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  • Draft Genome Assembly of the Entomopathogenic Bacterium Photorhabdus luminescens subsp. sonorensis Caborca

    Duong, Duy An; Espinosa-Artiles, Patricia; Orozco, Rousel A; Molnár, István; Stock, S Patricia; Univ Arizona, Ctr Insect Sci; Univ Arizona, Southwest Ctr Nat Prod Res; Univ Arizona, Dept Entomol; Univ Arizona, Sch Anim & Comparat Biomed Sci (AMER SOC MICROBIOLOGY, 2019-09)
    Photorhabdus luminescens subsp. sonorensis strain Caborca is an entomopathogenic bacterium with a dual lifestyle, namely, as a mutualist of the Heterorhabditis sonorensis nematode and a pathogen to a wide range of insect species. The genome assembly, in 231 contigs, is 5.2 Mbp long and includes 25 putative gene clusters for secondary metabolism.
  • Explaining the ANITA anomaly with inelastic boosted dark matter

    Heurtier, Lucien; Kim, Doojin; Park, Jong-Chul; Shin, Seodong; Univ Arizona, Dept Phys (AMER PHYSICAL SOC, 2019-09-05)
    We propose a new physics scenario in which the decay of a very heavy dark-matter candidate which does not interact with the neutrino sector could explain the two anomalous events recently reported by the Antarctic Impulsive Transient Antenna Collaboration. The model is composed of two components of dark matter, an unstable dark-sector state and a massive dark gauge boson. We assume that the heavier dark-matter particle of an EeV-range mass is distributed over the Galactic halo and disintegrates into a pair of lighter-highly boosted-dark-matter states in the present Universe which reach and penetrate the Earth. The latter scatters inelastically off a nucleon and produces a heavier dark-sector unstable state which subsequently decays back to the lighter dark matter along with hadrons, which induce extensive air showers, via on /off shell dark gauge boson. Depending on the mass hierarchy within the dark sector, either the dark gauge boson or the unstable dark-sector particle can be long-lived, hence transmitted significantly through the Earth. We study the angular distribution of the signal and show that our model favors emergence angles in the range similar to 25 degrees-35 degrees if the associated parameter choices bear the situation where the mean free path of the boosted incident particle is much larger than the Earth diameter, while its long-lived decay product has a decay length of dimensions comparable to the Earth radius. Our model, in particular, avoids any constraints from complementary neutrino searches such as IceCube or the Auger observatory.
  • Defective Transcriptional Programming of Effector CD8 T Cells in Aged Mice Is Cell-Extrinsic and Can Be Corrected by Administration of IL-12 and IL-18

    Jergović, Mladen; Thompson, Heather L.; Renkema, Kristin R.; Smithey, Megan J.; Nikolich-Žugich, Janko; Univ Arizona, Dept Immunobiol, Coll Med Tucson; Univ Arizona, Ctr Aging, Coll Med Tucson (FRONTIERS MEDIA SA, 2019-09-18)
    In response to infection with intracellular microorganisms, old mice mobilize decreased numbers of antigen-specific CD8T cells with reduced expression of effector molecules and impaired cytolytic activity. Molecular mechanisms behind these defects and the cell-intrinsic (affecting naive CD8 T cells themselves) vs. extrinsic, microenvironmental origin of such defects remain unclear. Using reciprocal transfer experiments of highly purified naive T cells from adult and old transgenic OT-1 mice, we decisively show that the dominant effect is cell-extrinsic. Naive adult OT-1 T cells failed to expand and terminally differentiate in the old organism infected with Listeria-OVA. This defect was preceded by blunted expression of the master transcription factor T-bet and impaired glycolytic switch when T cells are primed in the old organism. However, both old and adult naive CD8T cells proliferated and produced effector molecules to a similar extent when stimulated in vitro with polyclonal stimuli, as well as when transferred into adult recipients. Multiple inflammatory cytokines with direct effects on T cell effector differentiation were decreased in spleens of old animals, particularly IL-12 and IL-18. Of note, in vivo treatment of mice with IL-12 and IL-18 on days 4-6 of Listeria infection reconstituted cytotoxic T cell response of aged mice to the level of adult. Therefore, critical cytokine signals which are underproduced in the old priming environment can restore proper transcriptional programming of old naive CD8T cells and improve immune defense against intracellular microorganisms.
  • Targeting the Non-catalytic RVxF Site of Protein Phosphatase-1 With Small Molecules for Ebola Virus Inhibition

