Parental Segregation Study Reveals Rare Benign and Likely Benign Variants in a Brazilian Cohort of Rare Diseases

Genomic studies may generate massive amounts of data, bringing interpretation challenges. Efforts for the differentiation of benign and pathogenic variants gain importance.In this article, we used segregation analysis and other molecular data to reclassify to benign or likely benign several rare clinically curated variants of autosomal dominant inheritance from a cohort of 500 Brazilian patients with rare diseases.This study included only symptomatic patients who had undergone molecular investigation with exome sequencing for suspected diseases of genetic etiology. Variants clinically suspected as the causative etiology and harbored by genes associated with highly-penetrant conditions of autosomal dominant inheritance underwent Sanger confirmation in the proband and inheritance pattern determination because a “de novo” event was expected.Among all 327 variants studied, 321 variants were inherited from asymptomatic parents. Considering segregation analysis, we have reclassified 51 rare variants as benign (n=51) and 211 as likely benign (n=211).In our study, the inheritance of a highly penetrant variant expected to be de novo for pathogenicity assumption was considered as a non-segregation and, therefore, a key step for benign or likely benign classification. Studies like ours may help to identify rare benign variants and improve the correct interpretation of genetic findings.

PAPPA2 Promote the Proliferation of Dermal Papilla Cells in Hu Sheep (Ovis aries) by Regulating IGFBP5

Hu sheep (Ovis aries) is a rare white sheep breed, with four different types of lambskin patterns that have different values. However, the genetic mechanisms underlying different types of pattern formation remains unclear. This research aimed to characterize the molecular mechanism of differentially expressed gene PAPPA2 affecting the pattern type of Hu sheep’s lambskin at the cellular level. Thus, RT-qPCR, EdU and Cell Cycle detection were used to explore the effect of PAPPA2 and IGFBP5 (a protein that can be hydrolyzed by PAPPA2) on the proliferation of dermal papilla cells (DPCs) after overexpression or interference with PAPPA2 and IGFBP5. The expression level of PAPPA2 in straight DPCs was 4.79 ± 1.84 times higher than curved. Overexpression of PAPPA2 promoted the proliferation of DPCs and also increased the expression of IGFBP5. Conversely, overexpression of IGFBP5 reduced the proliferation of DPCs. However, the proliferation of DPCs was restored by co-overexpression of PAPPA2 and IGFBP5 compared with overexpression of IGFBP5 alone. Thus, PAPPA2 can affect the proliferation of DPCs through regulating IGFBP5 and then participate in lambskin pattern determination. Overall, we preliminarily clarified the critical role played by PAPPA2 during the formation of different pattern in Hu sheep lambskin.

Cracking pattern of indented ice sheet bending failures

Ice sheet bending failures have been investigated extensively for ice loads on conical offshore structures and icebreakers in arctic regions. Most previous theoretical studies focus on bending failures of semi-infinite level ice, ice wedges, or finite-sized rectangular ice floes. For indented ice sheet bending failures, Nevel (1992) and Lau (2004) developed analytical ice load models by assuming a radial-before-circumferential cracking pattern. Recently, real-time simulations of ice-structure interactions are gaining increasing traction due to their great application potential. The analytical or semi-analytical models implemented into the real-time simulator significantly influence the accuracy of real-time simulations. Against this backdrop, the cracking pattern assumption needs to be more critically examined, and the criterion for cracking pattern determinations is in demand for utilizing different models for different cracking patterns in real-time simulations. Motivated by this need, the current paper establishes the cracking pattern determination criterion for indented ice sheet bending failures, based on the theory of plates on elastic foundations and normalized formulae. It is found that large indentation lengths and radii of structure waterline curvature induce a circumferential-before-radial cracking pattern. Conversely, small indentation lengths and radii of structure waterline curvature result in a radial-before-circumferential cracking pattern.

