Search

The retinitis pigmentosa -GTPase regulator interacting protein 1-like gene (RPGRIP1L) encodes a ciliary protein essential for basic embryonic development. Biallelic variants of RPGRIP1L; cause Joubert syndrome (JS) with renal defects. In addition to characteristic JS features (cerebellar and brain stem malformations, developmental delays, hypotonia, irregular breathing patterns, eye movement abnormalities, ataxia, and intellectual disability), affected individuals typically also exhibit renal disorders, such as cystic kidney disease and nephronophthisis. Here, we describe a 10-year-old female of Chinese descent who was referred to hospital due to lower limb arthralgia. However, the presence of short stature, facial deformities, renal abnormalities, and renal failure suggested a diagnosis of congenital syndrome disorder. Whole-exome sequencing (WES) revealed that the patient was homozygous for a previously unreported RPGRIP1L variant featuring a missense mutation (NM_015272; c.2180G>A, p.Gly727Asp). A subsequent cranial MRI confirmed the presence of midbrain molar tooth sign and cerebellar Dandy-Walker malformation. However, no significant developmental delays or neurological abnormalities were noted. This study makes a significant contribution to the literature by expanding knowledge of the JS-causing RPGRIP1L variant spectrum, enhancing understanding of RPGRIP1L variant-associated JS phenotypes.

Aims/Introduction To investigate the genetic etiology and evaluate the diagnostic application of next‐generation sequencing for diabetes/persistent hyperglycemia in children and adolescents. Materials and Methods Patients with diabetes/persistent hyperglycemia, presenting with at least one other clinical manifestation (other than diabetes) or with a family history of diabetes, were recruited. The clinical and laboratory characteristics of the patients were recorded. Next‐generation sequencing was carried out, and candidate variants were verified by Sanger sequencing. Variant pathogenicity was further evaluated according to the American College of Medical Genetics and Genomics guidelines. Results This study included 101 potential probands, 36 of whom were identified as positive by genetic testing. A further 51.2 and 20.9% of variants were determined to be pathogenic or likely pathogenic, respectively. Variants associated with the disease were primarily identified in 21 genes and three regions of copy number variants. Among the 39 variants in 21 genes, 61.5% (24/39) were novel. The genetic diagnosis of 23 patients was confirmed based on genetic evidence and associated clinical manifestations. We reported GCK variants (21.7%, 5/23) as the most common etiology in our cohort. Different clinical manifestations were observed in one family with WFS1 variants. Conclusions Our findings support the use of next‐generation sequencing as a standard method in patients with diabetes/persistent hyperglycemia and provide insights into the etiologies of these conditions., Few studies have focused on examining the genetic etiology of diabetes in Chinese children and adolescents. A total of 101 potential probands were included in this study to investigate the clinical and genetic features of monogenic diabetes and genetic syndromes associated with it, and evaluate the diagnostic use of next‐generation sequencing for diabetes/persistent hyperglycemia. Our findings expand the gene mutation spectrum and phenotypic spectrum of the rare monogenic diabetes and genetic syndromes associated with diabetes, and provide insights into the current understanding of the underlying etiologies of diabetes/persistent hyperglycemia and support the use of next‐generation sequencing as a diagnostic method in Chinese patients with diabetes/persistent hyperglycemia.

Bi2S3 is a n-type (negative type) semiconductor that has a narrow band gap and an ideal band edge position for hydrogen generation. However, high charge recombination rate, low photoelectrochemical (PEC) efficiency and poor stability are of major concerns of Bi2S3 as a photoelectrode. Herein, we report an efficient Vanadium-rich Bi2S3 nanowires (atomic ratio of V to Bi is 1/22) that have been prepared on fluorine-doped tin oxide (FTO) substrate by an in-situ solution-processed reaction with BiVO4 film as precursor. The resulting V-rich photoelectrode demonstrates notably high charge separation efficiency and fast charge transport with respect to pristine Bi2S3 nanowires. As a result, the photocurrent density of ca. 10 mA·cm−2 at -0.2 V vs Ag/AgCl is obtained under visible light illumination. In addition, V-rich Bi2S3 generates IPCE (incident photocurrent-to-current conversion efficiency) of 50% at 460 nm and 45% at 760 nm, demonstrating a 2.0 and 2.8-fold increase, respectively, when compared with pristine Bi2S3. This enhancement is probably due to increased light absorption, less charge recombination, and faster charge transfer. More importantly, in contrast to pristine Bi2S3 sample that suffers detrimental photocorrosion in sulfide containing electrolyte, V-rich Bi2S3 nanowires retain 84.6% of its initial photocurrent over the course of 1 h. These findings are expected to shed light on engineering high-performance and robust metal sulfide materials for photoelectrochemical application.

A laryngotracheoesophageal cleft (LC) is a rare congenital anomaly of the upper aerodigestive tract resulting from the absence of fusion of the posterior cricoid lamina, which affects an abnormal communication between the larynx, trachea and esophagus. The genetic etiology of LC remains elusive. The involvement of genetic factors in the development of LC is suggested by reports of familial occurrence, and the increased prevalence of component features among first-degree relatives of affected individuals and murine knockout models. No consistent pattern of inheritance has been found in nonsyndromic patients, except for cases associated with described syndromes. Once the syndrome related to the laryngeal cleft is considered, an active search for the cleft must be initiated. The genetic evaluation of patients with LCs should be guided by the type and location of the malformation, specific medical history and a detailed physical examination. The application of genetic approaches, such as microarrays and exome sequencing might lead to elucidating the etiology of LCs.

