Real options analysis for valuation of climate adaptation pathways with application to transit infrastructure.

Climate change and sea-level rise (SLR) are expected to increase the frequency and intensity of coastal flood events, posing risks to coastal communities and infrastructure. While regional climate adaptation investments can provide substantive flood protection, existing plans often neglect uncertainty in future climate conditions and adaptation performance, consequently neglecting the option value of flexibly implementing proposed projects. Addressing this gap, we develop and employ a generalizable real options analysis (ROA) valuation framework that considers how uncertainty in adaptation project costs, SLR, flood severity, and flood losses inform the full range of adaptation performance outcomes. We further propose and apply a novel, computationally efficient flood loss sampling algorithm to estimate the consequences of randomly arriving coastal flood events. We apply this ROA framework to assess the option value of flexibly timing adaptation investments over time, investigating an adaptation pathway proposed by the City of Boston from the perspective of the regional transit system manager. Our results suggest that flexible implementation can provide significant option value in the near- to mid-term (>30 years), with the highest option values under low-probability, high-consequence scenarios. Our results also suggest adaptation pathway performance in the latter half of the 21st century is most sensitive to uncertainty in SLR, flood loss estimates, and flood frequency, underscoring the importance of uncertainty quantification in the long-term valuation of adaptation investments.

Profiling mouse brown and white adipocytes to identify metabolically relevant small ORFs and functional microproteins.

Microproteins (MPs) are a potentially rich source of uncharacterized metabolic regulators. Here, we use ribosome profiling (Ribo-seq) to curate 3,877 unannotated MP-encoding small ORFs (smORFs) in primary brown, white, and beige mouse adipocytes. Of these, we validated 85 MPs by proteomics, including 33 circulating MPs in mouse plasma. Analyses of MP-encoding mRNAs under different physiological conditions (high-fat diet) revealed that numerous MPs are regulated in adipose tissue in vivo and are co-expressed with established metabolic genes. Furthermore, Ribo-seq provided evidence for the translation of Gm8773, which encodes a secreted MP that is homologous to human and chicken FAM237B. Gm8773 is highly expressed in the arcuate nucleus of the hypothalamus, and intracerebroventricular administration of recombinant mFAM237B showed orexigenic activity in obese mice. Together, these data highlight the value of this adipocyte MP database in identifying MPs with roles in fundamental metabolic and physiological processes such as feeding.

Potential of Mean Force for Face-Face Interactions between Pairs of 2:1 Clay Mineral Platelets.

Bottom-up modeling of clay behavior from the molecular scale requires a detailed understanding of the free energy between pairs of clay platelets. We investigate the potential of mean force (PMF) for hydrated clays in face-to-face interactions with free energy perturbation (FEP) methods through molecular dynamics simulations using simple overlap sampling (SOS). We show that PMF results for open systems with one finite in-plane dimension are affected by migration of counterions from within the interlayer space compared with fully confined closed system conditions. We compare PMFs for two common 2:1 clay sheet minerals Illite (IMt-1) and Na-smectite. The PMFs for the open illite systems exhibit a strong attractive energy well at a basal layer separation, d = 11 Å and interlayer water content, wIL = ∼0.4% while the attractive minimum for the closed system occurs at d = 12 Å, wIL = 3.5%. In contrast, net repulsion occurs between pairs of Na-smectite platelets for both open and closed systems (for d < 15-16 Å). The free energy is closely related to the distribution of counterions; while K+ ions are bound closely to the surfaces of the illite platelets, Na+ ions are more spatially disperse. This PMF results contradict prior findings for Na-smectite and prompted further comparisons with other published results. We find that most of the published results do not represent accurately the free energy for face-face interactions between pairs of clay platelets that are effectively infinite (with width/thickness O[104]). The PMF results presented in this paper form a reliable basis for mesoscale, coarse-grained modeling of illite and smectite particle assemblies. We show that the Gay-Berne potential provides a reasonable first-order model for upscaling, while the solvation potential proposed by Masoumi enables a more accurate representation of the computed PMFs.

Effects of hydraulically disconnecting consumer pumps in an intermittent water supply.

