• (S)-lacosamide inhibition of CRMP2 phosphorylation reduces postoperative and neuropathic pain behaviors through distinct classes of sensory neurons identified by constellation pharmacology.

      Moutal, Aubin; Chew, Lindsey A; Yang, Xiaofang; Wang, Yue; Yeon, Seul Ki; Telemi, Edwin; Meroueh, Seeneen; Park, Ki Duk; Shrinivasan, Raghuraman; Gilbraith, Kerry B; et al. (LIPPINCOTT WILLIAMS & WILKINS, 2016-07)
      Chronic pain affects the life of millions of people. Current treatments have deleterious side effects. We have advanced a strategy for targeting protein interactions which regulate the N-type voltage-gated calcium (CaV2.2) channel as an alternative to direct channel block. Peptides uncoupling CaV2.2 interactions with the axonal collapsin response mediator protein 2 (CRMP2) were antinociceptive without effects on memory, depression, and reward/addiction. A search for small molecules that could recapitulate uncoupling of the CaV2.2-CRMP2 interaction identified (S)-lacosamide [(S)-LCM], the inactive enantiomer of the Food and Drug Administration-approved antiepileptic drug (R)-lacosamide [(R)-LCM, Vimpat]. We show that (S)-LCM, but not (R)-LCM, inhibits CRMP2 phosphorylation by cyclin dependent kinase 5, a step necessary for driving CaV2.2 activity, in sensory neurons. (S)-lacosamide inhibited depolarization-induced Ca influx with a low micromolar IC50. Voltage-clamp electrophysiology experiments demonstrated a commensurate reduction in Ca currents in sensory neurons after an acute application of (S)-LCM. Using constellation pharmacology, a recently described high content phenotypic screening platform for functional fingerprinting of neurons that uses subtype-selective pharmacological agents to elucidate cell-specific combinations (constellations) of key signaling proteins that define specific cell types, we investigated if (S)-LCM preferentially acts on certain types of neurons. (S)-lacosamide decreased the dorsal root ganglion neurons responding to mustard oil, and increased the number of cells responding to menthol. Finally, (S)-LCM reversed thermal hypersensitivity and mechanical allodynia in a model of postoperative pain, and 2 models of neuropathic pain. Thus, using (S)-LCM to inhibit CRMP2 phosphorylation is a novel and efficient strategy to treat pain, which works by targeting specific sensory neuron populations.
    • Safety and Efficacy of Daptomycin in Neonates with Coagulase-Negative Staphylococci: Case Series Analysis

      Mohzari, Yahya; Aljobair, Fahad; Alrashed, Ahmed; Asdaq, Syed Mohammed Basheeruddin; Alshuraim, Renad Abdullah; Asfour, Suzan Suhail; Al-Mouqdad, Mountasser Mohammad; Bamogaddam, Reem F.; Al-Anazi, Deemah; Zeilinger, Catherine E.; et al. (MDPI AG, 2021-02-07)
      There has been an increase in the prevalence of gram-positive bacteremia in neonates in the last two decades. However, as a consequence of better care, there has been an increase in the survival of premature neonates. Coagulase-negative staphylococci (CoNS) is the most prevalent bacteria, responsible for up to 60% of late-onset sepsis (LOS). Daptomycin, a lipopeptide antimicrobial agent, is active against CoNS. This was an observational, retrospective case series study carried out in the Pediatric Hospital of King Saud Medical City, Riyadh, Saudi Arabia. The medical records of 21 neonates, aged 0–28 days, who were treated in Neonatal Intensive Care Unit (NICU) with intravenous daptomycin as monotherapy or combination therapy for at least 4 days for proven gram-positive infection between June 2019 to July 2020, were included. The median gestational and chronological age were 27 weeks and 5 days, respectively. The most frequent diagnosis in neonates was infective endocarditis (42.9%). Of the 21 patients who received daptomycin therapy, 13 (62%) recovered and 8 died. The clinical cure rate was higher in Staphylococcus hominis (100%) and in patients who received 6 mg/kg/dose twice daily (62.5%). The mean of aspartate aminotransferase significantly elevated after starting daptomycin (p = 0.048). However, no muscular or neurological toxicity of daptomycin was documented in any of the cases. Overall, daptomycin was well tolerated, even with long-term treatment. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.
    • Safety and efficacy of ex vivo expanded CD34 stem cells in murine and primate models