    Lin, Xionghao; Ammosova, Tatiana; Choy, Meng S.; Pietzsch, Colette A.; Ivanov, Andrey; Ahmad, Asrar; Saygideğer, Yasemin; Kumari, Namita; Kovalskyy, Dmytro; Üren, Aykut; et al. (FRONTIERS MEDIA SA, 2019-09-13)
    Ebola virus (EBOV) is a non-segmented negative-sense RNA virus that causes a severe human disease. The ongoing EBOV outbreak in the Eastern part of Democratic Republic of the Congo has resulted to date in over 2500 confirmed cases including over 1500 deaths. Difficulties with vaccine administration indicate the necessity for development of new general drugs and therapeutic strategies against EBOV. Host Ser/Thr protein phosphatases, particularly PP1 and PP2A, facilitate EBOV transcription by dephosphorylating the EBOV VP30 protein and switching activity of the polymerase complex toward replication. Previously, we developed small molecule 1E7-03 that targeted host protein phosphatase-1 (PP1) and induces phosphorylation of EBOV VP30 protein thus shifting transcription-replication balance and inhibiting EBOV replication. Here, we developed a new EBOV inhibitor, 1E7-07, that potently inhibits EBOV replication and displays significantly improved metabolic stability when compared to previously described 1E7-03. Proteome analysis of VP30 shows that 1E7-07 increases its phosphorylation on Thr-119 and Ser-124 over 3-fold with p < 0.001, which likely contributes to EBOV inhibition. We analyzed 1E7-07 binding to PP1 using a mass spectrometry-based protein painting approach. Combined with computational docking, protein painting shows that 1E7-07 binds to several PP1 sites including the RVxF site, C-terminal groove and NIPP1-helix binding pocket. Further analysis using surface plasmon resonance and a split NanoBiT system demonstrates that 1E7-07 binds primarily to the RVxF site. Together, detailed analysis of 1E7-07 binding to PP1 and identification of the RVxF site as the main binding site opens up an opportunity for future development of PP1-targeting EBOV inhibitors.
  • Drivers of C cycling in three arctic-alpine plant communities

    Sørensen, Mia Vedel; Graae, Bente Jessen; Classen, Aimee; Enquist, Brian J.; Strimbeck, Richard; Univ Arizona, Dept Ecol & Evolutionary Biol, BioSci West (TAYLOR & FRANCIS LTD, 2019)
    Recent vegetation changes in arctic-alpine tundra ecosystems may affect several ecosystem processes that regulate microbe and soil functions. Such changes can alter ecosystem carbon (C) cycling with positive feedback to the atmosphere if plant C uptake is less than the amount of soil C released. Here, we examine how differences in plant functional traits, microbial activity, and soil processes within and across Salix-dominated shrub, dwarf shrub-dominated heath, and herb- and cryptogam-dominated meadow communities influence C cycling. We develop a hypothesized framework based on a priori model selection of variation in daytime growing season gross ecosystem photosynthesis (GEP) and above-and belowground respiration. The fluxes were standardized to light and temperature. Gross ecosystem photosynthesis was primarily related to soil moisture and secondarily to plant functional traits and aboveground biomass, and belowground respiration was dependent on the community weighted mean of specific leaf area (SLA(CWM)). Similarly, microbial activity was linked with SLA(CWM) and was highest in meadows, and carbon-degrading microbial activity decreased with vegetation woodiness. These results suggest that shrub expansion may influence summer C cycling differently depending on plant community, as belowground respiration might increase in the heath and decrease in the meadow communities.
  • Inheritance of HLA-Cw7 Associated With Autism Spectrum Disorder (ASD)