Kabuki syndrome (KS) is a rare disorder of transcriptional regulation with a complex phenotype that includes cranio-facial dysmorphism, intellectual disability, hypotonia, failure to thrive, short stature, and cardiac and renal anomalies. Heterozygous, de novo dominant mutations in either KMT2D or KDM6A underlie KS. Limited information is available about the phenotypic spectrum of KS in China. Fourteen Chinese patients with genetically confirmed KS were evaluated in addition to 11 Chinese patients who were identified from the medical literature. The clinical phenotype spectrum of these patients was compared to that of 449 patients with KS from non-Chinese ethnicities. Additionally, we explored the utility of a facial recognition software in recognizing KS. All 25 patients with KS carried de novo, likely pathogenic or pathogenic variants in either KMT2D or KDM6A. Eighteen patients were male, the age at diagnosis ranged from 2months to 11.6 years. The facial gestalt included arched and broad eyebrows (25/25; 100%), sparse lateral or notched eyebrows (18/18; 100%), short columella with a concave nasal tip (24/25; 96%) and large, prominent ears (24/24; 100%) which were more frequent in Chinese patients (p < .01). In contrast, microcephaly (2/25; 8%), cleft lip/palate (2/25; 8%), and cardiac defects (10/25; 40%) were less frequent in Chinese patients (not significant). The diagnosis of KS was correctly identified in 13 of 14 patients through facial recognition and clinical phenotyping, underscoring the utility of this approach. As expected, there is marked phenotypic overlap between Chinese and non-Chinese patients with KS, although subtle differences were identified.

Background Pathogenic variants in POC1A led to SOFT syndrome and variant POC1A-related (vPOC1A) syndrome. SOFT syndrome is a rare primordial dwarfism condition characterized by short stature, onychodysplasia, facial dysmorphism and hypotrichosis.The main clinical differences between SOFT and vPOC1A syndrome include dyslipidemia with insulin resistance and acanthosis nigricans. To our knowledge, this is the first report of a SOFT syndrome patient diagnosed with a homozygous splicing variant, which could help to extend our understanding of the genotypic and phenotypic information of the disease. Case presentation We reported a seven-year-old boy with SOFT syndrome. The patient presented symmetrical short stature and facial features, including prominent forehead, inverted triangular face, epicanthal fold, small teeth and enlarged ears. Laboratory tests displayed mild insulin resistance. Whole-exome sequencing (WES) led to the identification of a homozygous splicing variant (c.981+1G>A) in POC1A gene of the patient, which was inherited from his heterozygous parents confirmed by Sanger sequencing. Further transcriptional experiments of the splicing variant revealed aberrant percentage of exon 9 skipping transcripts. Conclusions This is the firstly reported case of a SOFT syndrome patient with a novel homozygous splicing variant and detailed delineation of the aberrant transcript in proband and carrier of the variant in Chinese. Our study enriched mutational spectrum of POC1A which could help in further genetic diagnosis and counselling of SOFT syndrome patients.

BackgroundChronic cough is a common complaint which affects a large number of patients worldwide. Increased cough sensitivity is a very important cause of chronic persistent cough. However, there are limited clinical diagnosis and treatment for increased cough sensitivity. Transient receptor potential vanilloid-1 (TRPVl) is a member of the transient receptor potential (TRP) family of channels which is very closely associated with respiratory diseases. However, the mechanism through which TRPV1 that influences downstream events is still poorly understood.ResultsCapsaicin induced increase in cough sensitivity by upregulating the protein level of TRPV1, leading to the secretions of Substance P and neurokinin A which stimulated neurogenic inflammation. However, sinomenine, a component of traditional Chinese medicine, significantly attenuated the capsaicin-induced cough by inhibiting the expression of TRPV1 in guinea pigs. In addition, capsaicin increased the expression of SOX5 which mediated the transcriptional upregulation of TRPV1. However, pretreatment with sinomenine reduced the expression of SOX5.ConclusionThese results indicate that capsaicin induced increase in cough sensitivity by activating neurogenic inflammation, while sinomenine attenuated the increase in cough sensitivity by inhibiting the expressions of SOX5 and TRPV1 in guinea pigs. This finding may provide a novel target for the treatment of aggravated cough sensitivity.

Background Allergic rhinitis (AR) is one of the most common respiratory diseases in children. It is caused by a combination of genetic and environmental factors. Moderate-to-severe AR decreases the quality of life and social performance in children. Objective To investigate whether polymorphisms in previously published genome-wide association studies (GWAS) allergic disease loci are associated with childhood AR and the severity of AR symptoms in a Chinese Han population. Methods A case-control study was conducted in 503 pediatric patients with AR and 393 control Chinese school-aged subjects. AR severity was classified as mild or moderate-to-severe according to the AR and its Impact on Asthma (ARIA) guidelines. Overall, 16 tagged single-nucleotide polymorphisms (tSNPs) of published GWAS associations with allergic diseases were selected. All subjects were genotyped and analyzed for the 16 selected tSNPs using the improved multiplex ligation detection reaction (iMLDR) technique. Results Both rs7130588_AG and rs7927894_CT genotypes in EMSY region were associated with a significantly increased risk of AR (1.75-fold and 1.50-fold) compared to the AA and CC genotypes, respectively, specific to moderate-to-severe AR. The difference of rs7130588 genotypes in cases vs. controls was still statistically significant under the additive model after multiple test correction to adjust the false discovery rate (FDR) with an adjusted odds ratio of 1.818 and 95% confidence interval (CI) of 1.240–2.664 (PFDR = 0.0349). The rs7130588_G allele was only associated with a high risk of moderate-to-severe AR (1.85-fold, Page and gender_adjustment = 0.003). The rs2227284_TG genotype at the IL4 locus was significantly associated with a 0.65-fold decreased risk of AR compared to the TT genotype. The protective effect of the rs2227284_G allele was also found in different severity of AR. Haplotype analysis showed a significantly increased AR risk associated with the haplotype G-T-T (rs7130588-rs2155219-rs7927894) and a protective effect with the haplotype C-G-C (rs2243250-rs2227284-s2243290). Conclusions The loci in EMSY and IL4 can be considered as a hereditary marker for childhood AR. The rs7130588_G allele seems to predispose only to moderate-to-severe AR, though other mechanisms are also likely to be involved.

