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Biomarkers encompass a wide range of different measurable indicators, representing a tangible link to physiological changes occurring within the body. Accessibility, sensitivity, and specificity are significant factors in biomarker suitability. New biomarkers continue to be discovered, and questions over appropriate selection and assessment of their usefulness remain. If traditional markers

Biomarkers encompass a wide range of different measurable indicators, representing a tangible link to physiological changes occurring within the body. Accessibility, sensitivity, and specificity are significant factors in biomarker suitability. New biomarkers continue to be discovered, and questions over appropriate selection and assessment of their usefulness remain. If traditional markers of inflammation are not sufficiently robust in their specificity, then perhaps alternative means of detection may provide more information. Epigenetic drift (epigenetic modifications as they occur as a direct function with age), and its ancillary elements, including platelets, secreted microvesicles (MVs), and microRNA (miRNA), may hold enormous predictive potential. The majority of epigenetic drift observed in blood is independent of variations in blood cell composition, addressing concerns affecting traditional blood-based biomarker efficacy. MVs are found in plasma and other biological fluids in healthy individuals. Altered MV/miRNA profiles may also be found in individuals with various diseases. Platelets are also highly reflective of physiological and lifestyle changes, making them extremely sensitive biomarkers of human health. Platelets release increased levels of MVs in response to various stimuli and under a plethora of disease states, which demonstrate a functional effect on other cell types.

ContributorsWallace, Robert G. (Author) / Twomey, Laura C. (Author) / Custaud, Marc-Antoine (Author) / Moyna, Niall (Author) / Cummins, Philip M. (Author) / Mangone, Marco (Author) / Murphy, Ronan P. (Author) / Biodesign Institute (Contributor)
Created2015-11-24
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Description

Cancer therapy selects for cancer cells resistant to treatment, a process that is fundamentally evolutionary. To what extent, however, is the evolutionary perspective employed in research on therapeutic resistance and relapse? We analyzed 6,228 papers on therapeutic resistance and/or relapse in cancers and found that the use of evolution terms

Cancer therapy selects for cancer cells resistant to treatment, a process that is fundamentally evolutionary. To what extent, however, is the evolutionary perspective employed in research on therapeutic resistance and relapse? We analyzed 6,228 papers on therapeutic resistance and/or relapse in cancers and found that the use of evolution terms in abstracts has remained at about 1% since the 1980s. However, detailed coding of 22 recent papers revealed a higher proportion of papers using evolutionary methods or evolutionary theory, although this number is still less than 10%. Despite the fact that relapse and therapeutic resistance is essentially an evolutionary process, it appears that this framework has not permeated research. This represents an unrealized opportunity for advances in research on therapeutic resistance.

ContributorsAktipis, C. Athena (Author) / Kwan, Sau (Author) / Johnson, Kathryn (Author) / Neuberg, Steven (Author) / Maley, Carlo C. (Author) / College of Liberal Arts and Sciences (Contributor)
Created2011-11-17
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Description

Land surface energy balance in a built environment is widely modelled using urban canopy models with representation of building arrays as big street canyons. Modification of this simplified geometric representation, however, leads to challenging numerical difficulties in improving physical parameterization schemes that are deterministic in nature. In this paper, we

Land surface energy balance in a built environment is widely modelled using urban canopy models with representation of building arrays as big street canyons. Modification of this simplified geometric representation, however, leads to challenging numerical difficulties in improving physical parameterization schemes that are deterministic in nature. In this paper, we develop a stochastic algorithm to estimate view factors between canyon facets in the presence of shade trees based on Monte Carlo simulation, where an analytical formulation is inhibited by the complex geometry. The model is validated against analytical solutions of benchmark radiative problems as well as field measurements in real street canyons. In conjunction with the matrix method resolving infinite number of reflections, the proposed model is capable of predicting the radiative exchange inside the street canyon with good accuracy. Modeling of transient evolution of thermal filed inside the street canyon using the proposed method demonstrate the potential of shade trees in mitigating canyon surface temperatures as well as saving of building energy use. This new numerical framework also deepens our insight into the fundamental physics of radiative heat transfer and surface energy balance for urban climate modeling.

