SMaRT-OnlineWDN: A Franco-German Project For The Online Security Management Of Water Distribution Networks

Water Distribution Networks (WDNs) are critical infrastructures that are exposed to deliberate or accidental chemical, biological or radioactive contamination which need to be detected in due time. However, until now, no monitoring system is capable of protecting a WDN in real time. Powerful online sensor systems are currently developed and the prototypes are able to detect a small change in water quality. In the immediate future, water service utilities will install their networks with water quantity and water quality sensors. For taking appropriate decisions and countermeasures, WDN operators will need to dispose of: 1) a fast and reliable detection of abnormal events in the WDNs; 2) reliable online models both for the hydraulics and water quality predictions; 3) methods for contaminant source identification backtracking from the data history. Actually, in general none of these issues (1) – (3) are available at the water suppliers. Consequently, the main objective of the project SMaRT-OnlineWDN is the development of an online security management toolkit for WDNs that is based on sensor measurements of water quality as well as water quantity. Its main innovations are the detection of abnormal events with a binary classifier of high accuracy and the generation of real-time, reliable (i) flow and pressure predictions, (ii) water quality indicator predictions of the whole water network. Detailed information regarding contamination sources (localization and intensity) will be explored by means of the online running model, which is automatically calibrated to the measured sensor data. Its field of application ranges from the detection of deliberate contamination including source identification and decision support for effective countermeasures to improved operation and control of a WDN under normal and abnormal conditions (dual benefit).In this project, the technical research work is completed with a sociological, economical and management analysis

Hepatic gene body hypermethylation is a shared epigenetic signature of murine longevity.

Dietary, pharmacological and genetic interventions can extend health- and lifespan in diverse mammalian species. DNA methylation has been implicated in mediating the beneficial effects of these interventions; methylation patterns deteriorate during ageing, and this is prevented by lifespan-extending interventions. However, whether these interventions also actively shape the epigenome, and whether such epigenetic reprogramming contributes to improved health at old age, remains underexplored. We analysed published, whole-genome, BS-seq data sets from mouse liver to explore DNA methylation patterns in aged mice in response to three lifespan-extending interventions: dietary restriction (DR), reduced TOR signaling (rapamycin), and reduced growth (Ames dwarf mice). Dwarf mice show enhanced DNA hypermethylation in the body of key genes in lipid biosynthesis, cell proliferation and somatotropic signaling, which strongly correlates with the pattern of transcriptional repression. Remarkably, DR causes a similar hypermethylation in lipid biosynthesis genes, while rapamycin treatment increases methylation signatures in genes coding for growth factor and growth hormone receptors. Shared changes of DNA methylation were restricted to hypermethylated regions, and they were not merely a consequence of slowed ageing, thus suggesting an active mechanism driving their formation. By comparing the overlap in ageing-independent hypermethylated patterns between all three interventions, we identified four regions, which, independent of genetic background or gender, may serve as novel biomarkers for longevity-extending interventions. In summary, we identified gene body hypermethylation as a novel and partly conserved signature of lifespan-extending interventions in mouse, highlighting epigenetic reprogramming as a possible intervention to improve health at old age

scNMT-seq enables joint profiling of chromatin accessibility DNA methylation and transcription in single cells.

Parallel single-cell sequencing protocols represent powerful methods for investigating regulatory relationships, including epigenome-transcriptome interactions. Here, we report a single-cell method for parallel chromatin accessibility, DNA methylation and transcriptome profiling. scNMT-seq (single-cell nucleosome, methylation and transcription sequencing) uses a GpC methyltransferase to label open chromatin followed by bisulfite and RNA sequencing. We validate scNMT-seq by applying it to differentiating mouse embryonic stem cells, finding links between all three molecular layers and revealing dynamic coupling between epigenomic layers during differentiation

Analisis Pengaruh Budaya Organisasi Dan Kompensasi Terhadap Kinerja Karyawan Dengan Motivasi Sebagai Variabel Intervening (Studi Kasus Pada PT. Lg Bagian Penjualan Indonesia Semarang)

