• 13,000 years of sociocultural plant use in the Atacama Desert of northern Chile

      Ugalde, Paula C.; McRostie, Virginia; Gayo, Eugenia M.; García, Magdalena; Latorre, Claudio; Santoro, Calogero M.; Univ Arizona, Sch Anthropol (SPRINGER, 2020-05-06)
      Throughout Earth's most extreme environments, such as the Kalahari Desert or the Arctic, hunter-gatherers found ingenious ways to obtain proteins and sugars provided by plants for dietary requirements. In the hyperarid Atacama Desert, wild plant resources are scarce and unevenly distributed due to limited water availability. This study brings together all available archaeobotanical evidence gathered in the Atacama Desert from the Late Pleistocene (ca. 13,000 cal bp) until the Inka epoch (ca. 450 cal bp) to help us comprehend when these populations acquired and managed useful plants from the coastal zone, Intermediate Depression, High Andes, as well as tropical and subtropical ecosystems. Widespread introduction of farming crops, water control techniques and cultivation of diverse plants by 3,000 cal bp ended not only a chronic food shortage, but also led to the establishment of a set of staple foods for the Atacama Desert dwellers, a legacy that remains visible today. By contrasting these trends with major sociocultural changes, together with palaeodemographic and climatic fluctuations, we note that humans adapted to, and transformed this hyperarid landscape and oscillating climate, with plants being a key factor in their success. This long-term process, which we term the "Green Revolution", coincided with an exponential increase in the number of social groups inhabiting the Atacama Desert during the Late Holocene.
    • 1H, 15N and 13C sequence specific backbone assignment of the vanadate inhibited hematopoietic tyrosine phosphatase

      Machado, Luciana E. S. F.; Page, Rebecca; Peti, Wolfgang; Univ Arizona, Dept Chem & Biochem (SPRINGER, 2018-04)
      The sequence-specific backbone assignment of hematopoietic protein tyrosine phosphatase (HePTP; PTPN7) in presence of vanadate has been determined, based on triple-resonance experiments using uniformly [C-13,N-15]-labeled protein. These assignments facilitate further studies of HePTP in the presence of inhibitors to target leukemia and provide further insights into the function of protein tyrosine phosphatases.
    • 2HDM neutral scalars under the LHC

      Kling, Felix; Su, Shufang; Su, Wei; Univ Arizona, Dept Phys (SPRINGER, 2020-06-26)
      Two Higgs Doublet Models (2HDM) provide a simple framework for new physics models with an extended Higgs sector. The current LHC results, including both direct searches for additional non-Standard Model (SM) Higgs bosons, as well as precision measurements of the SM-like Higgs couplings, already provide strong constraints on the 2HDM parameter spaces. In this paper, we examine those constraints for the neutral scalars in the Type-I and Type-II 2HDM. In addition to the direct search channels with SM final states: H/A → ff¯¯¯, VV, Vh, hh, we study in particular the exotic decay channels of H/A → AZ/HZ once there is a mass hierarchy between the non-SM Higgses. We found that H/A → AZ/H Z channel has unique sensitivity to the alignment limit region which remains unconstrained by conventional searches and Higgs precision measurements. This mode also extends the reach at intermediate tβ for heavy mA that are not covered by the other direct searches.
    • A strategy for a general search for new phenomena using data-derived signal regions and its application within the ATLAS experiment

      ATLAS Collaboration; Univ Arizona, Dept Phys (SPRINGER, 2019)
      This paper describes a strategy for a general search used by the ATLAS Collaboration to find potential indications of new physics. Events are classified according to their final state into many event classes. For each event class an automated search algorithm tests whether the data are compatible with the Monte Carlo simulated expectation in several distributions sensitive to the effects of new physics. The significance of a deviation is quantified using pseudo-experiments. A data selection with a significant deviation defines a signal region for a dedicated follow-up analysis with an improved background expectation. The analysis of the data-derived signal regions on a new dataset allows a statistical interpretation without the large look-elsewhere effect. The sensitivity of the approach is discussed using Standard Model processes and benchmark signals of new physics. As an example, results are shown for 3.2fb-1 of proton-proton collision data at a centre-of-mass energy of 13TeV collected with the ATLAS detector at the LHC in 2015, in which more than 700 event classes and more than 105 regions have been analysed. No significant deviations are found and consequently no data-derived signal regions for a follow-up analysis have been defined.
    • Adjudicating distributive disagreement