Background SHORT syndrome is a rare genetic disease named with the acronyms of short stature, hyper-extensibility of joints, ocular depression, Rieger anomaly and teething delay. It is inherited in an autosomal dominant manner confirmed by the identification of heterozygous mutations in PIK3R1. This study hereby presents a 15-year-old female with intrauterine growth restriction, short stature, teething delay, characteristic facial gestalts who was identified a novel de novo nonsense mutation in PIK3R1. Case presentation The proband was admitted to our department due to irregular menstrual cycle and hirsutism with short stature, who had a history of intrauterine growth restriction and presented with short stature, teething delay, characteristic facial gestalts, hirsutism, and thyroid disease. Whole-exome sequencing and Sanger sequencing revealed c.1960C > T, a novel de novo nonsense mutation, leading to the termination of protein translation (p. Gln654*). Conclusions This is the first case report of SHORT syndrome complicated with thyroid disease in China, identifying a novel de novo heterozygous nonsense mutation in PIK3R1 gene (p. Gln654*). The phenotypes are mildly different from other cases previously described in the literature, in which our patient presents with lipoatrophy, facial feature, and first reported thyroid disease. Thyroid disease may be a new clinical symptom of patients with SHORT syndrome.

Background Tricho‐rhino‐phalangeal syndrome (TRPS) is a rare autosomal dominant disorder characterized by craniofacial and skeletal malformations including short stature, thin scalp hair, sparse lateral eyebrows, a pear‐shaped nose, and cone‐shaped epiphyses. This condition is caused by haploinsufficiency or dominant‐negative effect of the TRPS1 gene. Methods In this study, we analyzed the clinical and genetic data of five unrelated TRPS patients. They were suspected of having TRPS on the basis of clinical and radiological features including typical hair and facial features, as well as varying degrees of skeletal abnormalities. Next‐generation sequencing was performed to identify variants of the TRPS1 gene in the five patients. Results In patient 1, we found a novel mutation at c.1338C>A (p.Tyr446*) (de novo). Patient 2 had a novel phenotype of hydrocephaly and Arnold–Chiari syndrome and we also found a maternally inherited novel mutation at c.2657C>A (p.Ser886*). Patient 3 had a de novo novel mutation at c.2726G>C (p.Cys909Ser) leading to more severe phenotypes. Patient 4 had a paternally inherited known mutation at c.2762G>A (p.Arg921Gln). Patient 5 with a novel phenotype of hepatopathy had a novel deletion at [GRCh37] del(8)(q23.3‐q24.11) chr8:g.116,420,724‐119,124,058 (over 2,700 kb). In addition, the patient 3 who harboring missense variants in the GATA binding domain of TRPS1 showed more severe craniofacial and skeletal phenotypes. Conclusions We describe four novel mutations and two novel phenotypes in five patients. The mutational and phenotypic spectrum of TRPS is broadened by our study on TRPS mutations. Our results reveal the significance of molecular analysis of TRPS1 for improving the clinical diagnosis of TRPS., In this study, we described five Chinese patients of TRPS, including the clinical presentation and molecular features of each patient. We found four novel mutations and two novel phenotypes in five patients. And we believe that our study makes a significant contribution to the literature because it adds to a growing body of studies that characterize the nature of conditions arising from mutations in the TRPS1 gene.

To evaluate the performance of proband-only medical exome sequencing (POMES) as a cost-effective first-tier diagnostic test for pediatric patients with unselected conditions. A total of 1,323 patients were tested by POMES, which targeted 2,742 known disease-causing genes. Clinical relevant variants were Sanger-confirmed in probands and parents. We assessed the diagnostic validity and clinical utility of POMES by means of a survey questionnaire. POMES, ordered by 136 physicians, identified 512 pathogenic or likely pathogenic variants associated with over 200 conditions. The overall diagnostic rate was 28.8%, ranging from 10% in neonatal intensive care unit patients to over 35% in pediatric intensive care unit patients. The test results had an impact on the management of the 45.1% of patients for whom there were positive findings. The average turnaround time was 57 days; the cost was $360/case. We adopted a relatively efficient and cost-effective approach in China for the molecular diagnosis of pediatric patients with suspected genetic conditions. While training for clinical geneticists and other specialists is lagging behind in China POMES is serving as a diagnostic equalizer for patients who do not normally receive extensive clinical evaluation and clinical diagnosis prior to testing. This Chinese experience should be applicable to other developing countries that are lacking clinical, financial, and personnel resources.

Background The phosphoglucomutase 1 (PGM1) enzyme plays a central role in glucose homeostasis by catalyzing the inter-conversion of glucose 1-phosphate and glucose 6-phosphate. Recently, PGM1 deficiency has been recognized as a cause of the congenital disorders of glycosylation (CDGs). Methods Two Chinese Han pediatric patients with recurrent hypoglycemia, hepatopathy and growth retardation are described in this study. Targeted gene sequencing (TGS) was performed to screen for causal genetic variants in the genome of the patients and their parents to determine the genetic basis of the phenotype. Results DNA sequencing identified three variations of the PGM1 gene (NM_002633.2). Patient 1 had a novel homozygous mutation (c.119delT, p.Ile40Thrfs*28). In patient 2, we found a compound heterozygous mutation of c.1172G>T(p.Gly391Val) (novel) and c.1507C>T(p.Arg503*) (known pathogenic). Conclusions This report deepens our understanding of the clinical features of PGM1 mutation. The early molecular genetic analysis and multisystem assessment were here found to be essential to the diagnosis of PGM1-CDG and the provision of timely and proper treatment.