We estimate 250 million people receive water using private pumps connected directly to intermittently pressurized distribution networks. Yet no previous studies have quantified the presumed effects of these pumps. In this paper, we investigate the effects of installing pressure-sustaining valves at consumer connections. These valves mimic pump disconnection by restricting flow. Installing these valves during the dry season at 94% of connections in an affluent neighborhood in Delhi, India, cut the prevalence of samples with turbidity > 4 NTU by two thirds. But considering the poor reputation of pumps, installed valves had surprisingly small average effects on turbidity (-8%; p<0.01) and free chlorine (+0.05 mg/L; p<0.001; N = 1,031). These effects were much smaller than the high variability in water quality supplied to both control and valve-installed neighborhoods. Site-specific responses to this variability could have confounded our results. At the study site, installed valves increased network pressure during 88% of the typical supply window; valves had a maximum pressure effect of +0.62 m (95% CI [0.54, 0.71]; a 40% increase vs. control). Further research is needed to generalize beyond our study site. Nevertheless, this paper provides unique evidence showing how the deployed valves mitigated pump effects, increased network pressure and improved water safety.

Microbial abundance and community composition in biofilms on in-pipe sensors in a drinking water distribution system.

Collecting biofilm samples from drinking water distribution systems (DWDSs) is challenging due to limited access to the pipes during regular operations. We report here the analysis of microbial communities in biofilm and water samples collected from sensors installed in a DWDS where monochloramine is used as a residual disinfectant. A total of 52 biofilm samples and 14 bulk water samples were collected from 17 pipe sections representing different water ages. Prokaryotic genome copies (bacterial and archaeal 16S rRNA genes, Mycobacterium spp., ammonia-oxidizing bacteria (AOB), and cyanobacteria) were quantified with droplet digital PCR, which revealed the abundance of these genes in both biofilm and water samples. Prokaryotic 16S rRNA gene sequencing analysis was carried out for a subset of the samples (12 samples from four sites). Mycobacterium and AOB species were dominant in the DWDS sections with low water age and sufficient residual monochloramine, whereas Nitrospira species (nitrite-oxidizing bacteria) dominated in the sections with higher water age and depleted monochloramine level, suggesting the occurrence of nitrification in the studied DWDS. The present study provides novel information on the abundance and identity of prokaryotes in biofilms and water in a full-scale operational DWDS.

Smokey the Beaver: beaver-dammed riparian corridors stay green during wildfire throughout the western United States.

Beaver dams are gaining popularity as a low-tech, low-cost strategy to build climate resiliency at the landscape scale. They slow and store water that can be accessed by riparian vegetation during dry periods, effectively protecting riparian ecosystems from droughts. Whether or not this protection extends to wildfire has been discussed anecdotally but has not been examined in a scientific context. We used remotely sensed Normalized Difference Vegetation Index (NDVI) data to compare riparian vegetation greenness in areas with and without beaver damming during wildfire. We include data from five large wildfires of varying burn severity and dominant landcover settings in the western United States in our analysis. We found that beaver-dammed riparian corridors are relatively unaffected by wildfire when compared to similar riparian corridors without beaver damming. On average, the decrease in NDVI during fire in areas without beaver is 3.05 times as large as it is in areas with beaver. However, plant greenness rebounded in the year after wildfire regardless of beaver activity. Thus, we conclude that, while beaver activity does not necessarily play a role in riparian vegetation post-fire resilience, it does play a significant role in riparian vegetation fire resistance and refugia creation.

Stereoscopic Display Is Superior to Conventional Display for Three-Dimensional Echocardiography of Congenital Heart Anatomy.

BACKGROUND: Three-dimensional echocardiography (3DE) improves visualization of cardiac lesions. Current viewing of 3DE studies on a conventional display diminishes the encoded stereoscopic (stereo) information for depth perception. This study aims to evaluate clinician subjective and objective experience of stereo display compared with nonstereo display of 3DE in congenital heart disease. METHODS: In this prospective study, 22 cardiologists, advanced cardiology trainees, and cardiothoracic surgeons used a commercially available stereo display system with proprietary software to view 10 3DE data sets, alternating between simple and complex lesions. In part A, participants viewed each data set, randomized to 1 minute of stereo display followed by 1 minute of nonstereo display, or vice versa. In part B, participants could freely toggle between stereo and nonstereo display for an additional 90 seconds per data set. Participants answered a series of questions and rated their subjective experience using stereo versus nonstereo display mode on a Likert scale. Objective data on time spent in each display mode during part B and duration of interaction and degree of movement of the 3DE data set in parts A and B were also collected. RESULTS: All clinician groups found stereo display preferable to nonstereo display of 3DE (P < .0001). Viewing complex lesions was rated lower than simple lesions when using nonstereo display (P < .01). Simple and complex lesions were equally well rated when using stereo display (P = .14). When given a choice of display modes in part B, participants spent more time in stereo display (P < .0001) and interacted more with the 3DE data sets in stereo display (P < .0001). CONCLUSIONS: Interactive stereoscopic display of 3DE was preferred over conventional nonstereo display by all clinician groups for viewing both simple and complex lesions. This preference is especially true for viewing complex lesions.

