Smart Grid State Estimation with PMUs Time Synchronization Errors

We consider the problem of PMU-based state estimation combining information coming from ubiquitous power demand time series and only a limited number of PMUs. Conversely to recent literature in which synchrophasor devices are often assumed perfectly synchronized with the Coordinated Universal Time (UTC), we explicitly consider the presence of time-synchronization errors in the measurements due to different non-ideal causes such as imperfect satellite localization and internal clock inaccuracy. We propose a recursive Kalman-based algorithm which allows for the explicit offline computation of the expected performance and for the real-time compensation of possible frequency mismatches among different PMUs. Based on the IEEE C37.118.1 standard on PMUs, we test the proposed solution and compare it with alternative approaches on both synthetic data from the IEEE 123 node standard distribution feeder and real-field data from a small medium voltage distribution feeder located inside the EPFL campus in Lausanne.Comment: 10 page, 7 figure

A surge of late-occurring meiotic double-strand breaks rescues synapsis abnormalities in spermatocytes of mice with hypomorphic expression of SPO11

Meiosis is the biological process that, after a cycle of DNA replication, halves the cellular chromosome complement, leading to the formation of haploid gametes. Haploidization is achieved via two successive rounds of chromosome segregation, meiosis I and II. In mammals, during prophase of meiosis I, homologous chromosomes align and synapse through a recombination-mediated mechanism initiated by the introduction of DNA double-strand breaks (DSBs) by the SPO11 protein. In male mice, if SPO11 expression and DSB number are reduced below heterozygosity levels, chromosome synapsis is delayed, chromosome tangles form at pachynema, and defective cells are eliminated by apoptosis at epithelial stage IV at a spermatogenesis-specific endpoint. Whether DSB levels produced in Spo11 +/− spermatocytes represent, or approximate, the threshold level required to guarantee successful homologous chromosome pairing is unknown. Using a mouse model that expresses Spo11 from a bacterial artificial chromosome, within a Spo11 −/− background, we demonstrate that when SPO11 expression is reduced and DSBs at zygonema are decreased (approximately 40 % below wild-type level), meiotic chromosome pairing is normal. Conversely, DMC1 foci number is increased at pachynema, suggesting that under these experimental conditions, DSBs are likely made with delayed kinetics at zygonema. In addition, we provide evidences that when zygotene-like cells receive enough DSBs before chromosome tangles develop, chromosome synapsis can be completed in most cells, preventing their apoptotic elimination

Sam68 marks the transcriptionally active stages of spermatogenesis and modulates alternative splicing in male germ cells

Sam68 plays an essential role in mouse spermatogenesis and male fertility. Herein, we report an interaction between Sam68 and the phosphorylated forms of the RNA polymerase II (RNAPII) in meiotic spermatocytes. RNase treatment decreased but did not abolish the interaction, consistently with in vitro binding of RNAPII to the Sam68 carboxyl-terminal region. Sam68 retention in the spermatocyte nucleus was dependent on the integrity of cellular RNAs, suggesting that the protein is recruited to transcriptionally active chromatin. Mouse knockout models characterized by stage-specific arrest of spermatogenesis and staining with the phosphorylated form of RNAPII documented that Sam68 expression is confined to the transcriptionally active stages of spermatogenesis. Furthermore, Sam68 associates with splicing regulators in germ cells and we report that alternative splicing of Sgce exon 8 is regulated in a Sam68-dependent manner during spermatogenesis. RNA and chromatin crosslink immunoprecipitation experiments showed that Sam68 binds in vivo to sequences surrounding the intron 7/exon 8 boundary, thereby affecting the recruitment of the phosphorylated RNAPII and of the general splicing factor U2AF65. These results suggest that Sam68 regulates alternative splicing at transcriptionally active sites in differentiating germ cells and provide new insights into the regulation of Sam68 expression during spermatogenesis

ATM Promotes the Obligate XY Crossover and both Crossover Control and Chromosome Axis Integrity on Autosomes

