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Water utilities incentivize turf replacement to promote water conservation, but the effects of such programs have received limited evaluations. In 2014, the Metropolitan Water District of Southern California (MWD) undertook an unprecedented investment to incentive turf replacement throughout Southern California in response to a serious Statewide drought. MWD devoted $350 million to the program, resulting in more than 46,000 rebate payments (25,000 in Los Angeles County) to remove 15.3 million square meters of turf. The program implementation provided a unique opportunity to address research gaps on turf replacement implementation. We analyzed socioeconomic and spatial trends of program participants and assessed landscape changes from turf replacement using a random sample of properties (4% of LA County participants in 2014–16). Specifically, we used a novel and cost-effective approach Google Earth Street View to characterize landscapes in front yards and created a typology of land cover types. Results showed: post-replacement landscapes had a diversity of land cover types – diverse yards with several land cover types, as well as more homogenous yards with a single land cover such as woodchips, bare soil, gravel, and artificial turf. Analysis also indicated some evidence of “neighborhood adoption” effects. We describe the need for longitudinal studies to understand long-term effects of turf replacement and associated water use, and suggest that water utilities should also evaluate results in backyards, which requires site visits. This study provides a novel contribution that can be replicated over space and time to further knowledge of turf replacement program implementations and evaluation.

Many utility and government programs exist to promote energy efficiency (EE) in residential buildings. While programs have succeeded in reducing per square foot energy usage intensity (EUI), they do not necessarily promote conservation, in terms of reduced total energy consumption. Using statistical analysis and data mining techniques, we examined relationships between home size, electricity and natural gas EUIs, and neighborhood level socio-economic attributes among ∼1.3 million single-family homes in Los Angeles County (LAC). We observed that among homes constructed between 1900 and 2010, the growth in median home size by construction vintage year has outpaced combined EUI reductions by 60%. Results of a Monte-Carlo sampling procedure derived from these observed trends indicate that past historical energy savings within LAC, attributable to state mandated EE policies, could have been equivalently achieved by constraining growth in the size of newly constructed homes. These findings have significant implications for the design of future energy conservation policies within growing urban areas.

Several developmental stages of spermatogenesis are transcriptionally quiescent which presents major challenges associated with the regulation of gene expression. Here we identify that the zygotene to pachytene transition is not only associated with the resumption of transcription but also a wave of programmed mRNA degradation that is essential for meiotic progression. We explored whether terminal uridydyl transferase 4- (TUT4-) or TUT7-mediated 3′ mRNA uridylation contributes to this wave of mRNA degradation during pachynema. Indeed, both TUT4 and TUT7 are expressed throughout most of spermatogenesis, however, loss of either TUT4 or TUT7 does not have any major impact upon spermatogenesis. Combined TUT4 and TUT7 (TUT4/7) deficiency results in embryonic growth defects, while conditional gene targeting revealed an essential role for TUT4/7 in pachytene progression. Loss of TUT4/7 results in the reduction of miRNA, piRNA and mRNA 3′ uridylation. Although this reduction does not greatly alter miRNA or piRNA expression, TUT4/7-mediated uridylation is required for the clearance of many zygotene-expressed transcripts in pachytene cells. We find that TUT4/7-regulated transcripts in pachytene spermatocytes are characterized by having long 3′ UTRs with length-adjusted enrichment for AU-rich elements. We also observed these features in TUT4/7-regulated maternal transcripts whose dosage was recently shown to be essential for sculpting a functional maternal transcriptome and meiosis. Therefore, mRNA 3′ uridylation is a critical determinant of both male and female germline transcriptomes. In conclusion, we have identified a novel requirement for 3′ uridylation-programmed zygotene mRNA clearance in pachytene spermatocytes that is essential for male meiotic progression.

Cancer sequencing studies have implicated regulators of pre-mRNA splicing as important disease determinants in acute myeloid leukemia (AML), but the underlying mechanisms have remained elusive. We hypothesized that “non-mutated” splicing regulators may also play a role in AML biology and therefore conducted an in vivo shRNA screen in a mouse model of CEBPA mutant AML. This has led to the identification of the splicing regulator RBM25 as a novel tumor suppressor. In multiple human leukemic cell lines, knockdown of RBM25 promotes proliferation and decreases apoptosis. Mechanistically, we show that RBM25 controls the splicing of key genes, including those encoding the apoptotic regulator BCL-X and the MYC inhibitor BIN1. This mechanism is also operative in human AML patients where low RBM25 levels are associated with high MYC activity and poor outcome. Thus, we demonstrate that RBM25 acts as a regulator of MYC activity and sensitizes cells to increased MYC levels., Splicing factors are often mutated in hematological malignancies. Here, the authors perform an in vivo shRNA screen in a CEBPA mutant AML mouse model and identify that RBM25 controls the splicing of pre-mRNAs encoding BCL-X and BIN1 to exert its tumour suppressor activities in AML.