      Zhang, Yu; Shen, Bin; Guan, Xin; Qin, Meng; Ren, Zhihua; Ma, Yupo; Dai, Wei; Ding, Xinxin; Jiang, Yongping; Univ Arizona, Coll Pharm, Dept Pharmacol & Toxicol (BMC, 2019-06-13)
      Background: Hematopoietic stem cell (HSC) transplantation has been widely applied to the treatment of malignant blood diseases. However, limited number of functional HSCs hinders successful transplantation. The purpose of our current study is to develop a new and cost-efficient medium formulation that could greatly enhance the expansion of HSCs while retaining their long-term repopulation and hematopoietic properties for effective clinical transplantation. Methods: Enriched human CD34(+) cells and mobilized nonhuman primate peripheral blood CD34(+) cells were expanded with a new, cost-efficient expansion medium formulation, named hematopoietic expansion medium (HEM), consisting of various cytokines and nutritional supplements. The long-term repopulation potential and hematologic-lineage differentiation ability of expanded human cells were studied in the non-obese diabetic/severe combined immunodeficiency mouse model. Furthermore, the efficacy and safety studies were performed by autologous transplantation of expanded primate cells in the nonhuman primate model. Results: HEM could effectively expand human CD34(+) cells by up to 129 fold within 9 days. Expanded HSCs retained long-term repopulation potential and hematologic-lineage differentiation ability, as indicated by (1) maintenance (over unexpanded HSCs) of immunophenotypes of CD38(-)CD90(+)CD45RA(-)CD49f(+) in CD34(+) cells after expansion; (2) significant presence of multiple human hematopoietic lineages in mouse peripheral blood and bone marrow following primary transplantation; (3) enrichment (over unexpanded HSCs) in SCID-repopulating cell frequency measured by limiting dilution analysis; and (4) preservation of both myeloid and lymphoid potential among human leukocytes from mouse bone marrow in week 24 after primary transplantation or secondary transplantation. Moreover, the results of autologous transplantation in nonhuman primates demonstrated that HEM-expanded CD34(+) cells could enhance hematological recovery after myelo-suppression. All primates transplanted with the expanded autologous CD34(+) cells survived for over 18 months without any noticeable abnormalities. Conclusions: Together, these findings demonstrate promising potential for the utility of HEM to improve expansion of HSCs for clinical application.
    • Safety and Efficacy of Stent-assisted Coiling in the Treatment of Unruptured Wide-necked Intracranial Aneurysms: A Single-center Experience

      Aguilar-Salinas, Pedro; Brasiliense, Leonardo B; Santos, Roberta; Cortez, Gustavo M; Gonsales, Douglas; Aghaebrahim, Amin; Sauvageau, Eric; Hanel, Ricardo A; Univ Arizona, Neurosurg (CUREUS INC, 2019-06-06)
      Introduction: Wide-necked intracranial aneurysms (IAs) are complex lesions that may require different microsurgical or endovascular strategies, and stent-assisted coiling (SAC) has emerged as a feasible alternative to treat this subset of aneurysms. Methods: The objective was to assess the rate of complications of unruptured wide-necked IAs treated with SAC. We retrospectively identified patients with unruptured wide-necked IAs treated with SAC. Medical charts, procedure reports, and imaging studies were analyzed. Results: One hundred twenty patients harboring 124 unruptured wide-necked IAs were included. Ninety-two aneurysms (74.2%) were located in the anterior circulation. The median aneurysm size was 7 mm (IQR = 5-10). The immediate complete aneurysm occlusion rate was 29% (36/124). The rate of procedural complications was 3.3 % (4/120), which included 2 intraprocedural aneurysm ruptures, 1 immediate postprocedure aneurysm rupture, and 1 vessel occlusion rescued with an open-cell stent. The median follow-up time was 21 months (IQR = 10.3-40.9). Kaplan-Meier analysis estimated a median time of complete aneurysm occlusion of 6.3 months (95%CI = 3.8-7.8). At 30-day follow-up, 80.7% of patients had a Glasgow Outcome Score (GOS) of 5 and at the latest follow-up 83.9%. Imaging follow-up was available for 102 patients. The rate of complete aneurysm occlusion was 73.5% (75/102), severe in-stent stenosis (>50%) was found in 1% (1/102), the recanalization rate was 6.6% (5/75), and the retreatment rate was 7.8% (8/102). Conclusion: SAC remains a safe and effective technique to treat wide-necked IAs, providing low rate of complications and recanalization with excellent long-term aneurysm occlusion rates.
    • Safety assessment of genetically modified crops for yield increase and resistance to both biotic and abiotic stresses and their impact on human and environment

