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The Colorado River supplies >40 million people in the United States Southwest with their daily water supply and is unable to meet the current demands. New approaches are needed to enhance sustainability and resilience. A net zero urban water (NZUW) approach meets the needs of a given community with a locally available and sustainable water supply, without detriment to interconnected systems and the long-term water supply. Transitioning to a NZUW future will require considerable modifications to governance and policy across the Southwest and its cities specifically. We identify five areas of governance and policy challenges: diversified water sources and sinks; planning, design, and operation; monitoring and enforcement; coordination; and addressing equity and justice. Four case study cities are investigated: Albuquerque, Denver, Los Angeles, and Tucson. Across these cities, the policy priorities include supporting potable water reuse, coordinating policies across jurisdictions for alternative water sources, addressing equity and justice, developing and incentivizing water conservation plans, and making aquifer storage and recovery projects easier and more economical to pursue. We conclude that a NZUW transition in the Southwest faces considerable governance and policy challenges, but moving cities toward this goal is crucial.

Fracture injection/shut-in tests are commonly used to measure the state of stress in the subsurface. Injection creates a hydraulic fracture (or in some cases, opens a preexisting fracture), and then the pressure after shut-in is monitored to identify fracture closure. Different interpretation procedures have been proposed for estimating closure, and the procedures sometimes yield significantly different results. In this study, direct, in-situ strain measurements are used to observe fracture reopening and closure. The tests were performed as part of the EGS Collab project, a mesoscale project performed at 1.25 and 1.5 km depth at the Sanford Underground Research Facility. The tests were instrumented with the SIMFIP tool, a double-packer probe with a high-resolution three-dimensional borehole displacement sensor. The measurements provide a direct observation of the fracture closure signature, enabling a high-fidelity estimate of the fracture closure stress (ie, the normal stress on the fracture). In two of the four tests, injection created an opening mode fracture, and so the closure stress can be interpreted as the minimum principal stress. In the other two tests, injection probably opened preexisting natural fractures, and so the closure stress can be interpreted as the normal stress on the fractures. The strain measurements are compared against different proposed methods for estimating closure stress from pressure transients. The shut-in transients are analyzed with two techniques that are widely used in the field of petroleum engineering – the ‘tangent’ method and the ‘compliance’ method. In three of the four tests, the tangent method significantly underestimates the closure stress. The compliance method is reasonably accurate in all four tests. Closure stress is also interpreted using two other commonly-used methods – ‘first deviation from linearity’ and the method of (Hayashi and Haimson, 1991). In comparison with the SIMFIP data, these methods tend to overestimate the closure stress, evidently because they identify closure from early-time transient effects, such as near-wellbore tortuosity. In two of the tests, microseismic imaging provides an independent estimate of the size of the fracture created by injection. When combined with a simple mass balance calculation, the SIMFIP stress measurements yield predictions of fracture size that are reasonably consistent with the estimates from microseismic. The calculations imply an apparent fracture toughness 2-3x higher than typical laboratory-derived values.

Abstract As water scarcity becomes the new norm in the Western United States, states such as California have increased their efforts to improve water resilience. Achieving water security under climate change, population growth, and urbanization requires an integrated multi-sectoral approach, where adaptation strategies combine supply and demand management interventions. Yet, most studies consider supply-side and demand-side management strategies separately. Water conservation efforts are mainly driven by policy requirements and publicly available data to assess the effectiveness of demand- and supply-side management policies is often hard to find and unstructured. Here we present CaRDS - the statewide California Residential water Demand and Supply open dataset. CaRDS encompasses nine years (2013-2021) of monthly water supply and demand time series for 404 water suppliers in California, USA, compiled from different open-access data sources. Access to detailed temporal and spatial water supply operations and demands at the state-level can be useful to researchers and practitioners to realize applications such as evaluating the effectiveness of water conservation policies and discovering regional differences in water resilience measures.

