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Malaria is a serious infectious disease that leads to massive casualties globally. Myanmar is a key battleground for the global fight against malaria because it is where the emergence of drug-resistant malaria parasites has been documented. Controlling the spread of malaria in Myanmar thus carries global significance, because the failure to do so would lead to devastating consequences in vast areas where malaria is prevalent in tropical/subtropical regions around the world. Thanks to its wide and consistent spatial coverage, remote sensing has become increasingly used in the public health domain. Specifically, remote sensing-based land cover/land use (LCLU) maps present a powerful tool that provides critical information on population distribution and on the potential human-vector interactions interfaces on a large spatial scale. Here, we present a 30-meter LCLU map that was created specifically for the malaria control and eradication efforts in Myanmar. This bottom-up approach can be modified and customized to other vector-borne infectious diseases in Myanmar or other Southeastern Asian countries.

Global estimates of burned areas, enabled by the wide-open access to the standard data products from the Moderate Resolution Imaging Spectroradiometer (MODIS), are heavily relied on by scientists and managers studying issues related to wildfire occurrence and its worldwide consequences. While these datasets, particularly the MODIS MCD64A1 product, have fundamentally improved our understanding of wildfire regimes at the global scale, their performance may be less reliable in certain regions due to a series of region- or ecosystem-specific challenges. Previous studies have indicated that global burned area products tend to underestimate the extent of the burned area within some parts of the boreal domain. Despite this, global products are still being regularly used by research activities and management efforts in the northern regions, likely due to a lack of understanding of the spatial scale of their Arctic-specific limitations, as well as an absence of more reliable alternative products. In this study, we evaluated the performance of two widely used global burned area products, MCD64A1 and FireCCI51, in the circumpolar boreal forests and tundra between 2001 and 2015. Our two-step evaluation shows that MCD64A1 has high commission and omission errors in mapping burned areas in the boreal forests and tundra regions in North America. The omission error overshadows the commission error, leading to MCD64A1 considerably underestimating burned areas in these high northern latitude domains. Based on our estimation, MCD64A1 missed nearly half the total burned areas in the Alaskan and Canadian boreal forests and the tundra during the 15-year period, amounting to an area (74,768 km2) that is equivalent to the land area of the United States state of South Carolina. While the FireCCI51 product performs much better than MCD64A1 in terms of commission error, we found that it also missed about 40% of burned areas in North America north of 60° N between 2001 and 2015. Our intercompar

While remotely sensed images of various resolutions have been widely used in identifying changes in urban and peri-urban environments, only very high resolution (VHR) imagery is capable of providing the information needed for understanding the changes taking place in remote rural environments, due to the small footprints and low density of man-made structures in these settings. However, limited by data availability, mapping man-made structures and conducting subsequent change detections in remote areas are typically challenging and thus require a certain level of flexibility in algorithm design that takes into account the specific environmental and image conditions. In this study, we mapped all buildings and corrals for two remote villages in Mozambique based on two single-date VHR images that were taken in 2004 and 2012, respectively. Our algorithm takes advantage of the presence of shadows and, through a fusion of both spectra- and object-based analysis techniques, is able to differentiate buildings with metal and thatch roofs with high accuracy (overall accuracy of 86% and 94% for 2004 and 2012, respectively). The comparison of the mapping results between 2004 and 2012 reveals multiple lines of evidence suggesting that both villages, while differing in many aspects, have experienced substantial increases in the economic status. As a case study, our project demonstrates the capability of a coupling of VHR imagery with locally adjusted classification algorithms to infer the economic development of small, remote rural settlements.

Organs are sculpted by extracellular as well as cell-intrinsic forces, but how collective cell dynamics are orchestrated in response to environmental cues is poorly understood. Here we apply advanced image analysis to reveal extracellular matrix-responsive cell behaviors that drive elongation of the Drosophila follicle, a model system in which basement membrane stiffness instructs three-dimensional tissue morphogenesis. Through in toto morphometric analyses of wild type and round egg mutants, we find that neither changes in average cell shape nor oriented cell division are required for appropriate organ shape. Instead, a major element is the reorientation of elongated cells at the follicle anterior. Polarized reorientation is regulated by mechanical cues from the basement membrane, which are transduced by the Src tyrosine kinase to alter junctional E-cadherin trafficking. This mechanosensitive cellular behavior represents a conserved mechanism that can elongate edgeless tubular epithelia in a process distinct from those that elongate bounded, planar epithelia.

Cell migration is indispensable to morphogenesis and homeostasis. Live imaging allows mechanistic insights, but long-term observation can alter normal biology, and tools to track movements in vivo without perturbation are lacking. We develop here a tool called M-TRAIL (matrix-labeling technique for real-time and inferred location), which reveals migration histories in fixed tissues. Using clones that overexpress GFP-tagged extracellular matrix (ECM) components, motility trajectories are mapped based on durable traces deposited onto basement membrane. We applied M-TRAIL to Drosophila follicle rotation, comparing in vivo and ex vivo migratory dynamics. The rate, trajectory, and cessation of rotation in wild-type (WT) follicles measured in vivo and ex vivo were identical, as was rotation failure in fat2 mutants. However, follicles carrying intracellularly truncated Fat2, previously reported to lack rotation ex vivo, in fact rotate in vivo at a reduced speed, thus revalidating the hypothesis that rotation is required for tissue elongation. The M-TRAIL approach could be applied to track and quantitate in vivo cell motility in other tissues and organisms.

