Identifying cancer-related microRNAs based on gene expression data

Motivation: MicroRNAs (miRNAs) are short non-coding RNAs that play important roles in post-transcriptional regulations as well as other important biological processes. Recently, accumulating evidences indicate that miRNAs are extensively involved in cancer. However, it is a big challenge to identify which miRNAs are related to which cancer considering the complex processes involved in tumors, where one miRNA may target hundreds or even thousands of genes and one gene may regulate multiple miRNAs. Despite integrative analysis of matched gene and miRNA expression data can help identify cancer-associated miRNAs, such kind of data is not commonly available. On the other hand, there are huge amount of gene expression data that are publicly accessible. It will significantly improve the efficiency of characterizing miRNA’s function in cancer if we can identify cancer miRNAs directly from gene expression data. Results: We present a novel computational framework to identify the cancer-related miRNAs based solely on gene expression profiles without requiring either miRNA expression data or the matched gene and miRNA expression data. The results on multiple cancer datasets show that our proposed method can effectively identify cancer-related miRNAs with higher precision compared with other popular approaches. Furthermore, some of our novel predictions are validated by both differentially expressed miRNAs and evidences from literature, implying the predictive power of our proposed method. In addition, we construct a cancer-miRNA-pathway network, which can help explain how miRNAs are involved in cancer

Redox dysregulation, neuroinflammation, and NMDA receptor hypofunction: A "central hub" in schizophrenia pathophysiology?

Accumulating evidence points to altered GABAergic parvalbumin-expressing interneurons and impaired myelin/axonal integrity in schizophrenia. Both findings could be due to abnormal neurodevelopmental trajectories, affecting local neuronal networks and long-range synchrony and leading to cognitive deficits. In this review, we present data from animal models demonstrating that redox dysregulation, neuroinflammation and/or NMDAR hypofunction (as observed in patients) impairs the normal development of both parvalbumin interneurons and oligodendrocytes. These observations suggest that a dysregulation of the redox, neuroimmune, and glutamatergic systems due to genetic and early-life environmental risk factors could contribute to the anomalies of parvalbumin interneurons and white matter in schizophrenia, ultimately impacting cognition, social competence, and affective behavior via abnormal function of micro- and macrocircuits. Moreover, we propose that the redox, neuroimmune, and glutamatergic systems form a "central hub" where an imbalance within any of these "hub" systems leads to similar anomalies of parvalbumin interneurons and oligodendrocytes due to the tight and reciprocal interactions that exist among these systems. A combination of vulnerabilities for a dysregulation within more than one of these systems may be particularly deleterious. For these reasons, molecules, such as N-acetylcysteine, that possess antioxidant and anti-inflammatory properties and can also regulate glutamatergic transmission are promising tools for prevention in ultra-high risk patients or for early intervention therapy during the first stages of the disease