Background: Leydig cell hypoplasia (LCH) is a rare disease and one of the causes of male disorder of sexual differentiation (DSD). Inactivating mutations in the luteinizing hormone/chorionic gonadotropin receptor (LHCGR) gene account for the underlying LCH pathogenicity. This study aimed to analyze the clinical presentation and diagnosis as well as highlight the molecular characteristics of a subject with LCH type 1. Case presentation: Clinical data were collected from the subject and analyzed. Next generation sequencing of the immediate family pedigree using peripheral blood genomic DNA was performed, and the relevant mutations were verified with Sanger sequencing. We describe the case of a 5-year-old patient with DSD, presenting with a lateral inguinal hernia accompanied by abnormal hormone tests. The genetic analysis revealed novel compound heterozygous variants in the LHCGR gene, including a splice site mutation (c.681-1 G>A) and a frameshift variant (c.1582_1585del ATAT, p.Ile528*). Conclusions: We identified novel compound heterozygous variants in the LHCGR gene, and expanded the genotype-phenotype correlation spectrum of LHCGR variants.

Chromosome 1p36 deletion is the most common subtelomeric deletion syndrome characterized by variable features including unique facial appearance, intellectual disability, developmental delay, cardiac defects, seizures and hypotonia. Here, we report a patient with developmental delay, dilated cardiomyopathy, seizures, hirsutism and cutis laxa who was diagnosed with 1p36 deletion syndrome by chromosome microarray analysis. This patient is the first reported case of 1p36 deletion syndrome associated with cutis laxa and our results suggest that the 1p36 region contains one or more genes relevant to cutis laxa. This case also indicates the importance of considering chromosome abnormalities (microdeletion/microduplication syndromes) in patients presenting skin disorders combined with unexplained developmental delay, intellectual disability or multiple congenital abnormalities.

Mapping Nearby Galaxies at Apache Point Observatory (MaNGA) is acquiring integral-field spectroscopy for the largest sample of galaxies to date. By 2020, the MaNGA Survey --- one of three core programs in the fourth-generation Sloan Digital Sky Survey (SDSS-IV) --- will have observed a statistically representative sample of 10$^4$ galaxies in the local Universe ($z\lesssim0.15$). In addition to a robust data-reduction pipeline (DRP), MaNGA has developed a data-analysis pipeline (DAP) that provides higher-level data products. To accompany the first public release of its code base and data products, we provide an overview of the MaNGA DAP, including its software design, workflow, measurement procedures and algorithms, performance, and output data model. In conjunction with our companion paper Belfiore et al., we also assess the DAP output provided for 4718 observations of 4648 unique galaxies in the recent SDSS Data Release 15 (DR15). These analysis products focus on measurements that are close to the data and require minimal model-based assumptions. Namely, we provide stellar kinematics (velocity and velocity dispersion), emission-line properties (kinematics, fluxes, and equivalent widths), and spectral indices (e.g., D4000 and the Lick indices). We find that the DAP provides robust measurements and errors for the vast majority ($>$99%) of analyzed spectra. We summarize assessments of the precision and accuracy of our measurements as a function of signal-to-noise, and provide specific guidance to users regarding the limitations of the data. The MaNGA DAP software is publicly available and we encourage community involvement in its development., 70 pages, 34 figures; AJ in press; see also Belfiore et al. 2019, AJ, 158, 160 (arXiv:1901.00866)

Short stature with optic atrophy and Pelger-Huet anomaly (SOPH; MIM 614800) syndrome is a genetic disease caused by mutation in the neuroblastoma amplified sequence (NBAS) gene.We present a 11-year-old Chinese boy with SOPH syndrome, growth hormone deficiency with a normal bone age. Gene sequencing in the patient revealed a novel compound heterozygous mutation of c.5752A C (Thr1918Pro) and c.500_501delTT (Phe167Cysfs*7) in the NBAS gene.To our best knowledge, these novel mutations in the NBAS gene have not been reported. Normal bone age with growth hormone deficiency in this patient is different from the patients with SOPH syndrome that have been previously reported. These findings enrich the mutant spectrum of the NBAS gene and add our understanding of SOPH syndrome.

With the rapid development of Internet technology, the popularity of social networking has enriched people's lives. A large number of social applications such as Facebook, WeChat and QQ often use a large number of image resources, which will consume much network traffic for transferring the images and affect the speed of loading. Therefore, most applications use the strategy of displaying the thumbnail images first and then loading the original images according to the users' requests. In the design and implementation of the image server, using caching technology can reduce disk I/O and increase image access speed. But current caching mechanisms have not considered the different access patterns for thumbnails and original images, nor the social relationships between image generators. In this paper, a two-layer image caching mechanism based on social relationships is pro-posed, which divides the image cache into the thumbnail layer and the original image layer, and comprehensively considers the social relationships between users and the relationships between the thumbnails and the original images. Experiments show that the two-layer image caching mechanism can effectively improve the cache hit rate for images.

Biallelic variants in the transmembrane O-mannosyltransferase targeting cadherins 3 (TMTC3) gene have been reported to cause two distinct types of neuron migration defect diseases, known as cobblestone lissencephaly (COB) and periventricular nodular heterotopia (PVNH), combined with intellectual disability and nocturnal seizures. The aim of the current study was to identify the genetic cause of a 22-month-old Chinese boy who presented with white matter plaques, a small frontal lobe, myelin dysplasia, microcephaly, psychomotor delay, language development delay, truncal hypotonia, intractable epilepsy, infantile spasm and bilateral single transverse palmar creases. Whole-exome sequencing revealed novel heterozygous variant compounds in the TMTC3 gene (c.1123G>A, p.Glu375Lys and c.1126_1129del, p.Arg376Tyrfs*13). Most of the clinical features of the patient are consistent with COB. However, the deformities in the brain (white matter plaques, small frontal lobe and myelin dysplasia) in the patient were more severe compared with those generally exhibited by PVNH, but less severe compared with those presented by COB. Moreover, the patient exhibited bilateral single transverse palmar creases, which, to the best of our knowledge, have not been described previously in patients with a TMTC3 variation. In summary, the current study reported a pediatric Chinese patient with COB-like syndrome caused by TMTC3 gene variations. The present results indicated that variation in the TMTC3 gene can lead to highly variable clinical phenotypes.