      Askari-Khorasgani, Omid; Pessarakli, Mohammad; Univ Arizona, Sch Plant Sci (MedCrave, 2018-03-06)
      Biotechnology has now accelerated the breeding evolution of agricultural products to obtain stress-tolerant crops with improved productivity to meet the increasing global demand which is in direct correlation with demographic trends. Nutritional quality, food allergies, toxicity effects, and unwanted resistance and alternations in gene sequences are the main concerns of genetically engineered products. Despite the numerous and overall benefits of genetically engineered crops, the questions raised by unwanted and unpredictable consequences about their safety concerns that may harm human, animal, and/or the ecosystem health require a long-term and a case-by-case transparent assessments before releasing the biotech crops into the food chain.
    • The SAGA Survey. I. Satellite Galaxy Populations around Eight Milky Way Analogs

      Geha, Marla; Wechsler, Risa H.; Mao, Yao-Yuan; Tollerud, Erik J.; Weiner, Benjamin; Bernstein, Rebecca; Hoyle, Ben; Marchi, Sebastian; Marshall, Phil J.; Muñoz, Ricardo; et al. (IOP PUBLISHING LTD, 2017-09-14)
      We present the survey strategy and early results of the "Satellites Around Galactic Analogs" (SAGA) Survey. The SAGA. Survey's goal is to measure the distribution of satellite galaxies around 100 systems analogous to the Milky Way down to the luminosity of the Leo I dwarf galaxy (M-r < -12.3). We define a Milky Way analog based on K-band luminosity and local environment. Here, we present satellite luminosity functions for eight Milky-Way-analog galaxies between 20 and 40. Mpc. These systems have nearly complete spectroscopic coverage of candidate satellites within the projected host virial radius down to r(o) < 20.75 using low-redshift gri color criteria. We have discovered a total of 25 new satellite galaxies: 14. new satellite galaxies meet our formal criteria around our complete host systems, plus 11 additional satellites in either incompletely surveyed hosts or below our formal magnitude limit. Combined with 13 previously known satellites, there are a total of 27 satellites around 8 complete Milky-Way-analog hosts. We find a wide distribution in the number of satellites per host, from 1 to 9, in the luminosity range for which there are 5 Milky Way satellites. Standard abundance matching extrapolated from higher luminosities predicts less scatter between hosts and a steeper luminosity function slope than observed. We find that the majority of satellites (26 of 27) are star-forming. These early results indicate that the Milky Way has a different satellite population than typical in our sample, potentially changing the physical interpretation of measurements based only on the Milky Way's satellite galaxies.
    • Salicylic acid regulates photosynthetic electron transfer and stomatal conductance of mung bean (Vigna radiata L.) under salinity stress

      Lotfi, Ramin; Ghassemi-Golezani, Kazem; Pessarakli, Mohammad; Univ Arizona, Coll Agr & Life Sci, Sch Plant Sci (ELSEVIER, 2020-07)
      The role of salicylic acid (0, 1 and 1.5 mM) on photosynthetic electron transfer chain of mung-bean plants grown under salt stress (0, 3, 6 and 9 dS/m(2)) was studied using chlorophyll a fluorescence (ChlF) measurements. Results indicated that accumulation of K+ content decreased but, Na+ content increased with increasing salt stress. SA-treated plants had more K+ and less Na+ content compared with the non-SA treated plants. Application of SA, especially with 1 mM, increased the I-P step of the OJIP transient curve of fluorescence. Salt stress decreased g(s), CCI, F-V, F-M, S-M and PIabs in plants. However, the time taken to reach FM (TFM) increased with increasing salt stress. Application of different concentrations of SA significantly improved gs, CCI, FV, SM, and PIabs of plants. Photosynthetic efficiency of plants improved as a result of SA application via decreasing F-o and increasing F-V/F-M, F-V/F-O, S-M/T-FM and Area under both saline and non-saline conditions. Accumulation of Na+ had negative, but K+ had a positive correlation with gs, CCI and most of the chlorophyll a fluorescence parameters (except, Fo and TFM). A positive correlation was found between g(s) and CCI with PIabs. This research indicated that low gs under saline condition seems to cause losses in PSII efficiency, but the application of SA with 1 mM concentration is the best treatment for the alleviation of salt stress injuries on PSII activity of mung bean plants.
    • Salience, Myopia, and Complex Dynamic Incentives: Evidence from Medicare Part D