With 40 million people and substantial county and regional variation in socio-demographics and health services, California is an important setting to study disparities. Its population -- 39.1% Latino, 5.3% Black, and 14.4% Asian -- experienced 54,124 COVID-19 deaths through March 7, 2021, the highest nationally. We analyzed California’s racial/ethnic disparities in COVID-19 exposure risks, testing rates, test positivity, and case rates, through October 2020. We combined data from 15.4 million SARS-CoV-2 tests with sub-county exposure risk estimates from the American Community Survey. Based on accumulated evidence, we defined “high exposure risk” households as those with ≥1 essential workers and fewer rooms than inhabitants. Latino individuals are 8.1 times more likely to live in high exposure risk households than White individuals (23.6% vs. 2.9%); overrepresented in cumulative cases (3,784 vs. 1,112 per 100,000); and underrepresented in cumulative testing (35,635 vs. 48,930 per 100,000). These risks and outcomes were worse for Latinos than for other racial/ethnic groups. Sub-county disparity analyses can inform local targeting of interventions and resources, including community-based testing and vaccine access and uptake measures. Tracking COVID-19 disparities and developing equity-focused public health programming that mitigates effects of systemic racism can help improve health outcomes among California’s populations of color.

Geothermal energy can provide answers to many of America’s essential energy questions. The United States has tremendous geothermal resources, as illustrated by the results of the DOE GeoVision analysis, but technical and non-technical barriers have historically stood in the way of widespread deployment of geothermal energy. The U.S. Department of Energy’s Geothermal Technologies Office within the Office of Energy Efficiency and Renewable Energy has invested more than $470 million in research and development (R&D) since 2015 to meet its three strategic goals: (1) unlock the potential of enhanced geothermal systems, (2) advance technologies to increase geothermal energy on the U.S. electricity grid, and (3) support R&D to expand geothermal energy opportunities throughout the United States. This paper describes many of those R&D initiatives and outlines future directions in geothermal research.

Differentiation of multipotent stem cells into mature cells is fundamental for development and homeostasis of mammalian tissues, and requires the coordinated induction of lineage-specific transcriptional programs and cell cycle withdrawal. To understand the underlying regulatory mechanisms of this fundamental process, we investigated how the tissue-specific transcription factors, CEBPA and CEBPE, coordinate cell cycle exit and lineage-specification in vivo during granulocytic differentiation. We demonstrate that CEBPA promotes lineage-specification by launching an enhancer-primed differentiation program and direct activation of CEBPE expression. Subsequently, CEBPE confers promoter-driven cell cycle exit by sequential repression of MYC target gene expression at the G1/S transition and E2F-meditated G2/M gene expression, as well as by the up-regulation of Cdk1/2/4 inhibitors. Following cell cycle exit, CEBPE unleashes the CEBPA-primed differentiation program to generate mature granulocytes. These findings highlight how tissue-specific transcription factors coordinate cell cycle exit with differentiation through the use of distinct gene regulatory elements. Here the authors show that differentiation of haematopoietic stem cells into mature blood cells is primed by cell type-specific transcription factors at the enhancer level during early differentiation, before they confere promoter-driven growth arrest, and activate post-mitotic terminal differentiation.

Polycomb group (PcG) proteins are transcriptional repressors, which regulate proliferation and cell fate decisions during development, and their deregulated expression is a frequent event in human tumours. The Polycomb repressive complex 2 (PRC2) catalyzes trimethylation (me3) of histone H3 lysine 27 (K27), and it is believed that this activity mediates transcriptional repression. Despite the recent progress in understanding PcG function, the molecular mechanisms by which the PcG proteins repress transcription, as well as the mechanisms that lead to the activation of PcG target genes are poorly understood. To gain insight into these mechanisms, we have determined the global changes in histone modifications in embryonic stem (ES) cells lacking the PcG protein Suz12 that is essential for PRC2 activity. We show that loss of PRC2 activity results in a global increase in H3K27 acetylation. The methylation to acetylation switch correlates with the transcriptional activation of PcG target genes, both during ES cell differentiation and in MLL-AF9-transduced hematopoietic stem cells. Moreover, we provide evidence that the acetylation of H3K27 is catalyzed by the acetyltransferases p300 and CBP. Based on these data, we propose that the PcG proteins in part repress transcription by preventing the binding of acetyltransferases to PcG target genes.

