Quality of Radiomic Features in Glioblastoma Multiforme: Impact of Semi-Automated Tumor Segmentation Software.

ObjectiveThe purpose of this study was to evaluate the reliability and quality of radiomic features in glioblastoma multiforme (GBM) derived from tumor volumes obtained with semi-automated tumor segmentation software.Materials and methodsMR images of 45 GBM patients (29 males, 16 females) were downloaded from The Cancer Imaging Archive, in which post-contrast T1-weighted imaging and fluid-attenuated inversion recovery MR sequences were used. Two raters independently segmented the tumors using two semi-automated segmentation tools (TumorPrism3D and 3D Slicer). Regions of interest corresponding to contrast-enhancing lesion, necrotic portions, and non-enhancing T2 high signal intensity component were segmented for each tumor. A total of 180 imaging features were extracted, and their quality was evaluated in terms of stability, normalized dynamic range (NDR), and redundancy, using intra-class correlation coefficients, cluster consensus, and Rand Statistic.ResultsOur study results showed that most of the radiomic features in GBM were highly stable. Over 90% of 180 features showed good stability (intra-class correlation coefficient [ICC] ≥ 0.8), whereas only 7 features were of poor stability (ICC < 0.5). Most first order statistics and morphometric features showed moderate-to-high NDR (4 > NDR ≥1), while above 35% of the texture features showed poor NDR (< 1). Features were shown to cluster into only 5 groups, indicating that they were highly redundant.ConclusionThe use of semi-automated software tools provided sufficiently reliable tumor segmentation and feature stability; thus helping to overcome the inherent inter-rater and intra-rater variability of user intervention. However, certain aspects of feature quality, including NDR and redundancy, need to be assessed for determination of representative signature features before further development of radiomics

Evaluation of rate law approximations in bottom-up kinetic models of metabolism.

BackgroundThe mechanistic description of enzyme kinetics in a dynamic model of metabolism requires specifying the numerical values of a large number of kinetic parameters. The parameterization challenge is often addressed through the use of simplifying approximations to form reaction rate laws with reduced numbers of parameters. Whether such simplified models can reproduce dynamic characteristics of the full system is an important question.ResultsIn this work, we compared the local transient response properties of dynamic models constructed using rate laws with varying levels of approximation. These approximate rate laws were: 1) a Michaelis-Menten rate law with measured enzyme parameters, 2) a Michaelis-Menten rate law with approximated parameters, using the convenience kinetics convention, 3) a thermodynamic rate law resulting from a metabolite saturation assumption, and 4) a pure chemical reaction mass action rate law that removes the role of the enzyme from the reaction kinetics. We utilized in vivo data for the human red blood cell to compare the effect of rate law choices against the backdrop of physiological flux and concentration differences. We found that the Michaelis-Menten rate law with measured enzyme parameters yields an excellent approximation of the full system dynamics, while other assumptions cause greater discrepancies in system dynamic behavior. However, iteratively replacing mechanistic rate laws with approximations resulted in a model that retains a high correlation with the true model behavior. Investigating this consistency, we determined that the order of magnitude differences among fluxes and concentrations in the network were greatly influential on the network dynamics. We further identified reaction features such as thermodynamic reversibility, high substrate concentration, and lack of allosteric regulation, which make certain reactions more suitable for rate law approximations.ConclusionsOverall, our work generally supports the use of approximate rate laws when building large scale kinetic models, due to the key role that physiologically meaningful flux and concentration ranges play in determining network dynamics. However, we also showed that detailed mechanistic models show a clear benefit in prediction accuracy when data is available. The work here should help to provide guidance to future kinetic modeling efforts on the choice of rate law and parameterization approaches

MicroRNA-153 targeting of KCNQ4 contributes to vascular dysfunction in hypertension.