    Harville, Terry; Rhodes-Clark, Bobbie; Bennuri, Sirish C.; Delhey, Leanna; Slattery, John; Tippett, Marie; Wynne, Rebecca; Rose, Shannon; Kahler, Stephen; Frye, Richard E.; et al. (FRONTIERS MEDIA SA, 2019-09-11)
    Autism spectrum disorder (ASD) is a behaviorally defined disorder that is now thought to affect approximately 1 in 69 children in the United States. In most cases, the etiology is unknown, but several studies point to the interaction of genetic predisposition with environmental factors. The immune system is thought to have a causative role in ASD, and specific studies have implicated T lymphocytes, monocytes, natural killer (NK) cells, and certain cytokines. The human leukocyte antigen (HLA) system is involved in the underlying process for shaping an individual's immune system, and specific HLA alleles are associated with specific diseases as risk factors. In this study, we determine whether a specific HLA allele was associated with ASD in a large cohort of patients with ASD. Identifying such an association could help in the identification of immune system components which may have a causative role in specific cohorts of patients with ASD who share similar specific clinical features. Specimens from 143 patients with ASD were analyzed with respect to race and ethnicity. Overall, HLA-Cw7 was present in a much greater frequency than expected in individuals with ASD as compared to the general population. Further, the cohort of patients who express HLA-Cw7 shares specific immune system/inflammatory clinical features including being more likely to have allergies, food intolerances, and chronic sinusitis as compared to those with ASD who did not express HLA-Cw7. HLA-Cw7 has a role in stimulating NK cells. Thus, this finding may indicate that chronic over-activation of NK cells may have a role in the manifestation of ASD in a cohort of patients with increased immune system/inflammatory features.
  • Secondary Aortoduodenal Fistula Presenting as Gastrointestinal Bleeding and Fungemia

    Vegunta, Radhakrishna; Vegunta, Rathnamitreyee; Kutti Sridharan, Gurusaravanan; Univ Arizona, Internal Med (CUREUS INC, 2019-09-05)
    A 55-year-old African American man with a history of abdominal aortic pseudoaneurysm repair presented to the ED with complaints of black-colored stools mixed with fresh blood and fever for three days duration. The exam was unremarkable except for abdominal bruits and pallor. CT angiogram showed perigraft fluid collection, bowel wall thickening, and loss of normal fat planes between the aorta and adjacent bowel at the level of the third portion of the duodenum. Polymicrobial infection was noted in the aortic graft and blood cultures grew Candida. The patient underwent urgent removal of the infected graft, duodenal repair along with appropriate antimicrobial therapy. He did well postoperatively and was discharged in a stable condition. Our case highlights the importance of maintaining a high index of suspicion of aortoenteric fistula (AEF) when a patient with a prior abdominal aortic graft develops gastrointestinal (GI) bleeding as this condition is universally fatal if unrecognized.
  • Hypoxia-induced PIM kinase and laminin-activated integrin alpha 6 mediate resistance to PI3K inhibitors in bone-metastatic CRPC

    Toth, Rachel K; Tran, Jack D; Muldong, Michelle T; Nollet, Eric A; Schulz, Veronique V; Jensen, Corbin C; Hazlehurst, Lori A; Corey, Eva; Durden, Donald; Jamieson, Christina; et al. (E-CENTURY PUBLISHING CORP, 2019)
    Bone-metastatic castration-resistant prostate cancer (CRPC) is lethal due to inherent resistance to androgen deprivation therapy, chemotherapy, and targeted therapies. Despite the fact that a majority of CRPC patients (approximately 70%) harbor a constitutively active PI3K survival pathway, targeting the PI3K/mTOR pathway has failed to increase overall survival in clinical trials. Here, we identified two separate and independent survival pathways induced by the bone tumor microenvironment that are hyperactivated in CRPC and confer resistance to PI3K inhibitors. The first pathway involves integrin α6β1-mediated adhesion to laminin and the second involves hypoxia-induced expression of PIM kinases. In vitro and in vivo models demonstrate that these pathways transduce parallel but independent signals that promote survival by reducing oxidative stress and preventing cell death. We further demonstrate that both pathways drive resistance to PI3K inhibitors in PTEN-negative tumors. These results provide preclinical evidence that combined inhibition of integrin α6β1 and PIM kinase in CRPC is required to overcome tumor microenvironment-mediated resistance to PI3K inhibitors in PTEN-negative tumors within the hypoxic and laminin-rich bone microenvironment.
  • Association of Cognitive Impairment With Treatment and Outcomes in Older Myocardial Infarction Patients: A Report From the NCDR Chest Pain-MI Registry