During meiosis in most sexually reproducing organisms, recombination forms crossovers between homologous maternal and paternal chromosomes and thereby promotes proper chromosome segregation at the first meiotic division. The number and distribution of crossovers are tightly controlled, but the factors that contribute to this control are poorly understood in most organisms, including mammals. Here we provide evidence that the ATM kinase or protein is essential for proper crossover formation in mouse spermatocytes. ATM deficiency causes multiple phenotypes in humans and mice, including gonadal atrophy. Mouse Atm−/− spermatocytes undergo apoptosis at mid-prophase of meiosis I, but Atm−/− meiotic phenotypes are partially rescued by Spo11 heterozygosity, such that ATM-deficient spermatocytes progress to meiotic metaphase I. Strikingly, Spo11+/−Atm−/− spermatocytes are defective in forming the obligate crossover on the sex chromosomes, even though the XY pair is usually incorporated in a sex body and is transcriptionally inactivated as in normal spermatocytes. The XY crossover defect correlates with the appearance of lagging chromosomes at metaphase I, which may trigger the extensive metaphase apoptosis that is observed in these cells. In addition, control of the number and distribution of crossovers on autosomes appears to be defective in the absence of ATM because there is an increase in the total number of MLH1 foci, which mark the sites of eventual crossover formation, and because interference between MLH1 foci is perturbed. The axes of autosomes exhibit structural defects that correlate with the positions of ongoing recombination. Together, these findings indicate that ATM plays a role in both crossover control and chromosome axis integrity and further suggests that ATM is important for coordinating these features of meiotic chromosome dynamics

Histone H2Ax is required for proper chromosome synapses and double strand breaks repair of mouse spermatocytes

In male mouse, chromosome dynamics and recombination are tightly regulated by a pachynema checkpoint that arrest meiotic progression of recombination defective spermatocytes, which are than eliminated by stage IV of the epithelial cell cycle. In addition, male mouse meiocytes cell death is also activated by the failure of meiotic sex chromosome inactivation (MSCI). In the latter case, the apoptotic arrest is driven by the lack of silencing of XY-linked genes. In most of meiotic recombination mutants studied, so far, have been shown that in presence of a grossly aberrant synapses, also XY gene silencing fail. Thus both a defective chromosome dynamic and impaired MSCI contributes to spermatocytes elimination. Among several mutants H2Ax-/- spermatocytes are considered to be a model for apoptotic elimination exclusively driven by MSCI failure; such that no defects have been reported in chromosome dynamic and recombination. In this study we demonstrate that a fraction (~ 30%) of H2Ax-/- spermatocytes are defective in proper chromosome pairing, indicating that MSCI failure is not the only cause for their elimination by stage IV. In agreement with this finding, we find that the absence of H2Ax impair the proper localization, onto chromatin, of DNA repair factors, such as MDC1, BRCA1, MSH4 and MLH3. Interestingly, the defects in chromosome synapses and MLH3 foci assembly are ameliorated by Spo11 heterozygosis. Overall these results demonstrate that, in meiotic cells, H2Ax is require for the efficient processing of Spo11-induced double strand breaks

The RNA-binding protein FUS/TLS interacts with SPO11 and PRDM9 and localize at meiotic recombination hotspots

: In mammals, meiotic recombination is initiated by the introduction of DNA double strand breaks (DSBs) into narrow segments of the genome, defined as hotspots, which is carried out by the SPO11/TOPOVIBL complex. A major player in the specification of hotspots is PRDM9, a histone methyltransferase that, following sequence-specific DNA binding, generates trimethylation on lysine 4 (H3K4me3) and lysine 36 (H3K36me3) of histone H3, thus defining the hotspots. PRDM9 activity is key to successful meiosis, since in its absence DSBs are redirected to functional sites and synapsis between homologous chromosomes fails. One protein factor recently implicated in guiding PRDM9 activity at hotspots is EWS, a member of the FET family of proteins that also includes TAF15 and FUS/TLS. Here, we demonstrate that FUS/TLS partially colocalizes with PRDM9 on the meiotic chromosome axes, marked by the synaptonemal complex component SYCP3, and physically interacts with PRDM9. Furthermore, we show that FUS/TLS also interacts with REC114, one of the axis-bound SPO11-auxiliary factors essential for DSB formation. This finding suggests that FUS/TLS is a component of the protein complex that promotes the initiation of meiotic recombination. Accordingly, we document that FUS/TLS coimmunoprecipitates with SPO11 in vitro and in vivo. The interaction occurs with both SPO11β and SPO11α splice isoforms, which are believed to play distinct functions in the formation of DSBs in autosomes and male sex chromosomes, respectively. Finally, using chromatin immunoprecipitation experiments, we show that FUS/TLS is localized at H3K4me3-marked hotspots in autosomes and in the pseudo-autosomal region, the site of genetic exchange between the XY chromosomes

Geophysical downhole logging analysis within the shallow depth ICDP STAR drilling project (Central Italy)

