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The development of high throughput technologies such as next generation sequencing (NGS) has allowed for thousands of DNA loci to be interrogated simultaneously in a fast and economical method for the detection of clinically deleterious variants. Whenever a clinical diagnosis is known, a targeted NGS approach involving the use of disease-specific gene panels can be employed. This approach is often valuable as it allows for a more specific and clinically relevant interpretation of results. Here we describe the customization, validation, and utilization of a commercially available targeted enrichment platform for the scalability of clinical diagnostic cardiovascular genetic tests, including the design of the gene panels, the technical parameters for the quality assurance (QA) and quality control (QC), the customization of the bioinformatics pipeline, and the post-bioinformatics analysis procedures. Regions of poor base coverage were detected and targeted by Sanger sequencing as needed. All panels were successfully validated using genotype-known DNA samples either commercially available or from research subjects previously tested in outside clinical laboratories. In our experience utilizing several of the sub-panels in a clinical setting with 33 real-life cardiovascular patients we found that 20% of tests requested were reported to have at least one pathogenic or likely pathogenic variant that could explain the patient phenotype. For each of these patients, the positive results may aid the clinical team and the patients in best developing a disease management plan and in identifying relatives at risk.

This paper presents a facile hydrolysis reaction and annealing for preparing a novel hierarchical nanoheterostructure via assembly of α-Fe

Xiuwen Lan,1,* Sen Li,1,* Hongyu Gao,1 Abiyasi Nanding,2 Lina Quan,3 Chunyan Yang,4 Shaohua Ding,2 Yingwei Xue1 1Department of Gastroenterological Surgery, 2Department of Pathology, 3Department of Hematology, The Affiliated Tumor Hospital, 4Department of Epidemiology and Biostatistic, Public Health School, Harbin Medical University, Harbin, People’s Republic of China *These authors contributed equally to this work Purpose: Deregulation of immune checkpoint molecules by tumor cells is related to immune escape. This study was conducted to investigate the relationship between the appearance of B- and T-lymphocyte attenuator (BTLA) and its ligand herpesvirus entry mediator (HVEM) with the prognosis in gastric cancer patients. Patients and methods: A total of 136 patients with curative gastrectomy were included. The expression of BTLA and HVEM was detected by immunohistochemistry, and its correlation with the clinical significance of gastric cancer was further analyzed. Results: The positivity of BTLA and HVEM was detected in 74.3% (101/136) and 89.0% (121/136) of the gastric cancer specimens, respectively. A high expression of BTLA and HVEM was detected, respectively, in 28.7% (39/136) and 44.9% (61/136) of the specimens. Characteristics analysis showed that the high expression of BTLA was significantly associated with lymph node metastasis (P=0.030). Similarly, the high expression of HVEM was also significantly correlated with lymph node metastasis (P=0.007) and depth of invasion (P=0.011). In addition, there was a positive correlation between the expression of BTLA and HVEM in gastric cancer specimens (r=0.245, P=0.004). Univariate analysis revealed that the high expression of BTLA and HVEM was associated with overall survival of patients along with tumor size, Borrmann type, depth of invasion, lymph node metastasis, and histological grade (P

This article provides an overview of the latest research developments on binary and ternary oxide coatings that have the potential to be used as solid lubricants at elevated temperatures. The review focuses on understanding the major mechanisms that lead to a reduction in friction and/or wear in high temperature lubricious oxides. Changes in the structural, chemical, and electronic properties of these oxides as a function of temperature will be correlated to their mechanical and tribological performance using a range of experimental tools in addition to modeling based on ab initio calculations and molecular dynamics simulation methods. This review also includes a discussion of the industrial applications of these coatings as well as of potential improvements to the coating design and other anticipated future developments.

Integration of viral vectors into a host genome is associated with insertional mutagenesis and subjects in clinical gene therapy trials must be monitored for this adverse event. Several PCR based methods such as ligase-mediated (LM) PCR, linear-amplification-mediated (LAM) PCR and non-restrictive (nr) LAM PCR were developed to identify sites of vector integration. Coupling the power of next-generation sequencing technologies with various PCR approaches will provide a comprehensive and genome-wide profiling of insertion sites and increase throughput. In this bioinformatics study, we aimed to develop and apply quality metrics to viral insertion data obtained using next-generation sequencing. We developed five simple metrics for assessing next-generation sequencing data from different PCR products and showed how the metrics can be used to objectively compare runs performed with the same methodology as well as data generated using different PCR techniques. The results will help researchers troubleshoot complex methodologies, understand the quality of sequencing data, and provide a starting point for developing standardization of vector insertion site data analysis.

Silver tantalate coatings were produced by reactive unbalanced magnetron sputtering from silver and tantalum sources as potential high temperature solid lubricants. The films were wear-tested at 750 °C under normal loads of 1, 2, 5, or 10 N against a Si 3 N 4 counterface. These sliding tests revealed that the friction monotonically increased as the load was increased. A systematic investigation of the surface and sub-surface regions of the wear track, using techniques such as Scanning Auger Nanoprobe, Atom Probe Tomography, and cross-sectional transmission electron microscopy, revealed the following trends with increasing load: (1) a decrease in the amount of Ag on the surface of the wear track; (2) a decrease in the thickness of the mechanically mixed layer that forms as a result of the reconstruction of AgTaO 3 to form Ta 2 O 5 and Ag; and (3) the formation of a porous structure throughout the tribofilm as a result of the segregation and migration of Ag from the original AgTaO 3 matrix. These results were complemented by molecular dynamics simulations, which confirmed the increase of friction with load. Further, the simulations support the hypothesis that this trend can be explained in terms of decreased presence of Ag clusters near the sliding surface and the associated decreased porosity.