AIMS: Kv7.4, a voltage-dependent potassium channel expressed throughout the vasculature, controls arterial contraction and is compromised in hypertension by an unknown mechanism. MicroRNAs (miRs) are post-transcriptional regulators of protein production and are altered in disease states such as hypertension. We investigated whether miRs regulate Kv7.4 expression. METHODS AND RESULTS: In renal and mesenteric arteries (MAs) of the spontaneously hypertensive rat (SHR), Kv7.4 protein decreased compared with the normotensive (NT) rat without a decrease in KCNQ4 mRNA, inferring that Kv7.4 abundance was determined by post-transcriptional regulation. In silico analysis of the 3' UTR of KCNQ4 revealed seed sequences for miR26a, miR133a, miR200b, miR153, miR214, miR218, and let-7d with quantitative polymerase chain reaction showing miR153 increased in those arteries from SHRs that exhibited decreased Kv7.4 levels. Luciferase reporter assays indicated a direct targeting effect of miR153 on the 3' UTR of KCNQ4. Introduction of high levels of miR153 to MAs increased vascular wall thickening and reduced Kv7.4 expression/Kv7 channel function compared with vessels receiving a non-targeting miR, providing a proof of concept of Kv7.4 regulation by miR153. CONCLUSION: This study is the first to define a role for aberrant miR153 contributing to the hypertensive state through targeting of KCNQ4 in an animal model of hypertension, raising the possibility of the use of miR153-related therapies in vascular disease

Orthogonal variability modeling to support multi-cloud application configuration

Cloud service providers benefit from a vast majority of customers due to variability and making profit from commonalities between the cloud services that they provide. Recently, application configuration dimensions has been increased dramatically due to multi-tenant, multi-device and multi-cloud paradigm. This challenges the configuration and customization of cloud-based software that are typically offered as a service due to the intrinsic variability. In this paper, we present a model-driven approach based on variability models originating from the software product line community to handle such multi-dimensional variability in the cloud. We exploit orthogonal variability models to systematically manage and create tenant-specific configuration and customizations. We also demonstrate how such variability models can be utilized to take into account the already deployed application parts to enable harmonized deployments for new tenants in a multi-cloud setting. The approach considers application functional and non-functional requirements to provide a set of valid multi-cloud configurations. We illustrate our approach through a case study

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

A practical approach to synthesize polyamide thin film nanocomposite (TFN) membranes with improved separation properties for water/wastewater treatment

TFN membranes containing 0.05 or 0.10 w/v% surface-functionalized TNTs in a PA selective layer were synthesized for better performances in water/wastewater treatment.</p

Исследование влияния технологического процесса изготовления обмоток на дефектность корпусной изоляции асинхронных двигателей

В работе проведено исследование влияния колебаний режимов работы статорообмоточных станков WST-660 и пазоизолировочных станков ИПС-3 на дефектность корпусной изоляции. Получены математические модели дефектообразования в корпусной изоляции обмотки с учетом режимов работы технологического оборудования и качества материала корпусной изоляции в состоянии поставки. Установлено, что изменением режимов работы технологического оборудования можно добиться требуемого качества корпусной изоляции при максимальной производительности оборудования

Is equal access to higher education in South Asia and sub-Saharan Africa achievable by 2030?

Higher education is back in the spotlight, with post-2015 sustainable development goals emphasising equality of access. In this paper, we highlight the long distance still to travel to achieve the goal of equal access to higher education for all, with a focus on poorer countries which tend to have lower levels of enrolment in higher education. Analysing Demographic and Health Survey data from 35 low- and middle-income countries in sub-Saharan Africa and South Asia, we show wide wealth inequalities in particular, with few if any of the poorest gaining access to higher education in some countries. We further identify that wealth and gender inequalities interact and tend to be wider in countries where levels of higher education are higher. This implies that expansion in access to higher education may predominantly benefit the rich, unless measures are taken to tackle inequalities. We find that that the rates of increase necessary for the attainment of the equal access goal by 2030 are particularly high. They pose a particularly difficult challenge given the access inequalities present from primary and secondary education in a wide majority of countries in our analysis. We therefore suggest that any measures aimed at attaining the goal need to tackle inequalities in access within a system-wide approach, focusing on the level of education at which inequalities initially manifest, alongside higher education.This is the final version of the article. It first appeared from Springer via http://dx.doi.org/10.1007/s10734-016-0039-