      Dalton, Christina M; Gowrisankaran, Gautam; Town, Robert J; Univ Arizona (OXFORD UNIV PRESS, 2020-03)
      The standard Medicare Part D drug insurance contract is non-linear-with reduced subsidies in a coverage gap-resulting in a dynamic purchase problem. We consider enrolees who arrived near the gap early in the year and show that they should expect to enter the gap with high probability, implying that, under a benchmark model with neoclassical preferences, the gap should impact them very little. We find that these enrolees have flat spending in a period before the doughnut hole and a large spending drop in the gap, providing evidence against the benchmark model. We structurally estimate behavioural dynamic drug purchase models and find that a price salience model where enrolees do not incorporate future prices into their decision-making at all fits the data best. For a nationally representative sample, full price salience would decrease enrolee spending by 31%. Entirely eliminating the gap would increase insurer spending 27%, compared to 7% for generic-drug-only gap coverage.
    • Salinomycin and its derivatives as potent RET transcriptional inhibitors for the treatment of medullary thyroid carcinoma

      Alqahtani, Tariq; Kumarasamy, Vishnu Muthuraj; Huczyński, Adam; Sun, Daekyu; Univ Arizona, Coll Pharm, Dept Pharmacol & Toxicol; Univ Arizona, BIO5 Inst; Univ Arizona, Arizona Canc Ctr (SPANDIDOS PUBL LTD, 2019-11-20)
      Rearranged during transfection kinase (RET) is a validated molecular target in medullary thyroid cancer (MTC), as activating mutations in RET are often associated with the development of MTC. The present study reports the first preclinical characterization of salinomycin and selected analogs as potent RET transcriptional inhibitors. Reverse transcription‑PCR and immunoblotting revealed that salinomycin profoundly decreased RET expression in the TT human MTC cell line by inhibiting RET transcription. Moreover, salinomycin resulted in remarkable anti‑proliferative activity against MTC that is driven by RET (gain of function mutation) by selectively inhibiting the intracellular PI3K/Akt/mTOR signaling pathway. Also, flow cytometry and fluorescence‑activated cell sorting showed that salinomycin induces G1 phase arrest and apoptosis by reducing the expression of retinoblastoma protein, E2F1, cyclin D and CDK4. The structure‑activity relationship of salinomycin was investigated in this study. Some of the salinomycin derivatives showed the ability to reduce RET expression where others fail to alter RET expression. These results suggest that the RET‑suppressing effect of salinomycin may be largely attributed to disruption of the Wnt pathway, presumably through interference with the ternary LRP6‑Frizzled‑Wnt complex. Furthermore, these findings support the further preclinical evaluation of salinomycin and its analogs as a promising new class of therapeutic agents for the improved treatment of MTC.
    • Salvage Hyperthermic Gemcitabine and Docetaxel Combination Chemotherapy After BCG Failure in Non-Muscle Invasive Bladder Cancer Patients