Early learning and development standards are generally understood as statements that reflect expectations for children’s development across a range of domains, including language and literacy, social and emotional development as well as physical health and cognitive development. China has applied the term ‘guidelines’ instead of ‘standards’ to avoid potential misuse of early learning standards for ‘classifying’ individual children according to the levels of accomplishments. With strong and continuous support from UNICEF, the Ministry of Education of China completed the Early Learning and Development Guidelines (hereinafter referred to as the “ELDG”) for children aged 3–6 years, which were officially released as part of the second annual national early childhood education advocacy month in May 2013.

Compared with the traditional gyros, Fiber optic gyroscope (FOG) based on sagnac effect has the significant features, such as, long life, low cost, wide dynamic range, etc. These features have developed new applications of the gyroscope not only in industrial application area but also in aerospace application area. Now, the FOG has played a very important role in shipborne Strapdown Inertial Navigation System (SINS). The fiber coil, as one of the most critical components in FOG, is extremely sensitive to changes in temperature. Here, by study the environment temperature in shipborne SINS, the temperature performance of the FOG was analyzed. Firstly, on the base of the research about the theory of Shupe non-reciprocal errors caused by temperature, the discrete mathematics formula of the temperature error in FOG of SINS was built .Then the element model of the fiber coil in SINS was built based on the discrete model of the fiber coil in temperature error in FOG. A turn-by-turn quantization temperature bias error model is establish. Finally, based on the temperature models mentioned above, the temperature performance of FOG in shipborne SINS was analyzed. With finite element analysis, numerical simulations were carried out to quantitatively analyze the angular error induced by temperature excitation in SINS. The model was validated by comparing numerical and experimental results.

In this study, we investigated the mechanical properties of AZ31B Mg alloy before and after laser shock peening (LSP). The hardness of the AZ31B Mg alloy increased from 57 HV to 69 HV after LSP. The yield strength increased from 128 MPa to 152 MPa. Wear resistance was significantly improved after LSP. Immersion testing showed that LSP did not significantly increase the element release and weight loss in simulated body fluid. We have demonstrated that LSP is an effective way to improve the mechanical properties of the AZ31B Mg alloy.

To investigate the features of clinicopathology and prognosis of gastric cancer in elderly patients over 75 years old.A total of 193 elderly gastric cancer patients(≥75 years old) were treated in the Tumour Hospital of Harbin Medical University from January 2007 to December 2010, accounting for 5.6%, 6.5%, 6.9%, 7.9% of gastric cancer patients in each year from 2007 to 2010, respectively. Among them, 99(51.3%) patients received radical operations (radical group), 35(18.1%) patients received palliative operations (palliative group), 11(5.7%) patients received simple gastrojejunal anastomosis or gastrostomosis (anastomosis and stomy group), and 48(24.9%) patients received non-operation treatments such as chemotherapy, biology or immunology and so on (non-operation group). Clinicopathological and follow-up data of these 193 elderly patients were retrospectively analyzed. Survival time was compared among different treatment groups by Log-rank test and risk factors affecting the survival time of patients undergoing radical operation were analyzed by multivariate regression analysis.The median age of these 193 elderly gastric cancer patients was 79 (75-98) years old. There were 140(72.5%) males and 53(27.5%) females. Among them, 79(40.9%) patients were complicated with anemia, 71(36.8%) with hypoproteinemia, 19(9.8%) had comorbid diabetes mellitus, 21(10.9%) had comorbid pneumonia, 54(28.0%) had history of smoking and alcohol, 14(7.3%) had genetic family history of cancer. The median overall survival time was 27.9 months. The median survival time was 38.2 months in the radical group, 17.4 months in the palliative group, 7.7 months in the anastomosis and stomy group, and 10.1 months in the non-operation group respectively, and the difference was statistically significant(P=0.000). The univariate analysis of survival time in radical group revealed that depth of invation(T stage, P=0.046), lymph node metastasis (N stage, P=0.000), tumor diameter (P=0.049), TNM staging (P=0.004), and CEA level (P=0.029) were associated with survival time. Gender, age, Borrmann type, tumor differentiation, surgical procedures, CA199 level anemia and hypoalbuminemia were not associated with the survival time(all P0.05). Multivariate analysis revealed that lymph node metastasis was the independent prognostic factor associated with shorter survival time in the elderly patients who underwent radical resection[N1 stage: P=0.005, OR=3.481, 95% CI:1.468-8.254; N2 stage: P=0.006, OR=2.848, 95% CI:1.341-6.050; N3 stage: P=0.000, OR=4.798, 95% CI:2.207-10.432].In gastric cancer patients, more and more elderly patients are being diagnosed. Radical resection can prolong their postoperative survival time, but if lymph node metastasis is present, the risk of shorter postoperative survival time elevates.

