EZH2 mutations are frequent and represent an early event in follicular lymphoma

Gain of function mutations in the H3K27 methyltransferase EZH2 represent a promising therapeutic target in germinal center lymphomas. In this study, we assessed the frequency and distribution of EZH2 mutations in a large cohort of patients with follicular lymphoma (FL) (n = 366) and performed a longitudinal analysis of mutation during the disease progression from FL to transformed FL (tFL) (n = 33). Mutations were detected at 3 recurrent mutation hot spots (Y646, A682, and A692) in 27% of FL cases with variant allele frequencies (VAF) ranging from 2% to 61%. By comparing VAF of EZH2 with other mutation targets (CREBBP, MLL2, TNFRSF14, and MEF2B), we were able to distinguish patients harbori…

Comparison of RNA-seq and microarray-based models for clinical endpoint prediction

Background Gene expression profiling is being widely applied in cancer research to identify biomarkers for clinical endpoint prediction. Since RNA-seq provides a powerful tool for transcriptome-based applications beyond the limitations of microarrays, we sought to systematically evaluate the performance of RNA-seq-based and microarray-based classifiers in this MAQC-III/SEQC study for clinical endpoint prediction using neuroblastoma as a model. Results We generate gene expression profiles from 498 primary neuroblastomas using both RNA-seq and 44 k microarrays. Characterization of the neuroblastoma transcriptome by RNA-seq reveals that more than 48,000 genes and 200,000 transcripts are being …

Robust H∞ synchronization of a hyper-chaotic system with disturbance input

Abstract This paper concerns the robust control problems on the synchronization of a hyper-chaotic system with disturbance input. Using an appropriate Lyapunov function, we design the multi-dimensional and the single-dimensional robust H ∞ synchronization controllers in terms of linear matrix inequalities for the application in practical engineering. Corresponding theoretical derivations are given subsequently. Finally, some numerical simulations are provided to demonstrate the effectiveness of the proposed techniques.

Calibration strategy of the JUNO experiment

We present the calibration strategy for the 20 kton liquid scintillator central detector of the Jiangmen Underground Neutrino Observatory (JUNO). By utilizing a comprehensive multiple-source and multiple-positional calibration program, in combination with a novel dual calorimetry technique exploiting two independent photosensors and readout systems, we demonstrate that the JUNO central detector can achieve a better than 1% energy linearity and a 3% effective energy resolution, required by the neutrino mass ordering determination. [Figure not available: see fulltext.]

Comparative study of modelling the thermal efficiency of a novel straight through evacuated tube collector with MLR, SVR, BP and RBF methods

Abstract Data-based methods are useful for accurate modelling of solar thermal systems. In this work, several artificial neural network (ANN) techniques are proposed to predict the thermal performance of an all-glass straight through evacuated tube solar collector. These are compared to support vector regression analysis. Extensive experimental data sets were collected for training the ANN models. Solar radiation intensity, ambient temperature, wind speed, mass flow rate and collector inlet temperature were selected as the input layer to predict the thermal efficiency of the solar collector. The prediction precision of the ANN models was compared to the multiple linear regression and suppor…

-Infinity robust controller design for the synchronization of master-slave chaotic systems with disturbance input

Published version of an article from the journal: Modeling, Identification and Control. Also available from the publisher: http://dx.doi.org/10.4173/mic.2012.1.3 This paper is concerned with the robust control problems for the synchronization of master-slave chaotic systems with disturbance input. By constructing a series of Lyapunov functions, novel H1 robust syn- chronization controllers are designed, whose control regulation possess the characteristic of simpleness and explicitness. Finally, numerical simulations are provided to demonstrate the e ectiveness of the proposed techniques.

The Design and Sensitivity of JUNO's scintillator radiopurity pre-detector OSIRIS

The European physical journal / C 81(11), 973 (2021). doi:10.1140/epjc/s10052-021-09544-4

Radioactivity control strategy for the JUNO detector

JUNO is a massive liquid scintillator detector with a primary scientific goal of determining the neutrino mass ordering by studying the oscillated anti-neutrino flux coming from two nuclear power plants at 53 km distance. The expected signal anti-neutrino interaction rate is only 60 counts per day, therefore a careful control of the background sources due to radioactivity is critical. In particular, natural radioactivity present in all materials and in the environment represents a serious issue that could impair the sensitivity of the experiment if appropriate countermeasures were not foreseen. In this paper we discuss the background reduction strategies undertaken by the JUNO collaboration…