      Rao, Mounica Y.; Kang, Paul; Tarajkowski, Jamaka C.; Mobley, Debra L.; Lamm, Donald L.; Univ Arizona, Coll Med (IOS PRESS, 2020-03-28)
      BACKGROUND: Bacillus Calmette-Guerin (BCG) is the recommended therapy for high and intermediate risk non-muscle invasive bladder cancer (NMIBC), but treatment failure is common. While a radical cystectomy is recommended after BCG failure, some patients desire bladder preservation and others are poor surgical candidates. Salvage chemotherapy treatments may be offered to this subgroup of patients. OBJECTIVE: To assess if combination, hyperthermic Gemcitabine and Docetaxel chemotherapy (GEM/DOCE) is a safe and effective salvage option for treating NMIBC. METHODS: Sixty patients who received our GEM/DOCE protocol between 2007-2017 were identified (51 BCG failures, 9 BCG naive). This study measured overall treatment success, defined as no recurrence, progression, cystectomy, nor death due to bladder cancer. Kaplan-Meier curves were used to ascertain probability of treatment success. The log-rank test was used to identify factors associated with treatment success. RESULTS: Sixty patients received treatment with a median follow-up of 14.9 months. All patients completed the induction course with no significant adverse effects. Overall treatment success was 83% at first surveillance, 69% at 1 year, and 55% at 2 years in the entire cohort, and 90% at first surveillance, 74% at 1 year, and 56% at 2 years in the BCG-failure patients. All-cause and bladder-cancer-specific survival were both 97.9% at 1 year, 85.9% and 94.6% respectively at 2 years. Three patients underwent cystectomy at a median of 10.2 months, two of these were secondary to recurrences. Three patients had progression of their disease. CONCLUSIONS: Hyperthermic GEM/DOCE seems to be a well-tolerated salvage regimen that demonstrates a reasonable efficacy and warrants further investigation.
    • Salvage Stereotactic Body Radiation Therapy for Locally Recurrent Previously Irradiated Head and Neck Squamous Cell Carcinoma: An Analysis from the RSSearch® Registry

      Ansinelli, Hayden; Singh, Raj; Sharma, Dana L; Jenkins, Jan; Davis, Joanne; Vargo, John A; Sharma, Sanjeev; Univ Arizona, Dept Radiat Oncol, Coll Med (CUREUS INC, 2018-08-31)
      Objectives To report on overall survival (OS), local control (LC), dose-outcome relationships, and related toxicities following stereotactic body radiation therapy (SBRT) for locally recurrent, previously irradiated squamous cell carcinoma of the head and neck (rSCCHN). Methods We queried the prospectively-maintained RSSearch (R) Registry for patients with rSCCHN treated with five-fraction SBRT from January 2008 to November 2016. Patients with non-squamous cell histology, missing registry data regarding prior irradiation, those treated with less than five fractions of SBRT, and those treated with SBRT in primary or boost settings were excluded. LC and OS were estimated using the Kaplan-Meier method with comparisons between groups completed using log-rank t-tests and multivariable Cox regression. Logistic regression analyses were used to examine factors predictive of toxicity. Results Forty-five rSCCHN patients treated with SBRT delivered in five fractions at 12 radiotherapy centers were identified. Prescription doses >= 40 Gy were associated with higher one-year rates of OS, LC, and a higher likelihood of experiencing toxicities. Acute and late toxicity rates were low (22.2% and 15.6%, respectively) and were all Grade 1-2 with only one late Grade 3 esophagitis. Conclusion Salvage SBRT for rSCCHN resulted in outcomes comparable to prior single-institutional reports in a multi-institutional cohort across clinical settings with low toxicity, thus supporting more widespread adoption of SBRT with recommended doses >= 40 Gy.
    • Salvia palmetorum (Lamiaceae), a new species from Sonora, Mexico

      González-Gallegos, Jesús Guadalupe; Carnahan, Susan D.; Univ Arizona, Herbarium (INST BIOLOGIA, UNIV NACIONAL AUTONOMA MEXICO, 2019-10-03)
      A new Salvia L. species was discovered in the vicinity of San Carlos Bay (Guaymas county) in Sonora, Mexico. The discovery was carried out during botanical explorations for the floristic inventory of the area. The new taxon is described and illustrated. This is an interesting addition to the Flora of Sonora because it constitutes the first Salvia endemic to this state. The species is characterized by an unusual combination of characters within Salvia subg. Calosphace (Benth.) Epling: densely white-tomentulose stems, presence of bracteoles, flowers arranged in thyrses, trimucronate upper calyx lip and ornate connective with an antrorse obtuse tooth. The taxon is also atypical among Mexican Salvia subg. Calosphace in growing in palm groves below 100 m elevation.
    • Sampling density and date along with species selection influence spatial representation of tree-ring reconstructions