The commonly observed linear variation in shear strength with contact pressure is explored using a model system consisting of a potassium chloride (KCl) film between two iron counterfaces, for which a linear dependence has been found experimentally. The effect of artificially changing the KCl lattice spacing is explored using molecular dynamics (MD) simulations, where the interaction potential between the iron and KCl was previously optimized using surface science experiments for KCl on iron. It is found that the shear plane can change from occurring within the KCl film to taking place between the film and iron, depending on lattice spacing. In addition, shear within the KCl film leads to an increase in friction force with lattice spacing, while shear at the KCl–Fe interface leads to a decrease in friction with lattice spacing. The transition between the two regimes depends on the applied load. MD simulations of an equilibrium KCl film reveal that shear occurs at the KCl–iron interface, consistent with experiment, where no KCl transfer is found. Accordingly, the friction force increases with load, where the MD simulations yield a proportionality constant between shear strength and contact pressure of 0.115 ± 0.004, in excellent agreement with the experimental value of 0.14 ± 0.02. This result can be interpreted using the Prandtl–Tomlinson model where the pressure dependence arises from the external work carried out on the system due to the change in interlayer spacing at the sliding interface.

A variety of microbial communities and their genes (the microbiome) exist throughout the human body, with fundamental roles in human health and disease. The National Institutes of Health (NIH)-funded Human Microbiome Project Consortium has established a population-scale framework to develop metagenomic protocols, resulting in a broad range of quality-controlled resources and data including standardized methods for creating, processing and interpreting distinct types of high-throughput metagenomic data available to the scientific community. Here we present resources from a population of 242 healthy adults sampled at 15 or 18 body sites up to three times, which have generated 5,177 microbial taxonomic profiles from 16S ribosomal RNA genes and over 3.5 terabases of metagenomic sequence so far. In parallel, approximately 800 reference strains isolated from the human body have been sequenced. Collectively, these data represent the largest resource describing the abundance and variety of the human microbiome, while providing a framework for current and future studies.

Motivation: No individual assembly algorithm addresses all the known limitations of assembling short-length sequences. Overall reduced sequence contig length is the major problem that challenges the usage of these assemblies. We describe an algorithm to take advantages of different assembly algorithms or sequencing platforms to improve the quality of next-generation sequence (NGS) assemblies. Results: The algorithm is implemented as a graph accordance assembly (GAA) program. The algorithm constructs an accordance graph to capture the mapping information between the target and query assemblies. Based on the accordance graph, the contigs or scaffolds of the target assembly can be extended, merged or bridged together. Extra constraints, including gap sizes, mate pairs, scaffold order and orientation, are explored to enforce those accordance operations in the correct context. We applied GAA to various chicken NGS assemblies and the results demonstrate improved contiguity statistics and higher genome and gene coverage. Availability: GAA is implemented in OO perl and is available here: http://sourceforge.net/projects/gaa-wugi/. Contact: lye@genome.wustl.edu

This article surveys the current state of security issues and available defense mechanisms regarding popular online social networks. It covers a wide variety of attacks and the corresponding defense mechanisms, if available. The authors organize these attacks into four categories - privacy breaches, viral marketing, network structural attacks, and malware attacks - and focus primarily on privacy concerns. They offer an in-depth discussion of each category and analyze the connections among the different security issues involved.

Background and Objectives Matrix metalloproteinases (MMPs) are one of the major classes of proteolytic enzymes involved in tumor invasion and metastasis, being inhibited by naturally occurring tissue inhibitors of metalloproteinases (TIMPs). We examined mRNA expression for MMP-2, MMP-7, MMP-9, MT1-MMP, TIMP-1, and TIMP-2 in human gastric adenocarcinoma tissues, and the correlation between their expression and clinicopathological variables. Methods Gastric tissue samples from 72 patients with gastric adenocarcinoma were available for this study. To determine mRNA expression for MMP-2, MMP-7, MMP-9, MT1-MMP, TIMP-1, and TIMP-2, semiquantitative reverse transcriptase-polymerase chain reaction (RT-PCR) was carried out on tumor and normal tissues, respectively. Results Mean MMP-2, MMP-7, MMP-9, MT1-MMP, TIMP-1, and TIMP-2 mRNA expression in the gastric adenocarcinomas was significantly higher than in the normal tissue. In terms of the invasion of the tumor, lymph node metastasis, and tumor stage of gastric adenocarcinoma, the differences in MMP-2, MMP-7, MMP-9, and MT1-MMP mRNA expression levels were significant. MMP-2, MMP-7, MMP-9, MT1-MMP, TIMP-1, and TIMP-2 mRNA expression did not differ significantly in relation to histological type of gastric adenocarcinoma. Conclusion The correlation between the increased expression of MMP-2, MMP-7, MMP-9, and MTI-MMP and clinicopathological parameters reflects a role in predicting the aggressive behavior of gastric cancer. J. Surg. Oncol. 2011; 103:243–247. © 2010 Wiley-Liss, Inc.

