Application of Single-Station Sigma and Site-Response Characterization in a Probabilistic Seismic-Hazard Analysis for a New Nuclear Site

Aleatory variability in ground-motion prediction, represented by the standard deviation (sigma) of a ground-motion prediction equation, exerts a very strong influence on the results of probabilistic seismic-hazard analysis (PSHA). This is especially so at the low annual exceedance frequencies considered for nuclear facilities; in these cases, even small reductions in sigma can have a marked effect on the hazard estimates. Proper separation and quantification of aleatory variability and epistemic uncertainty can lead to defensible reductions in sigma. One such approach is the single-station sigma concept, which removes that part of sigma corresponding to repeatable site-specific effects. However, the site-to-site component must then be constrained by site-specific measurements or else modeled as epistemic uncertainty and incorporated into the modeling of site effects. The practical application of the single-station sigma concept, including the characterization of the dynamic properties of the site and the incorporation of site-response effects into the hazard calculations, is illustrated for a PSHA conducted at a rock site under consideration for the potential construction of a nuclear power plant.Civil, Architectural, and Environmental Engineerin

The impact of selective genotyping on the response to selection using single-step genomic best linear unbiased prediction

Across the majority livestock species, routinely collected genomic and pedigree information has been incorporated into evaluations using single-step methods. As a result, strategies that reduce genotyping costs without reducing the response to selection are important as they could have substantial economic impacts on breeding programs. Therefore, the objective of the current study was to investigate the impact of selectively genotyping selection candidates on the selection response using simulation. Populations were simulated to mimic the genome and population structure of a swine and cattle population undergoing selection on an index comprised of the estimated breeding values (EBV) for 2 genetically correlated quantitative traits. Ten generations were generated and genotyping began generation 7. Two phenotyping scenarios were simulated that assumed the first trait was recorded early in life on all individuals and the second trait was recorded on all versus a random subset of the individuals. The EBV were generated from a bivariate animal model. Multiple genotyping scenarios were generated that ranged from not genotyping any selection candidates, a proportion of the selection candidates based on either their index value or chosen at random, and genotyping all selection candidates. An interim index value was utilized to decide who to genotype for the selective genotype strategy. The interim value assumed only the first trait was observed and the only genotypic information available was on animals in previous generations. Within each genotyping scenario 25 replicates were generated. Within each genotyping scenario the mean response per generation and the degree to which EBV were inflated/deflated was calculated. Across both species and phenotyping strategies, the plateau of diminishing returns was observed when 60% of the selection candidates with the largest index values were genotyped. When randomly genotyping selection candidates, either 80 or 100% of the selection candidates needed to be genotyped for there not to be a reduction in the index response. Across both populations, no differences in the degree that EBV were inflated/deflated for either trait 1 or 2 were observed between nongenotyped and genotyped animals. The current study has shown that animals can be selectively genotyped in order to optimize the response to selection as a function of the cost to conduct a breeding program using single-step genomic best linear unbiased prediction

STRONG GROUND MOTIONS AND DAMAGE PATTERNS FROM THE 1999 DUZCE EARTHQUAKE IN TURKEY

The Mw 7.1 Duzce earthquake occurred on 12 November 1999 along the North Anatolian Fault in northwestern Turkey. This paper documents observations from a field reconnaissance team, addressing two principal aspects of this significant earthquake: the recorded ground motions and the distribution and severity of the earthquake effects on the built environment. In general, the recorded ground motions from this earthquake were smaller than predicted by ground motion predictive equations available at the time of the event. One anomalous recording is presented and potential causes for this irregular motion based on observations from field reconnaissance are discussed. The effects of rupture directivity on the near-fault recordings are assessed and the effects of soil conditions on the recorded ground motions are examined. The patterns of building damage based on post-earthquake reconnaissance are presented for the most strongly shaken cities in the near-fault region: Duzce, Kaynasli, and Bolu. Damage in Duzce was concentrated in the southern part of the city, which is underlain by softer sediments. Damage in Bolu was distributed evenly throughout the city; whereas damage was concentrated on more recent alluvial sediments in Kaynasli. No evidence of liquefaction or ground failure was observed in the populated areas surveyed after the earthquake

Recent Advances in Geotechnical Post-earthquake Reconnaissance

Field observations are particularly important in geotechnical engineering, because it is difficult to replicate in the laboratory the response of soil deposits built by nature over thousands of years. Detailed mapping of damaged and undamaged areas provides the data for the well-documented case histories that drive the development of many current design procedures. Thus, documenting key insights from earthquakes advance research and practice. This has been a primary goal of the National Science Foundation-sponsored Geotechnical Extreme Events Reconnaissance (GEER) Association since its inception almost 20 years ago. New technologies are continually employed by GEER teams to capture ground deformation and its effects. These technologies include Light Imaging Detection and Ranging (LIDAR) and Structure-from-Motion (SfM) image processing techniques for generating and visualizing three-dimensional point cloud data sets. New sensor deployment platforms such as Unmanned Aerial Vehicles (UAVs) are playing an integral role in the data collection process. Unanticipated observations from major events often catalyze new research directions. An overview of some of these recent integrated technology deployments and their role at the core of earthquake disaster analysis is presented. Important advancements are possible through post-event research if their effects are captured and shared effectively

