[Expert consensus on clinical genetic counseling of α-thalassemia gene analysis].

α-thalassemia is a type of microcytic hypochromic anemia caused by variants of alpha-globin gene, and is one of the most common monogenic disorders in southern China. The population screening model based on hematologic phenotype has achieved great results in areas with high incidence of thalassemia. However, with the continuous decline of the cost of genetic testing and implementation of screening programs for thalassemia gene carriers, more variants in the alpha-globin gene have been discovered, which also brings great challenges to clinical genetic counseling. From the perspective of alpha-globin genetic analysis, this consensus has discussed the contents of pre- and post-test genetic counseling, with an aim to provide standardized guidance for clinicians.

Functional identification of two novel variants and a hypomorphic variant in ASS1 from patients with Citrullinemia type I.

Background: Citrullinemia type I (CTLN1) is a rare autosomal recessive inborn error of the urea cycle caused by mutations in the gene encoding the arginosuccinate synthetase (ASS1) enzyme. Classic CTLN1 often manifests with acute hyperammonemia and neurological symptoms. Molecular genetic testing is critical for patient diagnosis. Methods: Three unrelated families with clinically suspected CTLN1 were included in this study. Potential pathogenic variants were identified using whole exome sequencing (WES) and validated using Sanger sequencing. Western blotting, quantitative PCR, immunofluorescent staining, and ELISA were used to assess functional changes in candidate ASS1 variants. Results: Five variants were identified, two of which were novel, and one has been reported, but its pathogenicity was not validated. The novel variant c.649-651del (p.P217del) and the 5'UTR variant (c.-4C>T) resulted in a decrease in ASS1 expression at both the protein and transcription levels. The other novel variant, c.1048C>T (p.Q350*), showed a marked decrease in expression at the protein level, with the formation of truncated proteins but an increased transcription. Both c.649_651del (p.P217del) and c.1048C>T (p.Q350*) showed a highly significant reduction in enzyme activity, while c.-4C>T had no effect. Conclusion: We identified two novel variants and a hypomorphic non-coding variant in ASS1 and validated the pathogenicity using functional studies. Our findings contribute to expanding the spectrum of ASS1 variants and understanding the genotype-phenotype relationships of CTLN1.

A Pose-Only Solution to Visual Reconstruction and Navigation.

Visual navigation and three-dimensional (3D) scene reconstruction are essential for robotics to interact with the surrounding environment. Large-scale scenarios and computational robustness are great challenges facing the research community to achieve this goal. This paper raises a pose-only imaging geometry representation and algorithms that might help solve these challenges. The pose-only representation, equivalent to the classical multiple-view geometry, is discovered to be linearly related to camera global translations, which allows for efficient and robust camera motion estimation. As a result, the spatial feature coordinates can be analytically reconstructed and do not require nonlinear optimization. Comprehensive experiments demonstrate that the computational efficiency of recovering the scene and associated camera poses is significantly improved by 2-4 orders of magnitude.

Scattering response modeling scheme based on combined neural network inspired by the equivalent scattering center.

A novel scheme is proposed in this paper to model the complex scattering pattern of radar target with a small training data set. By employing the ideal equivalent scattering center as transfer function, the frequency domain response can be represented by series of parameters so that the aspect and frequency domain dependency can be decoupled, and modeled, independently. In specific, neural network is employed to model the aspect dependency considering the complexity. To maintain the continuity of transformed parameters, a parameter extraction algorithm based on the Orthogonal Matching Pursuit is designed. With the same amount of training set, the proposed scheme exhibits a much better performance than the existing representative modeling techniques such as Geometrical Theory of Diffraction (GTD)-based model, the polynomial scattering center model and so on. At the same time, the training speed of the proposed model is also faster than those techniques.

Singularity-Exponent-Domain Image Feature Transform.

Combining the generalized fractal theory and the time-frequency distribution, the image feature decomposition in the singularity exponent domain is studied in this paper. With the theoretical derivation and quantitative analysis, the singularity-exponent-domain image feature transform (SIFT) method is proposed to analyze and process images from new feature dimensions. If one derives from the generalized fractal characteristics of the image, the two-dimensional frequency variables of the 2D time-frequency transform of the image can be used to estimate the two-dimensional singularity power spectrum (SPS) in the space dimension. As a consequence, it leads to the SPS distribution of the original image in the spatial domain, i.e., SIFT images. Based on the SIFT, the feature transform images with different singularity exponent and feature curves of singularity power spectrum with respect to different physical regions can thus be obtained. The SIFT is rigorously derived from the 2D-SPS and the Pseudo Wigner-Ville distribution (PWVD). In addition, the feature images based on the SIFT is proved to be the SNR independence in the GWN background. In order to validate the effectiveness of feature extraction, the proposed methodology is tested on the breast ultrasound images, the visual images, and the synthetic aperture radar (SAR) images. Furthermore, the SAR target detection method based on the SIFT images is proposed, and the experiment results indicate that the proposed algorithm is superior in performance to the traditional CFAR or 2D-SPS method. In fact, this new SIFT is promising to provide a technical approach for image feature extraction, target detection, and recognition.