TRPP2, also known as polycystin-2, is a calcium permeable nonselective cation channel that is mutated in autosomal dominant polycystic kidney disease but has also been implicated in the regulation of cardiac development, renal tubular differentiation, and left-to-right (L-R) axis determination. For obtaining further insight into how TRPP2 exerts tissue-specific functions, this study took advantage of PACS-dependent trafficking of TRPP2 in zebrafish larvae. PACS proteins recognize an acidic cluster within the carboxy-terminal domain of TRPP2 that undergoes phosphorylation and mediate retrieval of TRPP2 to the Golgi and endoplasmic reticulum (ER). The interaction of human TRPP2 with PACS proteins can be inhibited by a Ser812Ala mutation (TRPP2(S812A)), thereby allowing TRPP2 to reach other subcellular compartments, and enhanced by a Ser812Asp mutation (TRPP2(S812D)), thereby trapping TRPP2 in the ER. It was found that the TRPP2(S812A) mutant rescued cyst formation of TRPP2-deficient zebrafish larvae to the same degree as wild-type TRPP2, whereas the TRPP2(S812D) mutant was significantly more effective in normalizing the distorted body axis of TRPP2-deficient fish. Surprisingly, the TRPP2(S812D) mutant rescued the abnormalities of L-R asymmetry more effectively than either wild-type or TRPP2(S812A), suggesting that the ER localization of TRPP2 plays an important role in the development of normal L-R asymmetry. Taken together, these findings support the hypothesis that TRPP2 assumes distinct subcellular localizations to exert tissue-specific functions.

We report on the process of post mortem evaluation and genetic testing following the death of a 25-year-old man due to ascending aortic dissection leading to aortic rupture. Following the negative clinical testing of a 12- gene thoracic aortic aneurysm and dissection panel, research testing revealed a novel c.5732A>T (p.E1911V) variant in exon 34 of the MYLK gene (NM_053025). Two likely pathogenic variants in this gene have been reported previously in individuals with familial thoracic aortic aneurysm and dissection. Given the unclear clinical consequence of the variant found in our proband, we have classified this change as a variant of uncertain significance. In addition to discussing the complexity involved in variant interpretation, we recognize the need for additional research for more accurate MYLK interpretation. Finally, we comment on the unique challenges of post mortem genetic testing.

Historically, a number of typing methods have been evaluated for Staphylococcus aureus strain characterization. The emergence of contemporary strains of community-associated S. aureus, and the ensuing epidemic with a predominant strain type (USA300), necessitates re-evaluation of the discriminatory power of these typing methods for discerning molecular epidemiology and transmission dynamics, essential to investigations of hospital and community outbreaks. We compared the discriminatory index of 5 typing methods for contemporary S. aureus strain characterization. Children presenting to St. Louis Children's Hospital and community pediatric practices in St. Louis, Missouri (MO), with community-associated S. aureus infections were enrolled. Repetitive sequence-based PCR (repPCR), pulsed-field gel electrophoresis (PFGE), multilocus sequence typing (MLST), staphylococcal protein A (spa), and staphylococcal cassette chromosome (SCC) mec typing were performed on 200 S. aureus isolates. The discriminatory index of each method was calculated using the standard formula for this metric, where a value of 1 is highly discriminatory and a value of 0 is not discriminatory. Overall, we identified 26 distinct strain types by repPCR, 17 strain types by PFGE, 30 strain types by MLST, 68 strain types by spa typing, and 5 strain types by SCCmec typing. RepPCR had the highest discriminatory index (D) of all methods (D = 0.88), followed by spa typing (D = 0.87), MLST (D = 0.84), PFGE (D = 0.76), and SCCmec typing (D = 0.60). The method with the highest D among MRSA isolates was repPCR (D = 0.64) followed by spa typing (D = 0.45) and MLST (D = 0.44). The method with the highest D among MSSA isolates was spa typing (D = 0.98), followed by MLST (D = 0.93), repPCR (D = 0.92), and PFGE (D = 0.89). Among isolates designated USA300 by PFGE, repPCR was most discriminatory, with 10 distinct strain types identified (D = 0.63). We identified 45 MRSA isolates which were classified as identical by PFGE, MLST, spa typing, and SCCmec typing (USA300, ST8, t008, SCCmec IV, respectively); within this collection, there were 5 distinct strain types identified by repPCR. The typing methods yielded comparable discriminatory power for S. aureus characterization overall; when discriminating among USA300 isolates, repPCR retained the highest discriminatory power. This property is advantageous for investigations conducted in the era of contemporary S. aureus infections.

The exosome and its nuclear specific subunit Rrp6 form a 3'-5' exonuclease complex that regulates diverse aspects of RNA biology including 3' end processing and degradation of a variety of noncoding RNAs (ncRNAs) and unstable transcripts. Known targets of the nuclear exosome include short (

A series of single genes protect soybean from the root and stem disease caused by the oomycete pathogen Phytophthora sojae. In the last two decades, Rps1-k has been the most stable and widely used Phytophthora resistance gene for the major soybean-producing regions of the United States. Four highly similar genes encoding coiled coil-nucleotide binding-leucine rich repeat (CC-NB-LRR)-type proteins were isolated from the Rps1-k locus. These genes were grouped into two classes based on their sequence identity. Class I contains three genes with identical open reading frames (ORF) and 5′ end regions. Two of these genes were also identical at the 3′ untranslated regions; the third gene showed a recombination breakpoint in the 3′ untranslated region resulting in the combination of 3′ end sequences of members from both classes. Reverse transcription-polymerase chain reaction analyses suggested that members of both classes of genes are transcribed at low levels. Representative members from each gene class were expressed in transgenic soybean plants. Analyses of independent R0, R1, R2, and R3 progeny populations suggested that both gene classes confer Phytophthora resistance in soybean. A possible evolutionary mechanism for the Class I gene family is proposed.