    Bagai, Akshay; Chen, Anita Y; Udell, Jacob A; Dodson, John A; McManus, David D; Maurer, Mathew S; Enriquez, Jonathan R; Hochman, Judith; Goyal, Abhinav; Henry, Timothy D; et al. (WILEY, 2019-08-29)
    Background-Little is known regarding use of cardiac therapies and clinical outcomes among older myocardial infarction (MI) patients with cognitive impairment. Methods and Results-Patients >= 65 years old with MI in the NCDR (National Cardiovascular Data Registry) Chest Pain-MI Registry between January 2015 and December 2016 were categorized by presence and degree of chart-documented cognitive impairment. We evaluated whether cognitive impairment was associated with all-cause in-hospital mortality after adjusting for known prognosticators. Among 43 812 ST-segment-elevation myocardial infarction (STEMI) patients, 3.9% had mild and 2.0% had moderate/severe cognitive impairment; among 90 904 non-ST-segment-elevation myocardial infarction (NSTEMI patients, 5.7% had mild and 2.6% had moderate/severe cognitive impairment. A statistically significant but numerically small difference in the use of primary percutaneous coronary intervention was observed between patients with STEMI with and without cognitive impairment (none, 92.1% versus mild, 92.8% versus moderate/severe, 90.4%; P=0.03); use of fibrinolysis was lower among patients with cognitive impairment (none, 40.9% versus mild, 27.4% versus moderate/severe, 24.2%; P<0.001). Compared with NSTEMI patients without cognitive impairment, rates of angiography, percutaneous coronary intervention, and coronary artery bypass grafting were significantly lower among patients with NSTEMI with mild (41%, 45%, and 70% lower, respectively) and moderate/severe cognitive impairment (71%, 74%, and 93% lower, respectively). After adjustment, compared with no cognitive impairment, presence of moderate/severe (STEW: odds ratio, 2.2, 95% CI, 1.8-2.7; NSTEMI: odds ratio, 1.7, 95% CI, 1.4-2.0) and mild cognitive impairment (STEMI: OR, 1.3, 95% CI, 1.1-1.5; NSTEMI: odds ratio, 1.3, 95% CI, 1.2-1.5) was associated with higher in-hospital mortality. Conclusions-Patients with NSTEMI with cognitive impairment are substantially less likely to receive invasive cardiac care, while patients with STEMI with cognitive impairment receive similar primary percutaneous coronary intervention but less fibrinolysis. Presence and degree of cognitive impairment was independently associated with increased in-hospital mortality. Approaching clinical decision making for older patients with MI with cognitive impairment requires further study.
  • The Astrolabe Project: Identifying and Curating Astronomical ‘Dark Data’ through Development of Cyberinfrastructure Resources

    Stahlman, Gretchen; Heidorn, P. Bryan; Steffen, Julie; Univ Arizona, Sch Informat (E D P SCIENCES, 2018-07-27)
    As research datasets and analyses grow in complexity, data that could be valuable to other researchers and to support the integrity of published work remain uncurated across disciplines. These data are especially concentrated in the "Long Tail" of funded research, where curation resources and related expertise are often inaccessible. In the domain of astronomy, it is undisputed that uncurated "dark data" exist, but the scope of the problem remains uncertain. The "Astrolabe" Project is a collaboration between University of Arizona researchers, the CyVerse cyberinfrastructure environment, and the American Astronomical Society, with a mission to identify and ingest previously-uncurated astronomical data, and to provide a robust computational environment for analysis and sharing of data, as well as services for authors wishing to deposit data associated with publications. Following expert feedback obtained through two workshops held in 2015 and 2016, Astrolabe is funded in part by National Science Foundation. The system is being actively developed within CyVerse, and Astrolabe collaborators are soliciting heterogeneous datasets and potential users for the prototype system. Astrolabe team members are currently working to characterize the properties of uncurated astronomical data, and to develop automated methods for locating potentially-useful data to be targeted for ingest into Astrolabe, while cultivating a user community for the new data management system.
  • Heart Transplantation Survival and the Use of Traumatically Brain-Injured Donors: UNOS Registry Propensity-Matched Analysis

