Levelling aeromagnetic survey data without the need for tie-lines

A new methodology that levels airborne magnetic data without orthogonal tie-lines is presented in this study. The technique utilizes the low-wavenumber content of the flight-line data to construct a smooth representation of the regional field at a scale appropriate to the line lengths of the survey. Levelling errors are then calculated between the raw flight-line data and the derived regional field through a least squares approach. Minimizing the magnitude of the error, with a first-degree error function, results in significant improvements to the unlevelled data. The technique is tested and demonstrated using three recent airborne surveys

Integrated data management and validation platform for phosphorylated tandem mass spectrometry data

MS/MS is a widely used method for proteome-wide analysis of protein expression and PTMs. The thousands of MS/MS spectra produced from a single experiment pose a major challenge for downstream analysis. Standard programs, such as MASCOT, provide peptide assignments for many of the spectra, including identification of PTM sites, but these results are plagued by false-positive identifications. In phosphoproteomic experiments, only a single peptide assignment is typically available to support identification of each phosphorylation site, and hence minimizing false positives is critical. Thus, tedious manual validation is often required to increase confidence in the spectral assignments. We have developed phoMSVal, an open-source platform for managing MS/MS data and automatically validating identified phosphopeptides. We tested five classification algorithms with 17 extracted features to separate correct peptide assignments from incorrect ones using over 2600 manually curated spectra. The naïve Bayes algorithm was among the best classifiers with an AUC value of 97% and PPV of 97% for phosphotyrosine data. This classifier required only three features to achieve a 76% decrease in false positives as compared with MASCOT while retaining 97% of true positives. This algorithm was able to classify an independent phosphoserine/threonine data set with AUC value of 93% and PPV of 91%, demonstrating the applicability of this method for all types of phospho-MS/MS data. PhoMSVal is available at http://csbi.ltdk.helsinki.fi/phomsval.National Science Foundation (U.S.). Graduate Research Fellowship Progra

Alternative splicing discriminates molecular subtypes and has prognostic impact in diffuse large B-cell lymphoma

Effect of alternative splicing (AS) on diffuse large B-cell lymphoma (DLBCL) pathogenesis and survival has not been systematically addressed. Here, we compared differentially expressed genes and exons in association with survival after chemoimmunotherapy, and between germinal center B-cell like (GCB) and activated B-cell like (ABC) DLBCLs. Genome-wide exon array-based screen was performed from samples of 38 clinically high-risk patients who were treated in a Nordic phase II study with dose-dense chemoimmunotherapy and central nervous system prophylaxis. The exon expression profile separated the patients according to molecular subgroups and survival better than the gene expression profile. Pathway analyses revealed enrichment of AS genes in inflammation and adhesion-related processes, and in signal transduction, such as phosphatidylinositol signaling system and adenosine triphosphate binding cassette transporters. Altogether, 49% of AS-related exons were protein coding, and domain prediction showed 28% of such exons to include a functional domain, such as transmembrane helix domain or phosphorylation sites. Validation in an independent cohort of 92 DLBCL samples subjected to RNA-sequencing confirmed differential exon usage of selected genes and association of AS with molecular subtypes and survival. The results indicate that AS events are able to discriminate GCB and ABC DLBCLs and have prognostic impact in DLBCL.Peer reviewe

Clinical Value of 18F-fluorodeoxyglucose Positron Emission Tomography/Computed Tomography in Response Evaluation after Primary Treatment of Advanced Epithelial Ovarian Cancer

Aims: To prospectively evaluate the use of F-18-fluorodeoxyglucose positron emission tomography/computed tomography (F-18-FDG-PET/CT) in the definition of the treatment response after primary treatment of advanced epithelial ovarian cancer (EOC). Materials and methods: Forty-nine patients with advanced EOC had an F-18-FDG PET/CT scan before and after primary treatment. The treatment response was defined with the currently used radiological and serological Response Criteria in Solid Tumors (RECIST1.1/GCIC) criteria and the modified PET Response Criteria in Solid Tumors (PERCIST). The concordance of the two methods was analysed. If the patient had a complete response to primary treatment by conventional criteria, the end of treatment F-18-FDG PET/CT scan (etPET/CT) was not opened until retrospectively at the time of disease progression. The ability of etPET/CT to predict the time to disease recurrence was analysed. The recurrence patterns were observed with an F-18-FDG PET/CT at the first relapse. Results: The agreement of the RECIST1.1/GCIC and modified PERCIST criteria in defining the primary treatment response in the whole patient cohort was good (weighted kappa coefficient = 0.78 ). Of the complete responders (n = 28), 34% had metabolically active lesions present in the etPET/CT, most typically in the lymph nodes. The same anatomical sites tended to activate at disease relapse, but were seldom the only site of relapse. In patients with widespread intra-abdominal carsinosis at diagnosis, the definition of metabolic response was challenging due to problems in distinguishing the physiological FDG accumulation in the bowel loops from the residual tumour in the same area. The presence of metabolically active lesions in the etPET/CT did not predict earlier disease relapse in the complete responders. Conclusions: In the present study, etPET/CT revealed metabolically active lesions in complete responders after EOC primary therapy, but they were insignificant for the patient's prognosis. The current study does not favour routine use of F-18-FDG PET/CT after EOC primary treatment for complete responders. (C) 2018 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.Peer reviewe