10th international Luebeck conference on the pathophysiology and pharmacology of erythropoietin and other hemopoietic growth factors

Recombinant erythropoietins (rEPOs) as well as other erythropoiesis-stimulating agents (ESAs) are used for medical treatment of anemia, but likewise ESAs can be misused for performance enhancing purposes in sports. Using small RNAseq, we investigated the effects of low dose administration of rEPO for 6 weeks on the miRNA profile of purified red blood cells (RBCs), in 7 male healthy recreational athletes. Despite lacking most of long RNAs, RBCs contain diverse and abundant miRNAs. For each of the 14 samples 100 ng total RNA, of highly purified RBCs, were used for sequencing with Illumina NextSeq500 system. Following bowtie alignment and mapping of the raw reads, edgeR was used for normalizat…

JUNO sensitivity to low energy atmospheric neutrino spectra

Atmospheric neutrinos are one of the most relevant natural neutrino sources that can be exploited to infer properties about cosmic rays and neutrino oscillations. The Jiangmen Underground Neutrino Observatory (JUNO) experiment, a 20 kton liquid scintillator detector with excellent energy resolution is currently under construction in China. JUNO will be able to detect several atmospheric neutrinos per day given the large volume. A study on the JUNO detection and reconstruction capabilities of atmospheric $\nu_e$ and $\nu_\mu$ fluxes is presented in this paper. In this study, a sample of atmospheric neutrino Monte Carlo events has been generated, starting from theoretical models, and then pro…

Neuromodulatory effect of interleukin 1β in the dorsal raphe nucleus on individual differences in aggression

Heightened aggressive behavior is considered as one of the central symptoms of many neuropsychiatric disorders including autism, schizophrenia, and dementia. The consequences of aggression pose a heavy burden on patient’s families, clinicians, and the patients themselves. At the same time, we have limited treatment options for aggression and lack mechanistic insight into the causes of aggression needed to inform new efforts in drug discovery and development. Levels of proinflammatory cytokines in the periphery or cerebrospinal fluid were previously reported to correlate with aggressive traits in humans. However, it is still unknown whether cytokines affect brain circuits to modulate aggress…

Molecular topology as novel strategy for discovery of drugs with aβ lowering and anti-aggregation dual activities for Alzheimer's disease.

Background and Purpose: In this study, we demonstrate the use of Molecular topology (MT) in an Alzheimer's disease (AD) drug discovery program. MT uses and expands upon the principles governing the molecular connectivity theory of numerically characterizing molecular structures, in the present case, active anti-AD drugs/agents, using topological descriptors to build models. Topological characterization has been shown to embody sufficient molecular information to provide strong correlation to therapeutic efficacy. Experimental Approach: We used MT to include multiple bioactive properties that allows for the identification of multifunctional single agent compounds, in this case, the dual func…

P2‐511: From in silico to in vitro to in vivo: ‐ Novel approach in Alzheimer's disease drug discovery

Fuzzy Variable Structure Control for Uncertain Systems with Disturbance

Published version of an article from the journal: Mathematical Problems in Engineering. Also available from the publisher:http://dx.doi.org/10.1155/2012/105074 This paper focuses on the fuzzy variable structure control for uncertain systems with disturbance. Specifically, the fuzzy control is introduced to estimate the control disturbance, the switching control is included to compensate for the approximation error, and they possess the characteristic of simpleness in design and effectiveness in attenuating the control chattering. Some typical numerical examples are presented to demonstrate the effectiveness and advantage of the fuzzy variable structure controller proposed.

Genome-wide adaptive complexes to underground stresses in blind mole rats Spalax

The blind mole rat (BMR), Spalax galili, is an excellent model for studying mammalian adaptation to life underground and medical applications. The BMR spends its entire life underground, protecting itself from predators and climatic fluctuations while challenging it with multiple stressors such as darkness, hypoxia, hypercapnia, energetics and high pathonecity. Here we sequence and analyse the BMR genome and transcriptome, highlighting the possible genomic adaptive responses to the underground stressors. Our results show high rates of RNA/DNA editing, reduced chromosome rearrangements, an over-representation of short interspersed elements (SINEs) probably linked to hypoxia tolerance, degene…