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1.
Proc Natl Acad Sci U S A ; 118(24)2021 06 15.
Article in English | MEDLINE | ID: mdl-34099569

ABSTRACT

Cities seek nuanced understanding of intraurban inequality in energy use, addressing both income and race, to inform equitable investment in climate actions. However, nationwide energy consumption surveys are limited (<6,000 samples in the United States), and utility-provided data are highly aggregated. Limited prior analyses suggest disparity in energy use intensity (EUI) by income is ∼25%, while racial disparities are not quantified nor unpacked from income. This paper, using new empirical fine spatial scale data covering all 200,000 households in two US cities, along with separating temperature-sensitive EUI, reveals intraurban EUI disparities up to a factor of five greater than previously known. We find 1) annual EUI disparity ratios of 1.27 and 1.66, comparing lowest- versus highest-income block groups (i.e., 27 and 66% higher), while previous literature indicated only ∼25% difference; 2) a racial effect distinct from income, wherein non-White block groups (highest quintile non-White percentage) in the lowest-income stratum reported up to a further ∼40% higher annual EUI than less diverse block groups, providing an empirical estimate of racial disparities; 3) separating temperature-sensitive EUI unmasked larger disparities, with heating-cooling electricity EUI of lowest-income block groups up to 2.67 times (167% greater) that of highest income, and high racial disparity within lowest-income strata wherein high non-White (>75%) population block groups report EUI up to 2.56 times (156% larger) that of majority White block groups; and 4) spatial scales of data aggregation impact inequality measures. Quadrant analyses are developed to guide spatial prioritization of energy investment for carbon mitigation and equity. These methods are potentially translatable to other cities and utilities.

2.
Nat Commun ; 5: 3502, 2014 Mar 20.
Article in English | MEDLINE | ID: mdl-24651317

ABSTRACT

Island biogeography is fundamental to understanding colonization, speciation and extinction. Remote volcanic archipelagoes represent ideal natural laboratories to study biogeography because they offer a discrete temporal and spatial context for colonization and speciation. The moth genus Hyposmocoma is one of very few lineages that diversified across the entire Hawaiian Archipelago, giving rise to over 400 species, including many restricted to the remote northwestern atolls and pinnacles, remnants of extinct volcanoes. Here, we report that Hyposmocoma is ~15 million years old, in contrast with previous studies of the Hawaiian biota, which have suggested that most lineages colonized the archipelago after the emergence of the current high islands (~5 Myr ago). We show that Hyposmocoma has dispersed from the remote Northwestern Hawaiian Islands to the current high islands more than 20 times. The ecological requirements of extant groups of Hyposmocoma provide insights into vanished ecosystems on islands that have long since eroded.


Subject(s)
Evolution, Molecular , Genetic Variation , Moths/genetics , Phylogeny , Animals , Carbamoyl-Phosphate Synthase (Ammonia)/genetics , Ecosystem , Electron Transport Complex IV/genetics , Geography , Hawaii , Insect Proteins/genetics , Malate Dehydrogenase/genetics , Molecular Sequence Data , Moths/classification , Peptide Elongation Factor 1/genetics , Population Dynamics , Ribosomal Proteins/genetics , Sequence Analysis, DNA , Time Factors
3.
Sensors (Basel) ; 13(9): 12392-405, 2013 Sep 13.
Article in English | MEDLINE | ID: mdl-24064603

ABSTRACT

Model membrane approaches have attracted much attention in biomedical sciences to investigate and simulate biological processes. The application of model membrane systems for biosensor measurements is partly restricted by the fact that the integrity of membranes critically depends on the maintenance of an aqueous surrounding, while various biosensors require a preconditioning of dry sensors. This is for example true for the well-established surface acoustic wave (SAW) biosensor SAM®5 blue. Here, a simple drying procedure of sensor-supported model membranes is introduced using the protective disaccharide trehalose. Highly reproducible model membranes were prepared by the Langmuir-Blodgett technique, transferred to SAW sensors and supplemented with a trehalose solution. Membrane rehydration after dry incorporation into the SAW device becomes immediately evident by phase changes. Reconstituted model membranes maintain their full functionality, as indicated by biotin/avidin binding experiments. Atomic force microscopy confirmed the morphological invariability of dried and rehydrated membranes. Approximating to more physiological recognition phenomena, the site-directed immobilization of the integrin VLA-4 into the reconstituted model membrane and subsequent VCAM-1 ligand binding with nanomolar affinity were illustrated. This simple drying procedure is a novel way to combine the model membrane generation by Langmuir-Blodgett technique with SAW biosensor measurements, which extends the applicability of SAM®5 blue in biomedical sciences.