Although cardiopulmonary bypass (CPB) has been previously studied as risking infection and inflammatory responses, few studies evaluate the relationship of preoperative high total immunoglobulin E (tIgE) to outcomes in pediatric patients predisposed to atopy undergoing cardiac surgery with CPB. Serum tIgE, tumor necrosis factor-α (TNF-α), interleukin-10 (IL-10), IL-4, interferon-γ (IFN-γ), and T-helper type 1/2 (Th1/Th2) ratio were quantified in 104 pediatric patients who underwent surgical repair with CPB. Blood samples were obtained: before operation (T1), at the beginning (T2), and before the completion of CPB (T3), after protamine administration (T4), 4 h after CPB (T5), and on postoperative days 1 and 2 (T6, T7). Data on clinical outcomes were collected prospectively. Compared to 50 cases with normal tIgE, 54 cases with high tIgE were found to have higher TNF-α, IL-10, and IL-4 affected by CPB on the specific timepoints (pTNF-α

Background 3-M syndrome is a clinically recognizable yet under-diagnosed primordial growth retardation disorder. Molecular testing for CUL7, OBSL1 or CCDC8 genes can provide confirmed diagnosis for patients at prenatal or early age. So far, the clinical and molecular features of Chinese 3-M syndrome patients have not been reported. Methods In this article, the authors performed prenatal and early diagnosis of Chinese patients with 3-M syndrome by Next-Generation Sequencing. Results The authors reported six unrelated Chinese 3-M syndrome patients. Five of the six patients were diagnosed before two years of age including one prenatal case. The authors identified six novel pathogenic variants and five previously reported pathogenic variants. The authors' clinical evaluations indicated that Chinese 3-M syndrome patients share similar recognizable features as those reported in patients of other ethnic background. The authors noticed some uncommon features in this small cohort of Chinese patients such as delayed motor development at early ages, undelayed bone age and presence of lower eyelid fat pads. Conclusion The authors' study of Chinese 3-M syndrome patients revealed novel mutations and clinical phenotypes.

Exome sequencing has become a formidable tool for identifying potential de novo variants in causative genes of human diseases, such as neurodegenerative disorders. This article describes a 16-month-old girl with spinal muscular atrophy with lower extremity predominance and a 13-month-old girl with malformations of cortical development. Exome sequencing identified a novel de novo heterozygous missense mutation c.3395G>A (p.Gly1132Glu) and a previously reported de novo heterozygous missense mutation c.10151G>A (p.Arg3384Gln) in the DYNC1H1 gene. Bioinformatics predictions for c.3395G>A and c.10151G>A indicated pathogenicity of the mutations. DYNC1H1 is a pivotal component of cytoplasmic dynein complex, which is a microtubule-related motor involved in retrograde transport. Previous studies indicated that mutant dynein showed decreased run-length of the motor proteins and diminished retrograde transport, which were clearly associated with neuronal death and neurologic diseases. The present findings expand the mutational spectrum of the DYNC1H1 gene, reemphasizing the significance of the DYNC1H1 protein in the functioning of neurons.

Background Pathogenic variants of ACAN have been reported to cause spondyloepiphyseal dysplasia Kimberley type, spondyloepimetaphyseal dysplasia, familial osteochondritis dissecans and idiopathic short stature with normal to advanced bone age. A recent international cohort study significantly expanded the ACAN mutation spectrum, further delineated the heterogeneous clinical characteristics of ACAN mutation patients. The prevalence of ACAN mutation in short stature patients is yet unknown. Methods Here we set to assess the frequency of ACAN variants among a cohort of 218 Chinese children with non-syndromic short stature. Results We identified three novel truncating variants at the 5′ end of ACAN gene. All these pathogenic variants co-segregate with severe short stature phenotype in families. In addition, none of the probands showed significant advanced bone age. All affected individuals showed no signs of significant dysmorphic features or skeletal abnormities. The prevalence of ACAN defect in this cohort is estimated to be 1.4% (3/218). It is higher among families with parents also affected with severe short stature, up to 7.0% (3/43) if parental height is Conclusion Our data suggest that ACAN mutation is a relative common cause of familial severe short stature.

Dai writing as the product of Dai civilization. Because of the limitation of culture and territory, it cant spread widely. In todays society, the utilization rate of it still very low, only few people are familiar with it and know it. Remain resources still very limited, cant touched by people. This article uses .net platform to develop Dai writing online inquiry system, meeting the learning requirement of people who want to learn Dai writing.

It’s a new idea to make computers be able to obtain “sensations” from a color image through some unsupervised ways. To let the idea come into true, a granule-based model, based on granular computing(GrC) which is a new way to simulate human thinking to help solve complicated problems in the field of computational intelligence, is proposed for color image processing. First, this paper deems data a hypercube, defines two new concepts, attribute granules(AtG) and connected granules(CoG), and presents the definitions of the granule-based model. Then, in order to fulfill the granule-based model, this paper designs a single attribute analyser(SAA), defines some theorems and lemmas related to decomposition, and describes the processing of extracting all attibute granules. Experimental results on over 300 color images show that the proposed analyser is accurate, robust, high-speed, and able to provide computers with “sensations”.

Objective The study was designed to identify pathogenic TSC1 or TSC2 gene mutations and provide solid evidence for the diagnosis of tuberous sclerosis complex (TSC). Methods 11 unrelated Chinese patients with TSC were investigated in the present study. Characteristic skin lesions such as hypomelanotic macules and the central nervous system features such as the epilepsy, cortical tubers and subependymal nodules were the most common symptoms that were observed in the patients. All exons and exon‐intron boundaries of the TSC1 and TSC2 gene of the patients were amplified by PCR. Results A total of 11 different TSC2 and one TSC1 mutations were identified in the present study, of which five TSC2 and 1 TSC1 gene mutations were novel. Among the 11 patients, 10 harbored TSC2 mutations, whereas only one patient had a TSC1 gene mutation. The identification of TSC1 / TSC2 gene mutations confirmed the diagnosis of the 11 patients with TSC. Conclusions Our study has expanded the spectrum of TSC1 and TSC2 gene mutations causing TSC. The identification of the TSC1 / TSC2 gene mutations confirmed the diagnosis of the 11 patients with TSC.