We investigate the influence of foliation orientation and fine-scale folding on the static and dynamic elastic properties and unconfined strength of the Poorman schist. Measurements from triaxial and uniaxial laboratory experiments reveal a significant amount of variability in the static and dynamic Young’s modulus depending on the sample orientation relative to the foliation plane. Dynamic P-wave modulus and S-wave modulus are stiffer in the direction parallel to the foliation plane as expected for transversely isotropic mediums with average Thomsen parameters values 0.133 and 0.119 for epsilon and gamma, respectively. Static Young’s modulus varies significantly between 21 and 117 GPa, and a peculiar trend is observed where some foliated sample groups show an anomalous decrease in the static Young’s modulus when the symmetry axis (x3-axis) is oriented obliquely to the direction of loading. Utilizing stress and strain relationships for transversely isotropic medium, we derive the analytical expression for Young’s modulus as a function of the elastic moduli E1, E3, ν31, and G13 and sample orientation to fit the static Young’s modulus measurements. Regression of the equation to the Young’s modulus data reveals that the decrease in static Young’s modulus at oblique symmetry axis orientations is directly influenced by a low shear modulus, G13, which we attribute to shear sliding along foliation planes during static deformation that occurs as soon as the foliation is subject to shear stress. We argue that such difference between dynamic and static anisotropy is a characteristic of near-zero porosity anisotropic rocks. The uniaxial compressive strength also shows significant variability ranging from 21.9 to 194.6MPa across the five sample locations and is the lowest when the symmetry axis is oriented 45° or 60° from the direction of loading, also a result of shear sliding along foliation planes during static deformation.

Rooftops provide accessible locations for solar energy installations. While rooftop solar arrays can offset in-building electricity needs, they may also stress electric grid operations. Here we present an analysis of net electricity generation potential from distributed rooftop solar in Los Angeles. We integrate spatial and temporal data for property-level electricity demands, rooftop solar generation potential, and grid capacity constraints to estimate the potential for solar to meet on-site demands and supply net exports to the electric grid. In the study area with 1.2 million parcels, rooftop solar could meet 7200 Gigawatt Hours (GWh) of on-site building demands (~29% of demand). Overall potential net generation is negative, meaning buildings use more electricity than they can produce. Yet, cumulative net export potential from solar to grid circuits is 16,400 GWh. Current policies that regulate solar array interconnection to the grid result in unutilized solar power output of 1700 MW. Lower-income and at-risk communities in LA have greater potential for exporting net solar generation to the grid. This potential should be recognized through investments and policy innovations. The method demonstrates the need for considering time-dependent calculations of net solar potential and offers a template for distributed renewable energy planning in cities.

The threat of introduction of coronavirus disease 2019 (COVID-19) into the United States with the potential for community transmission prompted U.S. federal officials in February 2020 to screen travelers from China, and later Iran, and collect and transmit their demographic and contact information to states for follow-up. During February 5-March 17, 2020, the California Department of Public Health (CDPH) received and transmitted contact information for 11,574 international travelers to 51 of 61 local health jurisdictions at a cost of 1,694 hours of CDPH personnel time. If resources permitted, local health jurisdictions contacted travelers, interviewed them, and oversaw 14 days of quarantine, self-monitoring, or both, based on CDC risk assessment criteria for COVID-19. Challenges encountered during follow-up included errors in the recording of contact information and variation in the availability of resources in local health jurisdictions to address the substantial workload. Among COVID-19 patients reported to CDPH, three matched persons previously reported as travelers to CDPH. Despite intensive effort, the traveler screening system did not effectively prevent introduction of COVID-19 into California. Effectiveness of COVID-19 screening and monitoring in travelers to California was limited by incomplete traveler information received by federal officials and transmitted to states, the number of travelers needing follow-up, and the potential for presymptomatic and asymptomatic transmission. More efficient methods of collecting and transmitting passenger data, including electronic provision of flight manifests by airlines to federal officials and flexible text-messaging tools, would help local health jurisdictions reach out to all at-risk travelers quickly, thereby facilitating timely testing, case identification, and contact investigations. State and local health departments should weigh the resources needed to implement incoming traveler monitoring against community mitigation activities, understanding that the priorities of each might shift during the COVID-19 pandemic.