Reelin is modulated by diet-induced obesity and has direct actions on arcuate proopiomelanocortin neurons.

OBJECTIVE: Reelin (RELN) is a large glycoprotein involved in synapse maturation and neuronal organization throughout development. Deficits in RELN signaling contribute to multiple psychological disorders, such as autism spectrum disorder, schizophrenia, and bipolar disorder. Nutritional stress alters RELN expression in brain regions associated with these disorders; however, the involvement of RELN in the neural circuits involved in energy metabolism is unknown. The RELN receptors apolipoprotein E receptor 2 (ApoER2) and very low-density lipoprotein receptor (VLDLR) are involved in lipid metabolism and expressed in the hypothalamus. Here we explored the involvement of RELN in hypothalamic signaling and the impact of diet-induced obesity (DIO) on this system. METHODS: Adult male mice were fed a chow diet or maintained on a high-fat diet (HFD) for 12-16 weeks. HFD-fed DIO mice exhibited decreased ApoER2 and VLDLR expression and increased RELN protein in the hypothalamus. Electrophysiology was used to determine the mechanism by which the central fragment of RELN (CF-RELN) acts on arcuate nucleus (ARH) satiety-promoting proopiomelanocortin (POMC) neurons and the impact of DIO on this circuitry. RESULTS: CF-RELN exhibited heterogeneous presynaptic actions on inhibitory inputs onto ARH-POMC-EGFP neurons and consistent postsynaptic actions. Additionally, central administration of CF-RELN caused a significant increase in ARH c-Fos expression and an acute decrease in food intake and body weight. CONCLUSIONS: We conclude that RELN signaling is modulated by diet, that RELN is involved in synaptic signaling onto ARH-POMC neurons, and that altering central CF-RELN levels can impact food intake and body weight.

Adipocyte-secreted BMP8b mediates adrenergic-induced remodeling of the neuro-vascular network in adipose tissue.

Activation of brown adipose tissue-mediated thermogenesis is a strategy for tackling obesity and promoting metabolic health. BMP8b is secreted by brown/beige adipocytes and enhances energy dissipation. Here we show that adipocyte-secreted BMP8b contributes to adrenergic-induced remodeling of the neuro-vascular network in adipose tissue (AT). Overexpression of bmp8b in AT enhances browning of the subcutaneous depot and maximal thermogenic capacity. Moreover, BMP8b-induced browning, increased sympathetic innervation and vascularization of AT were maintained at 28 °C, a condition of low adrenergic output. This reinforces the local trophic effect of BMP8b. Innervation and vascular remodeling effects required BMP8b signaling through the adipocytes to 1) secrete neuregulin-4 (NRG4), which promotes sympathetic axon growth and branching in vitro, and 2) induce a pro-angiogenic transcriptional and secretory profile that promotes vascular sprouting. Thus, BMP8b and NRG4 can be considered as interconnected regulators of neuro-vascular remodeling in AT and are potential therapeutic targets in obesity.

Multiview Three-Dimensional Echocardiography Image Fusion Using a Passive Measurement Arm.

Three-dimensional (3D) echocardiography offers a fast and efficient way to scan and assess the structures and function of the heart. However, due to limitations inherent to 3D echocardiography such as limited field-of-view and low signal-to-noise ratio, 3D assessment of the heart is performed only in a minority of patients who undergo transthoracic echocardiography. One approach for improving the field-of-view and image quality is to scan the heart from multiple locations by moving the transducer and fusing the resulting images into a single volume, which requires 3D alignment of individual volumetric echocardiography scans. Previous approaches relied on optical or electromagnetic trackers for transducer tracking. This study proposes a passive measurement arm system for tracking the position of the ultrasound transducer and thereby aligning multiple echocardiography scans. The proposed system does not suffer from line-of-sight limitation as in the case of an optical tracking based fusion system. Additionally, in contrast to an electromagnetic based tracking system, measurement arm measurements are not affected by other ferromagnetic materials in the vicinity. The proposed approach was tested by scanning a heart phantom and fusing nine echocardiography volumes acquired from different locations. The fusion of all nine scans yielded a percentage field-of-view improvement of 98.5%.

Analytical scaling relations to evaluate leakage and intrusion in intermittent water supply systems.