Elongation of a tissue along one body axis is a conserved morphogenetic process that happens repeatedly during embryo and organ morphogenesis. While the mechanisms of tissue elongation in 2D sheet-like tissues are increasingly well understood, the molecular and cellular mechanisms that elongate topologically distinct tubular and acinar organs may be distinct. In this dissertation, I utilize Drosophila egg chamber (follicle) morphogenesis in the adult female ovary as a model system to understand tissue elongation in the unbounded tube-like organs. The follicle grows spherically during early oogenesis and then elongates during mid-oogenesis along the anterior-posterior axis to become an ellipsoidal organ. Whole-tissue rotation of the follicle during the elongation phase is thought to provide Planar Cell Polarity (PCP) information that orients basal actin bundles and basement membrane Collagen IV fibrils around the circumference, through a process requiring the atypical cadherin Fat2. Despite its essential role in the process, how Fat2 regulates PCP symmetry-breaking to specify rotation in one chirality was unresolved. With long-term live imaging, I showed that the follicle initiates rotation immediately after it buds off from the germarium. To trace the earliest sign of chiral symmetry-breaking, I developed an in toto 3D image analysis platform to comprehensively chart the cytoskeletal PCP in curved structures. In collaboration with my labmate Katherine Lipari, we found that microtubule growth polarity exhibits a bias within the germarium, prior to follicle budding and rotation. This germarial microtubule bias is dependent on Fat2, and provides chiral information that breaks the PCP symmetry prior to rotation. We propose a PCP relay mechanism that initiates from germarial microtubule chirality, to rotational polarity and actin bundle alignment, to finally a polarized basement membrane organization that elongates the organ.The limitations of current ex vivo cultures fo

Planar cell polarity (PCP) information is a critical determinant of organ morphogenesis. While PCP in bounded epithelial sheets is increasingly well understood, how PCP is organized in tubular and acinar tissues is not. Drosophila egg chambers (follicles) are an acinus-like "edgeless epithelium" and exhibit a continuous, circumferential PCP that does not depend on pathways active in bounded epithelia; this follicle PCP directs formation of an ellipsoid rather than a spherical egg. Here, we apply an imaging algorithm to "unroll" the entire 3D tissue surface and comprehensively analyze PCP onset. This approach traces chiral symmetry breaking to plus-end polarity of microtubules in the germarium, well before follicles form and rotate. PCP germarial microtubules provide chiral information that predicts the direction of whole-tissue rotation as soon as independent follicles form. Concordant microtubule polarity, but not microtubule alignment, requires the atypical cadherin Fat2, which acts at an early stage to translate plus-end bias into coordinated actin-mediated collective cell migration. Because microtubules are not required for PCP or migration after follicle rotation initiates, while dynamic actin and extracellular matrix are, polarized microtubules lie at the beginning of a handoff mechanism that passes early chiral PCP of the cytoskeleton to a supracellular planar polarized extracellular matrix and elongates the organ.

Ample interest has been evoked in using placental angiogenesis as a target for the development of diagnosis tools and potential therapeutics for pregnancy complications based on the knowledge of placental angiogenesis in normal and aberrant pregnancies. Although these goals are still far from reach, one would expect that two complementary processes should be balanced for therapeutic angiogenesis to be successful in restoring a mature and functional vascular network in the placenta in any pregnancy complication: (i) pro-angiogenic stimulation of new vessel growth and (ii) anti-angiogenic inhibition of vessel overgrowth. As the best model of physiological angiogenesis, investigations of placental angiogenesis provide critical insights not only for better understanding of normal placental endothelial biology but also for the development of diagnosis tools for pregnancy complications. Such investigations will potentially identify novel pro-angiogenic factors for therapeutic intervention for tissue damage in various obstetric complications or heart failure or anti-angiogenic factors to target on cancer or vision loss in which circulation needs to be constrained. This review summarizes the genetic and molecular aspects of normal placental angiogenesis as well as the signaling mechanisms by which the dominant angiogenic factor vascular endothelial growth factor regulates placental angiogenesis with a focus on placental endothelial cells.

MicroRNAs are a class of noncoding small RNAs that regulate the expression of nearly 30% of all the human genes and participate in all fundamental cell processes. Genome-wide analysis has revealed that human placenta expresses more than 600 miRNA species, including placenta-specific ones with high levels of expression. Comparative analysis also has revealed many differentially expressed miRNAs with either high or low levels of expression in human placentas from normal versus preeclamptic pregnancies, indicating an important role of miRNAs in normal and pathological placental physiology. Although limited information is currently available as to how miRNA regulates human placental development and function, there are studies suggesting that preeclampsia-associated differentially expressed miRNAs possess critical roles in regulating placental development and function via targeting specific genes with diverse known functions. Herein we summarize the current findings regarding the expression of placental miRNAs and their function, especially in the trophoblast cells. We have recently found that the angiogenesis-associated miR-17-family miRNAs are upregulated in preeclamptic compared with normotensive placentas and they target the ephrin-B2/Eph receptor B4 (EPHB4) system. Because ephrin-B2 and EPHB4 has been previously shown to play a crucial role in trophoblast invasion into maternal spiral artery and vascular patterning during early human placental development, the miR-17-ephrin-B2/EPHB4 pathway seems to be a novel miRNA pathway for regulating normal and aberrant placental development during preeclampsia.

For functional data lying on an unknown nonlinear low-dimensional space, we study manifold learning and introduce the notions of manifold mean, manifold modes of functional variation and of functional manifold components. These constitute nonlinear representations of functional data that complement classical linear representations such as eigenfunctions and functional principal components. Our manifold learning procedures borrow ideas from existing nonlinear dimension reduction methods, which we modify to address functional data settings. In simulations and applications, we study examples of functional data which lie on a manifold and validate the superior behavior of manifold mean and functional manifold components over traditional cross-sectional mean and functional principal components. We also include consistency proofs for our estimators under certain assumptions.