IntroductionProinflammatory cytokines are implicated in pancreatic ß cell failure in type 1 and type 2 diabetes and are known to stimulate alternative RNA splicing and the expression of nonsense-mediated RNA decay (NMD) components. Here, we investigate whether cytokines regulate NMD activity and identify transcript isoforms targeted in ß cells.MethodsA luciferase-based NMD reporter transiently expressed in rat INS1(832/13), human-derived EndoC-ßH3, or dispersed human islet cells is used to examine the effect of proinflammatory cytokines (Cyt) on NMD activity. The gain- or loss-of-function of two key NMD components, UPF3B and UPF2, is used to reveal the effect of cytokines on cell viability and function. RNA-sequencing and siRNA-mediated silencing are deployed using standard techniques.ResultsCyt attenuate NMD activity in insulin-producing cell lines and primary human ß cells. These effects are found to involve ER stress and are associated with the downregulation of UPF3B. Increases or decreases in NMD activity achieved by UPF3B overexpression (OE) or UPF2 silencing raise or lower Cyt-induced cell death, respectively, in EndoC-ßH3 cells and are associated with decreased or increased insulin content, respectively. No effects of these manipulations are observed on glucose-stimulated insulin secretion. Transcriptomic analysis reveals that Cyt increases alternative splicing (AS)-induced exon skipping in the transcript isoforms, and this is potentiated by UPF2 silencing. Gene enrichment analysis identifies transcripts regulated by UPF2 silencing whose proteins are localized and/or functional in the extracellular matrix (ECM), including the serine protease inhibitor SERPINA1/α-1-antitrypsin, whose silencing sensitizes ß-cells to Cyt cytotoxicity. Cytokines suppress NMD activity via UPR signaling, potentially serving as a protective response against Cyt-induced NMD component expression.ConclusionOur findings highlight the central importance of RNA turnover in ß cell responses to inflammatory stress.

Abstract The myeloid transcription factor CEBPA is recurrently biallelically mutated (i.e., double mutated; CEBPA DM) in acute myeloid leukemia (AML) with a combination of hypermorphic N-terminal mutations (CEBPA NT), promoting expression of the leukemia-associated p30 isoform, and amorphic C-terminal mutations. The most frequently co-mutated genes in CEBPA DM AML are GATA2 and TET2, however the molecular mechanisms underlying this co-mutational spectrum are incomplete. By combining transcriptomic and epigenomic analyses of CEBPA-TET2 co-mutated patients with models thereof, we identify GATA2 as a conserved target of the CEBPA-TET2 mutational axis, providing a rationale for the mutational spectra in CEBPA DM AML. Elevated CEBPA levels, driven by CEBPA NT, mediate recruitment of TET2 to the Gata2 distal hematopoietic enhancer thereby increasing Gata2 expression. Concurrent loss of TET2 in CEBPA DM AML induces a competitive advantage by increasing Gata2 promoter methylation, thereby rebalancing GATA2 levels. Of clinical relevance, demethylating treatment of Cebpa-Tet2 co-mutated AML restores Gata2 levels and prolongs disease latency.

Abstract Single-cell resolution analysis of complex biological tissues is fundamental to capture cell-state heterogeneity and distinct cellular signaling patterns that remain obscured with population-based techniques. The limited amount of material encapsulated in a single cell however, raises significant technical challenges to molecular profiling. Due to extensive optimization efforts, single-cell proteomics by Mass Spectrometry (scp-MS) has emerged as a powerful tool to facilitate proteome profiling from ultra-low amounts of input, although further development is needed to realize its full potential. To this end, we carry out comprehensive analysis of orbitrap-based data-independent acquisition (DIA) for limited material proteomics. Notably, we find a fundamental difference between optimal DIA methods for high- and low-load samples. We further improve our low-input DIA method by relying on high-resolution MS1 quantification, thus enhancing sensitivity by more efficiently utilizing available mass analyzer time. With our ultra-low input tailored DIA method, we are able to accommodate long injection times and high resolution, while keeping the scan cycle time low enough to ensure robust quantification. Finally, we demonstrate the capability of our approach by profiling mouse embryonic stem cell culture conditions, showcasing heterogeneity in global proteomes and highlighting distinct differences in key metabolic enzyme expression in distinct cell subclusters.