Intermittent water supplies (IWS) deliver piped water to one billion people; this water is often microbially contaminated. Contaminants that accumulate while IWS are depressurized are flushed into customers' homes when these systems become pressurized. In addition, during the steady-state phase of IWS, contaminants from higher-pressure sources (e.g., sewers) may continue to intrude where pipe pressure is low. To guide the operation and improvement of IWS, this paper proposes an analytic model relating supply pressure, supply duration, leakage, and the volume of intruded, potentially-contaminated, fluids present during flushing and steady-state. The proposed model suggests that increasing the supply duration may improve water quality during the flushing phase, but decrease the subsequent steady-state water quality. As such, regulators and academics should take more care in reporting if water quality samples are taken during flushing or steady-state operational conditions. Pipe leakage increases with increased supply pressure and/or duration. We propose using an equivalent orifice area (EOA) to quantify pipe quality. This provides a more stable metric for regulators and utilities tracking pipe repairs. Finally, we show that the volume of intruded fluid decreases in proportion to reductions in EOA. The proposed relationships are applied to self-reported performance indicators for IWS serving 108 million people described in the IBNET database and in the Benchmarking and Data Book of Water Utilities in India. This application shows that current high-pressure, continuous water supply targets will require extensive EOA reductions. For example, in order to achieve national targets, utilities in India will need to reduce their EOA by a median of at least 90%.

Benefits of Genomic Insights and CRISPR-Cas Signatures to Monitor Potential Pathogens across Drinking Water Production and Distribution Systems.

The occurrence of pathogenic bacteria in drinking water distribution systems (DWDSs) is a major health concern, and our current understanding is mostly related to pathogenic species such as Legionella pneumophila and Mycobacterium avium but not to bacterial species closely related to them. In this study, genomic-based approaches were used to characterize pathogen-related species in relation to their abundance, diversity, potential pathogenicity, genetic exchange, and distribution across an urban drinking water system. Nine draft genomes recovered from 10 metagenomes were identified as Legionella (4 draft genomes), Mycobacterium (3 draft genomes), Parachlamydia (1 draft genome), and Leptospira (1 draft genome). The pathogenicity potential of these genomes was examined by the presence/absence of virulence machinery, including genes belonging to Type III, IV, and VII secretion systems and their effectors. Several virulence factors known to pathogenic species were detected with these retrieved draft genomes except the Leptospira-related genome. Identical clustered regularly interspaced short palindromic repeats-CRISPR-associated proteins (CRISPR-Cas) genetic signatures were observed in two draft genomes recovered at different stages of the studied system, suggesting that the spacers in CRISPR-Cas could potentially be used as a biomarker in the monitoring of Legionella related strains at an evolutionary scale of several years across different drinking water production and distribution systems. Overall, metagenomics approach was an effective and complementary tool of culturing techniques to gain insights into the pathogenic characteristics and the CRISPR-Cas signatures of pathogen-related species in DWDSs.

Hypothalamic AMPK-ER Stress-JNK1 Axis Mediates the Central Actions of Thyroid Hormones on Energy Balance.

Thyroid hormones (THs) act in the brain to modulate energy balance. We show that central triiodothyronine (T3) regulates de novo lipogenesis in liver and lipid oxidation in brown adipose tissue (BAT) through the parasympathetic (PSNS) and sympathetic nervous system (SNS), respectively. Central T3 promotes hepatic lipogenesis with parallel stimulation of the thermogenic program in BAT. The action of T3 depends on AMP-activated protein kinase (AMPK)-induced regulation of two signaling pathways in the ventromedial nucleus of the hypothalamus (VMH): decreased ceramide-induced endoplasmic reticulum (ER) stress, which promotes BAT thermogenesis, and increased c-Jun N-terminal kinase (JNK) activation, which controls hepatic lipid metabolism. Of note, ablation of AMPKα1 in steroidogenic factor 1 (SF1) neurons of the VMH fully recapitulated the effect of central T3, pointing to this population in mediating the effect of central THs on metabolism. Overall, these findings uncover the underlying pathways through which central T3 modulates peripheral metabolism.

Nat1 Deficiency Is Associated with Mitochondrial Dysfunction and Exercise Intolerance in Mice.