Subject(s)
Biomimetics/instrumentation , Biosensing Techniques/instrumentation , Immunoassay/instrumentation , Lipid Bilayers/chemistry , Membranes, Artificial , Micro-Electrical-Mechanical Systems/instrumentation , Equipment Design , Equipment Failure Analysis , Reproducibility of Results , Sensitivity and Specificity
5.
Thromb Res ; 129(5): 603-10, 2012 May.
Article in English | MEDLINE | ID: mdl-22099706

ABSTRACT

INTRODUCTION: The integrin VLA-4-mediated binding is important for the metastatic dissemination of melanoma cells. Recently we found that heparin possesses a binding capacity to VLA-4. This could contribute to the heparin function to attenuate metastasis in a selectin-dependent manner. Aiming to a purposive, anti-adhesive heparin application, structural requirements of heparin for VLA-4 recognition have to be elucidated. MATERIALS AND METHODS: A series of non-anticoagulant heparin derivatives were investigated concerning their inhibitory capacities for VLA-4 mediated binding of human melanoma MV3 cells to VCAM-1 under physiological flow conditions in vitro. A surface acoustic wave biosensor was applied to detect kinetic constants of selected derivatives binding to both, VLA-4 or P- and L-selectin. RESULTS: Experimental metastasis of MV3 cells in mice confirmed the relevance of VLA-4 for metastatic dissemination. LMWHs (enoxaparin, tinzaparin) efficiently blocked VLA-4 cell binding, dominantly via the integrin`s α-chain. Desulfation at 2-O-position, N-acetylation or a size smaller than tetradecasaccharide disfavoured VLA-4 inhibition. Glycol-splitting of heparin and thus higher chain flexibility is a tolerable parameter. A derivative with 50% 6-O-desulfation appeared promising and exceeded tinzaparin in VLA-4 inhibition, both compounds displayed binding affinities to VLA-4 in the low micromolar range. CONCLUSIONS: These findings provide structure-activity relationships for heparin VLA-4 binding, which partly differ from P- and L-selectin requirements. The data confirm that anti-coagulative and anti-adhesive function of heparin can be distinguished favouring applications of non-anticoagulant heparins in antimetastatic approaches without the risk of bleeding complications. The 50% 6-O-desulfated heparin-derivative appears promising to further evaluate the interference with selectin and VLA-4 binding functions in vivo.


Subject(s)
Anticoagulants/metabolism , Heparin/analogs & derivatives , Integrin alpha4beta1/antagonists & inhibitors , Melanoma/drug therapy , Melanoma/metabolism , Acetylation , Animals , Antibodies, Monoclonal, Humanized/pharmacology , Anticoagulants/pharmacology , Cell Adhesion/physiology , Cell Line, Tumor , Disease Models, Animal , Enoxaparin/chemistry , Enoxaparin/pharmacokinetics , Enoxaparin/pharmacology , Female , Gene Knockdown Techniques , Heparin/chemistry , Heparin/pharmacokinetics , Heparin/pharmacology , Heparin, Low-Molecular-Weight/chemistry , Heparin, Low-Molecular-Weight/pharmacokinetics , Heparin, Low-Molecular-Weight/pharmacology , Humans , Integrin alpha4beta1/genetics , Integrin alpha4beta1/metabolism , Melanoma/pathology , Mice , Natalizumab , Neoplasm Metastasis , RNA, Small Interfering/administration & dosage , RNA, Small Interfering/genetics , Structure-Activity Relationship , Tinzaparin , Vascular Cell Adhesion Molecule-1/chemistry , Vascular Cell Adhesion Molecule-1/metabolism
6.
Proc Natl Acad Sci U S A ; 107(13): 5903-6, 2010 Mar 30.
Article in English | MEDLINE | ID: mdl-20308549