Prenatal case of Simpson-Golabi-Behmel syndrome with a de novo 370Kb-sized microdeletion of Xq26.2 compassing partial GPC3 gene and review.

BACKGROUND: Simpson-Golabi-Behmel syndrome type 1 (SGBS1) is a rare X-linked recessive disorder characterized by pre- and postnatal overgrowth and a broad spectrum of anomalies including craniofacial dysmorphism, heart defects, renal, and genital anomalies. Due to the ultrasound findings are not pathognomonic for this syndrome, most clinical diagnosis of SGBS1 are made postnatally. METHODS: A pregnant woman with abnormal prenatal sonographic findings was advised to perform molecular diagnosis. Single nucleotide polymorphism array (SNP array) was performed in the fetus, and the result was validated with multiplex ligation-dependent probe amplification (MLPA) and real-time quantitative PCR (qPCR). RESULTS: The prenatal sonographic presented with increased nuchal translucency at 13 gestational weeks, and later at 21 weeks with cleft lip and palate, heart defect, increased amniotic fluid index and over growth. A de novo 370Kb-deletion covering the 5'-UTR and exon 1 of GPC3 gene was detected in the fetus by SNP array, which was subsequently confirmed by MLPA and qPCR. CONCLUSION: The de novo 370Kb hemizygous deletion of 5'-UTR and exon 1 of GPC3 results in the SGBS1 of this Chinese family. Combination of ultrasound and genetics tests helped us effectively to diagnose the prenatal cases of SGBS1. Our findings also enlarge the spectrum of mutations in GPC3 gene.

Inverse synthetic aperture ladar imaging based on modified cubic phase function.

Inverse synthetic aperture imaging ladar (ISAL) can achieve high-resolution images, and yet it faces pulse-to-pulse high-order phase errors that the microwave radar can ignore. The high-order phase errors are almost caused by mechanical vibrations in general, which blur the azimuth focusing effect. This paper presents an ISAL imaging model to obtain high-resolution images. A novel modified cubic phase function (CPF) algorithm is proposed to compensate the additional high-order phase errors. Some high-resolution well-focused ISAL simulation images and real target images are shown to validate the methods. It is shown that the third-order phase errors are compensated by the distinctive digital signal process and the image entropy of real target images is reduced significantly.

Whole genome sequencing reveals translocation breakpoints disrupting TP63 gene underlying split hand/foot malformation in a Chinese family.

BACKGROUND: Split hand/foot malformation (SHFM) is a congenital limb developmental disorder, which impairs the fine activities of hand/foot in the affected individuals seriously. SHFM is commonly inherited as an autosomal dominant disease with incomplete penetrance. Chromosomal aberrations such as copy number variations and translocations have been linked to SHFM. This study aimed to identify the genetic cause for three patients with bilateral hand and foot malformation in a Chinese family. METHODS: Karyotyping, single-nucleotide polymorphism (SNP) array, whole exome sequencing, whole genome sequencing, and Sanger sequencing were applied to identify the pathogenic variant. RESULTS: Karyotyping revealed that the three patients had balanced reciprocal translocation, 46, XX, t(3;15) (q29;q22). SNP array identified no pathogenic copy number variation in the proband. Trio-WES (fetus-mother-father) sequencing results revealed no pathogenic variants in the genes related to SHFM. Whole-genome low-coverage mate-pair sequencing (WGL-MPS), breakpoint PCR, and Sanger sequencing identified the breakpoints disrupting TP63 in the patients, but not in healthy family members. CONCLUSION: This study firstly reports that a translocation breakpoint disrupting TP63 contributes to the SHFM in a Chinese family, which expands our knowledge of genetic risk and counseling underlying SHFM. It provides a basis for genetic counseling and prenatal diagnosis (preimplantation genetic diagnosis) for this family.

Influence of mouse defective zona pellucida in folliculogenesis on apoptosis of granulosa cells and developmental competence of oocytes†.

Zona pellucida (ZP), which enwraps the oocyte during folliculogenesis, initially forms in the primary follicle and plays an important role in female fertility. Here, we investigated a mouse strain ("mutant mice" for short) carrying two types of ZP defects in folliculogenesis, i.e., ZP thinned (but intact) and ZP cracked, caused by targeted mutation in the Zp1 gene. Using this mutant mouse strain and wild-type mouse as control, we studied the effects of the ZP defects on the development of oocytes and granulosa cells during folliculogenesis. For each ZP defect, we examined the morphology of transzonal projections and apoptosis of granulosa cells in the corresponding growing follicles, as well as the morphology of corresponding ovulated eggs and their abilities to develop into viable individuals. Our results suggested that ZP integrity rather than thickness or porosity is crucial for preventing the ectopia of granulosa cells, maintaining adequate routine bilateral signaling between oocyte and surrounding granulosa cells, and thus for ensuring the survival of granulosa cells and the establishment of the full developmental competence of oocytes. This is the first study to elucidate the effects of different degrees of ZP defects caused by the same gene mutation, on the apoptosis of granulosa cells and developmental competence of oocytes, and to explore the potential mechanisms underlying these effects.