The EGS Collab project is performing well-monitored rock stimulation and flow tests at the 10-m scale in an underground research laboratory to inform challenges in implementing enhanced geothermal systems (EGS). This project, supported by the US Department of Energy, is gathering data and observations from the field tests and comparing these to simulation results to understand processes and to build confidence in numerical modeling of the processes. Experiment 1 (now complete) examined hydraulic fracturing in an underground test bed at the Sanford Underground Research Facility (SURF) in Lead, South Dakota, at a depth of approximately 1.5 km in a well-characterized phyllite. Geophysical monitoring instrumentation in six of eight sub-horizontal boreholes monitored stimulation events and flow tests. The other two boreholes were used to perform and carefully measure water injection and production. More than a dozen stimulations and nearly one year of flow tests in the testbed were performed. Detailed observations of processes occurring during stimulation and dynamic flow tests were collected and analyzed. Flow tests using ambient-temperature and chilled water were performed with intermittent tracer tests to examine system behavior. We achieved adaptive control of the tests using close monitoring of rapidly disseminated data and near-real-time simulation. Numerical simulation was critical in answering key experimental design questions, forecasting fracture behavior, and analyzing results. We were successful in performing many simulations in near-real-time in conjunction with the field experiments, with more detailed simulations performed later. The primary objective of Experiment 2 is to examine hydraulic shearing of natural fractures at a depth of 1.25 km in amphibolite at SURF. The stresses, rock type, and fracture conditions are different than in Experiment 1. The testbed consists of 9 boreholes, in addition to two earlier-drilled characterization boreholes. One borehole is used for injection, two fans of 2 monitoring wells have several geophysical measurement tools grouted in, and four open boreholes surrounding the injection hole are adaptively used for production and monitoring. We have encountered approximately five fracture set orientations in the testbed, and designed our testbed accordingly to maximize the potential for shear stimulation. Three stimulations have been performed to date from the injection borehole, each intersecting at least one production borehole. Different methods have been used for each stimulation, including a ramped flow, a high flow rate, and oscillating pressure.

Abstract Background Idiopathic non-clonal cytopenia (ICUS) and clonal cytopenia (CCUS) are common in the elderly population. While these entities have similar clinical presentations with peripheral blood cytopenia and less than 10% bone marrow dysplasia, their malignant potential is different and the biological relationship between these disorders and myeloid neoplasms such as myelodysplastic syndrome (MDS) is not fully understood. Aberrant DNA methylation has previously been described to play a vital role in MDS and acute myeloid leukemia (AML) pathogenesis. In addition, obesity confers a poorer prognosis in MDS with inferior overall survival and a higher rate of AML transformation. In this study, we measured DNA methylation of the promoter for the obesity-regulated gene LEP, encoding leptin, in hematopoietic cells from ICUS, CCUS and MDS patients and healthy controls. We investigated whether LEP promoter methylation is an early event in the development of myeloid neoplasms and whether it is associated with clinical outcome. Results We found that blood cells of patients with ICUS, CCUS and MDS all have a significantly hypermethylated LEP promoter compared to healthy controls and that LEP hypermethylation is associated with anemia, increased bone marrow blast percentage, and lower plasma leptin levels. MDS patients with a high LEP promoter methylation have a higher risk of progression, shorter progression-free survival, and inferior overall survival. Furthermore, LEP promoter methylation was an independent risk factor for the progression of MDS in a multivariate Cox regression analysis. Conclusion In conclusion, hypermethylation of the LEP promoter is an early and frequent event in myeloid neoplasms and is associated with a worse prognosis.

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 194.6 MPa 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.

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.

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.

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.

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.

Acute water shortages for large metropolitan regions are likely to become more frequent as climate changes impact historic precipitation levels and urban population grows. California and Los Angeles County have just experienced a severe four year drought followed by a year of high precipitation, and likely drought conditions again in Southern California. We show how the embedded preferences for distant sources, and their local manifestations, have created and/or exacerbated fluctuations in local water availability and suboptimal management. As a socio technical system, water management in the Los Angeles metropolitan region has created a kind of scarcity lock-in in years of low rainfall. We come to this through a decade of coupled research examining landscapes and water use, the development of the complex institutional water management infrastructure, hydrology and a systems network model. Such integrated research is a model for other regions to unpack and understand the actual water resources of a metropolitan region, how it is managed and potential ability to become more water self reliant if the institutions collaborate and manage the resource both parsimoniously, but also in an integrated and conjunctive manner. The Los Angeles County metropolitan region, we find, could transition to a nearly water self sufficient system.