    Barac, Yaron D; Jawitz, Oliver K; Klapper, Jacob; Schroder, Jacob; Daneshmand, Mani A; Patel, Chet; Hartwig, Matt G; Sweitzer, Nancy K; Milano, Carmelo A; Univ Arizona, Sarver Heart Ctr, Div Cardiol (WILEY, 2019-08-30)
    Background-The transplantation of hearts from traumatically brain-injured (TBI) donors has been associated with inferior long-term survival in single-center analyses. However, in a more recent analysis, death caused by cerebrovascular accident was associated with worse posttransplant survival in recipients. The purpose of this study was to explore the outcomes of heart transplantation in recipients receiving donor hearts from TBI and non-TBI donors in a large national registry. Methods and Results-We performed a retrospective cohort analysis of the UNOS (United Network of Organ Sharing) Registry Organ Procurement and Transplantation Network between 2006 and 2018 for adult candidates wait-listed for isolated heart transplantation. Recipients were stratified into 2 groups, TBI and non-TBI donors. Propensity score matching was performed. Kaplan-Meier analysis was used to estimate survival posttransplant. A total of 24 894 candidates met inclusion criteria. TBI was the leading cause of death in the donor population. Recipients of TBI donor hearts (N=13 07) were younger (median age, 55 versus 57 years; P<0.001) and less likely women (21.6% versus 29.8%; P<0.001). At 10 years, the TBI group had better long-term survival compared with the non-TBI group (62.8% versus 59.9%; P<0.001). After propensity group matching, the 10-year survival was similar between groups. Conclusions-In the largest analysis of heart transplants and their survival, according to the type of donor injury (TBI versus non-TBI), we found similar survival in heart transplant recipients. Future studies should address specific subpopulations (eg, hemorrhagic stroke) in the non-TBI group to address concerns about reduced posttransplant survival.
  • Influence of low-dose radiation on abscopal responses in patients receiving high-dose radiation and immunotherapy

    Menon, Hari; Chen, Dawei; Ramapriyan, Rishab; Verma, Vivek; Barsoumian, Hampartsoum B; Cushman, Taylor R; Younes, Ahmed I; Cortez, Maria A; Erasmus, Jeremy J; de Groot, Patricia; et al. (BMC, 2019-09-04)
    Background Preclinical evidence suggests that low-dose radiation may overcome the inhibitory effects of the tumor stroma and improve a tumor's response to immunotherapy, when combined with high-dose radiation to another tumor. The aim of this study was to evaluate tumor responses to this combination in a clinical setting. Methods A post-hoc analysis of 3 ongoing immunoradiation trials was performed. Twenty-six (of 155) patients received low-dose radiation (1-20 Gy total), either as scatter from high-dose radiation or from intentional treatment of a second isocenter with low-dose radiation, were evaluated for response. The low-dose lesions were compared to lesions that received no radiation (< 1 Gy total). Response rates, both defined as complete and partial responses as defined by RECIST criteria were used to compare lesion types. Results The 26 patients had a total of 83 lesions for comparison (38 receiving low-dose, 45 receiving no-dose). The average dose given to low-dose lesions was 7.3 Gy (1.1-19.4 Gy), and the average time to response was 56 days. Twenty-two out of 38 (58%) low-dose lesions met the PR/CR criteria for RECIST compared with 8 out of 45 (18%) no-dose lesions (P = 0.0001). The median change for longest diameter size for low-dose lesions was - 38.5% compared to 8% in no-dose lesions (P < 0.0001). Among the low-dose lesions that had at least one no-dose lesion within the same patient as a control (33 and 45 lesions respectively), 12 low-dose lesions (36%) responded without a corresponding response in their no-dose lesions; Conversely, two (4%) of the no-dose lesions responded without a corresponding response in their low-dose lesion (P = 0.0004). Conclusions Low-dose radiation may increase systemic response rates of metastatic disease treated with high-dose radiation and immunotherapy.
  • Acute and 1-Year Hospitalization Costs for Acute Myocardial Infarction Treated With Percutaneous Coronary Intervention: Results From the TRANSLATE-ACS Registry