The matrix metalloproteinase-9, E-cadherin, and vascular endothelial growth factor play an important role in behavior of tumor cell growth, invasion, and metastasis. In this study, we investigated the relationships of matrix metalloproteinase-9, E-cadherin, and vascular endothelial growth factor expression with clinicopathological features and results of chemosensitivity tested by collagen gel droplet–embedded culture–drug sensitivity test in gastric cancer. Fresh specimens were used for collagen gel droplet–embedded culture–drug sensitivity test and paired fixed specimens were used for immunohistochemistry. Positive expression of matrix metalloproteinase-9 was associated with poorly differentiated carcinoma (p = 0.032), lymph node metastasis (p = 0.022), and tumor stage (p = 0.023). Negative expression of E-cadherin was associated with poorly differentiated carcinoma (p = 0.007), lymph node metastasis (p = 0.012), and tumor stage (p = 0.007). Positive expression of vascular endothelial growth factor was associated with tumor size (p = 0.040) and stage (p = 0.007). Collagen gel droplet–embedded culture–drug sensitivity test was successfully evaluated in 56 patients. Among them, 29 (51.7%) patients were resistant to TS-1 and 31 (55.3%) patients were resistant to L-OHP. The L-OHP resistance rate in vascular endothelial growth factor positive patients was significantly higher than that in negative patients (p = 0.031). The L-OHP resistance rate in E-cadherin negative patients was significantly higher than that in positive patients (p = 0.014). In conclusion, matrix metalloproteinase-9, E-cadherin, and vascular endothelial growth factor were involved in tumor invasion and metastasis. Positive expression of matrix metalloproteinase-9 and vascular endothelial growth factor and negative expression of E-cadherin were malignant markers for gastric cancer. Positive expression of vascular endothelial growth factor and negative expression of E-cadherin were associated with L-OHP resistance.

Background/Objectives: Hematopoietic stem cell transplantation (HSCT) is a high risk but curative treatment for many patients with malignant and non-malignant disorders; however, comes with significant and varying chemotherapy-induced toxicities. Here we probe variability in response of DNA collected pre-versus-post autologous-HSCT from pediatric patients. Germline DNA mutations in this population have not been assessed. The overall hypothesis is that new germline mutations are generated by exposure to high-dose chemotherapy in pediatric patients receiving autologous-HSCT and that these genetic changes may also be potential biomarkers of therapeutic response. It has been reported that activation of complement protein, C3, can decrease the risk of infections following HSCT by enabling stem cells to home to the bone marrow and stimulate their differentiation to various immune cells. This process then helps mediate the reconstitution of the immune system via regulatory mechanisms. In this study, chemotherapy-induced germline mutations among pre- and post-autologous HSCT pediatric patients, and the complement component, C3 were evaluated. Developing strategies to identify predictive biomarkers such as variability in chemotherapy-induced mutational burden of C3 among pediatric HSCT patients, could result in innovative approaches to treating these high-risk patients. Design/Methods: Whole exome sequencing from an HSCT biorepository was exploited to assess genetic mutations and search for molecular signatures induced by anti-cancer therapy and autologous HSCT. Peripheral blood mononuclear cells (PBMCs) were isolated pre- and post-HSCT in six pediatric subjects undergoing autologous HSCT following myeloablative conditioning regimen involving carboplatin in combination with other standard of care agents. Whole exome sequencing was performed on germline DNA followed by canonical ingenuity pathway analysis® (IPA). Miliplex MAP Human Complement Panel 2 Multiplex Assay was performed on plasma from each patient pre- and post-HSCT to gain insight into status of the C3 complement protein levels following HSCT. Results: Whole exome DNA sequencing indicated that approximately 10% of genes analyzed (959 genes) were commonly mutated in the germline DNA isolated from the post-HSCT versus the pre-HSCT, which included C3 complement component. Canonical IPA analysis using hypergeometric test indicated that the 10% commonly mutated genes are relevant in at least thirty-six statistically significant biological. Specifically, C3 was found to be associated with the PI3K signaling pathway in immune cells such as B lymphocytes (p=0.04). Preliminary multiplex complement panel data revealed a trend for increased complement protein concentrations for C3 in plasma at day 7 post-HSCT versus plasma collected pre-HSCT. Conclusion: These preliminary experimental findings demonstrate that among the 959 commonly mutated genes, C3 consists of germline DNA mutations, as well as, having differences in expression at the protein level in patients pre- and post-HSCT. While investigation of the other commonly mutated genes and the thirty-five other relevant pathways elucidated in these studies is still ongoing, these studies highlight the importance for further investigation of the complement component C3 and its role in PI3K signaling in immune cells following chemotherapy-induced genetic mutations which may impact patient prognosis and care. Future studies using high-throughput exome sequencing may help elucidate predictive signatures and/or immune biomarkers such as differences in C3 gene and protein for developing personalized treatments for HSCT therapy, for properly managing HSCT-induced toxicities, and ameliorating clinical outcomes. Citation Format: Pankita H. Pandya, Hongyu Gao, ChienWei Chiang, Sydney Ross, Steven Rhodes, Jenny Then, Laura Haneline, Mary Murray, Lang Li, Karen Pollok, Jamie Renbarger. Comparative analysis of germline mutations of immune biomarkers pre- and post-HSCT in pediatric cancer patients. [abstract]. In: Proceedings of the AACR Special Conference on Translational Control of Cancer: A New Frontier in Cancer Biology and Therapy; 2016 Oct 27-30; San Francisco, CA. Philadelphia (PA): AACR; Cancer Res 2017;77(6 Suppl):Abstract nr A43.