ABSTRACT

Insects are the most diverse form of life on the planet, dominating both terrestrial and freshwater ecosystems, yet no species has a life stage able to breath, feed, and develop either continually submerged or without access to water. Such truly amphibious insects are unrecorded. In mountain streams across the Hawaiian Islands, some caterpillars in the endemic moth genus Hyposmocoma are truly amphibious. These larvae can breathe and feed indefinitely both above and below the water's surface and can mature completely submerged or dry. Remarkably, a molecular phylogeny based on 2,243 bp from both nuclear (elongation factor 1alpha and carbomoylphosphate synthase) and mitochondrial (cytochrome oxidase I) genes representing 216 individuals and 89 species of Hyposmocoma reveals that this amphibious lifestyle is an example of parallel evolution and has arisen from strictly terrestrial clades at least three separate times in the genus starting more than 6 million years ago, before the current high islands existed. No other terrestrial genus of animals has sponsored so many independent aquatic invasions, and no other insects are able to remain active indefinitely above and below water. Why and how Hyposmocoma, an overwhelmingly terrestrial group, repeatedly evolved unprecedented aquatic species is unclear, although there are many other evolutionary anomalies across the Hawaiian archipelago. The uniqueness of the community assemblages of Hawaii's isolated biota is likely critical in generating such evolutionary novelty because this amphibious ecology is unknown anywhere else.


Subject(s)
Ecosystem , Evolution, Molecular , Moths/classification , Moths/genetics , Animals , Environment , Genes, Insect , Hawaii , Marine Biology , Models, Genetic , Molecular Sequence Data , Phylogeny , Time Factors
7.
Thromb Haemost ; 102(5): 816-22, 2009 Nov.
Article in English | MEDLINE | ID: mdl-19888514

ABSTRACT

Heparin possesses antimetastatic effects that were related to various molecular mechanisms beyond anticoagulant activities. The ability of heparin to interfere with the function of adhesion receptors in the metastatic course appears as a promising therapeutic approach. This refers to numerous findings that heparin attenuates metastasis in a selectin-dependent manner. We recently demonstrated that heparin interferes with the integrin VLA-4 on murine melanoma cells binding to VCAM-1. To confirm this activity and to obtain further insight into molecular recognition of heparin by VLA-4, we investigated the inhibition of VLA-4 mediated binding of human melanoma MV3 cells to immobilised VCAM-1 by different heparins. The size of heparin has an important impact on inhibition. Unfractionated heparin (UFH) and tinzaparin, a low-molecular-weight heparin (LMWH) representing a mean of about 18-20 monomers, displayed high inhibitory activity. Fractionating tinzaparin to 14-18 monomers reduced inhibition slightly, while the pentasaccharide fondaparinux was without effects. To confirm molecular recognition of tinzaparin by VLA-4, a surface acoustic wave-biosensor was applied. A VLA-4 containing membrane preparation of MV3 cells was immobilised at the sensors to allow for detection of kinetic binding constants of tinzaparin compared to VCAM-1. Tinzaparin binds to VLA-4 with affinity in the low micromolar range (4.61 x 10(-6) M), which clearly indicates specific molecular recognition. Furthermore, tinzaparin displays a nearly identical k(off) compared to VCAM-1 (5.13 x 10(-3) s(-1) versus 3.44 x 10(-3) s(-1)) which is evident for interference with the ligand binding. The data provide evidence for a direct confirmation of heparin binding to VLA-4 and thus, contribute to understand the antimetastatic activity of heparin.


Subject(s)
Cell Adhesion/drug effects , Heparin, Low-Molecular-Weight/pharmacology , Heparin/metabolism , Integrin alpha4beta1/metabolism , Melanoma/pathology , Acoustics , Antibodies, Monoclonal/metabolism , Antibodies, Monoclonal, Humanized , Biosensing Techniques , Cell Line/drug effects , Cell Line, Tumor/cytology , Cell Line, Tumor/drug effects , Drug Screening Assays, Antitumor , Endothelial Cells/cytology , Endothelial Cells/drug effects , Fondaparinux , Heparin/pharmacology , Heparin, Low-Molecular-Weight/chemistry , Humans , In Vitro Techniques , Integrin alpha4beta1/drug effects , Natalizumab , Neoplasm Metastasis , P-Selectin/antagonists & inhibitors , Polysaccharides/pharmacology , Recombinant Fusion Proteins/metabolism , Rheology , Tinzaparin , Tumor Necrosis Factor-alpha/pharmacology , Vascular Cell Adhesion Molecule-1/chemistry , Vascular Cell Adhesion Molecule-1/metabolism
8.
J Magn Reson Imaging ; 29(1): 141-5, 2009 Jan.
Article in English | MEDLINE | ID: mdl-19097115