    Cowper, Patricia A; Knight, J David; Davidson-Ray, Linda; Peterson, Eric D; Wang, Tracy Y; Mark, Daniel B; Univ Arizona, Univ Phys Healthcare Hosp (WILEY, 2019-04-12)
    Background-Hospitalization for acute myocardial infarction (MI) in the United States is both common and expensive, but those features alone provide little insight into cost-saving opportunities. Methods and Results-To understand the cost drivers during hospitalization for acute MI and in the following year, we prospectively studied 11 969 patients with acute MI undergoing percutaneous coronary intervention at 233 US hospitals (2010-2013) from the TRANSLATE-ACS (Treatment With ADP Receptor Inhibitors: Longitudinal Assessment of Treatment Patterns and Events After Acute Coronary Syndrome) registry. Baseline costs were collected in a random subset (n=4619 patients, 54% ST-segment-elevation MI [STEMID, while follow-up costs out to 1 year were collected for all patients. The mean index length of stay was 3.1 days (for both STEMI and non-STEMI) and mean intensive care unit length of stay was 1.2 days (1.4 days for STEMI and 1.0 days for non-STEMI). Index hospital costs averaged $18 931 ($19 327 for STEMI, $18 465 for non-STEMI), with 45% catheterization laboratory-related and 20% attributable to postprocedure hospital stay. Patient factors, including severity of illness and extent of coronary disease, and hospital characteristics, including for profit status and geographic region, identified significant variations in cost. Intensive care was used for 53% of non-STEMI and increased costs by $3282. Postdischarge 1-year costs averaged $8037, and 48% of patients were rehospitalized (half within 2 months and 57% with a cardiovascular diagnosis). Conclusions-While much of the cost of patients with acute MI treated with percutaneous coronary intervention is probably not modifiable by the care team, cost reductions are still possible through quality-preserving practice efficiencies, such as need-based use rather than routine use of intensive care unit for patients with stable non-STEMI.
  • Replacing Saturated Fat With Walnuts or Vegetable Oils Improves Central Blood Pressure and Serum Lipids in Adults at Risk for Cardiovascular Disease: A Randomized Controlled-Feeding Trial

    Tindall, Alyssa M; Petersen, Kristina S; Skulas-Ray, Ann C; Richter, Chesney K; Proctor, David N; Kris-Etherton, Penny M; Univ Arizona, Dept Nutr Sci (WILEY, 2019-05-01)
    Background-Walnuts have beneficial effects on cardiovascular risk factors, but it is unclear whether these effects are attributable to the fatty acid (FA) content, including alpha-linolenic acid (ALA), and/or bioactives. Methods and Results-A randomized, controlled, 3-period, crossover, feeding trial was conducted in individuals at risk for cardiovascular disease (n=45). Following a 2-week standard Western diet run-in (12% saturated FAs [SFA], 7% polyunsaturated FAs, 12% monounsaturated FAs), participants consumed 3 isocaloric weight-maintenance diets for 6 weeks each: a walnut diet (WD; 7% SFA, 16% polyunsaturated FAs, 3% ALA, 9% monounsaturated FAs); a walnut FA-matched diet; and an oleic acid-replaced-ALA diet (7% SFA, 14% polyunsaturated FAs, 0.5% ALA, 12% monounsaturated FAs), which substituted the amount of ALA from walnuts in the WD with oleic acid. This design enabled evaluation of the effects of whole walnuts versus constituent components. The primary end point, central systolic blood pressure, was unchanged, and there were no significant changes in arterial stiffness. There was a treatment effect (P=0.04) for central diastolic blood pressure; there was a greater change following the WD versus the oleic acid-replaced-ALA diet (-1.78 +/- 1.0 versus 0.15 +/- 0.7 mm Hg, P=0.04). There were no differences between the WD and the walnut fatty acid-matched diet (-0.22 +/- 0.8 mm Hg, P=0.20) or the walnut FA-matched and oleic acid-replaced-ALA diets (P=0.74). The WD significantly lowered brachial and central mean arterial pressure. All diets lowered total cholesterol, LDL (low-density lipoprotein) cholesterol, HDL (high-density lipoprotein) cholesterol, and non-HDL cholesterol. Conclusions-Cardiovascular benefits occurred with all moderate-fat, high-unsaturated-fat diets. As part of a low-SFA diet, the greater improvement in central diastolic blood pressure following the WD versus the oleic acid-replaced-ALA diet indicates benefits of walnuts as a whole-food replacement for SFA.
  • Imaging of π-conjugated polymer/fullerene blends used in organic photovoltaics by nonlinear photoluminescence emission