Cities across the globe manage stormwater to enhance water supplies. Capturing and using stormwater in urban watersheds can have benefits for groundwater recharge, reduced pollutant loading in downstream watersheds, and habitat management. In California, metropolitan areas in the southern coastal regions of the state have for decades captured an average of 493 Million Cubic Meters (400,000 acre-feet) of runoff annually to recharge groundwater. But in a state with highly managed watersheds and seasonal precipitation, capturing stormwater for water supply goals can affect urban streamflows. Using a model with simulation and optimization of regional urban water resources management in Los Angeles County (Artes), we analyze the potential effects of increasing stormwater capture and infiltration on urban streamflow volumes. Results indicate that for many watersheds in LA, further increasing stormwater capture and use would significantly reduce urban streamflow volumes, especially in downstream basins. But in some basins, streamflows are increased to preferentially direct water to existing stormwater capture basins. Results illustrate potential tradeoffs in water supply, in-stream water flows, and aquatic habitat that must be considered when looking to increase use of local water sources through more stormwater capture.

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.

Stormwater utility fees provide dedicated revenues for managing stormwater. In setting fees, household-level affordability should be considered. Existing research does not address methods to evaluate the affordability of stormwater utility fees, especially alongside other household water costs. This paper aims to fill that gap. We present a scenario-based approach to evaluate household affordability of stormwater utility fees in a municipality, which considers other essential household water service charges. We estimate the relative contribution of stormwater utility fees to total household water costs and evaluate affordability across income brackets by integrating data for socioeconomic status, land use, water utility charges, and impervious surface cover. Using data for a case study region, results indicate that stormwater utility fees are small contributors to overall household urban water costs and comprise no more than 2% of the median household income across nearly all income quintiles. For low-income households, stormwater charges only exceed 1% of the household income for the lowest-income brackets (

Myeloproliferative neoplasms are stem cell–driven cancers associated with a large burden of morbidity and mortality. Most patients present with early-stage disease, but a substantial proportion progress to myelofibrosis or secondary leukemia, advanced cancers with a poor prognosis and high symptom burden. Currently, it remains difficult to predict progression, and therapies that reliably prevent or reverse fibrosis are lacking. A major bottleneck to the discovery of disease-modifying therapies has been an incomplete understanding of the interplay between perturbed cellular and molecular states. Several cell types have individually been implicated, but a comprehensive analysis of myelofibrotic bone marrow is lacking. We therefore mapped the cross-talk between bone marrow cell types in myelofibrotic bone marrow. We found that inflammation and fibrosis are orchestrated by a "quartet" of immune and stromal cell lineages, with basophils and mast cells creating a TNF signaling hub, communicating with megakaryocytes, mesenchymal stromal cells, and proinflammatory fibroblasts. We identified the β-galactoside–binding protein galectin-1 as a biomarker of progression to myelofibrosis and poor survival in multiple patient cohorts and as a promising therapeutic target, with reduced myeloproliferation and fibrosis in vitro and in vivo and improved survival after galectin-1 inhibition. In human bone marrow organoids, TNF increased galectin-1 expression, suggesting a feedback loop wherein the proinflammatory myeloproliferative neoplasm clone creates a self-reinforcing niche, fueling progression to advanced disease. This study provides a resource for studying hematopoietic cell–niche interactions, with relevance for cancer-associated inflammation and disorders of tissue fibrosis. Editor's summary: Myeloproliferative neoplasms can transition to advanced cancers with poor prognosis. Predicting progression and reversing the associated myelofibrosis remain difficult. Li, Colombo, and Wang et al. present a mouse cancer-stroma interactome for myelofibrosis and show that galectin-1 is a potential inflammation-related target for treating disease. Mesenchymal stem cells, eosinophils, basophils, and mast cells were each implicated in an inflammatory niche that drove myelofibrosis progression. Inhibiting galectin-1 with a monoclonal antibody in a mouse model of myeloproliferative neoplasm decreased fibrosis and cell proliferation and had a beneficial effect on survival. Galectin-1 was associated with myelofibrosis and poor survival in multiple human cohorts. These results suggest that galectin-1 may be a target to alter the inflammatory niche and to reduce fibrosis in myeloproliferative neoplasms. —Brandon Berry [ABSTRACT FROM AUTHOR]

The article discusses the presence of myeloid-derived suppressor cells (MDSCs) in patients with clonal cytopenia of undetermined significance (CCUS) and low-risk myelodysplastic syndrome (LR-MDS). The study found that MDSCs were activated in the bone marrow of these patients, along with an increased proportion of CTLA-4+ T cells and alterations in T-cell memory subsets in peripheral blood. These immune changes suggest an early inflammatory state in CCUS/LR-MDS patients, highlighting the potential role of MDSCs in disease progression. Further research is needed to explore the relationship between immune dysregulation and molecular characteristics in these patients. [Extracted from the article]