In online social networks (OSNs), spam originating from friends and acquaintances not only reduces the joy of Internet surfing but also causes damage to less security-savvy users. Prior countermeasures combat OSN spam from different angles. Due to the diversity of spam, there is hardly any existing method that can independently detect the majority or most of OSN spam. In this paper, we empirically analyze the textual pattern of a large collection of OSN spam. An inspiring finding is that the majority (63.0%) of the collected spam is generated with underlying templates. We therefore propose extracting templates of spam detected by existing methods and then matching messages against the templates toward accurate and fast spam detection. We implement this insight through Tangram, an OSN spam filtering system that performs online inspection on the stream of user-generated messages. Tangram automatically divides OSN spam into segments and uses the segments to construct templates to filter future spam. Experimental results show that Tangram is highly accurate and can rapidly generate templates to throttle newly emerged campaigns. Specifically, Tangram detects the most prevalent template-based spam with 95.7% true positive rate, whereas the existing template generation approach detects only 32.3%. The integration of Tangram and its auxiliary spam filter achieves an overall accuracy of 85.4% true positive rate and 0.33% false positive rate.

Background and Objective Dyslipidemia is associated with aggressive periodontitis, a condition characterized by the rapid destruction of the periodontium. Apolipoprotein E (APOE) and low-density lipoprotein receptor-related protein 5 (LRP5) are involved in immunomodulation and inflammatory activity. We evaluated the association of LRP5 and APOE polymorphisms with serum lipid concentrations and generalized aggressive periodontitis within a Chinese population. Material and Methods Mean serum lipid concentrations were compared across LRP5 and APOE polymorphisms, among cases (n = 185) and controls (n = 138). Multivariable logistic regression was used to evaluate the independent and combined associations of LRP5 and APOE polymorphisms with generalized aggressive periodontitis. Results Compared with controls, individuals with generalized aggressive periodontitis exhibited significantly lower serum total cholesterol (TC) and lower high-density lipoprotein cholesterol (HDL-c). Individuals with LRP5 polymorphisms (rs682429-AA or rs312016-GG) exhibited higher TC, higher HDL-c and decreased odds for generalized aggressive periodontitis. Haplotype (A-G), determined by rs682429 and rs312016, was also associated with decreased odds for generalized aggressive periodontitis. Furthermore, individuals with the combined polymorphisms (LRP5-rs682429-AA and APOE-rs429358-CC/CT) had higher levels of low-density lipoprotein cholesterol, higher levels of TC and decreased odds for generalized aggressive periodontitis. Conclusion Independently or combined with APOE, LRP5 polymorphisms may lead to dyslipidemia and are associated with generalized aggressive periodontitis. Dyslipidemia may be a risk indicator for generalized aggressive periodontitis in the Chinese population. Furthermore, two LRP5 polymorphisms (rs682429 and rs312016) might be useful for identifying subjects at higher risk of generalized aggressive periodontitis.

We have applied both the master equation method and harmonic transition state theory to interpret the velocity-dependent friction behavior observed in atomic friction experiments. To understand the discrepancy between attempt frequencies measured in atomic force microscopy experiments and those estimated by theoretical models, both thermal noise and instrumental noise are introduced into the model. It is found that the experimentally observed low attempt frequency and the transition point at low velocity regimes can be interpreted in terms of the instrumental noise inherent in atomic force microscopy. In contrast to previous models, this model also predicts (1) the existence of a two-slope curve of velocity dependence and (2) the decrease of critical velocity with temperature, which provides clues for further experimental verification of the influence of instrumental noise in friction measurements.

The chemical properties of a surface determine the friction and wear behavior of a material during sliding. In this article, we study the mechanisms underlying the sliding behavior of the AgTaO3 perovskite material, a promising high-temperature solid lubricant that presents excellent friction properties and is chemically inert. In particular, by employing a combination of molecular dynamics simulations and density-functional theory calculations, we show that the low friction of AgTaO3 at high temperature is explained by silver aggregation on the surface, which is enabled by the low energy barriers associated with silver migration. Two different surface terminations (AgO and TaO2) are studied, and we show that the migration barrier on the AgO surface is smaller, favoring silver aggregation, which affects both friction and wear. Regardless of the termination, the formation of soft silver clusters dominates the sliding behavior when enough energy (mechanical or thermal) is imparted to the surface.