    Vardeny, Shai R.; Baniya, Sangita; Kieu, Khanh; Peyghambarian, Nasser; Vardeny, Z. Valy; Univ Arizona, Coll Opt Sci (SPIE-SOC PHOTO-OPTICAL INSTRUMENTATION ENGINEERS, 2019-05-20)
    A number of image microscopies have been applied to films of p-conjugated polymers and their fullerene blends used in photovoltaic applications; however, they seldom are able to map the polymer/fullerene grain interfaces and detect microscopic defects in the blend films. We have conducted multiphoton microscopy using a 65-fs mode-locked laser at 1.56 mu m for spectroscopy and mapping of films of two prototype p-conjugated polymers, namely MEHPPVand P3HT combined with their blends of PCBM fullerene molecules. The pristine polymer films have shown third harmonic generation and three-photon photoluminescence emission bands that are used for mapping the film topography with micrometer spatial resolution. Since the nonlinear photoluminescence band of the photogenerated charge transfer excitons (CTE) at the polymer/fullerene interfaces in films of polymer/fullerene blends is substantially redshifted compared to that of the excitons in pristine polymers, we could readily map the polymer/fullerene grain interfaces using the nonlinear CTE photoluminescence emission. From the multiphoton imaging of the polymer/fullerene films, we show that the polymer super-grains in MEH-PPV/PCBM are substantially larger than those in P3HT/PCBM, which may be detrimental to charge transport and, in turn, to photovoltaic applications, in agreement with smaller power conversion efficiencies obtained for solar cells based on the former blend. In addition, we also found second harmonic generation emission bands in the MEH-PPV/PCBM blend that result from micron-size embedded defects that do not possess inversion symmetry that forms during the film deposition process at ambient conditions. Multiphoton microscopy and spectroscopy are valuable additions to the tools of organic semiconductor films and devices for investigating the properties and growth of polymer/fullerene blends used for photovoltaic applications with micron spatial resolution. (C) 2019 Society of Photo-Optical Instrumentation Engineers (SPIE).
  • Impact of chronic migraine attacks and their severity on the endogenous μ-opioid neurotransmission in the limbic system

    Jassar, Hassan; Nascimento, Thiago D; Kaciroti, Niko; DosSantos, Marcos F; Danciu, Theodora; Koeppe, Robert A; Smith, Yolanda R; Bigal, Marcelo E; Porreca, Frank; Casey, Kenneth L; et al. (ELSEVIER SCI LTD, 2019-01-01)
    We scanned 15 migraine patients during the spontaneous headache attack (ictal phase): 7 individuals with CM and 8 with episodic migraine (EM), as well as 7 healthy controls (HC), using positron emission tomography (PET) with the selective μ-opioid receptor (μOR) radiotracer [11C]carfentanil. Migraineurs were scanned in two paradigms, one with thermal pain threshold challenge applied to the site of the headache, and one without thermal challenge. Multivariable analysis was performed between the μ-opioid receptor availability and the clinical data.
  • Proximal small bowel obstruction in a patient with cystic fibrosis: a case report

    Alattar, Zana; Thornley, Caitlin; Behbahaninia, Milad; Sisley, Amy; Univ Arizona, Coll Med, Phoenix Integrated Surg Residency; Univ Arizona, Coll Med (SPRINGEROPEN, 2019-09-13)
    Background As advancements are made in the management of cystic fibrosis (CF), survival of the CF patient into adulthood has increased, leading to the discovery of previously unknown CF complications. Though gastrointestinal complications of CF, such as distal intestinal obstruction syndrome, are common, this case demonstrates a variant presentation of small bowel obstruction in this population. Case presentation We describe a 42-year-old male with CF who presented with 2 days of worsening upper abdominal pain, emesis, and loss of bowel function. The patient had no history of any prior abdominal surgeries; however, imaging was concerning for high-grade mechanical small bowel obstruction possibly related to internal hernia. Given leukocytosis and diffusely tender abdomen found on further workup, the decision was made to proceed with diagnostic laparoscopy after a brief period of intravenous fluid resuscitation. Intraoperatively, the transition point was found in the mid-jejunum and was noted to be due to kinking of the bowel causing vascular congestion in the proximal portion. Surgical manipulation of the bowel was required for return of normal perfusion and patency. Conclusion Though the exact mechanism cannot be definitively delineated, we speculate that the increased viscosity and prolonged intestinal transit time, characteristic of CF, resulted in inspissated fecal content in the proximal small bowel, which then acted as a lead point for obstruction. Thus, though small bowel obstruction in patients with CF is often attributed to distal intestinal obstruction syndrome, a broader differential must be considered. Early surgical intervention may be necessary to prevent bowel ischemia and subsequent small bowel resection in a patient presenting with concerning clinical and image findings, as was seen in this patient.
  • Lower Bounds on the Redundancy of Huffman Codes With Known and Unknown Probabilities