ContributorsWang, Zhi-Hua (Author) / Ira A. Fulton Schools of Engineering (Contributor)
Created2014-12-01
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Description

Studies on urban heat island (UHI) have been more than a century after the phenomenon was first discovered in the early 1800s. UHI emerges as the source of many urban environmental problems and exacerbates the living environment in cities. Under the challenges of increasing urbanization and future climate changes, there

Studies on urban heat island (UHI) have been more than a century after the phenomenon was first discovered in the early 1800s. UHI emerges as the source of many urban environmental problems and exacerbates the living environment in cities. Under the challenges of increasing urbanization and future climate changes, there is a pressing need for sustainable adaptation/mitigation strategies for UHI effects, one popular option being the use of reflective materials. While it is introduced as an effective method to reduce temperature and energy consumption in cities, its impacts on environmental sustainability and large-scale non-local effect are inadequately explored. This paper provides a synthetic overview of potential environmental impacts of reflective materials at a variety of scales, ranging from energy load on a single building to regional hydroclimate. The review shows that mitigation potential of reflective materials depends on a set of factors, including building characteristics, urban environment, meteorological and geographical conditions, to name a few. Precaution needs to be exercised by city planners and policy makers for large-scale deployment of reflective materials before their environmental impacts, especially on regional hydroclimates, are better understood. In general, it is recommended that optimal strategy for UHI needs to be determined on a city-by-city basis, rather than adopting a “one-solution-fits-all” strategy.

ContributorsYang, Jiachuan (Author) / Wang, Zhi-Hua (Author) / Kaloush, Kamil (Author) / Ira A. Fulton Schools of Engineering (Contributor)
Created2015-07-01
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Description

The hysteresis effect in diurnal cycles of net radiation R-n and ground heat flux G(0) has been observed in many studies, while the governing mechanism remains vague. In this study, we link the phenomenology of hysteresis loops to the wave phase difference between the diurnal evolutions of various terms in

The hysteresis effect in diurnal cycles of net radiation R-n and ground heat flux G(0) has been observed in many studies, while the governing mechanism remains vague. In this study, we link the phenomenology of hysteresis loops to the wave phase difference between the diurnal evolutions of various terms in the surface energy balance. R-n and G(0) are parameterized with the incoming solar radiation and the surface temperature as two control parameters of the surface energy partitioning. The theoretical analysis shows that the vertical water flux W and the scaled ratio A(s)*/A(T)* (net shortwave radiation to outgoing longwave radiation) play crucial roles in shaping hysteresis loops of R-n and G(0). Comparisons to field measurements indicate that hysteresis loops for different land covers can be well captured by the theoretical model, which is also consistent with Camuffo-Bernadi formula. This study provides insight into the surface partitioning and temporal evolution of the energy budget at the land surface.

ContributorsSun, Ting (Author) / Wang, Zhi-Hua (Author) / Ni, Guang-Heng (Author) / Ira A. Fulton Schools of Engineering (Contributor)
Created2013-09-18
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Description

Investigation into the causes underlying the rapid, global amphibian decline provides critical insight into the effects of changing ecosystems. Hypothesized and confirmed links between amphibian declines, disease, and environmental changes are increasingly represented in published literature. However, there are few long-term amphibian studies that include data on population size, abnormality/injury

Investigation into the causes underlying the rapid, global amphibian decline provides critical insight into the effects of changing ecosystems. Hypothesized and confirmed links between amphibian declines, disease, and environmental changes are increasingly represented in published literature. However, there are few long-term amphibian studies that include data on population size, abnormality/injury rates, disease, and habitat variables to adequately assess changes through time. We cultured and identified microorganisms isolated from abnormal/injured and repressed tissue regeneration sites of the endangered Ozark Hellbender, Cryptobranchus alleganiensis bishopi, to discover potential causative agents responsible for their significant decline in health and population. This organism and our study site were chosen because the population and habitat of C. a. bishopi have been intensively studied from 1969–2009, and the abnormality/injury rate and apparent lack of regeneration were established.

Although many bacterial and fungal isolates recovered were common environmental organisms, several opportunistic pathogens were identified in association with only the injured tissues of C.a. bishopi. Bacterial isolates included Aeromonas hydrophila, a known amphibian pathogen, Granulicetella adiacens, Gordonai terrae, Stenotrophomonas maltophilia, Aerococcus viridans, Streptococcus pneumoniae and a variety of Pseudomonads, including Pseudomonas aeruginosa, P. stutzeri, and P. alcaligenes. Fungal isolates included species in the genera Penicillium, Acremonium, Cladosporium, Curvularia, Fusarium, Streptomycetes, and the Class Hyphomycetes. Many of the opportunistic pathogens identified are known to form biofilms. Lack of isolation of the same organism from all wounds suggests that the etiological agent responsible for the damage to C. a. bishopi may not be a single organism. To our knowledge, this is the first study to profile the external microbial consortia cultured from a Cryptobranchid salamander. The incidence of abnormalities/injury and retarded regeneration in C. a. bishopi may have many contributing factors including disease and habitat degradation. Results from this study may provide insight into other amphibian population declines.