This paper proposes a public opinion propagation model on social networks based on SEIR. This model consider impacts of the node degree, social networks peculiar dissemination rules and users' habits, utilizes epidemiology and complex network theories, and establishes the dynamic evolution equations by building mathematical models of informed probability and disseminate probability. Simulation results show that pages of updating information can affect the propagation behavior of S, E nodes directly, the value of spread probability is the key impact factor of propagation velocity and scale. Additional, the number of infected nodes should be maintained at an appropriate range in order to make the maximum range of public opinion propagation.

The control of the information risk is an important task in the business administration, the information risk seriously affect the efficiency of the supply chain. This paper puts forward a model based on set pair analysis about information risk evaluation. This model can not only divide the extent of the information risk, but describe the trend of the information risk. It could describe the information risk from static and dynamic.

The exosome and its nuclear specific subunit Rrp6 form a 3’-5’ exonuclease complex that regulates diverse aspects of RNA biology including 3’ end processing and degradation of a variety of noncoding RNAs (ncRNAs) and unstable transcripts. Known targets of the nuclear exosome include short (, Author Summary RNAPII is responsible for transcription of protein-coding genes and short, regulatory RNAs. In Saccharomyces cerevisiae, termination of RNAPII-transcribed RNAs ≤1000 bases requires the NNS complex (comprised of Nrd1, Nab3, and Sen1), processing by the exosome, and the nuclear specific catalytic subunit, Rrp6. It has been shown that Rrp6 interacts directly with Nrd1, but whether or not Rrp6 is required for NNS-dependent termination is unclear. Loss of Rrp6 function may result in extension (or inhibition of termination) of NNS-dependent transcripts, or Rrp6 may only function after the fact to carry out RNA 3’ end processing. Here, we performed in-depth differential expression analyses and compare RNA-sequencing data of transcript length and abundance in cells lacking RRP6 to ChIP-exo analysis of RNAPII localization. We find many transcripts that were defined as unterminated upon loss of Nrd1 activity are of similar length in rrp6Δ, and expression levels of downstream genes are significantly decreased. This suggests a similar transcription interference mechanism occurs in cells lacking either Nrd1 or Rrp6. Indeed we find increased RNAPII located downstream of its termination site at many know Nrd1-regulated transcripts. Overall, our findings clearly demonstrate that Rrp6 activity is required for efficient NNS termination in vivo.

Tumor necrosis factor alpha-induced protein 8 (TNFAIP8) is an apoptosis regulator proven to have an important function in the proliferation, invasion, metastasis, and progression of malignancies. In this study, we investigated the clinical role of TNFAIP8 overexpression in endometrial cancer (EC) and determined the relationship of TNFAIP8 with the proliferative antigen Ki-67 and metastasis-related gene matrix metallopeptidase 9 (MMP9) in 225 tumor specimens by immunohistochemistry and western blot, in order to elucidate more information on the role of TNFAIP8 protein with regard to the pathogenesis of EC. An association was observed between TNFAIP8 overexpression and clinicopathologic factors, such as advanced International Federation of Gynecology and Obstetrics stage (P0.001), higher histologic grade (P=0.017), deep myometrial invasion (P=0.030), lymphovascular space invasion (P=0.011), lymph node metastasis (P0.001), and recurrence. Furthermore, TNFAIP8 overexpression was strongly correlated with MMP9 and Ki-67 expression in the progression of ECs. Patients with high expression of TNFAIP8 (P0.001 for both) and Ki-67 (P=0.007 and P=0.008) had poor overall survival and disease-free survival (DFS) rates. MMP9 overexpression did not affect survival outcomes (P0.05). Multivariate Cox regression analysis revealed that TNFAIP8 (P=0.029) and lymph node metastasis (P=0.022) were independent factors of DFS in patients with EC. These findings suggested that TNFAIP8 may be used as a prognostic marker for the recurrence of EC, and its promotion of the proliferation and metastasis in EC may be due to its mediation of Ki-67 and MMP9.

Twig pattern matching is core operation in XML query processing. Although holistic twig pattern matching algorithms have been studied intensively nowadays, little attention is paid on positional predicates defined on navigation axis. These algorithms cannot be used to implement XPath queries with positional predicates, since the query results fail to be selected from the pattern matching results. For implementation of XPath query with the positional predicates, this paper extends the traditional twig pattern to a new one called ExTwig to deal with both positional predicates and following sibling axis. The corresponding holistic twig pattern matching algorithm TwigPos is also proposed to process ExTwig query. Comparison experiments on large benchmarks show that our algorithm is efficient and practical.

The current pathogen-typing methods have suboptimal sensitivities and specificities. DNA sequencing offers an opportunity to type pathogens with greater degrees of discrimination using single nucleotide polymorphisms (SNPs) than with pulsed-field gel electrophoresis (PFGE) and other methodologies. In a recent cluster of Escherichia coli O157:H7 infections attributed to salad bar exposures and romaine lettuce, a subset of cases denied exposure to either source, although PFGE and multiple-locus variable-number tandem-repeat analysis (MLVA) suggested that all isolates had the same recent progenitor. Interrogation of a preselected set of 3,442,673 nucleotides in backbone open reading frames (ORFs) identified only 1 or 2 single nucleotide differences in 3 of 12 isolates from the cases who denied exposure. The backbone DNAs of 9 of 9 and 3 of 3 cases who reported or were unsure about exposure, respectively, were isogenic. Backbone ORF SNP set sequencing offers pathogen differentiation capabilities that exceed those of PFGE and MLVA.

