Reconstructing the natural hydrology of the San Francisco Bay - Delta watershed

We evaluated the impact of landscape changes on the amount of delta outflow reaching San Francisco Bay. The natural landscape was reconstructed and water balances were used to estimate the long-term annual average delta outflow that would have occurred under natural landscape conditions if the climate from 1922 to 2009 were to repeat itself. These outflows are referred to as natural delta outflows and are the first published estimate of natural delta outflow. These natural delta outflows were then compared with current delta outflows for the same climate and existing landscape, including its re-engineered system of reservoirs, canals, aqueducts, and pumping plants. This analysis shows that the long-term, annual average delta outflow under current conditions is consistent with outflow under natural landscape conditions. The amount of water currently used by farms, cities, and others is about equal to the amount of water formerly used by native vegetation. Development of water resources in California’s Central Valley transferred water formerly used by native vegetation to new beneficial uses without substantially reducing the longterm annual average supply to the San Francisco Bay–Delta estuary. Based on this finding, it is unlikely that observed declines in native freshwater aquatic species are the result of annual average delta outflow reductions

Estimation of the genetic contribution of presenilin-1 and -2 mutations in a population-based study of presenile Alzheimer disease

Two closely related genes, the presenilins ( PS ), located at chromosomes 14q24.3 and 1q42.1, have been identified for autosomal dominant Alzheimer disease (AD) with onset age below 65 years (presenile AD). We performed a systematic mutation analysis of all coding and 5'-non-coding exons of PS -1 and PS -2 in a population-based epidemiological series of 101 unrelated familial and sporadic presenile AD cases. The familial cases included 10 patients of autosomal dominant AD families sampled for linkage analysis studies. In all pat

Soluble forms of tau are toxic in Alzheimer's disease

Accumulation of neurofibrillary tangles (NFT), intracellular inclusions of fibrillar forms of tau, is a hallmark of Alzheimer Disease. NFT have been considered causative of neuronal death, however, recent evidence challenges this idea. Other species of tau, such as soluble misfolded, hyperphosphorylated, and mislocalized forms, are now being implicated as toxic. Here we review the data supporting soluble tau as toxic to neurons and synapses in the brain and the implications of these data for development of therapeutic strategies for Alzheimer’s disease and other tauopathies

Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2,3,4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease

Program to develop acoustic emission-flow relationship for inservice monitoring of nuclear pressure vessels. Progress report, February 1 - July 1, 1977. [BWR; PWR]

The purpose of the program reported is to evaluate experimentally the feasibility of further assuring reactor safety by detecting and analyzing flaw growth in reactor pressure boundaries through continuous monitoring for acoustic emission (AE). Program objectives are: (1) characterize AE from a limited range of defects and material property conditions; (2) characterize AE from innocuous sources (including defects); (3) develop criteria for distinguishing significant flaws from innocuous sources; (4) develop an AE-flaw damage model to serve as a basis for relating inservice AE to pressure vessel integrity. Steel plate required for the program has been procured and test specimens are being fabricated. Specimen test system has been assembled and calibrated. A technique for rating AE monitor system sensitivity has been developed. An HSST pressure vessel test has been successfully monitored for AE, and data analysis is in progress

Develop the application of a digital memory acoustic emission system to aircraft flaw monitoring

The purpose of the program is to evaluate the use of the acoustic emission (AE) technique to provide a definitive continuous monitor of fatigue crack growth in a critical aircraft structural member. The program started in September, 1977, with Phase I consisting of defining technical and procedural details and developing and fabricating an AE monitor system. A unique AE monitoring system was fabricated and laboratory tested. It utilizes a source isolation feature to distinguish AE signals originating from an identified area of interest. Two parameters of AE information are recorded on one solid state digital memory for later retrieval and analysis. Phase I was completed in April, 1978. Phase 2 was concerned with installing and testing the AE monitoring system in an aircraft. Installation was made in RAAF Macchi 326 aircraft A7-201 during a major maintenance overhaul. The system is monitoring AE from fatigue cracks in a fastener hole in the tension member of the wing structure center section continuously during flight. Installation was completed in August, 1978, with four test flights to evaluate system performance and make necessary adjustments. Follow-up support to the Australian Aeronautical Research Laboratory (ARL) on this program is continuing