Self-organising comprehensive handover strategy for multi-tier LTE-advanced heterogeneous networks

Long term evolution (LTE)-advanced was introduced as real fourth generation (4G) with its new features and additional functions, satisfying the growing demands of quality and network coverage for the network operators' subscribers. The term muti-tier has also been recently used with respect to the heterogeneity of the network by applying the various subnetwork cooperative systems and functionalities with self-organising capabilities. Using indoor short-range low-power cellular base stations, for example, femtocells, in cooperation with existing long-range macrocells are considered as the key technical challenge of this multi-tier configuration. Furthermore, shortage of network spectrum is a major concern for network operators which forces them to spend additional attentions to overcome the degradation in performance and quality of services in 4G HetNets. This study investigates handover between the different layers of a heterogeneous LTE-advanced system, as a critical attribute to plan the best way of interactive coordination within the network for the proposed HetNet. The proposed comprehensive handover algorithm takes multiple factors in both handover sensing and decision stages, based on signal power reception, resource availability and handover optimisation, as well as prioritisation among macro and femto stations, to obtain maximum signal quality while avoiding unnecessary handovers

Recurrent histone mutations in T-cell acute lymphoblastic leukaemia.

Mutations affecting key modifiable histone type 3 (H3; Supplementary Table 1) residues are frequent oncogenic events in certain solid tumours (Feinberg, et al 2016), and have also recently been implicated in a subset of acute myeloid leukaemia (AML)(Lehnertz, et al 2017). Here, we systematically reviewed the somatic mutations in >20,000 cancer specimens to identify tumours harbouring H3 mutations. In a subset of T-cell acute lymphoblastic leukaemia (T-ALL) we identified non-methionine mutations of the key modifiable H3 residues, lysine (K) 27 and 36

First international workshop on Multi Product Line Engineering (MultiPLE 2013)

In an industrial context, software systems are rarely developed by a single organization. For software product lines, this means that various organizations collaborate to provide and integrate the assets used in a product line. It is not uncommon that these assets themselves are built as product lines, a practice which is referred to as multi product lines. This cross-organizational distribution of reusable assets leads to numerous challenges, such as inconsistent configuration, costly and time-consuming integration, diverging evolution speed and direction, and inadequate testing. The MultiPLE workshop is aimed at discussing the challenges involved with the development and evolution of multi product lines and the assets used for their production. © 2013 Authors

The driver landscape of sporadic chordoma.

Chordoma is a malignant, often incurable bone tumour showing notochordal differentiation. Here, we defined the somatic driver landscape of 104 cases of sporadic chordoma. We reveal somatic duplications of the notochordal transcription factor brachyury (T) in up to 27% of cases. These variants recapitulate the rearrangement architecture of the pathogenic germline duplications of T that underlie familial chordoma. In addition, we find potentially clinically actionable PI3K signalling mutations in 16% of cases. Intriguingly, one of the most frequently altered genes, mutated exclusively by inactivating mutation, was LYST (10%), which may represent a novel cancer gene in chordoma.Chordoma is a rare often incurable malignant bone tumour. Here, the authors investigate driver mutations of sporadic chordoma in 104 cases, revealing duplications in notochordal transcription factor brachyury (T), PI3K signalling mutations, and mutations in LYST, a potential novel cancer gene in chordoma

Recurrent mutation of IGF signalling genes and distinct patterns of genomic rearrangement in osteosarcoma

Osteosarcoma is a primary malignancy of bone that affects children and adults. Here, we present the largest sequencing study of osteosarcoma to date, comprising 112 childhood and adult tumours encompassing all major histological subtypes. A key finding of our study is the identification of mutations in insulin-like growth factor (IGF) signalling genes in 8/112 (7%) of cases. We validate this observation using fluorescence in situ hybridization (FISH) in an additional 87 osteosarcomas, with IGF1 receptor (IGF1R) amplification observed in 14% of tumours. These findings may inform patient selection in future trials of IGF1R inhibitors in osteosarcoma. Analysing patterns of mutation, we identify distinct rearrangement profiles including a process characterized by chromothripsis and amplification. This process operates recurrently at discrete genomic regions and generates driver mutations. It may represent an age-independent mutational mechanism that contributes to the development of osteosarcoma in children and adults alike