Reproducibility of the computational fluid dynamic analysis of a cerebral aneurysm monitored over a decade

Computational fluid dynamics (CFD) simulations are increasingly utilised to evaluate intracranial aneurysm (IA) haemodynamics to aid in the prediction of morphological changes and rupture risk. However, these models vary and differences in published results warrant the investigation of IA-CFD reproducibility. This study aims to explore sources of intra-team variability and determine its impact on the aneurysm morphology and CFD parameters. A team of four operators were given six sets of magnetic resonance angiography data spanning a decade from one patient with a middle cerebral aneurysm. All operators were given the same protocol and software for model reconstruction and numerical analysis. The morphology and haemodynamics of the operator models were then compared. The segmentation, smoothing factor, inlet and outflow branch lengths were found to cause intra-team variability. There was 80% reproducibility in the time-averaged wall shear stress distribution among operators with the major difference attributed to the level of smoothing. Based on these findings, it was concluded that the clinical applicability of CFD simulations may be feasible if a standardised segmentation protocol is developed. Moreover, when analysing the aneurysm shape change over a decade, it was noted that the co-existence of positive and negative values of the wall shear stress divergence (WSSD) contributed to the growth of a daughter sac

Demography and Environment in Grassland Settlement: Using Linked Longitudinal and Cross-Sectional Data to Explore Household and Agricultural Systems

The Demography and Environment in Grassland Settlement project (DEGS) is a study of the relationship between population and environment in Kansas during its settlement and conversion from grassland to grain cultivation and rangeland. The research team involved in this project had as its goal to bring together data about farms and farm families in order to understand the core transformations in land use and family dynamics that took place during the process of settling and developing an agricultural landscape. For reasons we will explain later, the state of Kansas – located near the centre of the U.S. in a grassland ecosystem – is ideally suited for this study by virtue of its location, history and the documents that exist about it. In order to capture the environmental variability of Kansas, we are assembling a linked database of farm and family census records for twenty-five townships scattered across the state. This paper is about the process of choosing that sample, about the data we have accumulated and about the process we are undertaking to link records about families and farms through time and to attempt to find their locations in space.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/60442/1/sylvester_etal.demography and environment.pd

Therapeutic targets for HIV-1 infection in the host proteome

BACKGROUND: Despite the success of HAART, patients often stop treatment due to the inception of side effects. Furthermore, viral resistance often develops, making one or more of the drugs ineffective. Identification of novel targets for therapy that may not develop resistance is sorely needed. Therefore, to identify cellular proteins that may be up-regulated in HIV infection and play a role in infection, we analyzed the effects of Tat on cellular gene expression during various phases of the cell cycle. RESULTS: SOM and k-means clustering analyses revealed a dramatic alteration in transcriptional activity at the G1/S checkpoint. Tat regulates the expression of a variety of gene ontologies, including DNA-binding proteins, receptors, and membrane proteins. Using siRNA to knock down expression of several gene targets, we show that an Oct1/2 binding protein, an HIV Rev binding protein, cyclin A, and PPGB, a cathepsin that binds NA, are important for viral replication following induction from latency and de novo infection of PBMCs. CONCLUSION: Based on exhaustive and stringent data analysis, we have compiled a list of gene products that may serve as potential therapeutic targets for the inhibition of HIV-1 replication. Several genes have been established as important for HIV-1 infection and replication, including Pou2AF1 (OBF-1), complement factor H related 3, CD4 receptor, ICAM-1, NA, and cyclin A1. There were also several genes whose role in relation to HIV-1 infection have not been established and may also be novel and efficacious therapeutic targets and thus necessitate further study. Importantly, targeting certain cellular protein kinases, receptors, membrane proteins, and/or cytokines/chemokines may result in adverse effects. If there is the presence of two or more proteins with similar functions, where only one protein is critical for HIV-1 transcription, and thus, targeted, we may decrease the chance of developing treatments with negative side effects

Reply to : Proofreading deficiency in mitochondrial DNA polymerase does not affect total dNTP pools in mouse embryos

Non peer reviewe

PIK3R1 fusion drives chemoresistance in ovarian cancer by activating ERK1/2 and inducing rod and ring-like structures

Gene fusions are common in high-grade serous ovarian cancer (HGSC). Such genetic lesions may promote tumorigenesis, but the pathogenic mechanisms are currently poorly understood. Here, we investigated the role of a PIK3R1-CCDC178 fusion identified from a patient with advanced HGSC. We show that the fusion induces HGSC cell migration by regulating ERK1/2 and increases resistance to platinum treatment. Platinum resistance was associated with rod and ring-like cellular structure formation. These structures contained, in addition to the fusion protein, CIN85, a key regulator of PI3K-AKT-mTOR signaling. Our data suggest that the fusion-driven structure formation induces a previously unrecognized cell survival and resistance mechanism, which depends on ERK1/2-activation