The ICDP STAR drilling project aims to study the seismic and aseismic fault slip behaviour of the active low-angle Alto Tiberina normal Fault (ATF) in the Northern Apennines, Central Italy, drilling and instrumenting six shallow boreholes with seismometers and strainmeters. During the STAR field work, a geophysical downhole logging campaign was carried on defining the optimal target depth for instrument deployment and formation rock characterization. In particular, the main objectives of this study were to define in situ physical properties of the rocks and the tectonic discontinuity geometry along the boreholes. The downhole logging data provide new findings and knowledge especially with regards to the physical properties such as resistivity, gamma ray and wave velocity. The collected parameters were compared to the results of literature data collected in similar lithologies, as well as with the results of logging performed in deeper wells drilled for commercial purposes. The physical properties of the Mesozoic-Early Tertiary calcareous formations show low Gamma Ray values and high compressional (Vp) and shear wave (Vs) velocities (up to 5.3 km/s and 2.9 km/s, respectively), whereas the overlying clay-rich Late Tertiary formations exhibit high Gamma Ray and low resistivity and relatively low Vp and Vs values (up to 3.5 km/s and 2.0 km/s, respectively). The results obtained from the analysis of the orientations of the tectonic structures, measured along the six boreholes, show a good agreement with the orientations of the present-day extensional stress field, NE-SW oriented. Our study allowed to bridge the gap between the physical properties obtained from literature data and those obtained from the deep wells measurements, representing a possible case history for future projects. These new data will contribute to the advancement of knowledge of the physical properties of the rocks at shallow depths, typically overlooked

Multi-color dSTORM microscopy in Hormad1^-/spermatocytes reveals alterations in meiotic recombination intermediates and synaptonemal complex structure

Recombinases RAD51 and its meiosis-specific paralog DMC1 accumulate on single-stranded DNA (ssDNA) of programmed DNA double strand breaks (DSBs) in meiosis. Here we used three-color dSTORM microscopy, and a mouse model with severe defects in meiotic DSB formation and synapsis (Hormad1-/-) to obtain more insight in the recombinase accumulation patterns in relation to repair progression. First, we used the known reduction in meiotic DSB frequency in Hormad1-/- spermatocytes to be able to conclude that the RAD51/DMC1 nanofoci that preferentially localize at distances of ~300 nm form within a single DSB site, whereas a second preferred distance of ~900 nm, observed only in wild type, represents inter-DSB distance. Next, we asked whether the proposed role of HORMAD1 in repair inhibition affects the RAD51/DMC1 accumulation patterns. We observed that the two most frequent recombinase configurations (1 DMC1 and 1 RAD51 nanofocus (D1R1), and D2R1) display coupled frequency dynamics over time in wild type, but were constant in the Hormad1-/- model, indicating that the lifetime of these intermediates was altered. Recombinase nanofoci were also smaller in Hormad1-/- spermatocytes, consistent with changes in ssDNA length or protein accumulation. Furthermore, we established that upon synapsis, recombinase nanofoci localized closer to the synaptonemal complex (SYCP3), in both wild type and Hormad1-/- spermatocytes. Finally, the data also revealed a hitherto unknown function of HORMAD1 in inhibiting coil formation in the synaptonemal complex. SPO11 plays a similar but weaker role in coiling and SYCP1 had the opposite effect. Using this large super-resolution dataset, we propose models with the D1R1 configuration representing one DSB end containing recombinases, and the other end bound by other ssDNA binding proteins, or both ends loaded by the two recombinases, but in below-resolution proximity. This may then often evolve into D2R1, then D1R2, and finally back to D1R1, when DNA synthesis has commenced.</p

Control of Meiotic and Mitotic Progression by the F Box Protein \u3b2-Trcp1 In Vivo

SCF ubiquitin ligases, composed of three major sub- units, Skp1, Cul1, and one of many F box proteins (Fbps), control the proteolysis of important cellular regulators. We have inactivated the gene encoding the Fbp -Trcp1 in mice. -Trcp1/ males show reduced fer- tility correlating with an accumulation of methaphase I spermatocytes. -Trcp1/ MEFs display a lengthened mitosis, centrosome overduplication, multipolar meta- phase spindles, and misaligned chromosomes. Fur- thermore, cyclin A, cyclin B, and Emi1, an inhibitor of the anaphase promoting complex, are stabilized in mitotic -Trcp1/ MEFs. Indeed, we demonstrate that Emi1 is a bona fide substrate of -Trcp1. In contrast, stabilization of -catenin and IB, two previously re- ported -Trcp1 substrates, does not occur in the ab- sence of -Trcp1 and instead requires the additional silencing of -Trcp2 by siRNA. Thus, -Trcp1 regulates the timely order of meiotic and mitotic events