Improvement of Noise Uncertainty and Signal-To-Noise Ratio Wall in Spectrum Sensing Based on Optimal Stochastic Resonance.

Noise uncertainty and signal-to-noise ratio (SNR) wall are two very serious problems in spectrum sensing of cognitive radio (CR) networks, which restrict the applications of some conventional spectrum sensing methods especially under low SNR circumstances. In this study, an optimal dynamic stochastic resonance (SR) processing method is introduced to improve the SNR of the receiving signal under certain conditions. By using the proposed method, the SNR wall can be enhanced and the sampling complexity can be reduced, accordingly the noise uncertainty of the received signal can also be decreased. Based on the well-studied overdamped bistable SR system, the theoretical analyses and the computer simulations verify the effectiveness of the proposed approach. It can extend the application scenes of the conventional energy detection especially under some serious wireless conditions especially low SNR circumstances such as deep wireless signal fading, signal shadowing and multipath fading.

MiR-21 in extracellular vesicles contributes to the growth of fertilized eggs and embryo development in mice.

Human preimplantation embryo development is susceptible to high rates of early embryo wastage. We determined the miR-21 expression of extracellular vesicles (EVs) in fertilized eggs and embryos of varying stages and their response to miR-21 microinjection. Sexually mature female and male mice were mated. Next, the expression and immunohistochemistry intensity of surface markers (CD9 and CD63) of EVs were detected in pregnant and non-pregnant mice. Exosomes were co-cultured with embryos for detection of blastocyst formation rate, and embryo apoptosis. Moreover, the expressions of Bcl-2 associated X protein (Bax), B cell lymphoma 2 (Bcl-2), and octamer-binding transcription factor-4 (Oct4) were determined. Finally, we detected miR-21 expression in EVs of uterus in pregnant mice, in embryos after embryo implantation and after embryo co-cultured with exosomes in uterine luminal fluid. MiR-21 was up-regulated in EVs of uterus, and higher immunohistochemistry intensity of CD9 and CD63, suggesting more EVs secreted in uterine luminal fluid in pregnant mice. After microinjection, miR-21 inhibitor suppresses embryo development of mice. Moreover, embryos co-cultured with exosomes display higher blastocyst formation rate, reduced apoptotic rate of embryos in pregnant mice. In addition, miR-21 was down-regulated with the development of embryos after embryo implantation, while miR-21 expression in embryos was up-regulated by exosomes in uterine luminal fluid in the pregnant mice. Increased miR-21 expression in EVs of uterus and increased miR-21 expression after implantation, which indicate the key role in the growth of fertilized eggs and embryo development in mice.

Learning the Conformal Transformation Kernel for Image Recognition.

In this paper, we present a multiclass data classifier, denoted by optimal conformal transformation kernel (OCTK), based on learning a specific kernel model, the CTK, and utilize it in two types of image recognition tasks, namely, face recognition and object categorization. We show that the learned CTK can lead to a desirable spatial geometry change in mapping data from the input space to the feature space, so that the local spatial geometry of the heterogeneous regions is magnified to favor a more refined distinguishing, while that of the homogeneous regions is compressed to neglect or suppress the intraclass variations. This nature of the learned CTK is of great benefit in image recognition, since in image recognition we always have to face a challenge that the images to be classified are with a large intraclass diversity and interclass similarity. Experiments on face recognition and object categorization show that the proposed OCTK classifier achieves the best or second best recognition result compared with that of the state-of-the-art classifiers, no matter what kind of feature or feature representation is used. In computational efficiency, the OCTK classifier can perform significantly faster than the linear support vector machine classifier (linear LIBSVM) can.

A trajectory and orientation reconstruction method for moving objects based on a moving monocular camera.

We propose a monocular trajectory intersection method to solve the problem that a monocular moving camera cannot be used for three-dimensional reconstruction of a moving object point. The necessary and sufficient condition of when this method has the unique solution is provided. An extended application of the method is to not only achieve the reconstruction of the 3D trajectory, but also to capture the orientation of the moving object, which would not be obtained by PnP problem methods due to lack of features. It is a breakthrough improvement that develops the intersection measurement from the traditional "point intersection" to "trajectory intersection" in videometrics. The trajectory of the object point can be obtained by using only linear equations without any initial value or iteration; the orientation of the object with poor conditions can also be calculated. The required condition for the existence of definite solution of this method is derived from equivalence relations of the orders of the moving trajectory equations of the object, which specifies the applicable conditions of the method. Simulation and experimental results show that it not only applies to objects moving along a straight line, or a conic and another simple trajectory, but also provides good result for more complicated trajectories, making it widely applicable.