The concentration precision of the sand/dust test and the attrition of key parts are affected seriously by the inertia efficiency separator, so the study on the separator performance is needed in the design of the sand/dust test system. With the application of discrete phase model, the performances of the manifold inertia separation components are simulated in various air velocities. The trajectories of motion of the particles in the separator are obtained, and the main factors which affect the separation efficiency are analyzed separately. According to the numerical simulation results, three types of separation components are designed and used in the experiment study, the results of the experiment study and the numerical simulation are consistent. The study results indicated that the increase of the particle dynamic energy is the main cause which leads to the separation efficiency drop rapidly while the air velocity increases. The efficiency of the slab-sided separation component with a semicircle bottom is higher than the traditional square short component and affected by the air velocity slightly, so this kind of separation component is adapted to be used in the sand/dust test system where air velocity varies in an extensive range.

Hereditary multiple osteochondroma (HMO) is one of the most common genetic skeletal disorders. It is caused by mutations in either EXT1 or EXT2 resulting in abnormal skeletal growth and morphogenesis. However, the spectrum and frequency of EXT1 and EXT2 mutations in Chinese patients with HMO was not previously investigated. Mutations were identified by performing Sanger sequencing analysis of the complete coding regions and flanking intronic sequences of EXT1 and EXT2, followed by multiplex ligation-dependent probe amplification (MLPA) analysis to detect gene deletions or duplications that could not be identified by the Sanger sequencing method. The present study identified pathogenic mutations in 93% (68/73) of unrelated HMO probands from 73 pedigrees. Mutations in EXT1 and EXT2 were identified in 53% (39/73) and 40% (29/73) of families. We identified 58 distinct mutations in EXT1 and EXT2, including 20 frameshift mutations, 16 nonsense mutations, 7 missense mutations, 9 splice site mutations, 5 large deletions, and 1 in-frame deletion mutation. Twenty-six of these mutations were novel and 32 were previously reported. Most of the mutations in EXT1 were base deletions or insertions (21/33), whereas the majority of those in EXT2 were single base substitution (18/25). Complete sequencing of both the EXT1 and EXT2 followed by MLPA analysis is recommended for genetic analysis of Chinese patients with HMO. This study provides a comprehensive characterization of the genetic aberrations found in Chinese patients with HMO and highlights the diagnostic value of molecular genetic analysis in this particular disease.

To verify the accessibility and workspace of tool operation in virtual assembly system, this paper presented a tool-part operation method based on force feedback. According to characters of common tool-part operations, standard fastening tools and parts were modeled using features and parameters at initial stage. Then operator was enabled to conduct different kinds of fastening and unfastening operations in virtual assembly system by three steps namely identification, interactive positioning and operation. With feedback force, the operator can feel corresponding motion constraints of tool during virtual fastening and unfastening operation, so the immersion of virtual assembly operation is promoted.

This paper presents a lifting wavelet based edge detection algorithm for NaXi Pictographs, effectively reducing noises while improving the precision, which makes up the drawbacks of traditional edge detection. It is proved by emulation that compared with Laplace operator, Sobel operator, Canny operator, and multi-scale wavelet edge detection algorithm, this algorithm has better detection effect.

Preprocessing, a major component of Character Recognition System, has direct effect on the recognition system by its performance. Using wavelet transform, this paper mainly focuses on noise filtering and Edge Detection in a Preprocessing method for NaXi Pictographs Character Recognition. Image denoising is an important issue in image preprocessing. Based on the analysis of thresholding function and thresholding, which are very important in image denoising, we put forward the procedures of wavelet denoising for NaXi Pictographs. The experimental results turned out that wavelet denoising is a better method for NaXi Pictographs Recognition Preprocessing than linear denoising, median denoising or adaptive denoising. The images are broken down into the approximate parts and detail parts by wavelet. The approximate part is an approximate representation for the original image after filtering the high frequency part. Removed the high frequency component, the approximate part can detect the edge which the original image cannot detect. The wavelet based edge detection also has better effect than the traditional operators like Prewitt, Sobel, Roberts, Laplacian of Gaussian, Canny and others.

By using the super-resolution near-field structure (super-RENS) method, the super-resolution recording marks are obtained practically by an organic photochromic diarylethene mask layer, under much lower recording laser power of 0.45 mW. The size of recording marks is decreased by 60% (from 1.6 μm to 0.7 μm) for a diarylethene (photo-mode) recording layer by the optical detection method (limited by optical diffraction), or decreased by 97% (from 1600 nm to 50 nm) for a heptaoxyl copper phthalocyanine (thermo-optical) recording layer, the latter is much smaller than the limitation of optical diffraction. In order to obtain a desirable result, a proper extent of photochemistry reaction in the mask layer is needed. Thus, the super-resolution recording marks can be obtained by adjusting the concentration of diarylethene in the mask layer, the recording laser power, and the moving speed of the sample disc.