The performance and operational characteristics of the DNS protocol are of deep interest to the research and network operations community. In this paper, we present measurement results from a unique dataset containing more than 26 billion DNS query-response pairs collected from more than 600 globally distributed recursive DNS resolvers. We use this dataset to reaffirm findings in published work and notice some significant differences that could be attributed both to the evolving nature of DNS traffic and to our differing perspective. For example, we find that although characteristics of DNS traffic vary greatly across networks, the resolvers within an organization tend to exhibit similar behavior. We further find that more than 50% of DNS queries issued to root servers do not return successful answers, and that the primary cause of lookup failures at root servers is malformed queries with invalid TLDs. Furthermore, we propose a novel approach that detects malicious domain groups using temporal correlation in DNS queries. Our approach requires no comprehensive labeled training set, which can be difficult to build in practice. Instead, it uses a known malicious domain as anchor, and identifies the set of previously unknown malicious domains that are related to the anchor domain. Experimental results illustrate the viability of this approach, i.e. , we attain a true positive rate of more than 96%, and each malicious anchor domain results in a malware domain group with more than 53 previously unknown malicious domains on average.

Like their public counterpart such as Facebook and Twitter, enterprise social networks are poised to revolutionize how people interact in the workplace. There is a pressing need to understand how people are using these social networks. Unlike the public social networks like Facebook or Twitter which are normally characterized using the social graph or the interaction graph, enterprise social networks are also governed by an organization graph. Based on a six month dataset collected from May through October 2011 of a large enterprise social network, we study the characteristics of activities of its enterprise social network. We observe that the user attributes in the organization graph such as geographic location (eg. country) and his/her rank in the company hierarchy have a significant impact on how the user uses the social network and how user interacts with each other. We then build formal statistical models of user interaction graphs in enterprise social network and quantify effects of user attributes from organization graphs on these interactions. Furthermore, as the enterprise social network medium bring users from diverse locations and social status forming ad-hoc communities, our statistical model can be further enhanced by including these ad-hoc communities.

XQuery is a functional language with implicit parallelism. It is an important approach to improve the efficiency of XML query by taking full advantage of multi-core environment in the parallel implementation of XQuery language. In this paper, we propose an implementation method for parallelizing XML query represented by XQuery programs automatically. According to the features of its functional language, an XQuery program is divided into a number of tasks that can be executed in parallel. Then, on the basis of the running cost evaluation, three kinds of parallelism are applied to different tasks and they are data parallelism, task parallelism and pipeline parallelism. Under the guidance of a novel scheduling strategy, the execution of the XQuery program is parallelized automatically. The experiments show that this approach improves the efficiency of the execution of XQuery programs and the computing resources of multi-core computer are used efficiently.

Objectives The objective of this study was to explore the prognostic values of Yes-associated protein (YAP) expression in cervical carcinoma. Methods We compared the YAP expression of 120 samples from squamous cell carcinomas (SCCs) and 42 samples from adenocarcinomas with 22 normal cervical specimens by immunohistochemistry. The expressions of cytoplasmic and nuclear YAP were analyzed separately. Result Yes-associated protein expression in tumors is significantly higher than the level in normal tissues. In SCCs, cytoplasmic YAP expression is associated with histologic grading, lymph node metastasis, and recurrence. Nuclear expression of YAP is absent in SCC. In adenocarcinomas, cytoplasmic YAP overexpression is associated with histologic grading, and nuclear overexpression is associated with shorter overall survival and disease-free survival. Conclusions Our results indicate the oncogenic potential of YAP in cervical cancer and its distinct functions in SCC and adenocarcinoma.

Development of daptomycin (DAP) resistance in Enterococcus faecalis has recently been associated with mutations in genes encoding proteins with two main functions: (i) control of the cell envelope stress response to antibiotics and antimicrobial peptides (LiaFSR system) and (ii) cell membrane phospholipid metabolism (glycerophosphoryl diester phosphodiesterase and cardiolipin synthase [ cls ]). However, the genetic bases for DAP resistance in Enterococcus faecium are unclear. We performed whole-genome comparative analysis of a clinical strain pair, DAP-susceptible E. faecium S447 and its DAP-resistant derivative R446, which was recovered from a single patient during DAP therapy. By comparative whole-genome sequencing, DAP resistance in R446 was associated with changes in 8 genes. Two of these genes encoded proteins involved in phospholipid metabolism: (i) an R218Q substitution in Cls and (ii) an A292G reversion in a putative cyclopropane fatty acid synthase enzyme. The DAP-resistant derivative R446 also exhibited an S333L substitution in the putative histidine kinase YycG, a member of the YycFG system, which, similar to LiaFSR, has been involved in cell envelope homeostasis and DAP resistance in other Gram-positive cocci. Additional changes identified in E. faecium R446 (DAP resistant) included two putative proteins involved in transport (one for carbohydrate and one for sulfate) and three enzymes predicted to play a role in general metabolism. Exchange of the “susceptible” cls allele from S447 for the “resistant” one belonging to R446 did not affect DAP susceptibility. Our results suggest that, apart from the LiaFSR system, the essential YycFG system is likely to be an important mediator of DAP resistance in some E. faecium strains.