      Maxwell, Justin T.; Harley, Grant L.; Matheus, Trevis J.; Strange, Brandon M.; Van Aken, Kayla; Au, Tsun Fung; Bregy, Joshua C.; Univ Arizona, Sch Nat Resources & Environm (COPERNICUS GESELLSCHAFT MBH, 2020-10-19)
      Our understanding of the natural variability of hydroclimate before the instrumental period (ca. 1900 CE in the United States) is largely dependent on tree-ring-based reconstructions. Large-scale soil moisture reconstructions from a network of tree-ring chronologies have greatly improved our understanding of the spatial and temporal variability in hydroclimate conditions, particularly extremes of both drought and pluvial (wet) events. However, certain regions within these large-scale network reconstructions in the US are modeled by few tree-ring chronologies. Further, many of the chronologies currently publicly available on the International Tree-Ring Data Bank (ITRDB) were collected in the 1980s and 1990s, and thus our understanding of the sensitivity of radial growth to soil moisture in the US is based on a period that experienced multiple extremely severe droughts and neglects the impacts of recent, rapid global change. In this study, we expanded the tree-ring network of the Ohio River valley in the US, a region with sparse coverage. We used a total of 72 chronologies across 15 species to examine how increasing the density of the tree-ring network influences the representation of reconstructing the Palmer Meteorological Drought Index (PMDI). Further, we tested how the sampling date and therefore the calibration period influenced the reconstruction models by creating reconstructions that ended in the year 1980 and compared them to reconstructions ending in 2010 from the same chronologies. We found that in- creasing the density of the tree-ring network resulted in reconstructed values that better matched the spatial variability of instrumentally recorded droughts and, to a lesser extent, pluvials. By extending the calibration period to 2010 compared to 1980, the sensitivity of tree rings to PMDI decreased in the southern portion of our region where severe drought conditions have been absent over recent decades. We emphasize the need of building a high-density tree-ring network to better represent the spatial variability of past droughts and pluvials. Further, chronologies on the ITRDB need updating regularly to better understand how the sensitivity of tree rings to climate may vary through time.
    • Sarcomere length-dependent effects on Ca2+-troponin regulation in myocardium expressing compliant titin

      Li, King-Lun; Methawasin, Mei; Tanner, Bertrand C W; Granzier, Henk L; Solaro, R John; Dong, Wen-Ji; Univ Arizona, Dept Cellular & Mol Med (ROCKEFELLER UNIV PRESS, 2019-01-07)
      Cardiac performance is tightly regulated at the cardiomyocyte level by sarcomere length, such that increases in sarcomere length lead to sharply enhanced force generation at the same Ca2+ concentration. Length-dependent activation of myofilaments involves dynamic and complex interactions between a multitude of thick- and thin-filament components. Among these components, troponin, myosin, and the giant protein titin are likely to be key players, but the mechanism by which these proteins are functionally linked has been elusive. Here, we investigate this link in the mouse myocardium using in situ FRET techniques. Our objective was to monitor how length-dependent Ca2+-induced conformational changes in the N domain of cardiac troponin C (cTnC) are modulated by myosin-actin cross-bridge (XB) interactions and increased titin compliance. We reconstitute FRET donor- and acceptor-modified cTnC(13C/51C)AEDANS-DDPM into chemically skinned myocardial fibers from wild-type and RBM20-deletion mice. The Ca2+-induced conformational changes in cTnC are quantified and characterized using time-resolved FRET measurements as XB state and sarcomere length are varied. The RBM20-deficient mouse expresses a more compliant N2BA titin isoform, leading to reduced passive tension in the myocardium. This provides a molecular tool to investigate how altered titin-based passive tension affects Ca2+-troponin regulation in response to mechanical stretch. In wild-type myocardium, we observe a direct association of sarcomere length-dependent enhancement of troponin regulation with both Ca2+ activation and strongly bound XB states. In comparison, measurements from titin RBM20-deficient animals show blunted sarcomere length-dependent effects. These results suggest that titin-based passive tension contributes to sarcomere length-dependent Ca2+-troponin regulation. We also conclude that strong XB binding plays an important role in linking the modulatory effect of titin compliance to Ca2+-troponin regulation of the myocardium.
    • SARS-CoV-2 (COVID-19) Vaccine Development and Production: An Ethical Way Forward

      Iserson, Kenneth V.; Univ Arizona, Dept Emergency Med (Cambridge University Press (CUP), 2020-06-05)
      The world awaits a SARS-CoV-2 virus (i.e., COVID-19 disease) vaccine to keep the populace healthy, fully reopen their economies, and return their social and healthcare systems to “normal.” Vaccine safety and efficacy requires meticulous testing and oversight; this paper describes how despite grandiose public statements, the current vaccine development, testing, and production methods may prove to be ethically dubious, medically dangerous, and socially volatile. The basic moral concern is the potential danger to the health of human test subjects and, eventually, many vaccine recipients. This is further complicated by economic and political pressures to reduce government oversight on rushed vaccine testing and production, nationalistic distribution goals, and failure to plan for the widespread immunization needed to produce global herd immunity. As this paper asserts, the public must be better informed to assess promises about the novel vaccines being produced and to tolerate delays and uncertainty.
    • Satellite data reveal a common combustion emission pathway for major cities in China