There is a variety of well completion and hydraulic fracturing technologies available for liquid-rich resource plays. The industry approach tends to include horizontal wells with multiple fracturing treatments, and depending on the selection criteria, it may result in certain operational efficiency and production enhancement advantages. Thus a comprehensive strategy to properly select the applicable technologies is based upon geology, subsurface understanding, well design, production expectations, and operational readiness. Following the successful completion of the exploration phase of the Jimusaer project located in the Jungger Basin of West China, a pilot drilling program was initiated that included multiple horizontal wells being drilled from selected well pads. The completion and fracturing operations were completed in two phases that included the evaluation of different completion technologies, placement methodologies, and fracturing designs being optimized for later wells based on initial well results. The initial phase was done in 2013 and included 62 fracturing stages on four wells completed with an openhole sliding sleeve system. The six remaining wells were completed in the following year which involved 130 stages. Besides optimizing the fracturing design approach, it included a shift towards cased-hole completion techniques involving the plug & perf approach. Overall technical understanding and recognition of underlying trends were improved by reviewing the abundance of reservoir and well data from the 10 horizontal wells completed to date. Additional insight was obtained by the incorporation of hydraulic fracturing monitoring measurements with flowback performance and monitoring of individual fracturing stages through the deployment of unique chemical tracers. Despite the variation in completion and fracturing technology, reservoir understanding and well placement were the primary factors impacting individual well performance. In conclusion, the overall pilot project was designed to reduce the uncertainty in key reservoir parameters, test various completion/drilling technologies, and assess full-field development issues while moving towards fairway sweet spots.

Aimed at cultivating economics and management talents with high quality, this paper builds an experimental teaching system in economics and management, designs a five-in-one framework of multi-dimensional integration in the economics and management of experimental teaching, and innovates methods of experimental teaching with diversification and forms of cross-border experiment teaching, builds the experiment teaching platform of "integration of teaching and research,” as well as perfecting the guarantee system of experiment teaching management, thus reforming and innovating the training mode for professional talents in economics and management. What’s more important, the experimental teaching system highlights the integration of knowledge in varied disciplines, the cultivation of students' innovative and comprehensive ability; the system also realizes the combination of students' self-study and teachers' guidance, of the professional knowledge learning and relevant knowledge learning, and of theory and practice.

In this paper the electronic recognition system based on internet of things technology for railway logistics is designed and implemented. The 4 level information transfer mode is used between RFID Tag, train carriage identifier, station yard identifier and computer sever. Radio communication is used between RFID Tag, train carriage identifier, station yard identifier. Wired communication is used between station yard identifier and station computer. The problems of information collision between multi-tags, long-distance transmission of information and communication interference are solved in this article. The experimental results show that the system is effective when the speed of the train within 120Km/h and it is applicable to the railway logistics. Introduction With the rapid development of railway logistics informationization in China, the TMIS(Transportation Management Information System),HMIS(H Management Information System) and DMIS(Dispatch Management Information System) have been used to realize real-time tracking of the train and real-time query of the goods. Data acquisition is the key problem of railway logistics informationization[1][2]. Refinement is needed in getting hold of information and real-time tracking of the goods. At present, manual process is the main method in railway logistics data acquisition. The automatic identification technology based on RFID needs to be popularized[3][4]. The technology of internet of things(IoT) should be used to realize informationization, digitization and intelligent in railway logistics and promote the transition of railroad freight transportation. The application of IoT technology will have a significant impact on the construction of railway logistics informationization[5]. In this paper the electronic recognition system based on internet of things technology for railway logistics is designed and implemented. The problems of information collision between multi-tags, long-distance transmission of information and communication interference are solved. RFID tag, identifier and communication interface unit are designed to realize railway logistics electronic recognition and meet actual requirements. System Constitution The electronic recognition system is shown in Figure 1. The unique code that represents the goods’ characteristics is provided by RFID tags through dedicated protocol which uses the frequency 433.2MHz. The tag is active and its voltage is 3.3V. The code is received by train carriage identifier and the information is stored in its flash ROM and the goods state of on or off train carriage is determined. The train carriage identifier transmits information to station yard identifier through WIFI protocol which uses the frequency 2.4GHz and the information includes goods code, time of on or off train carriage, state of on or off train carriage, battery voltage etc. When the information reaches station yard identifier, it will be stored in identifier’s flash ROM and determine the time that the train enters or leaves the station. The International Conference on Information Sciences, Machinery, Materials and Energy (ICISMME 2015) © 2015. The authors Published by Atlantis Press 56 station yard identifier transmits the goods information and time to repeater or communication interface unit through CAN bus. The computer sever in railway station receives the information through communication interface unit or internet and then the information will be analyzed and processed to form documents needed. These documents can be queried by administrator in railway station[6]-[9].

Rationale:The CTNNB1 (β-catenin) gene is well known for its crucial role in cell adhesion and the Wnt-signaling pathway. Previous studies have shown that gain-of-function mutations in the CTNNB1 gene contribute to the occurrence and development of a variety of carcinomas in humans. Recently

The effect of aging with ultrasonic treatment on the synthesis of zeolite MCM-49 has been investigated under the conditions of static hydrothermal crystallization using hexamethyleneimine (HMI) as the template. As a result of using ultrasound, highly crystalline MCM-49 is obtained from a silica source with a low specific surface area. Aging with ultrasound can noticeably broaden the crystallization range of MCM-49 and shorten the crystallization time as well as decrease the HMI/SiO2 ratio.

The concept of high-throughput imaging Fourier transform spectrometer is introduced. Starting from the principle of the lateral shearing interferometer, it analyses the decline reason for the signal modulation efficiency and theoretically analyses the several aspects of the surface errors of the plane mirror, the beamsplitter properties change and the incident light angle influence the modulation efficiency. Based on analysis results, some expressions of modulation efficiency are provided. Furthermore, the relationship between modulation efficiency and performance parameters is pointed out. The reasons for the interferometer signal modulation efficiency decline can contain the following several aspects: (1) the influence of the surface errors of the plane mirror, (2) the polarization state change because of the influence of the reflection and the transmission in the light incident process makes the signal modulation efficiency decline, (3) the influence of the incident light angle. The results show that: this class of system is inherently optomechanics robust, no-moving part system, simple and compact structure, easy assembly and adjustment, strong vibration resistance as well as high resolution and high-throughput. Our results will provide a theoretical and practical guide for studying, developing and engineering Michelson lateral shearing interference imaging spectrometers. It can be widely used in the long-wave infrared (LWIR) imaging spectrometer system for thermal infrared remote sensing community.