A 3-Year Single Surgeon Experience of the Arterial Switch Operation

Background: The arterial switch operation [ASO] is the surgical procedure of choice for correction of the TGA. This is one of the most complex cardiac surgeries, with coronary artery transfer being the most important factor determining the success of the surgery. Objectives: This study aims to investigate the outcomes of ASO operated by a single surgeon and assess the accuracy of echocardiography in identifying the coronary artery pattern before the ASO, this may lead to a better familiarization with the ASO. Methods: A retrospective study was conducted by operative and postoperative case note review of 125 patients from March 2015 to 2018. We assessed the outcomes of the arterial switch operation. Concomitant defects as atrial septal defects, patent ductus arteriosus and small ventricular septal defects were defined as the simple TGA and other defects were defined as the complex TGA. Coronary artery pattern determination by echocardiography prior to the surgery and during the operation was investigated, as well. 30-day mortality, post-operative neurologic complications, cardiac anatomic complications, arrhythmia, plasma lactate level and cardiopulmonary bypass time [CPB time] during the surgery were recorded. Results: The mean age and weight of the patients were 29.09 (1 - 180) days and 3506.48 (2400 - 9700) grams. Most of the patients (64%) were male. 105 (84%) of the patients had simple and 20 (16%) had complex TGA. Unusual coronary pattern during echocardiography was observed in 17 (13.6%) subjects and unusual coronary pattern during the operation was observed in 7 (5.6%) patients. The incidence of the major anatomical lesions was not significant. 20 (16%) had neurologic complications, including seizure in 14 (11.2%) patients, brain hemorrhage was found in 5 (4%) patients, as well as chorea and wrist drop in the remaining patients. Post-operative arrhythmia was observed in 16 (12.8%) patients. The mortality rate was 4% (5 patients). The CPB time was 202.73 ± 36.99 minutes. Conclusions: Our post-operative results of the ASO indicate excellent results. This signifies high experience and knowledge regarding this surgery.

Neural Network Backpropagation Identification of Jakarta Islamic Index (JII) Stock Price Patterns

Jakarta Islamic Index (JII) is an organization engaged in the economy with the aim to pay attention to stock movements every day. With the JII, people who do not understand about shares and their movements, will be easy to know and understand the movement of shares that occur at certain times. The problem in this research is that many investors are unable to predict the rise and fall of stock prices. The prediction process can be done with a backpropagation algorithm. The algorithm is a concept of computer science which is widely used in the case of analysis, prediction and pattern determination. The process starts from the analysis of the variables used namely interest rates, exchange rates, inflation rates and stock prices that occurred in the previous period. The variables used are continued in the formation of network patterns and continued in the process of training and testing in order to produce the best network patterns so that they are used as a process of identifying JII stock price movements. The results obtained in the form of the value of stock price movements with an error rate based on the MSE value of 11.85% so that this study provides information in the form of knowledge for making a decision. The purpose of the research is used as input for investors in identifying share prices. In the end, the benefits felt from the results of this study, investors can make an initial estimate before investing in JII.

Methodology for pattern determination in electroencephalographic signals

A methodology for the selection and determination of electroencephalographic (EEG) signal patterns is presented at the case study level, which can later be used as on-off control signals in other applications. Electroencephalographic signals are acquired through the use of a brain-computer interface (BCI). These systems capture electrical signals from the cortex of the brain and transfer them to a computer so that they can be analyzed by algorithms and some action is taken. In this case, the EEG signals are acquired through the wireless 14-channel Epoc+ platform. The methodology used consists first in acquiring signals from the user sample in three scenarios: in relaxation, thinking about turning on and off. Subsequently, the wavelet transform of each of the channels is obtained for each of the cases and the most significant coefficients are taken into account. Then, through digital signal processing algorithms, descriptive parameters are obtained for the on and off cases, which are used as patterns to describe each of the actions. With this information, a comparison between the incoming signals and the previously stored patterns is made to execute one of the established commands.

Structural and optical properties of Ba(Co1−xZnx)SiO4 (x = 0.2, 0.4, 0.6, 0.8)

Structural characterization and X-ray reference powder pattern determination have been conducted for the Co- and Zn-containing tridymite derivatives Ba(Co1−xZnx)SiO4 (x = 0.2, 0.4, 0.6, 0.8). The bright blue series of Ba(Co1−xZnx)SiO4 crystallized in the hexagonal P63 space group (No. 173), with Z = 6. While the lattice parameter “a” decreases from 9.126 (2) Å to 9.10374(6) Å from x = 0.2 to 0.8, the lattice parameter “c” increases from 8.69477(12) Å to 8.72200(10) Å, respectively. Apparently, despite the similarity of ionic sizes of Zn2+ and Co2+, these opposing trends are due to the framework tetrahedral tilting of (ZnCo)O4. The lattice volume, V, remains comparable between 626.27 Å3 and 626.017 (7) Å3 from x = 0 to x = 0.8. UV-visible absorption spectrum measurements indicate the band gap of these two materials to be ≈3.3 and ≈3.5 eV, respectively, therefore potential UV photocatalytic materials. Reference powder X-ray diffraction patterns of these compounds have been submitted to be included in the Powder Diffraction File (PDF).