Created2011-12-19
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Description

This study examines the spatial and temporal patterns of the surface urban heat island (SUHI) intensity in the Phoenix metropolitan area and the relationship with land use land cover (LULC) change between 2000 and 2014. The objective is to identify specific regions in Phoenix that have been increasingly heated and

This study examines the spatial and temporal patterns of the surface urban heat island (SUHI) intensity in the Phoenix metropolitan area and the relationship with land use land cover (LULC) change between 2000 and 2014. The objective is to identify specific regions in Phoenix that have been increasingly heated and cooled to further understand how LULC change influences the SUHI intensity. The data employed include MODerate-resolution Imaging Spectroradiometer (MODIS) land surface temperature (LST) 8-day composite June imagery, and classified LULC maps generated using 2000 and 2014 Landsat imagery. Results show that the regions that experienced the most significant LST changes during the study period are primarily on the outskirts of the Phoenix metropolitan area for both daytime and nighttime. The conversion to urban, residential, and impervious surfaces from all other LULC types has been identified as the primary cause of the UHI effect in Phoenix. Vegetation cover has been shown to significantly lower LST for both daytime and nighttime due to its strong cooling effect by producing more latent heat flux and less sensible heat flux. We suggest that urban planners, decision-makers, and city managers formulate new policies and regulations that encourage residential, commercial, and industrial developers to include more vegetation when planning new construction.

ContributorsWang, Chuyuan (Author) / Myint, Soe (Author) / Wang, Zhi-Hua (Author) / Song, Jiyun (Author) / College of Liberal Arts and Sciences (Contributor)
Created2016-02-26
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Description

A distinct pathovar of Salmonella enterica serovar Typhimurium, ST313, has emerged in sub-Saharan Africa as a major cause of fatal bacteremia in young children and HIV-infected adults. D23580, a multidrug resistant clinical isolate of ST313, was previously shown to have undergone genome reduction in a manner that resembles that of

A distinct pathovar of Salmonella enterica serovar Typhimurium, ST313, has emerged in sub-Saharan Africa as a major cause of fatal bacteremia in young children and HIV-infected adults. D23580, a multidrug resistant clinical isolate of ST313, was previously shown to have undergone genome reduction in a manner that resembles that of the more human-restricted pathogen, Salmonella enterica serovar Typhi. It has since been shown through tissue distribution studies that D23580 is able to establish an invasive infection in chickens. However, it remains unclear whether ST313 can cause lethal disease in a non-human host following a natural course of infection. Herein we report that D23580 causes lethal and invasive disease in a murine model of infection following peroral challenge. The LD50 of D23580 in female BALB/c mice was 4.7 x 105 CFU. Tissue distribution studies performed 3 and 5 days post-infection confirmed that D23580 was able to more rapidly colonize the spleen, mesenteric lymph nodes and gall bladder in mice when compared to the well-characterized S. Typhimurium strain SL1344. D23580 exhibited enhanced resistance to acid stress relative to SL1344, which may lend towards increased capability to survive passage through the gastrointestinal tract as well as during its intracellular lifecycle. Interestingly, D23580 also displayed higher swimming motility relative to SL1344, S. Typhi strain Ty2, and the ST313 strain A130. Biochemical tests revealed that D23580 shares many similar metabolic features with SL1344, with several notable differences in the Voges-Proskauer and catalase tests, as well alterations in melibiose, and inositol utilization. These results represent the first full duration infection study using an ST313 strain following the entire natural course of disease progression, and serve as a benchmark for ongoing and future studies into the pathogenesis of D23580.