We recently identified human N-acetyltransferase 2 (NAT2) as an insulin resistance (IR) gene. Here, we examine the cellular mechanism linking NAT2 to IR and find that Nat1 (mouse ortholog of NAT2) is co-regulated with key mitochondrial genes. RNAi-mediated silencing of Nat1 led to mitochondrial dysfunction characterized by increased intracellular reactive oxygen species and mitochondrial fragmentation as well as decreased mitochondrial membrane potential, biogenesis, mass, cellular respiration, and ATP generation. These effects were consistent in 3T3-L1 adipocytes, C2C12 myoblasts, and in tissues from Nat1-deficient mice, including white adipose tissue, heart, and skeletal muscle. Nat1-deficient mice had changes in plasma metabolites and lipids consistent with a decreased ability to utilize fats for energy and a decrease in basal metabolic rate and exercise capacity without altered thermogenesis. Collectively, our results suggest that Nat1 deficiency results in mitochondrial dysfunction, which may constitute a mechanistic link between this gene and IR.

Soluble LR11/SorLA represses thermogenesis in adipose tissue and correlates with BMI in humans.

Thermogenesis in brown adipose tissue (BAT) is an important component of energy expenditure in mammals. Recent studies have confirmed its presence and metabolic role in humans. Defining the physiological regulation of BAT is therefore of great importance for developing strategies to treat metabolic diseases. Here we show that the soluble form of the low-density lipoprotein receptor relative, LR11/SorLA (sLR11), suppresses thermogenesis in adipose tissue in a cell-autonomous manner. Mice lacking LR11 are protected from diet-induced obesity associated with an increased browning of white adipose tissue and hypermetabolism. Treatment of adipocytes with sLR11 inhibits thermogenesis via the bone morphogenetic protein/TGFß signalling pathway and reduces Smad phosphorylation. In addition, sLR11 levels in humans are shown to positively correlate with body mass index and adiposity. Given the need for tight regulation of a tissue with a high capacity for energy wastage, we propose that LR11 plays an energy conserving role that is exaggerated in states of obesity.

Flexible Reconfiguration of Existing Urban Water Infrastructure Systems.

This paper presents a practical methodology for the flexible reconfiguration of existing water distribution infrastructure, which is adaptive to the water utility constraints and facilitates in operational management for pressure and water loss control. The network topology is reconfigured into a star-like topology, where the center node is a connected subset of transmission mains, that provides connection to water sources, and the nodes are the subsystems that are connected to the sources through the center node. In the proposed approach, the system is first decomposed into the main and subsystems based on graph theory methods and then the network reconfiguration problem is approximated as a single-objective linear programming problem, which is efficiently solved using a standard solver. The performance and resiliency of the original and reconfigured systems are evaluated through direct and surrogate measures. The methodology is demonstrated using two large-scale water distribution systems, showing the flexibility of the proposed approach. The results highlight the benefits and disadvantages of network decentralization.

Light and chemical control of neuronal circuits: possible applications in neurotherapy.

Millions of people worldwide suffer from diseases that result from a failure of central pathways to regulate behavioral and physiological processes. Advances in genetics and pharmacology have already allowed us to appreciate that rather than this dysregulation being systemic throughout the brain, it is usually rooted in specific subsets of dysfunctional cells within discrete neurological circuits. This article discusses the advent of opto- and chemogenetic tools and how they are providing the means to dissect these circuits with a degree of temporal and spatial sensitivity not previously possible. We also highlight the potential applications for treating disease and the key developments likely to have the greatest impact over the next 5 years.

Pharmacological strategies for targeting BAT thermogenesis.

Biopsies following positron emission tomography coupled to computer tomography (PET-CT) imaging have confirmed the presence of thermogenically active brown adipose tissue (BAT) in adult humans, leading to suggestions that it could be stimulated to treat obesity and its associated morbidities. The mechanisms regulating thermogenesis in BAT are better understood than ever before, and many new hypotheses for increasing the amount of brown fat or its activity are currently being explored. The challenge now is to identify safe ways to manipulate specific aspects of the physiological regulation of thermogenesis, in a manner that will be bioenergetically effective. This review outlines the nature of these regulatory mechanisms both in terms of their cellular specificity and probable effectiveness given the physiological paradigms in which thermogenesis is activated. Similarly, their potential for being targeted by new or existing drugs is discussed, drawing on the known mechanisms of action of various pharmacological agents and some probable limitations that should be considered.

When BAT is lacking, WAT steps up.

Brown adipose tissue (BAT) has evolved to generate heat to maintain core body temperature, but it is also of great importance for the regulation of energy balance. In addition to BAT, mammals can induce the formation of "brown adipocyte-like" or "beige" fat cells in white adipose tissue and understanding their regulation could have implications for the treatment of metabolic diseases.