    Blanes, Ian; Hernandez-Cabronero, Miguel; Serra-Sagrista, Joan; Marcellin, Michael W.; Univ Arizona, Dept Elect & Comp Engn (IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC, 2019-07-31)
    In this paper, we provide a method to obtain tight lower bounds on the minimum redundancy achievable by a Huffman code when the probability distribution underlying an alphabet is only partially known. In particular, we address the case where the occurrence probabilities are unknown for some of the symbols in an alphabet. Bounds can be obtained for alphabets of a given size, for alphabets of up to a given size, and alphabets of arbitrary size. The method operates on a computer algebra system, yielding closed-form numbers for all results. Finally, we show the potential of the proposed method to shed some light on the structure of the minimum redundancy achievable by the Huffman code.
  • Local temporal trajectories explain population‐level responses to climate change in saguaro (Carnegiea gigantea)

    Rodríguez‐Buriticá, Susana; Winkler, Daniel E.; Webb, Robert H.; Venable, D. Lawrence; Univ Arizona, Sch Nat Resources; Univ Arizona, Dept Ecol & Evolutionary Biol (WILEY, 2019-08-21)
    Population demography is typically assumed to be strongly influenced by climatic factors, particularly with succulent plants and cacti. The saguaro cactus (Carnegiea gigantea) is a long-lived columnar cactus of the Sonoran Desert that experiences episodic recruitment and mortality. Previous studies have attributed long-term changes in saguaro populations to climatic factors, including increased germination and establishment during wet periods and mortality and reduced establishment during droughts and extreme freezes. We used a 48-yr data set of marked individuals at the Desert Laboratory in Tucson, Arizona, to test the hypothesis that local, temporal population trajectories are mediated by topographic heterogeneity that interacts with fluctuating climatic conditions. We tested the influence of local slope and aspect vs. climatic variability on a population of saguaro using >5800 marked individuals that have been measured since 1964. We examined the relationship between demography and climatic variables (drought, precipitation, and extreme temperatures) and found significant differences in growth and survival among aspects and among census periods. Saguaro population growth was higher during wet and cool periods (e.g., 1964-1970), and changes in age structures suggest that topographic differences interact with climatic fluctuations to produce unexpected demographic patterns including large recruitment events during periods of relatively unfavorable climate conditions. Our results highlight the importance of long-term data to detect demographic responses to climate that could not be predicted from short-term studies of plant physiology and population demography.
  • Differentiating lung cancer and infection based on measurements of extracellular pH with acidoCEST MRI

    Lindeman, Leila R; Jones, Kyle M; High, Rachel A; Howison, Christine M; Shubitz, Lisa F; Pagel, Mark D; Univ Arizona, Dept Med Imaging; Univ Arizona, Valley Fever Ctr Excellence; Univ Arizona, Canc Biol Grad Interdisciplinary Program; Univ Arizona, Bioengn Grad Interdisciplinary Program (NATURE PUBLISHING GROUP, 2019-09-10)
    Lung cancer diagnosis via imaging may be confounded by the presence of indolent infectious nodules in imaging studies. This issue is pervasive in the southwestern US where coccidioidomycosis (Valley Fever) is endemic. AcidoCEST MRI is a noninvasive imaging method that quantifies the extracellular pH (pHe) of tissues in vivo, allowing tumor acidosis to be used as a diagnostic biomarker. Using murine models of lung adenocarcinoma and coccidoidomycosis, we found that average lesion pHe differed significantly between tumors and granulomas. Our study shows that acidoCEST MRI is a promising tool for improving the specificity of lung cancer diagnosis.

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