Global Retinoblastoma Presentation and Analysis by National Income Level

Importance: Early diagnosis of retinoblastoma, the most common intraocular cancer, can save both a child's life and vision. However, anecdotal evidence suggests that many children across the world are diagnosed late. To our knowledge, the clinical presentation of retinoblastoma has never been assessed on a global scale. Objectives: To report the retinoblastoma stage at diagnosis in patients across the world during a single year, to investigate associations between clinical variables and national income level, and to investigate risk factors for advanced disease at diagnosis. Design, Setting, and Participants: A total of 278 retinoblastoma treatment centers were recruited from June 2017 through December 2018 to participate in a cross-sectional analysis of treatment-naive patients with retinoblastoma who were diagnosed in 2017. Main Outcomes and Measures: Age at presentation, proportion of familial history of retinoblastoma, and tumor stage and metastasis. Results: The cohort included 4351 new patients from 153 countries; the median age at diagnosis was 30.5 (interquartile range, 18.3-45.9) months, and 1976 patients (45.4) were female. Most patients (n = 3685 84.7%) were from low-and middle-income countries (LMICs). Globally, the most common indication for referral was leukocoria (n = 2638 62.8%), followed by strabismus (n = 429 10.2%) and proptosis (n = 309 7.4%). Patients from high-income countries (HICs) were diagnosed at a median age of 14.1 months, with 656 of 666 (98.5%) patients having intraocular retinoblastoma and 2 (0.3%) having metastasis. Patients from low-income countries were diagnosed at a median age of 30.5 months, with 256 of 521 (49.1%) having extraocular retinoblastoma and 94 of 498 (18.9%) having metastasis. Lower national income level was associated with older presentation age, higher proportion of locally advanced disease and distant metastasis, and smaller proportion of familial history of retinoblastoma. Advanced disease at diagnosis was more common in LMICs even after adjusting for age (odds ratio for low-income countries vs upper-middle-income countries and HICs, 17.92 95% CI, 12.94-24.80, and for lower-middle-income countries vs upper-middle-income countries and HICs, 5.74 95% CI, 4.30-7.68). Conclusions and Relevance: This study is estimated to have included more than half of all new retinoblastoma cases worldwide in 2017. Children from LMICs, where the main global retinoblastoma burden lies, presented at an older age with more advanced disease and demonstrated a smaller proportion of familial history of retinoblastoma, likely because many do not reach a childbearing age. Given that retinoblastoma is curable, these data are concerning and mandate intervention at national and international levels. Further studies are needed to investigate factors, other than age at presentation, that may be associated with advanced disease in LMICs. © 2020 American Medical Association. All rights reserved

Event-triggered anytime control with two controllers

In networked and multi-tasking environments, measurement data and processing resources may not be available at times when control calculations need to be executed. In this paper, we present an anytime algorithm which features two control policies: a coarse policy and a fine policy. The fine control policy requires more processing resources than the coarse policy. With this scheme, the network and processing resources can be used more efficiently, and performance can be improved. Specifically, for a given packet dropout rate and process availability which are independent and identically distributed (i.i.d.), the proposed two-controller scheme achieves better closed-loop performance with a lower channel utilization than alternative control formulations

Effect of neutrase, alcalase, and papain hydrolysis of whey protein concentrates on iron uptake by Caco-2 cells

Effects of enzymatic hydrolysates of whey protein concentrates (WPC) on iron absorption were studied using in vitro digestion combined with Caco-2 cell models for improved iron absorption. Neutrase- and papain-treated WPC could improve iron absorption; especially hydrolysates by Neutrase could significantly increase iron absorption to 12.8% compared to 3.8% in the control. Hydrolysates by alcalase had negative effects to the lowest at 0.57%. Two new bands at molecular weights (MW) around and below 10 kDa occurred at tricine-SDS-PAGE of hydrolysates by Neutrase, and one new band at MW below 10 kDa occurred in hydrolysates by papain. No new band was observed in hydrolysates by alcalase. Concentration of free amino acids indicated that, except for tyrosine and phenylalanine, amino acids in papain-treated hydrolysates were higher than that of alcalase, and no cysteine and proline were found in hydrolysates by alcalase. The results suggested that hydrolysate by Neutrase-treated WPC is a promising facilitator for iron absorption. Peptides of MW around and lower than 10 kDa and aspartic acid, serine, glutamic acid, glycin, cysteine, histidine, and proline may be contributors to enhancemen

Learning a non‐linear combination of Mahalanobis distances using statistical inference for similarity measure

