The neurological and non-neurological roles of the primary microcephaly-associated protein ASPM

Primary microcephaly (MCPH), is a neurological disorder characterized by small brain size that results in numerous developmental problems, including intellectual disability, motor and speech delays, and seizures. Hitherto, over 30 MCPH causing genes ( MCPHs ) have been identified. Among these MCPHs , MCPH5 , which encodes abnormal spindle-like microcephaly-associated protein (ASPM), is the most frequently mutated gene. ASPM regulates mitotic events, cell proliferation, replication stress response, DNA repair, and tumorigenesis. Moreover, using a data mining approach, we have confirmed that high levels of expression of ASPM correlate with poor prognosis in several types of tumors. Here, we summarize the neurological and non-neurological functions of ASPM and provide insight into its implications for the diagnosis and treatment of MCPH and cancer

The neurological and non-neurological roles of the primary microcephaly-associated protein ASPM

Primary microcephaly (MCPH), is a neurological disorder characterized by small brain size that results in numerous developmental problems, including intellectual disability, motor and speech delays, and seizures. Hitherto, over 30 MCPH causing genes (MCPHs) have been identified. Among these MCPHs, MCPH5, which encodes abnormal spindle-like microcephaly-associated protein (ASPM), is the most frequently mutated gene. ASPM regulates mitotic events, cell proliferation, replication stress response, DNA repair, and tumorigenesis. Moreover, using a data mining approach, we have confirmed that high levels of expression of ASPM correlate with poor prognosis in several types of tumors. Here, we summarize the neurological and non-neurological functions of ASPM and provide insight into its implications for the diagnosis and treatment of MCPH and cancer

The development of a competency assessment standard for general practitioners in China

This paper describes the development of a competency assessment standard for General Practitioners in Shenzhen, China. The standard is to be used for developing and delivering the training curriculum for General Practitioners and to enable rigorous assessment of the mastery of the standards by GP trainees. The requirement for the training of General Practitioners in China is mandated by government policy requires an international standard curriculum to meet the needs of patients and the community. A modified Delphi process was employed to arrive at a curriculum consensus. An expert panel and 14 expert working groups derived from the expert panel were established to review and evaluate national and international competency standards for General Practice and develop a set of standards, through a modified Delphi methodology. Forty three experts were involved in the project. The project resulted in a detailed curriculum statement. The curriculum was then used in 2017 and 2018 where pilot examinations of GP trainees (n = 298 and n = 315, respectively) were conducted to assess the trainee's competencies against the Standards. The examination included two modules, a written test (Module A) and a practical test (Module B). The success rate for participants was relatively low with the majority not successfully completing the assessments. The assessments will be further refined in subsequent work. The project achieved its goal of developing a rigorously evaluated standard to support clinical practice and the training and assessment of GPs. © Copyright © 2020 Rao, Lai, Wu, Li, Xu, Browning and Thomas

Genomic heterogeneity of multiple synchronous lung cancer

Multiple synchronous lung cancers (MSLCs) present a clinical dilemma as to whether individual tumours represent intrapulmonary metastases or independent tumours. In this study we analyse genomic profiles of 15 lung adenocarcinomas and one regional lymph node metastasis from 6 patients with MSLC. All 15 lung tumours demonstrate distinct genomic profiles, suggesting all are independent primary tumours, which are consistent with comprehensive histopathological assessment in 5 of the 6 patients. Lung tumours of the same individuals are no more similar to each other than are lung adenocarcinomas of different patients from TCGA cohort matched for tumour size and smoking status. Several known cancer-associated genes have different mutations in different tumours from the same patients. These findings suggest that in the context of identical constitutional genetic background and environmental exposure, different lung cancers in the same individual may have distinct genomic profiles and can be driven by distinct molecular events

Comprehensive molecular characterization of gastric adenocarcinoma

Gastric cancer is a leading cause of cancer deaths, but analysis of its molecular and clinical characteristics has been complicated by histological and aetiological heterogeneity. Here we describe a comprehensive molecular evaluation of 295 primary gastric adenocarcinomas as part of The Cancer Genome Atlas (TCGA) project. We propose a molecular classification dividing gastric cancer into four subtypes: tumours positive for Epstein–Barr virus, which display recurrent PIK3CA mutations, extreme DNA hypermethylation, and amplification of JAK2, CD274 (also known as PD-L1) and PDCD1LG2 (also knownasPD-L2); microsatellite unstable tumours, which show elevated mutation rates, including mutations of genes encoding targetable oncogenic signalling proteins; genomically stable tumours, which are enriched for the diffuse histological variant and mutations of RHOA or fusions involving RHO-family GTPase-activating proteins; and tumours with chromosomal instability, which show marked aneuploidy and focal amplification of receptor tyrosine kinases. Identification of these subtypes provides a roadmap for patient stratification and trials of targeted therapies

