the genome or present with a recurrence, mainly due to peculiar genomic features of the surrounding regions. We report about three non-related individuals, harboring chromosomal structural rearrangements interrupting SETBP1, leading to gene haploinsufficiency. Two out of them resulted negative to Chromosomal Microarray Analysis (CMA), being the rearrangement balanced at a microarray resolution. The third one, presenting with a complex three-chromosome rearrangement, had been previously diagnosed with SETBP1haploinsufficiency due to a partial gene deletion at one of the chromosomal breakpoints. We thoroughly characterized the rearrangements by means of Optical Genome Mapping (OGM) and Whole Genome Sequencing (WGS), providing details about the involved sequences and the underlying mechanisms. We propose structural variants as a recurrent event in SETBP1haploinsufficiency, which may be overlooked by laboratory routine genomic analyses (CMA and Whole Exome Sequencing) or only partially determined when associated with genomic losses at breakpoints. We finally introduce a possible role of SETBP1in a Noonan-like phenotype.

This study applies complexity sciences to analyze the game of Padel. Data from 18 professional matches were collected, and the probability distributions of the total number of shots and the probability distribution of rallies' duration were analyzed. Based on these empirical observations and previous reports, a probabilistic model with two parameters was proposed to describe the game dynamics. One of them controls the probability of making a shot and the other probability of doing it offensively. The model also considers the offensive advantage of the team serving the ball. Using this model, an analytical expression for the probability distribution of the total number of shots was obtained and fit to the data. The results reveal that the complex dynamics of Padel can be effectively approximated as a stochastic process governed by simple probabilistic rules. • We visualized 18 elite professional Padel games. • Extracted information from over 5000 rallies. • Found link between rallies' length, serve possession, and success. • Proposed a model for the dynamics of the game. • The model explains emergence of rally length probability. [ABSTRACT FROM AUTHOR]

This paper presents the comparison between the numerical and analytical results of a spacecraft attitude propagation for a spin-stabilized satellite. Some external torques are introduced in the equations of the motion and the comparisons are done considering that these torques are acting together, which are: gravity gradient, aerodynamic, solar radiation, magnetic residual and eddy current. In the numerical approach it is used the quaternion to represent the attitude. This numerical approach can be applied for any kind of satellite. The analytical approach is applied directly for a spin-stabilized satellite and the equations of motion are described in terms of the spin velocity, spin axis right ascension and declination angles. An analytical solution of these equations is presented and valid for one orbit period. Applications are developed considering the Brazilian spin-stabilized satellites SCD1 and SCD2. The comparisons are important to validate some simplifications that are required in the analytical approach. The results show that the average components of the external torque are sufficient to observe the main influence of the considered torques.

This paper presents EvacTrain 2.0 a new model to simulate and explore the results of different evacuation strategies in passenger trains. This model is stochastic and can generate several results within a few seconds. This is why it is intended to be used for decision support during emergencies. EvacTrain is compared with another evacuation model and partially validated against a fire drill. Results show that this model can provide an accurate representation of real evacuation process. The general findings suggest a new paradigm for the application of evacuation modelling in passenger trains: their potential use for supporting emergency decisions in real-time.

New cyclofunctionalized 2,3-benzodiazepines characterized by a triazolone or triazindione ring fused on the “c” edge of the heptatomic nucleus have been prepared. These compounds were evaluated as potential anticonvulsant agents, and some of them proved to be more potent noncompetitive 2-amino-3-(3-hydroxy-5-methylisoxazol-4-yl)propionate (AMPA) receptor antagonists. In particular, 8,9-dimethoxy-6-(4-bromophenyl)-11H-[1,2,4]triazolo[4,5-c][2,3]benzodiazepin-3(2H)-one (5b) was almost 10-fold more active than GYKI-52466 and 3.5-fold more active than Talampanel. Furthermore, 5b potently reduced AMPA-evoked currents in electrophysiological experiments.

The operation of a flowmeter which accurately measures the mass flow of fluid is described. Compared with conventional flowmeters, this instrument has many advantages, including a linear torque output easily adaptable to direct reading, remote indication, or control initiation. It is more easily installed in pipe lines than most flowmeters and can be mounted in any attitude. It has high accuracy, low pressure loss, small size, and light weight. The sample was tested using liquid petroleum fuels of various viscosities and densities, giving errors less than 0.5 per cent of full scale.

•In real life, DMF reduced the annualized relapse rate (ARR) by 75% respect to the pre-treatment ARR.•Age of onset of MS was related with rate or relapses, with younger age being protective.•De-escalating from second-line therapies was associated to higher risk of relapsing.•Disease duration was associated with higher rate of NEDA-3 failure.•Higher pre-treatment EDSS was associated with DMF discontinuation.

ABSTRACTγδ T cells usually infiltrate many different types of cancer, but it is unclear whether they inhibit or promote tumor progression. Moreover, properties of tumor-infiltrating γδ T cells and those in the corresponding normal tissue remain largely unknown. Here we have studied features of γδ T cells in colorectal cancer, normal colon tissue and peripheral blood, and correlated their levels with clinicopathologic hallmarks. Flow cytometry and transcriptome analyses showed that the tumor comprised a highly variable rate of TILs (5–90%) and 4% γδ T cells on average, with the majority expressing Vδ1. Most Vδ1 and Vδ2 T cells showed a predominant effector memory phenotype and had reduced production of IFN- γ which was likely due to yet unidentified inhibitory molecules present in cancer stem cell secretome. Transcriptome analyses revealed that patients containing abundant γδ T cells had significantly longer 5-year disease free survival rate, suggesting their efficacy in controlling tumor at very early stage.

For Abstract see ChemInform Abstract in Full Text.