ContributorsYang, Jiseon (Author) / Barrila, Jennifer (Author) / Roland, Kenneth (Author) / Kilbourne, Jacquelyn (Author) / Ott, C. Mark (Author) / Forsyth, Rebecca (Author) / Nickerson, Cheryl (Author) / ASU Biodesign Center Immunotherapy, Vaccines and Virotherapy (Contributor) / Biodesign Institute (Contributor)
Created2015-06-19
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Description

Background: Medical and public health scientists are using evolution to devise new strategies to solve major health problems. But based on a 2003 survey, medical curricula may not adequately prepare physicians to evaluate and extend these advances. This study assessed the change in coverage of evolution in North American medical schools

Background: Medical and public health scientists are using evolution to devise new strategies to solve major health problems. But based on a 2003 survey, medical curricula may not adequately prepare physicians to evaluate and extend these advances. This study assessed the change in coverage of evolution in North American medical schools since 2003 and identified opportunities for enriching medical education.

Methods: In 2013, curriculum deans for all North American medical schools were invited to rate curricular coverage and perceived importance of 12 core principles, the extent of anticipated controversy from adding evolution, and the usefulness of 13 teaching resources. Differences between schools were assessed by Pearson’s chi-square test, Student’s t-test, and Spearman’s correlation. Open-ended questions sought insight into perceived barriers and benefits.

Results: Despite repeated follow-up, 60 schools (39%) responded to the survey. There was no evidence of sample bias. The three evolutionary principles rated most important were antibiotic resistance, environmental mismatch, and somatic selection in cancer. While importance and coverage of principles were correlated (r = 0.76, P < 0.01), coverage (at least moderate) lagged behind importance (at least moderate) by an average of 21% (SD = 6%). Compared to 2003, a range of evolutionary principles were covered by 4 to 74% more schools. Nearly half (48%) of responders anticipated igniting controversy at their medical school if they added evolution to their curriculum. The teaching resources ranked most useful were model test questions and answers, case studies, and model curricula for existing courses/rotations. Limited resources (faculty expertise) were cited as the major barrier to adding more evolution, but benefits included a deeper understanding and improved patient care.

Conclusion: North American medical schools have increased the evolution content in their curricula over the past decade. However, coverage is not commensurate with importance. At a few medical schools, anticipated controversy impedes teaching more evolution. Efforts to improve evolution education in medical schools should be directed toward boosting faculty expertise and crafting resources that can be easily integrated into existing curricula.

ContributorsHidaka, Brandon H. (Author) / Asghar, Anila (Author) / Aktipis, C. Athena (Author) / Nesse, Randolph (Author) / Wolpaw, Terry M. (Author) / Skursky, Nicole K. (Author) / Bennett, Katelyn J. (Author) / Beyrouty, Matthew W. (Author) / Schwartz, Mark D. (Author) / Department of Psychology (Contributor)
Created2015-03-08
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Description

Background: Lizards are evolutionarily the most closely related vertebrates to humans that can lose and regrow an entire appendage. Regeneration in lizards involves differential expression of hundreds of genes that regulate wound healing, musculoskeletal development, hormonal response, and embryonic morphogenesis. While microRNAs are able to regulate large groups of genes, their

Background: Lizards are evolutionarily the most closely related vertebrates to humans that can lose and regrow an entire appendage. Regeneration in lizards involves differential expression of hundreds of genes that regulate wound healing, musculoskeletal development, hormonal response, and embryonic morphogenesis. While microRNAs are able to regulate large groups of genes, their role in lizard regeneration has not been investigated.

Results: MicroRNA sequencing of green anole lizard (Anolis carolinensis) regenerating tail and associated tissues revealed 350 putative novel and 196 known microRNA precursors. Eleven microRNAs were differentially expressed between the regenerating tail tip and base during maximum outgrowth (25 days post autotomy), including miR-133a, miR-133b, and miR-206, which have been reported to regulate regeneration and stem cell proliferation in other model systems. Three putative novel differentially expressed microRNAs were identified in the regenerating tail tip.

Conclusions: Differentially expressed microRNAs were identified in the regenerating lizard tail, including known regulators of stem cell proliferation. The identification of 3 putative novel microRNAs suggests that regulatory networks, either conserved in vertebrates and previously uncharacterized or specific to lizards, are involved in regeneration. These findings suggest that differential regulation of microRNAs may play a role in coordinating the timing and expression of hundreds of genes involved in regeneration.

ContributorsHutchins, Elizabeth (Author) / Eckalbar, Walter (Author) / Wolter, Justin (Author) / Mangone, Marco (Author) / Kusumi, Kenro (Author) / College of Liberal Arts and Sciences (Contributor)
Created2016-05-05