High Proportion of 22q13 Deletions and SHANK3 Mutations in Chinese Patients with Intellectual Disability

Intellectual disability (ID) is a heterogeneous disorder caused by chromosomal abnormalities, monogenic factors and environmental factors. 22q13 deletion syndrome is a genetic disorder characterized by severe ID. Although the frequency of 22q13 deletions in ID is unclear, it is believed to be largely underestimated. To address this issue, we used Affymetrix Human SNP 6.0 array to detect the 22q13 deletions in 234 Chinese unexplained ID patients and 103 controls. After the Quality Control (QC) test of raw data, 22q13 deletions were found in four out of 230 cases (1.7%), while absent in parents of the cases and 101 controls. A review of genome-wide microarray studies in ID was performed and the frequency of 22q13 deletions from the literatures was 0.24%, much lower than our report. The overlapping region shared by all 4 cases encompasses the gene SHANK3. A heterozygous de novo nonsense mutation Y1015X of SHANK3 was identified in one ID patient. Cortical neurons were prepared from embryonic mice and were transfected with a control plasmid, shank3 wild-type (WT) or mutant plasmids. Overexpression of the Y1015 mutant in neurons significantly affected neurite outgrowth compared with shank3 WT. These findings suggest that 22q13 deletions may be a more frequent cause for Chinese ID patients than previously thought, and the SHANK3 gene is involved in the neurite development

A Hartree-Fock Application Using UPC++ and the New DArray Library

The Hartree-Fock (HF) method is the fundamental first step for incorporating quantum mechanics into many-electron simulations of atoms and molecules, and it is an important component of computational chemistry toolkits like NWChem. The GTFock code is an HF implementation that, while it does not have all the features in NWChem, represents crucial algorithmic advances that reduce communication and improve load balance by doing an up-front static partitioning of tasks, followed by work stealing whenever necessary. To enable innovations in algorithms and exploit next generation exascale systems, it is crucial to support quantum chemistry codes using expressive and convenient programming models and runtime systems that are also efficient and scalable. This paper presents an HF implementation similar to GTFock using UPC++, a partitioned global address space model that includes flexible communication, asynchronous remote computation, and a powerful multidimensional array library. UPC++ offers runtime features that are useful for HF such as active messages, a rich calculus for array operations, hardware-supported fetch-and-add, and functions for ensuring asynchronous runtime progress. We present a new distributed array abstraction, DArray, that is convenient for the kinds of random-access array updates and linear algebra operations on block-distributed arrays with irregular data ownership. We analyze the performance of atomic fetch-and-add operations (relevant for load balancing) and runtime attentiveness, then compare various techniques and optimizations for each. Our optimized implementation of HF using UPC++ and the DArrays library shows up to 20% improvement over GTFock with Global Arrays at scales up to 24,000 cores

A Hartree-Fock Application Using UPC++ and the New DArray Library

The Hartree-Fock (HF) method is the fundamental first step for incorporating quantum mechanics into many-electron simulations of atoms and molecules, and it is an important component of computational chemistry toolkits like NWChem. The GTFock code is an HF implementation that, while it does not have all the features in NWChem, represents crucial algorithmic advances that reduce communication and improve load balance by doing an up-front static partitioning of tasks, followed by work stealing whenever necessary. To enable innovations in algorithms and exploit next generation exascale systems, it is crucial to support quantum chemistry codes using expressive and convenient programming models and runtime systems that are also efficient and scalable. This paper presents an HF implementation similar to GTFock using UPC++, a partitioned global address space model that includes flexible communication, asynchronous remote computation, and a powerful multidimensional array library. UPC++ offers runtime features that are useful for HF such as active messages, a rich calculus for array operations, hardware-supported fetch-and-add, and functions for ensuring asynchronous runtime progress. We present a new distributed array abstraction, DArray, that is convenient for the kinds of random-access array updates and linear algebra operations on block-distributed arrays with irregular data ownership. We analyze the performance of atomic fetch-and-add operations (relevant for load balancing) and runtime attentiveness, then compare various techniques and optimizations for each. Our optimized implementation of HF using UPC++ and the DArrays library shows up to 20% improvement over GTFock with Global Arrays at scales up to 24,000 cores

One-year outcome of biological and synthetic bioabsorbable meshes for augmentation of large abdominal wall defects in a rabbit model

BACKGROUND: Long-term efficacy of biological and synthetic bioabsorbable meshes for large hernia repair is currently unclear. This rabbit study is aimed at investigating 1-y outcome of biological and synthetic bioabsorbable meshes for augmentation of large abdominal wall defects. MATERIALS AND METHODS: In 46 rabbits, an 11 x 4 cm, full-thickness abdominal wall defect was repaired primarily, or with cross-linked (Permacol, Collamend) or non-cross-linked (Surgisis 4-ply, Surgisis Biodesign) biological, synthetic bioabsorbable (GORE BIO-A Tissue Reinforcement [TR], TIGR Matrix Surgical Mesh [MSM]), or polypropylene (Bard Mesh) meshes, using the underlay augmentation technique. One year after surgery, primary outcome was recurrence; secondary outcomes were tensile strength, histologic degree of tissue remodeling, and intraabdominal adhesion formation. RESULTS: Only two Surgisis 4-ply animals (50%) presented with a recurrent hernia. All GORE BIO-A TR meshes were completely resorbed and, as after primary repair, well-organized connective tissue without inflammation was present, with moderate adhesion formation and sufficient tensile strength. Cross-linked biological and TIGR MSM meshes demonstrated highest tensile strength but were only partially incorporated, with similar foreign body reaction and adhesion formation as polypropylene meshes in the TIGR MSM group, and minimal degradation and moderate adhesion formation in the cross-linked biological group. In the non-cross-linked biological group sufficient tensile strength and moderate adhesion formation were found, with pronounced inflammation if mesh remnants were present. CONCLUSIONS: Synthetic bioabsorbable GORE BIO-A TR meshes were associated with optimal tissue remodeling, with complete resorption, presence of well-organized tissue, and no inflammation. However, mesh augmentation had no advantages regarding recurrence rate versus primary repair of large abdominal wall defects