In this study, the authors learn a similarity measure that discriminates between inter‐class and intra‐class samples based on a statistical inference perspective. A non‐linear combination of Mahalanobis is proposed to reflect the properties of a likelihood ratio test. Since an object's appearance is influenced by the identity of the object and variations in the capturing process, the authors represent the feature vector, which is the difference between two samples in the differences space, as a sample that is drawn from a mixture of many distributions. This mixture consists of the identities distribution and other distributions of the variations in the capturing process, in case of dissimilar samples. However, in the case of similar samples, the mixture consists of the variations in the capturing process distributions only. Using this representation, the proposed similarity measure accurately discriminates between inter‐class and intra‐class samples. To highlight the good performance of the proposed similarity measure, it is tested on different computer vision applications: face verification and person re‐identification. To illustrate how the proposed learning method can easily be used on large scale datasets, experiments are conducted on different challenging datasets: labelled faces in the wild (LFW), public figures face database, ETHZ and VIPeR. Moreover, in these experiments, the authors evaluate different stages, for example, features detector, descriptor type and descriptor dimension, which constitute the face verification pipeline. The experimental results confirm that the learning method outperforms the state‐of‐the‐art

Effects of fluoride on proliferation and mineralization in periodontal ligament cells in vitro

Fluoride, which is often added to toothpaste or mouthwash in order to protect teeth from decay, may be a novel therapeutic approach for acceleration of periodontal regeneration. Therefore, we investigated the effects of fluoride on proliferation and mineralization in human periodontal ligament cells in vitro. The periodontal ligament cells were stimulated with various concentrations of NaF added into osteogenic inductive medium. Immunohistochemistry of cell identification, cell proliferation, alkaline phosphatase (ALP) activity assay, Alizarin red S staining and quantitative real-time-polymerase chain reaction (RT-PCR) were performed. Moderate concentrations of NaF (50-500 μmol/L) had pro-proliferation effects, while 500 μmol/L had the best effects. ALP activity and calcium content were significantly enhanced by 10 μmol/L NaF with osteogenic inductive medium. Quantitative RT-PCR data varied in genes as a result of different NaF concentrations and treatment periods. We conclude that moderate concentrations of NaF can stimulate proliferation and mineralization in periodontal ligament cells. These in vitro findings may provide a novel therapeutic approach for acceleration of periodontal regeneration by addition of suitable concentrations of NaF into the medication for periodontitis treatment, i.e., into periodontal packs and tissue patches

Doping effect on magnetic and transport properties of Pr 2-xSrxCoO4

10.1088/0953-8984/20/39/395213Journal of Physics Condensed Matter2039-JCOM

LA-ICP-MS and EDS characterization of electrode/electrolyte interfaces in IT-SOFCs materials

Laser Ablation Inductively Coupled Plasma Mass Spectrometry (LA-ICP-MS) in combination with SEM is used for the determination of elemental spatial distribution in ceramic multi-layer systems as those found in Intermediate Temperature Solid Oxide Fuel Cells (IT-SOFCs). Because layer sintering occurs at high temperature (usually well over 1000°C), there may be mutual diffusion of ions from one layer to the other, with dramatic consequences on cell performances. In this work, two model materials have been used to test LA-ICP-MS: La0.83Sr0.17Ga0.83Mg0.17O2.83 (LSGM), one of the most promising electrolytes for IT-SOFCs, and La0.8Sr0.2MnO3 (LSM), a highly representative material of perovskites, which are amply used to design electrode materials. A two-layer system screen-printed onto an LSM pellet (LSM-LSGM-LSM pellet) was successively sintered at a typical processing temperature, i.e. 1300 °C, for a short time (1h). Elemental spatial distribution was determined by line profile analyses carried out on fracture surfaces; for comparison SEM-EDS line profiles were tested on the same surface. LA-ICP-MS line profile analysis evidenced that, notwithstanding the relatively low sintering temperature, and short firing time (1 h per sintering), manganese cation diffusion into LSGM is relatively abundant, in agreement with previous literature reports and present EDS results. While line scan EDX analyses are not conclusive as for Ga and Mg diffusion, LA-ICP-MS shows that both ions diffuse across both interfaces, and Ga diffuses even over very long distances into the LSM pellet; on the contrary, only trace amounts of Mg can be found far from the LSGM/LSM interface