      Tang, Wenfu; Arellano, Avelino F.; Gaubert, Benjamin; Miyazaki, Kazuyuki; Worden, Helen M.; Univ Arizona, Dept Hydrol & Atmospher Sci (COPERNICUS GESELLSCHAFT MBH, 2019-04-03)
      Extensive fossil fuel combustion in rapidly developing cities severely affects air quality and public health. We report observational evidence of decadal changes in the efficiency and cleanness of bulk combustion over large cities in mainland China. In order to estimate the trends in enhancement ratios of CO and SO2 to NO2 (Delta CO/Delta NO2 and Delta SO2/Delta NO2) and infer emergent bulk combustion properties over these cities, we combine air quality retrievals from widely used satellite instruments across 2005-2014. We present results for four Chinese cities (Shenyang, Beijing, Shanghai, and Shenzhen) representing four levels of urban development. Our results show a robust coherent progression of declining to growing Delta CO/Delta NO2 relative to 2005 (-5.4 +/- 0.7 to +8.3 +/- 3.1 % yr(-1)) and slowly declining Delta SO2/Delta NO2 (-6.0 +/- 1.0 to -3.4 +/- 1.0 % yr(-1)) across the four cities. The coherent progression we find is not evident in the trends of emission ratios reported in Representative Concentration Pathway (RCP8.5) inventory. This progression is likely due to a shift towards cleaner combustion from industrial and residential sectors in Shanghai and Shenzhen that is not yet seen in Shenyang and Beijing. This overall trend is presently obfuscated by China's still relatively higher dependence on coal. Such progression is well-correlated with economic development and traces a common emission pathway that resembles evolution of air pollution in more developed cities. Our results highlight the utility of augmenting observing and modeling capabilities by exploiting enhancement ratios in constraining the time variation in emission ratios in current inventories. As cities and/or countries continue to socioeconomically develop, the ability to monitor combustion efficiency and effectiveness of pollution control becomes increasingly important in assessing sustainable control strategies.
    • Satellite hydrology observations as operational indicators of forecasted fire danger across the contiguous United States

      Farahmand, Alireza; Stavros, E. Natasha; Reager, John T.; Behrangi, Ali; Randerson, James T.; Quayle, Brad; Univ Arizona, Dept Hydrol & Atmospher Sci (COPERNICUS GESELLSCHAFT MBH, 2020-04-24)
      Traditional methods for assessing fire danger often depend on meteorological forecasts, which have reduced reliability after similar to 10 d. Recent studies have demonstrated long lead-time correlations between pre-fire-season hydrological variables such as soil moisture and later fire occurrence or area burned, yet the potential value of these relationships for operational forecasting has not been studied. Here, we use soil moisture data refined by remote sensing observations of terrestrial water storage from NASA's Gravity Recovery and Climate Experiment (GRACE) mission and vapor pressure deficit from NASA's Atmospheric Infrared Sounder (AIRS) mission to generate monthly predictions of fire danger at scales commensurate with regional management. We test the viability of predictors within nine US geographic area coordination centers (GACCs) using regression models specific to each GACC. Results show that the model framework improves interannual wildfire-burned-area prediction relative to climatology for all GACCs. This demonstrates the importance of hydrological information to extend operational forecast ability into the months preceding wildfire activity.
    • The Satellite Luminosity Function of M101 into the Ultra-faint Dwarf Galaxy Regime