Integrated genomic characterization of oesophageal carcinoma

Oesophageal cancers are prominent worldwide; however, there are few targeted therapies and survival rates for these cancers remain dismal. Here we performed a comprehensive molecular analysis of 164 carcinomas of the oesophagus derived from Western and Eastern populations. Beyond known histopathological and epidemiologic distinctions, molecular features differentiated oesophageal squamous cell carcinomas from oesophageal adenocarcinomas. Oesophageal squamous cell carcinomas resembled squamous carcinomas of other organs more than they did oesophageal adenocarcinomas. Our analyses identified three molecular subclasses of oesophageal squamous cell carcinomas, but none showed evidence for an aetiological role of human papillomavirus. Squamous cell carcinomas showed frequent genomic amplifications of CCND1 and SOX2 and/or TP63, whereas ERBB2, VEGFA and GATA4 and GATA6 were more commonly amplified in adenocarcinomas. Oesophageal adenocarcinomas strongly resembled the chromosomally unstable variant of gastric adenocarcinoma, suggesting that these cancers could be considered a single disease entity. However, some molecular features, including DNA hypermethylation, occurred disproportionally in oesophageal adenocarcinomas. These data provide a framework to facilitate more rational categorization of these tumours and a foundation for new therapies

The Somatic Genomic Landscape of Chromophobe Renal Cell Carcinoma

We describe the landscape of somatic genomic alterations of 66 chromophobe renal cell carcinomas (ChRCCs) based on multidimensional and comprehensive characterization, including mitochondrial DNA (mtDNA) and whole genome sequencing. The result is consistent that ChRCC originates from the distal nephron compared to other kidney cancers with more proximal origins. Combined mtDNA and gene expression analysis implicates changes in mitochondrial function as a component of the disease biology, while suggesting alternative roles for mtDNA mutations in cancers relying on oxidative phosphorylation. Genomic rearrangements lead to recurrent structural breakpoints within TERT promoter region, which correlates with highly elevated TERT expression and manifestation of kataegis, representing a mechanism of TERT up-regulation in cancer distinct from previously-observed amplifications and point mutations

Multiplatform Analysis of 12 Cancer Types Reveals Molecular Classification within and across Tissues of Origin

Recent genomic analyses of pathologically-defined tumor types identify “within-a-tissue” disease subtypes. However, the extent to which genomic signatures are shared across tissues is still unclear. We performed an integrative analysis using five genome-wide platforms and one proteomic platform on 3,527 specimens from 12 cancer types, revealing a unified classification into 11 major subtypes. Five subtypes were nearly identical to their tissue-of-origin counterparts, but several distinct cancer types were found to converge into common subtypes. Lung squamous, head & neck, and a subset of bladder cancers coalesced into one subtype typified by TP53 alterations, TP63 amplifications, and high expression of immune and proliferation pathway genes. Of note, bladder cancers split into three pan-cancer subtypes. The multi-platform classification, while correlated with tissue-of-origin, provides independent information for predicting clinical outcomes. All datasets are available for data-mining from a unified resource to support further biological discoveries and insights into novel therapeutic strategies

Detection of the side faces of the image (part two)

As the appearance of a person had always been the primary identity, many had researched and introduced different ways to identify people. That includes fingerprint identification and handprint identification. Face detection is one of the ways to identify a human face in images. It had since improved and used in multiple applications such as person identification and surveillance. Though the side face detection have not been able to live up to the expectation, it will be beneficial to implement side face detection on applications for criminal identification and image annotation. This project focuses on using the Viola-Jones method to detect side-view faces and analyses the results that will be obtain. The algorithm uses the Haar-basis functions to get features to be learned in the AdaBoost learning algorithm. It is implemented for the selection of features. The features then will be used to go through classifiers. C++ Computing language and OpenCV is chosen as the platform to analyze the side face detection.Bachelor of Engineerin

Design of short-circuit protection circuit for switching power supply

Short-circuit protection circuit for switching power supply is designed. The circuit is for sampling and protection based on capacitance ripple characteristics. It has the advantages of rapid fault protection adjustable trigger time and recovery time. It shows that the circuit scheme has a good protective effect on the power converter in various load environments, and it has reached desired effect, according to the simulation results and the circuit application results