The problems that occurred in the employee portion of sales LG Indonesia Semarang is adecline in performance is indicated by not achieving the target for 2015. The employeeperformance and motivation is also thought to be influenced by factors of organizationalculture and also compensation deemed not feasible by most employees. This study aimedto analyze the influence of organizational culture on the motivation and compensationand employee performance parts sales LG Indonesia Semarang. The population used inthis study were all employees of LG Indonesia Semarang. The sampling technique usedwas purposive sampling. Criteria samples taken were all employees of the salesdepartment LG Indonesia Semarang who have worked more than two years are 71nurses. The method of collecting the data in this study using questionnaires andinterviews. Methods of data analysis using path analysis. Based on the research,organizational culture and compensation have a positive effect on motivation andperformance, while motivation is also a positive effect on performance. Based on theresults Sobel Test to determine whether there is mediating the relationship between theindependent and dependent variables, it is known that motivation mediates the effect ofcompensation and organizational culture on performance

Kajian Pengelolaan Lahan Subdas Secang Kulonprogo YOGYAKARTA

Penelitian ini bertujuan untuk mengevaluasi kemampuan lahan, menyusun arahan penggunaanlahan dan mengkaji pengelolaan lahan SubDAS Secang. Metode yang digunakan dalam penelitianadalah sampel terpilih pada 48 satuan lahan. Penelitian menunjukkan bahwa kemampuan lahanSubDAS Secang terdiri atas kelas lahan I seluas 187 ha, kelas lahan II seluas 147 ha, kelas lahan IIIseluas 515,2 ha, kelas lahan IV seluas 1522,7 ha, kelas lahan V seluas 7,3 ha dan kelas lahan VI seluas1223,2 ha. Arahan penggunaan lahan SubDAS Secang berupa pertanian lahan basah seluas 326,85 ha,kawasan permukiman dan budidaya tanaman semusim seluas 200,55 ha, kawasan budidaya tanamanlahan kering seluas 525,81 ha, kawasan budidaya tanaman tahunan seluas 1981,31 ha, kawasanpenyangga seluas 716,54 ha. Pengelolaan lahan memberikan pedoman pemanfaatan lahan; daerah hilirsebagai daerah pemanfaatan untuk pertanian irigasi; daerah tengah diperuntukan permukiman danpembudidayaan tanaman lahan kering; serta daerah hulu sebagai daerah imbuhan diperuntukkanwanatani dan hutan penyangga

Demonstration of all-or-none loss of imprinting in mRNA expression in single cells

Loss of imprinting (LOI) is the reactivation of the silenced allele of an imprinted gene, leading to perturbation of monoallelic expression. We tested the hypothesis that LOI of PLAGL1, a representative maternally imprinted gene, occurs through an all-or-none process leading to a mixture of fully imprinted and nonimprinted cells. Herein using a quantitative RT-PCR-based experimental approach, we measured LOI at the single cell level in human trophoblasts and demonstrated a broad distribution of LOI among cells exhibiting LOI, with the mean centered at ∼100% LOI. There was a significant (P < 0.01) increase in expression after 2 days of 5-aza-2′-deoxycytidine (AZA) treatment and a significant (P < 0.01) increase in LOI after both 1 and 2 days of AZA treatment, while the distribution remained broad and centered at ∼100% LOI. We propose a transcriptional pulsing model to show that the broadness of the distribution reflects the stochastic nature of expression between the two alleles in each cell. The mean of the distribution of LOI in the cells is consistent with our hypothesis that LOI occurs by an all-or-none process. All-or-none LOI could lead to a second distinct cell population that may have a selective advantage, leading to variation of LOI in normal tissues, such as the placenta, or in neoplastic cells

Multi-omics profiling of mouse gastrulation at single-cell resolution.

Formation of the three primary germ layers during gastrulation is an essential step in the establishment of the vertebrate body plan and is associated with major transcriptional changes1-5. Global epigenetic reprogramming accompanies these changes6-8, but the role of the epigenome in regulating early cell-fate choice remains unresolved, and the coordination between different molecular layers is unclear. Here we describe a single-cell multi-omics map of chromatin accessibility, DNA methylation and RNA expression during the onset of gastrulation in mouse embryos. The initial exit from pluripotency coincides with the establishment of a global repressive epigenetic landscape, followed by the emergence of lineage-specific epigenetic patterns during gastrulation. Notably, cells committed to mesoderm and endoderm undergo widespread coordinated epigenetic rearrangements at enhancer marks, driven by ten-eleven translocation (TET)-mediated demethylation and a concomitant increase of accessibility. By contrast, the methylation and accessibility landscape of ectodermal cells is already established in the early epiblast. Hence, regulatory elements associated with each germ layer are either epigenetically primed or remodelled before cell-fate decisions, providing the molecular framework for a hierarchical emergence of the primary germ layers.CRUK, Wellcome Trust, MRC, BBSRC, EMBL, E