Signal-to-noise Ratio of hyper-spectral imaging FTIR interferometer system plays a decisive role on the performance of the instrument. It is necessary to analyze them in the development process. Based on the simplified target/background model, the energy transfer model of the LWIR hyper-spectral imaging interferometer has been discussed. The noise equivalent spectral radiance (NESR) and its influencing factors of the interferometer system was analyzed, and the signal-to-noise（SNR） was calculated by using the properties of NESR and incident radiance. In a typical application environment, using standard atmospheric model of USA(1976 COESA) as a background, and set a reasonable target/background temperature difference, and take Michelson spatial modulation Fourier Transform interferometer as an example, the paper had calculated the NESR and the SNR of the interferometer system which using the commercially LWIR cooled FPA and UFPA detector. The system noise sources of the instrument were also analyzed in the paper. The results of those analyses can be used to optimize and pre-estimate the performance of the interferometer system, and analysis the applicable conditions of use different detectors. It has important guiding significance for the LWIR interferometer spectrometer design.

In this study, taking the advantage of ultrasonic motors, a locking device driven by ultrasonic motor for magnetic bearing flywheel has been manufacture and evaluated. A locking device is used to eliminate the gap between the rotor and the stator of magnetic bearing flywheel in order to prevent it from shock and vibration. Since the present locking devices driven by initiating explosive device or magnetic motor have the disadvantages such as high, shock, large size, and heavy weight. The system of locking device includes mechanical structure and motion control. The driving component of mechanical structure applies a traveling rotary wave ultrasonic motor (TRUM). The transmission employs worm gear so as to drive the executive body. Then the flywheel is protected. The power input of the ultrasonic motor is stable and the temperature rise of ultrasonic motor is 4°C. The force of actuated clutch is 17.1 N along with the radial. So the locking device has a highly-efficient locking performance.

Organic solar cells based on small molecules and conjugated polymers are attracting much attention due to their merits of low costs, simple fabrication processes, light weights, and mechanical flexibilities. Metals are usually considered as promising candidates for the semi-transparent electrodes. In such devices, a strong microcavity resonance can be supported between the two electrodes, resulting in a narrowed bandwidth of light absorption, which, unfortunately, will lower the performances of organic solar cells since broadband absorption is always highly desired. To overcome this obstacle, people have proposed many designs such as using ultra-thin electrodes or using dielectric-metal hybrid electrodes. Although the light absorption bandwidth can be improved considerably, the absorption efficiency would be lowered due to the weakened microcavity resonance. This is a tough problem that always bothers both researchers and engineers. To solve this problem, we propose a light trapping scheme based on broadband hybrid modes due to the hybridization between microcavity resonance and antireflection resonance. By introducing a capping layer outside the device structure, antireflection resonance can be excited inside the capping layer and can then couple with the intrinsic microcavity resonance, inducing dual microcavity-antireflection resonance hybrid modes. The hybrid modes are of broadband and their resonant wavelengths can be easily designed by tuning the capping layer thickness and cavity length, since the capping layer thickness would affect the antireflection resonance while the cavity length would affect the microcavity resonance. By matching the resonance with the high absorption region of the active layer, the overall absorptivity of the proposed device can be greatly enhanced by~37% compared to the conventional microcavity based device where only one mode, that is, the microcavity resonance can be supported. Moreover, we compare our light trapping scheme with the surface plasmon-polaritons based scheme where surface waves are excited to help improve the light absorption. We find that the overall absorptivity of the proposed device cannot be further improved when we introduce grating structure into the device in order to excite surface plasmon-polaritons. This is mainly because the light absorption based on our hybrid mode scheme is already thorough so that the introduction of grating structure can only improve the light loss dissipated in the metal electrodes due to scatterings and diffractions by the gratings. Therefore, the proposed hybrid mode based scheme can be considered as a simple and effective light trapping scheme for organic solar cells and may find applications in both polymer and small molecular based organic solar cells.

A new fast neutron spectrometer named n-TPC has been designed by LPRI (Key Laboratory of Particle & Radiation Imaging, Ministry of Education) at Tsinghua University. The neutron energy spectrum can be calculated from the recoil angle and energy of the recoil proton detected by a 704-pad GEM-TPC. In beam tests at IHIP (Institute of Heavy Ion Physics, Peking University) in 2014, n-TPC performed better than 6%@6 MeV energy resolution and 5‰ detection efficiency. To find the best working parameters (the component and proportion of the gas, the high voltage between each GEM layer, etc.) of the n-TPC and support its application in various conditions, a multichannel distributed DAQ has been designed to read out the signals from the 704 channels. With over 25 Ms/s sampling rate and 12 bit resolution for each channel, it can record the time and amplitude information as well as traditional DAQs in the TPC application domain. The main design objective of this distributed DAQ, however, is more flexible parameter modulation and operation. It can support the n-TPC without the limitation of the chassis and categorize signals arriving from the 704 channels at the same time by different events without event triggers.

Disassembling operations play an important role in maintenance and assembly sequence planning of mechanical products. This chapter developed a virtual disassembly system which enables operators to disassemble products interactively in a virtual environment. By loading virtual assembly models transformed from models designed in commercial CAD software, the virtual disassembly environment is constructed. Parts to be disassembled are recommended to users for guiding the disassembly operations by analyzing the stability of products for users. During interactive disassembly, the part being disassembled can only move along defined directions which are analyzed from joint state of parts using DOF reduction methods. The collision between virtual prototypes is also detected, so the disassembly sequence can be evaluated and improved. The presented system is a cross-platform system, and can be run on different computer operating systems.

Measurement and control system is main section of friction & wear testing machines. But current measurement and control systems have low versatility and high design cost. To solve these problems, this paper designed an Ethernet-based measurement and control system, which can be used in most types of friction & wear testing machines with a few modifications of programs. The DSP processor and touch screen system were successfully integrated into the presented measurement and control system. The functions and implementation processes of each module were introduced in detail, and a reconfigurable software system was designed according to ideas of virtual instruments theory.