ABSTRACT

PURPOSE: To compare an automated scan planning method to manual scan positioning in routine knee magnetic resonance imaging (MRI) studies. MATERIALS AND METHODS: The automated scan planning method uses anatomical landmarks in a 3D survey of the knee. The method is trained by example plannings, consisting of manual slice positioning by an experienced technologist in 15 MRI studies. Automated knee MR examinations obtained in three geometries in 50 consecutive patients were compared to those obtained in 50 consecutive control patients, where imaging planes were planned manually. Anatomical coverage and slice angulation were scored for each geometry on a 4-grade scale by an experienced radiologist blinded to the way of planning; groups were compared using a Mann-Whitney U-test. RESULTS: In 150 automated sequences the technologist adapted slice positioning in four cases (addition of slices to adapt to the size of the knee), representing the only automated sequences that received a poor rating. Thirteen sequences with manual planning received a poor rating. No difference in quality was found (P > 0.05) between automated and manual plannings for coronal coverage, sagittal coverage and angulation, and transverse angulation. Rating of automated planning was higher for transverse coverage, but lower than manual planning for coronal angulation. CONCLUSION: Automated sequence prescription for knee MRI is feasible in clinical practice, with similar quality as manual positioning.


Subject(s)
Algorithms , Artificial Intelligence , Image Enhancement/methods , Image Interpretation, Computer-Assisted/methods , Imaging, Three-Dimensional/methods , Knee Joint/anatomy & histology , Magnetic Resonance Imaging/methods , Pattern Recognition, Automated/methods , Humans , Observer Variation , Reproducibility of Results , Sensitivity and Specificity
9.
Philos Trans R Soc Lond B Biol Sci ; 363(1508): 3453-8, 2008 Oct 27.
Article in English | MEDLINE | ID: mdl-18765358

ABSTRACT

To gain insight into the early stages of speciation, we reconstructed a DNA-based phylogeny, using combined mitochondrial (cytochrome c oxidase subunits I and II: 1008 bp) and nuclear (elongation factor 1-alpha and wingless: 1062 bp) markers of populations of the moth Galagete darwini endemic to the Galápagos, which belongs to an insular radiation similar in size to that of Darwin's finches. Adults of G. darwini were collected in the arid lowlands of 11 of the Galápagos Islands (Baltra, Española, Fernandina, Floreana, Isabela, Pinta, Pinzón, San Cristobal, Santa Cruz, Santiago and Seymour) and the humid highlands of a subset of 5 of them (Fernandina, Floreana, Isabela, Santa Cruz and Santiago). The combined phylogeographic analysis surprisingly revealed that G. darwini populations at higher elevation on the western islands (Fernandina, Isabela and Santiago) represent a distinct lineage from the one in the low arid zones of these same islands. This is the first reported case in the archipelago of genetic cryptic differentiation correlated with elevation on the western Galápagos volcanoes.


Subject(s)
Environment , Genetic Speciation , Genetic Variation , Moths/genetics , Phylogeny , Animals , Base Sequence , DNA, Mitochondrial/genetics , Ecuador , Geography , Likelihood Functions , Models, Genetic , Molecular Sequence Data , Sequence Analysis, DNA
10.
Mol Phylogenet Evol ; 45(1): 180-92, 2007 Oct.
Article in English | MEDLINE | ID: mdl-17604184

ABSTRACT

Galagete is a genus of microlepidoptera including 12 nominate species endemic to the Galapagos Islands. In order to better understand the diversification of this endemic insular radiation, to unravel relationships among species and populations, and to get insight into the early stages of speciation, we developed a phylogenetic reconstruction based on the combined mitochondrial cytochrome oxidase I (555bp) and II (453bp), and the nuclear elongation factor-1alpha (711bp) and wingless (351bp) genes. Monophyly of the genus is strongly supported in the Bayesian and maximum likelihood analyses suggesting a single colonization event by a common ancestor. Two cases of paraphyly observed between species are hypothesized to represent imperfect species limits for G. espanolaensis nested within the G. turritella clade, and introgressive hybridization or lineage sorting in the case of the population of G. protozona from Santa Fe nested within the G. gnathodoxa clade. A geologically calibrated, relaxed molecular clock model was used for the first time to unravel the chronological sequence of an insular radiation. The first split occurring within the Galagete lineage on the archipelago is estimated at 3.3+/-0.4million years ago. The genus radiated relatively quickly in about 1.8million years, and gives an estimated speciation rate of 0.8 species per million years. Although the colonization scenario shows a stochastic dispersal pattern, the arrival of the ancestor and the diversification of the radiation coincide with the chronological emergence of the major islands.


Subject(s)
Evolution, Molecular , Genes, Mitochondrial , Moths/genetics , Moths/radiation effects , Phylogeny , Radiation , Animals , Cell Nucleus/genetics , Ecuador , Sequence Analysis, DNA , Time Factors
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