Unequal allelic expression of wild-type and mutated β-myosin in familial hypertrophic cardiomyopathy

Familial hypertrophic cardiomyopathy (FHC) is an autosomal dominant disease, which in about 30% of the patients is caused by missense mutations in one allele of the β-myosin heavy chain (β-MHC) gene (MYH7). To address potential molecular mechanisms underlying the family-specific prognosis, we determined the relative expression of mutant versus wild-type MYH7-mRNA. We found a hitherto unknown mutation-dependent unequal expression of mutant to wild-type MYH7-mRNA, which is paralleled by similar unequal expression of β-MHC at the protein level. Relative abundance of mutated versus wild-type MYH7-mRNA was determined by a specific restriction digest approach and by real-time PCR (RT-qPCR). Fourteen samples from M. soleus and myocardium of 12 genotyped and clinically well-characterized FHC patients were analyzed. The fraction of mutated MYH7-mRNA in five patients with mutation R723G averaged to 66 and 68% of total MYH7-mRNA in soleus and myocardium, respectively. For mutations I736T, R719W and V606M, fractions of mutated MYH7-mRNA in M. soleus were 39, 57 and 29%, respectively. For all mutations, unequal abundance was similar at the protein level. Importantly, fractions of mutated transcripts were comparable among siblings, in younger relatives and unrelated carriers of the same mutation. Hence, the extent of unequal expression of mutated versus wild-type transcript and protein is characteristic for each mutation, implying cis-acting regulatory mechanisms. Bioinformatics suggest mRNA stability or splicing effectors to be affected by certain mutations. Intriguingly, we observed a correlation between disease expression and fraction of mutated mRNA and protein. This strongly suggests that mutation-specific allelic imbalance represents a new pathogenic factor for FHC

Linking the Epigenome to the Genome: Correlation of Different Features to DNA Methylation of CpG Islands

DNA methylation of CpG islands plays a crucial role in the regulation of gene expression. More than half of all human promoters contain CpG islands with a tissue-specific methylation pattern in differentiated cells. Still today, the whole process of how DNA methyltransferases determine which region should be methylated is not completely revealed. There are many hypotheses of which genomic features are correlated to the epigenome that have not yet been evaluated. Furthermore, many explorative approaches of measuring DNA methylation are limited to a subset of the genome and thus, cannot be employed, e.g., for genome-wide biomarker prediction methods. In this study, we evaluated the correlation of genetic, epigenetic and hypothesis-driven features to DNA methylation of CpG islands. To this end, various binary classifiers were trained and evaluated by cross-validation on a dataset comprising DNA methylation data for 190 CpG islands in HEPG2, HEK293, fibroblasts and leukocytes. We achieved an accuracy of up to 91% with an MCC of 0.8 using ten-fold cross-validation and ten repetitions. With these models, we extended the existing dataset to the whole genome and thus, predicted the methylation landscape for the given cell types. The method used for these predictions is also validated on another external whole-genome dataset. Our results reveal features correlated to DNA methylation and confirm or disprove various hypotheses of DNA methylation related features. This study confirms correlations between DNA methylation and histone modifications, DNA structure, DNA sequence, genomic attributes and CpG island properties. Furthermore, the method has been validated on a genome-wide dataset from the ENCODE consortium. The developed software, as well as the predicted datasets and a web-service to compare methylation states of CpG islands are available at http://www.cogsys.cs.uni-tuebingen.de/software/dna-methylation/

LINEAR FREQUENCY DOMAIN PREDICTIONS OF DYNAMIC DERIVATIVES FOR THE DLR F12 WIND TUNNEL MODEL

Structural loads for full aircraft configurations can be represented by evaluating dynamic derivatives over a wide parameter space mainly including different mode shapes, an- gle of attack and Mach numbers. Traditionally, these values are determined by wind tunnel tests applying forced periodic motions to aircraft models. The ability of numerical simula- tions provide an excellent addendum to wind tunnel tests. Instead of time-accurate unsteady Reynolds-averaged Navier-Stokes (URANS) solvers which are recognized as extremely compu- tational expensive this paper considers a linearized frequency domain solver (LFD). With this approach the unsteady simulation reduces to a single steady state computation and a single linear simulation in the frequency domain. By the assumption of small perturbations and har- monic oscillations dynamic derivatives can be computed efficiently within a wide parameter space. In addition, the theoretical background for the LFD will be presented. Based on the linearization of the RANS equations and modeling of small perturbations with Fourier series a complex valued linear system has to be solved