To tackle the global antibiotic resistance crisis, antibiotic resistance acquired either vertically by chromosomal mutations or horizontally through antibiotic resistance genes (ARGs) have been studied. Yet, little is known about the interactions between the two, which may impact the evolution of antibiotic resistance. Here, we develop a multiplexed barcoded approach to assess the fitness of 144 mutant-ARG combinations in Escherichia coli subjected to eight different antibiotics at 11 different concentrations. While most interactions are neutral, we identify significant interactions for 12% of the mutant-ARG combinations. The ability of most ARGs to confer high-level resistance at a low fitness cost shields the selective dynamics of mutants at low drug concentrations. Therefore, high-fitness mutants are often selected regardless of their resistance level. Finally, we identify strong negative epistasis between two unrelated resistance mechanisms: the tetA tetracycline resistance gene and loss-of-function nuo mutations involved in aminoglycoside tolerance. Our study highlights important constraints that may allow better prediction and control of antibiotic resistance evolution., The authors study the interactions between chromosomal mutations and horizontally acquired genes in the evolution of antibiotic resistance in experimental evolution assays. They identify constraints that may allow better prediction and control of antibiotic resistance evolution.

Reducing energy consumption for urban water management may yield economic and environmental benefits. Few studies provide comprehensive assessments of energy needs for urban water sectors that include both utility operations and household use. Here, we evaluate the energy needs for urban water management in metropolitan Los Angeles (LA) County. Using planning scenarios that include both water conservation and alternative supply options, we estimate energy requirements of water imports, groundwater pumping, distribution in pipes, water and wastewater treatment, and residential water heating across more than one hundred regional water agencies covering over 9 million people. Results show that combining water conservation with alternative local supplies such as stormwater capture and water reuse (nonpotable or indirect potable) can reduce the energy consumption and intensity of water management in LA. Further advanced water treatment for direct potable reuse could increase energy needs. In aggregate, water heating represents a major source of regional energy consumption. The heating factor associated with grid-supplied electricity drives the relative contribution of energy-for-water by utilities and households. For most scenarios of grid operations, energy for household water heating significantly outweighs utility energy consumption. The study demonstrates how publicly available and detailed data for energy and water use supports sustainability planning. The method is applicable to cities everywhere.

Ciprofloxacin (CIP) is used to treat Pseudomonas aeruginosa biofilm infections. We showed that the pathways of CIP-resistance development during exposure of biofilms and planktonic P. aeruginosa populations to subinhibitory levels of CIP depend on the mode of growth. In the present study, we analyzed CIP-resistant isolates obtained from previous evolution experiments, and we report a variety of evolved phenotypic and genotypic changes that occurred in parallel with the evolution of CIP-resistance. Cross-resistance to beta-lactam antibiotics was associated with mutations in genes involved in cell-wall recycling (ftsZ, murG); and could also be explained by mutations in the TCA cycle (sdhA) genes and in genes involved in arginine catabolism. We found that CIP-exposed isolates that lacked mutations in quorum-sensing genes and acquired mutations in type IV pili genes maintained swarming motility and lost twitching motility, respectively. Evolved CIP-resistant isolates showed high fitness cost in planktonic competition experiments, yet persisted in the biofilm under control conditions, compared with ancestor isolates and had an advantage when exposed to CIP. Their persistence in biofilm competition experiments in spite of their fitness cost in planktonic growth could be explained by their prolonged lag-phase. Interestingly, the set of mutated genes that we identified in these in vitro-evolved CIP-resistant colonies, overlap with a large number of patho-adaptive genes previously reported in P. aeruginosa isolates from cystic fibrosis (CF) patients. This suggests that the antibiotic stress is contributing to the bacterial evolution in vivo, and that adaptive laboratory evolution can be used to predict the in vivo evolutionary trajectories.

Web-based tools which support interactive data visualizations and queries have become increasingly important within the environmental sciences (Vitolo et al. 2015). It is incumbent on the creators of these tools to think carefully about user experience and the visual presentation of data (Grainger et al. 2016). This chapter describes the development and current functionalities of the public-facing Energy Atlas website, from stakeholder engagement through the features available on the site today, demonstrating the extent to which the Atlas is a product of a public participatory GIS development process (Sieber 2006). The final section of this chapter examines the challenges of visualizing data with strict privacy aggregation protocols and the effects these rules have on data access.