Semi-empirical relationships to assess the seismic performance of slopes from an updated version of the Italian seismic database

Funder: Dipartimento della Protezione Civile, Presidenza del Consiglio dei Ministri; doi: http://dx.doi.org/10.13039/100012783; Grant(s): ReLUIS research project - Working Pachage 16: Geotechnical Engineering - Task Group 2: Slope stabilityAbstractSeismic performance of slopes can be assessed through displacement-based procedures where earthquake-induced displacements are usually computed following Newmark-type calculations. These can be adopted to perform a parametric integration of earthquake records to evaluate permanent displacements for different slope characteristics and seismic input properties. Several semi-empirical relationships can be obtained for different purposes: obtaining site-specific displacement hazard curves following a fully-probabilistic approach, to assess the seismic risk associated with the slope; providing semi-empirical models within a deterministic framework, where the seismic-induced permanent displacement is compared with threshold values related to different levels of seismic performance; calibrating the seismic coefficient to be used in pseudo-static calculations, where a safety factor against limit conditions is computed. In this paper, semi-empirical relationships are obtained as a result of a parametric integration of an updated version of the Italian strong-motion database, that, in turn, is described and compared to older versions of the database and to well-known ground motion prediction equations. Permanent displacement is expressed as a function of either ground motion parameters, for a given yield seismic coefficient of the slope, or of both ground motion parameters and the seismic coefficient. The first are meant to be used as a tool to develop site-specific displacement hazard curves, while the last can be used to evaluate earthquake-induced slope displacements, as well as to calibrate the seismic coefficient to be used in a pseudo-static analysis. Influence of the vertical component of seismic motion on these semi-empirical relationships is also assessed.</jats:p

The contribution of sex chromosome conflict to disrupted spermatogenesis in hybrid house mice

Incompatibilities on the sex chromosomes are important in the evolution of hybrid male sterility, but the evolutionary forces underlying this phenomenon are unclear. House mice (Mus musculus) lineages have provided powerful models for understanding the genetic basis of hybrid male sterility. X chromosome-autosome interactions cause strong incompatibilities in Mus musculus F1 hybrids, but variation in sterility phenotypes suggests a more complex genetic basis. Additionally, X-Y chromosome conflict has resulted in rapid expansions of ampliconic genes with dosage-dependent expression that is essential to spermatogenesis. Here we evaluated the contribution of X-Y lineage mismatch to male fertility and stage-specific gene expression in hybrid mice. We performed backcrosses between two house mouse subspecies to generate reciprocal Y-introgression strains and used these strains to test the effects of X-Y mismatch in hybrids. Our transcriptome analyses of sorted spermatid cells revealed widespread overexpression of the X chromosome in sterile F1 hybrids independent of Y chromosome subspecies origin. Thus, postmeiotic overexpression of the X chromosome in sterile F1 mouse hybrids is likely a downstream consequence of disrupted meiotic X-inactivation rather than X-Y gene copy number imbalance. Y-chromosome introgression did result in subfertility phenotypes and disrupted expression of several autosomal genes in mice with an otherwise non-hybrid genomic background, suggesting that Y-linked incompatibilities contribute to reproductive barriers, but likely not as a direct consequence of X-Y conflict. Collectively, these findings suggest that rapid sex chromosome gene family evolution driven by genomic conflict has not resulted in strong male reproductive barriers between these subspecies of house mice

Incidence, Reproductive Outcome, and Economic Impact of Reciprocal Translocations in the Domestic Pig

Pigs (Sus scrofa) have vast economic importance, with pork accounting for over 30% of the global meat consumption. Chromosomal abnormalities, and in particular reciprocal translocations (RTs), are an important cause of hypoprolificacy (litter size reduction) in pigs. However, these do not necessarily present with a recognizable phenotype and may cause significant economic losses for breeders when undetected. Here, we present a reappraisal of the incidence of RTs across several European pig herds, using contemporary methodology, as well as an analysis modelling the economic impact of these abnormalities. Molecular cytogenetic investigation was completed by karyotyping and/or multiprobe FISH (fluorescence in situ hybridisation) between 2016–2021, testing 2673 animals. We identified 19 types of chromosome abnormalities, the prevalence of these errors in the database was 9.1%, and the estimated incidence of de novo errors was 0.90%. Financial modelling across different scenarios revealed the potential economic impact of an undetected RT, ranging from £69,802 for an individual affected terminal boar in a commercial farm selling weaned pigs, to £51,215,378 for a genetics company with an undetected RT in a dam line boar used in a nucleus farm. Moreover, the added benefits of screening by FISH instead of karyotyping were estimated, providing a strong case for proactive screening by this approach

A high-affinity, bivalent PDZ domain inhibitor complexes PICK1 to alleviate neuropathic pain