Groundwater basins are important sources of water supply and storage for many cities. Groundwater exchange pools offer additional opportunities for utilizing these common pool resources, but their potential role in urban water management is not clear, and modeling such exchanges can be challenging. This paper presents an analysis of the potential for groundwater basin exchange pools to contribute to urban water supply sustainability. Building on an existing model of urban water management in Los Angeles, the analysis assesses the potential for groundwater exchange pools to reduce scarcity and demonstrates a method for modeling two-way (undirected) flows within a directed-network model using linear programming. Results indicate that exchange pools can help alleviate shortages from operational changes (reduced imported water) in Los Angeles, but providing more parties with access to storage improves their effectiveness. Exchange pools could potentially provide 6-12% of total supplies and reduce shortages as much as 86%. Considerations for organizing exchange pools are discussed to explore policy implications for managing common pool resources. The analytical method for embedding undirected network flows within a larger directed-network model has wide applicability for water resource systems analysis applications, including modeling water markets and interbasin transfers.

Los Angeles imports water over long distances to supplement local supplies. Reduced reliability of the available imports is driving many local agencies to promote conservation and enhance local water sources. These include stormwater capture, water reuse and groundwater. But financial considerations are often a significant impediment to project development, especially when comparing new and existing sources. Here we demonstrate a comprehensive approach for evaluating the economic implications of shifting to local water reliance in Los Angeles County. We show that local water supplies are economically competitive. Results from integrated hydroeconomic modelling of urban water in Los Angeles identify cost-effective water supply portfolios and conservation targets. Considering costs across the 'full-cycles' of urban water supply that span agency boundaries yields better comparisons of planning alternatives. Throughout the region, many water retailers could successfully mitigate effects of imported water cuts while still supporting drought-tolerant landscapes, but some would suffer due to over-reliance on imports. Updating economic assessment methods would support needed innovations to achieve local reliance in Los Angeles, including infrastructure investments, institutional reforms, many more drought-tolerant landscapes and reallocated groundwater rights.

School buildings are significant energy consumers. They are important targets for energy efficiency improvements, which can reduce energy spending and meet energy policy goals for state and federal governments. In the US, few studies have quantified electricity and natural gas consumption patterns in schools. Such information vitally supports energy planning and benchmarking. We present an analysis of high-detail electricity and natural gas consumption for schools in Los Angeles County over an extended period of time. Using a robust database of monthly account-level consumption, we examine electricity and natural gas consumption trends for hundreds of schools in relation to key structural and categorical characteristics, including size, geography, and school type. Results show that school energy use varies greatly across socio-demographic, structural, and climate factors. Correlations between electricity and natural gas consumption are time dependent and seasonally distinct. The analysis provides a useful case study with benchmarks for US public schools and demonstrates challenges with devising large-scale studies of school energy use. We conclude with a discussion of policy implications.

This report assesses the potential to improve water quality standards while integrating complementary One Water Management practices that can increase potential local water supplies for the City of Los Angeles (the City).  This final report summarizes the current practices and future opportunities at the City-owned Water Reclamation Plants and underlying groundwater basins and highlights the importance of considering all aspects of integrated water management even when dealing with water quality or supply-focused projects.  Implementing watershed-scale best management practice programs to meet stormwater permit requirements will significantly improve water quality in all watersheds.  However, additional mechanisms such as increasing Low Impact Development implementation and comprehensive source tracking and source control mechanisms will be required to potentially eliminate water quality exceedances.  There are multiple efforts occurring in the City and the region to increase the recharge of recycled water into the ground and the volumes of remediated groundwater extracted. This research further assessed the impacts of potential water supply portfolios, with greater volumes of locally-supplied water, on GHG emissions and energy needs of supplying LA’s water.  Conservation will be another powerful tool to decrease our dependence on imported water.  This research demonstrates the complex interrelationships between all aspects of urban water management, including, for example, stormwater management and local water supply.

Single-cell proteomics can provide insights into the molecular basis for cellular heterogeneity. Here, the authors develop a multiplexed single-cell proteomics and computational workflow, and show that their strategy captures the cellular hierarchies in an Acute Myeloid Leukemia culture model.