Effects of Circulating and Local Uteroplacental Angiotensin II in Rat Pregnancy.

The renin-angiotensin (Ang) system is important during placental development. Dysregulation of the renin-Ang system is important in preeclampsia (PE). Female rats transgenic for the human angiotensinogen gene crossed with males transgenic for the human renin gene develop the PE syndrome, whereas those of the opposite cross do not. We used this model to study the role of Ang II in trophoblast invasion, which is shallow in human PE but deeper in this model. We investigated the following groups: PE rats, opposite-cross rats, Ang II–infused rats (1000 ng/kg per day), and control rats. Ang II infusion increased only circulating Ang II levels (267.82 pg/mL), opposite cross influenced only uteroplacental Ang II (13.52 fmol/mg of protein), and PE increased both circulating (251.09 pg/mL) and uteroplacental (19.24 fmol/mg of protein) Ang II. Blood pressure and albuminuria occurred in the models with high circulating Ang II but not in the other models. Trophoblast invasion increased in PE and opposite-cross rats but not in Ang II–infused rats. Correspondingly, uterine artery resistance index increased in Ang II–infused rats but decreased in PE rats. We then studied human trophoblasts and villous explants from first-trimester pregnancies with time-lapse microscopy. Local Ang II dose-dependently increased migration by 75%, invasion by 58%, and motility by 282%. The data suggest that local tissue Ang II stimulates trophoblast invasion in vivo in the rat and in vitro in human cells, a hitherto fore unrecognized function. Conceivably, upregulation of tissue Ang II in the maternal part of the placenta represents an important growth factor for trophoblast invasion and migration

openWAR: An Open Source System for Evaluating Overall Player Performance in Major League Baseball

Within baseball analytics, there is substantial interest in comprehensive statistics intended to capture overall player performance. One such measure is Wins Above Replacement (WAR), which aggregates the contributions of a player in each facet of the game: hitting, pitching, baserunning, and fielding. However, current versions of WAR depend upon proprietary data, ad hoc methodology, and opaque calculations. We propose a competitive aggregate measure, openWAR, that is based upon public data and methodology with greater rigor and transparency. We discuss a principled standard for the nebulous concept of a "replacement" player. Finally, we use simulation-based techniques to provide interval estimates for our openWAR measure.Comment: 27 pages including supplemen

Privacy mediators:helping IoT cross the chasm

Unease over data privacy will retard consumer acceptance of IoT deployments. The primary source of discomfort is a lack of user control over raw data that is streamed directly from sensors to the cloud. This is a direct consequence of the over-centralization of today’s cloud-based IoT hub designs. We propose a solution that interposes a locally-controlled software component called a privacy mediator on every raw sensor stream. Each mediator is in the same administrative domain as the sensors whose data is being collected, and dynamically enforces the current privacy policies of the owners of the sensors or mobile users within the domain. This solution necessitates a logical point of presence for mediators within the administrative boundaries of each organization. Such points of presence are provided by cloudlets, which are small locally-administered data centers at the edge of the Internet that can support code mobility. The use of cloudlet-based mediators aligns well with natural personal and organizational boundaries of trust and responsibility

Early Life Socioeconomic Circumstance and Late Life Brain Hyperintensities : A Population Based Cohort Study

Funding: Image acquisition and image analysis for this study was funded by the Alzheimer's Research Trust (now Alzheimer's Research UK). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Acknowledgments The authors would like to thank the participants of the Aberdeen 1936 Birth Cohort (ABC36), without whom this research would not have been possible.Peer reviewedPublisher PD

Frequent somatic loss of BRCA1 in breast tumours from BRCA2 germ-line mutation carriers and vice versa

Breast cancer susceptibility genes BRCA1 and BRCA2 are tumour suppressor genes the alleles of which have to be inactivated before tumour development occurs. Hereditary breast cancers linked to germ-line mutations of BRCA1 and BRCA2 genes almost invariably show allelic imbalance (AI) at the respective loci. BRCA1 and BRCA2 are believed to take part in a common pathway in maintenance of genomic integrity in cells. We carried out AI and fluorescence in situ hybridization (FISH) analyses of BRCA2 in breast tumours from germ-line BRCA1 mutation carriers and vice versa. For comparison, 14 sporadic breast tumours were also studied. 8 of the 11 (73%) informative BRCA1 mutation tumours showed AI at the BRCA2 locus. 53% of these tumours showed a copy number loss of the BRCA2 gene by FISH. 5 of the 6 (83%) informative BRCA2 mutation tumours showed AI at the BRCA1 locus. Half of the tumours (4/8) showed a physical deletion of the BRCA1 gene by FISH. Combined allelic loss of both BRCA1 and BRCA2 gene was seen in 12 of the 17 (71%) informative hereditary tumours, whereas copy number losses of both BRCA genes was seen in only 4/14 (29%) sporadic control tumours studied by FISH. In conclusion, the high prevalence of AI at BRCA1 in BRCA2 mutation tumours and vice versa suggests that somatic events occurring at the other breast cancer susceptibility gene locus may be selected in the cancer development. The mechanism resulting in AI at these loci seems more complex than a physical deletion.   http://www.bjcancer.com © 2001 Cancer Research Campaig

Intellectual engagement and cognitive ability in later life (the "use it or lose it" conjecture) : Longitudinal, prospective study

Data sharing: All data are available by application to the Aberdeen Birth Cohort steering group (https://www.abdn.ac.uk/birth-cohorts/1921/for-researchers/).Peer reviewedPublisher PD

Late Quaternary Tectonics, Incision, and Landscape Evolution of the Calchaquí River Catchment, Eastern Cordillera, NW Argentina

Unraveling the relative impacts of climate, tectonics, and lithology on landscape evolution is complicated by the temporal and spatial scale over which observations are made. We use soil and desert pavement classification, longitudinal river profiles, 10Be-derived catchment mean modern and paleo-erosion rates, and vertical incision rates to test whether, if we restrict our analyses to a spatial scale over which climate is relatively invariant, tectonic and lithologic factors will dominate the late Quaternary landscape evolution of the Calchaquí River Catchment, NW Argentina. We find that the spatial distribution of erosion rates, normalized channel steepness indices, and concavity indices reflect active tectonics and lithologic resistance. Knickpoints are spatially coincident with tectonic and/or lithologic discontinuities, indicating local base-level control by faulting. Catchment mean erosion rates, ranging from 22.5 ± 2.6 to 121.9 ± 13.7 mm/kyr, and paleo-erosion rates, ranging from 56 +43/-19 to 105 +60/-33 mm/kyr, are similar, possibly suggesting that Quaternary climate changes have not had a strong enough influence on erosion rates to be detected using cosmogenic 10Be. However, punctuated abandonment of pediment and strath terraces at 43.6 +15.0/-11.6, 91.2 +54.2/-22.2, and 151 +92.7/-34.1 ka and disparities between vertical incision rates and catchment mean erosion rates could suggest periods of landscape transience, possibly reflecting climate cyclicity. Our results emphasize the role of tectonic uplift and lithologic contrasts in shaping long-term erosion rates and channel morphology at the relatively local scale of the Calchaqui River Catchment, in contrast to regional-scale studies which find precipitation to exert the dominant control