      Bennet, P.; Sand, D. J.; Crnojević, D.; Spekkens, K.; Karunakaran, A.; Zaritsky, D.; Mutlu-Pakdil, B.; Univ Arizona, Steward Observ (IOP PUBLISHING LTD, 2020-04-08)
      We have obtained deep Hubble Space Telescope (HST) imaging of four faint and ultra-faint dwarf galaxy candidates in the vicinity of M101-Dw21, Dw22, Dw23 and Dw35, originally discovered by Bennet et al. Previous distance estimates using the surface brightness fluctuation technique have suggested that these four dwarf candidates are the only remaining viable M101 satellites identified in ground-based imaging out to the virial radius of M101 (D 250 kpc). Advanced Camera for Surveys imaging of all four dwarf candidates shows no associated resolved stellar populations, indicating that they are thus background galaxies. We confirm this by generating simulated HST color-magnitude diagrams of similar brightness dwarfs at the distance of M101. Our targets would have displayed clear, resolved red giant branches with dozens of stars if they had been associated with M101. With this information, we construct a satellite luminosity function for M101, which is 90% complete to M-V = -7.7 mag and 50% complete to M-V = -7.4 mag, that extends into the ultra-faint dwarf galaxy regime. The M101 system is remarkably poor in satellites in comparison to the Milky Way and M31, with only eight satellites down to an absolute magnitude of M-V = -7.7 mag, compared to the 14 and 26 seen in the Milky Way and M31, respectively. Further observations of Milky Way analogs are needed to understand the halo-to-halo scatter in their faint satellite systems, and connect them with expectations from cosmological simulations.
    • Satellite patches, patch expansion, and doubling time as decision metrics for invasion control: Pennisetum ciliare expansion in southwestern Arizona

      Weston, Jaron D.; McClaran, Mitchel P.; Whittle, Richard K.; Black, Christian W.; Fehmi, Jeffrey S.; Univ Arizona, Sch Nat Resources & Environm (CAMBRIDGE UNIV PRESS, 2019-03)
      Essential variables to consider for an efficient control strategy for invasive plants include dispersion pattern (i.e., satellite or invasion front) and patch expansion rate. These variables were demonstrated for buffelgrass [Pennisetum ciliare (L.) Link], a C-4 perennial grass introduced from Africa, which has invaded broadly around the world. The study site was along a roadway in southern Arizona (USA). The P. ciliare plant distributions show the pattern of clumping associated with the satellite (nascent foci) colonization pattern (average nearest neighbor test, z-score -47.2, P <0.01). The distance between patches ranged from 0.743 to 12.8 km, with an average distance between patches of 5.6 km. Median patch expansion rate was 271% over the 3-yr monitoring period versus 136% found in other studies of established P. ciliare patches. Targeting P. ciliare satellite patches as a control strategy may exponentially reduce the areal doubling time, while targeting the largest patches may have less effect on the invasion speed.
    • Satellite-derived foresummer drought sensitivity of plant productivity in Rocky Mountain headwater catchments: spatial heterogeneity and geological-geomorphological control

      Wainwright, Haruko M.; Steefel, Christoph; Trutner, Sarah D.; Henderson, Amanda N.; Nikolopoulos, Efthymios, I; Wilmer, Chelsea F.; Chadwick, K. Dana; Falco, Nicola; Schaettle, Karl Bernard; Brown, James Bentley; et al. (IOP PUBLISHING LTD, 2020-08)
      Long-term plot-scale studies have found water limitation to be a key factor driving ecosystem productivity in the Rocky Mountains. Specifically, the intensity of early summer (the 'foresummer' period from May to June) drought conditions appears to impose critical controls on peak ecosystem productivity. This study aims to (1) assess the importance of early snowmelt and foresummer drought in controlling peak plant productivity, based on the historical Landsat normalized-difference vegetation index (NDVI) and climate data; (2) map the spatial heterogeneity of foresummer drought sensitivity; and (3) identify the environmental controls (e.g. geomorphology, elevation, geology, plant types) on drought sensitivity. Our domain (15 x 15 km) includes four drainages within the East Water watershed near Gothic, Colorado, USA. We define foresummer drought sensitivity based on the regression slopes of the annual peak NDVI against the June Palmer Drought Severity Index between 1992 and 2010. Results show that foresummer drought sensitivity is spatially heterogeneous, and primarily dependent on the plant type and elevation. In support of the plot-based studies, we find that years with earlier snowmelt and drier foresummer conditions lead to lower peak NDVI; particularly in the low-elevation regions. Using random forest analysis, we identify additional key controls related to surface energy exchanges (i.e. potential net radiation), hydrological processes (i.e. microtopography and slope), and underlying geology. This remote-sensing-based approach for quantifying foresummer drought sensitivity can be used to identify the regions that are vulnerable or resilient to climate perturbations, as well as to inform future sampling, characterization, and modeling studies.