Maladaptive plasticity involving increased expression of AMPA‐type glutamate receptors is involved in several pathologies, including neuropathic pain, but direct inhibition of AMPARs is associated with side effects. As an alternative, we developed a cell‐permeable, high‐affinity (~2 nM) peptide inhibitor, Tat‐P$_4$‐(C5)$_2$, of the PDZ domain protein PICK1 to interfere with increased AMPAR expression. The affinity is obtained partly from the Tat peptide and partly from the bivalency of the PDZ motif, engaging PDZ domains from two separate PICK1 dimers to form a tetrameric complex. Bivalent Tat‐P$_4$‐(C5)$_2$ disrupts PICK1 interaction with membrane proteins on supported cell membrane sheets and reduce the interaction of AMPARs with PICK1 and AMPA‐receptor surface expression in vivo. Moreover, Tat‐P$_4$‐(C5)$_2$ administration reduces spinal cord transmission and alleviates mechanical hyperalgesia in the spared nerve injury model of neuropathic pain. Taken together, our data reveal Tat‐P$_4$‐(C5)$_2$ as a novel promising lead for neuropathic pain treatment and expand the therapeutic potential of bivalent inhibitors to non‐tandem protein–protein interaction domains

A Conserved Requirement for fbxo7 during Male Germ Cell Cytoplasmic Remodelling

Fbxo7 is the substrate-recognition subunit of an SCF-type ubiquitin E3 ligase complex. It has physiologically important functions in regulating mitophagy, proteasome activity and the cell cycle in multiple cell types, like neurons, lymphocytes and erythrocytes. Here, we show that in addition to the previously known Parkinsonian and hematopoietic phenotypes, male mice with reduced Fbxo7 expression are sterile. In these males, despite successful meiosis, nuclear elongation and eviction of histones from chromatin, the developing spermatids are phagocytosed by Sertoli cells during late spermiogenesis, as the spermatids undergo cytoplasmic remodeling. Surprisingly, despite the loss of all germ cells, there was no evidence of the symplast formation and cell sloughing that is typically associated with spermatid death in other mouse sterility models, suggesting that novel cell death and/or cell disposal mechanisms may be engaged in Fbxo7 mutant males. Mutation of the Drosophila Fbxo7 ortholog, nutcracker (ntc) also leads to sterility with germ cell death during cytoplasmic remodeling, indicating that the requirement for Fbxo7 at this stage is conserved. The ntc phenotype was attributed to decreased levels of the proteasome regulator, DmPI31 and reduced proteasome activity. Consistent with the fly model, we observe a reduction in PI31 levels in mutant mice; however, there is no alteration in proteasome activity in whole mouse testes. Our results are consistent with findings that Fbxo7 regulates PI31 protein levels, and indicates that a defect at the late stages of spermiogenesis, possibly due to faulty spatial dynamics of proteasomes during cytoplasmic remodeling, may underlie the fertility phenotype in mice

Microarray profiling for differential gene expression in PMSG-hCG stimulated preovulatory ovarian follicles of Chinese Taihu and Large White sows

<p>Abstract</p> <p>Background</p> <p>The Chinese Taihu is one of the most prolific pig breeds in the world, which farrows at least five more piglets per litter than Western pig breeds partly due to a greater ovulation rate. Variation of ovulation rate maybe associated with the differences in the transcriptome of Chinese Taihu and Large White ovaries. In order to understand the molecular basis of the greater ovulation rate of Chinese Taihu sows, expression profiling experiments were conducted to identify differentially expressed genes in ovarian follicles at the preovulatory stage of a PMSG-hCG stimulated estrous cycle from 3 Chinese Taihu and 3 Large White cycling sows by using the Affymetrix Porcine Genechip™.</p> <p>Results</p> <p>One hundred and thirty-three differentially expressed genes were identified between Chinese Taihu and Large White sows by using Affymetrix porcine GeneChip (<it>p </it>≤ 0.05, Fold change ≥ 2 or ≤ 0.5). Gene Ontology (GO) analysis revealed that these genes belonged to the class of genes that participated in regulation of cellular process, regulation of biological process, biological regulation, developmental process, cell communication and signal transduction and so on. Significant differential expression of 6 genes including <it>WNT10B </it>and <it>DKK2 </it>in the WNT signaling pathway was detected. Real-time RT-PCR confirmed the expression pattern in seven of eight selected genes. A search of chromosomal location revealed that 92 differentially expressed transcripts located to the intervals of quantitative trait loci (QTLs) for reproduction traits. Furthermore, SNPs of two differentially expressed genes- <it>BAX </it>and <it>BMPR1B </it>were showed to be associated with litter size traits in Large White pigs and Chinese DIV line pigs (<it>p </it>≤ 0.1 or <it>p </it>≤ 0.05).</p> <p>Conclusions</p> <p>Our study detected many genes that showed differential expression between ovary follicles of two divergent breeds of pigs. Genes involved with regulation of cellular process, regulation of biological process, in addition to several genes not previously associated with ovarian physiology or with unknown function, were differentially expressed between two breeds. The suggestive or significant associations of <it>BAX </it>and <it>BMPR1B </it>gene with litter size indicated these genetic markers had the potentials to be used in pig industry after further validation of their genetic effects. Taken together, this study reveals many potential avenues of investigation for seeking new insights into ovarian physiology and the genetic control of reproduction.</p