Diagnostic value of H3F3A mutations in giant cell tumour of bone compared to osteoclast-rich mimics

Driver mutations in the two histone 3.3 (H3.3) genes, H3F3A and H3F3B, were recently identified by whole genome sequencing in 95% of chondroblastoma (CB) and by targeted gene sequencing in 92% of giant cell tumour of bone (GCT). Given the high prevalence of these driver mutations, it may be possible to utilise these alterations as diagnostic adjuncts in clinical practice. Here, we explored the spectrum of H3.3 mutations in a wide range and large number of bone tumours (n 5 412) to determine if these alterations could be used to distinguish GCT from other osteoclast-rich tumours such as aneurysmal bone cyst, nonossifying fibroma, giant cell granuloma, and osteoclast-rich malignant bone tumours and others. In addition, we explored the driver landscape of GCT through whole genome, exome and targeted sequencing (14 gene panel). We found that H3.3 mutations, namely mutations of glycine 34 in H3F3A, occur in 96% of GCT. We did not find additional driver mutations in GCT, including mutations in IDH1, IDH2, USP6, TP53. The genomes of GCT exhibited few somatic mutations, akin to the picture seen in CB. Overall our observations suggest that the presence of H3F3A p.Gly34 mutations does not entirely exclude malignancy in osteoclast-rich tumours. However, H3F3A p.Gly34 mutations appear to be an almost essential feature of GCT that will aid pathological evaluation of bone tumours, especially when confronted with small needle core biopsies. In the absence of H3F3A p.Gly34 mutations, a diagnosis of GCT should be made with caution

Recurrent rearrangements of FOS and FOSB define osteoblastoma.

The transcription factor FOS has long been implicated in the pathogenesis of bone tumours, following the discovery that the viral homologue, v-fos, caused osteosarcoma in laboratory mice. However, mutations of FOS have not been found in human bone-forming tumours. Here, we report recurrent rearrangement of FOS and its paralogue, FOSB, in the most common benign tumours of bone, osteoblastoma and osteoid osteoma. Combining whole-genome DNA and RNA sequences, we find rearrangement of FOS in five tumours and of FOSB in one tumour. Extending our findings into a cohort of 55 cases, using FISH and immunohistochemistry, provide evidence of ubiquitous mutation of FOS or FOSB in osteoblastoma and osteoid osteoma. Overall, our findings reveal a human bone tumour defined by mutations of FOS and FOSB

Somatic mutations and single-cell transcriptomes reveal the root of malignant rhabdoid tumours.

Malignant rhabdoid tumour (MRT) is an often lethal childhood cancer that, like many paediatric tumours, is thought to arise from aberrant fetal development. The embryonic root and differentiation pathways underpinning MRT are not firmly established. Here, we study the origin of MRT by combining phylogenetic analyses and single-cell mRNA studies in patient-derived organoids. Comparison of somatic mutations shared between cancer and surrounding normal tissues places MRT in a lineage with neural crest-derived Schwann cells. Single-cell mRNA readouts of MRT differentiation, which we examine by reverting the genetic driver mutation underpinning MRT, SMARCB1 loss, suggest that cells are blocked en route to differentiating into mesenchyme. Quantitative transcriptional predictions indicate that combined HDAC and mTOR inhibition mimic MRT differentiation, which we confirm experimentally. Our study defines the developmental block of MRT and reveals potential differentiation therapies

A Pathogenic Mosaic TP53 Mutation in Two Germ Layers Detected by Next Generation Sequencing.

Li-Fraumeni syndrome is caused by germline TP53 mutations and is clinically characterized by a predisposition to a range of cancers, most commonly sarcoma, brain tumours and leukemia. Pathogenic mosaic TP53 mutations have only rarely been described