      Motchoulski, Alexander; Univ Arizona, Social Sci (SPRINGER, 2019-10-24)
      This paper examines different mechanisms for adjudicating disagreement about distributive justice. It begins with a case where individuals have deeply conflicting convictions about distributive justice and must make a social choice regarding the distribution of goods. Four mechanisms of social choice are considered: social contract formation, Borda count vote, simple plurality vote, and minimax bargaining. I develop an agent-based model which examines which mechanisms lead to the greatest degree of satisfying justice-based preferences over the course iterated social choices. Agents are ascribed two kinds of motivations: they wish to realize justice and to receive a greater package of goods. Each agent seeks to realize her ideal distribution, and the failure to do so leaves agents "disappointed," resulting in their trading off the pursuit of gains in justice in favor of gains in self-interest. Mechanisms are assessed using the metric of how many agents remain interested in justice over the course of iterated adjudication. The mechanisms are also examined under some non-ideal conditions, such as the presence of power asymmetries or strategic behavior. Several significant results are addressed: social contract formation and simple plurality voting are robust under the conditions considered, bargaining is a highly ineffective means of adjudicating distributive disagreement, and lastly allowing for concessions in justice for gains in self-interest proves to be a crucial mechanism for ensuring the stability of resolutions.
    • Administering the HPV Vaccine to People Living with HIV: Providers' Perspectives

      Koskan, Alexis; Brennhofer, Stephanie A; Helitzer, Deborah; Univ Arizona, Mel & Enid Zuckerman Coll Publ Hlth (SPRINGER, 2020-08)
      HIV-positive patients suffer disproportionate burden of anal cancer, a disease which is primarily caused by persistent infection with human papillomavirus (HPV) and is potentially preventable with the completion of the HPV vaccine series. Past research qualitatively explored HIV-positive patients' perspectives about the HPV vaccine. However, little is known about their healthcare practitioners' vaccine recommendation behaviors, the strongest influence on vaccine uptake. This study reports on in-depth interviews conducted with 25 healthcare practitioners who provide care for HIV-positive patients. Qualitative themes that emerged from the study included clinicians' HPV vaccination behaviors, HIV patient's willingness to get the HPV vaccine, the role of HIV-positive patients' immune functioning in terms of timing of HPV vaccine administration, and vaccinating HIV-positive patients over age 26. The majority of providers offered the vaccine at their healthcare facility. Participants varied in their opinions related to the importance of patients' CD4 count in terms of timing of HPV vaccine administration; some believed that patients' immune functioning should first be stabilized to receive the most benefit from the vaccine series. They also differed in the perceived benefit of offering the vaccine to patients over age 26. In light of the U.S. Food and Drug Administration's recent approval to extend HPV vaccination to adults up to age 45 years, more HIV-positive adults may benefit by receiving this vaccine series. Future efforts should ensure that providers regularly promote the HPV vaccine to their adult HIV-positive patients. Vaccinating HIV-positive patients may help reduce the burden of HPV-related cancers, particularly anal cancer.
    • Analysts’ annual earnings forecasts and changes to the I/B/E/S database

      Call, Andrew C.; Hewitt, Max; Watkins, Jessica; Yohn, Teri Lombardi; Univ Arizona (SPRINGER, 2020-09-16)
      I/B/E/S is a common source of analyst earnings forecast data, and the reliability of these data is important for practice and academic research. Examining a common sample period, we compare annual earnings forecasts across two versions of the I/B/E/S detail file, one made available in 2009 and the other made available in 2015. We find substantial differences in the contents of these two versions of the detail file as well as significant differences in the attributes of the earnings forecasts available in each version. Specifically, the earnings forecasts in the more recent version are more accurate and less biased, and they identify substantially different firms as meeting or just beating analysts' expectations than those in the older version. To highlight the potential impact of these differences, we show that the economic magnitude of the effects of analyst experience and brokerage size on earnings forecast accuracy change by over 30% when we use the more recent version. Additional analyses suggest that the differences across versions of the detail file are ongoing. In contrast, we find that different versions of the summary file exhibit only minor differences over time. We also find significant differences in the properties of consensus earnings forecasts calculated from the individual earnings forecasts available in the detail file and consensus earnings estimates from the summary file. Finally, we provide guidance to researchers using I/B/E/S for analyst earnings forecast data.
    • Anatomy of exotic Higgs decays in 2HDM

      Kling, Felix; No, Jose Miguel; Su, Shufang; Univ Arizona, Dept Phys (SPRINGER, 2016-09-16)
      Large mass splittings between new scalars in two-Higgs-doublet models (2HDM) open a key avenue to search for these new states via exotic heavy Higgs decays. We discuss in detail the different search channels for these new scalars at the LHC in the presence of a sizable mass splitting, i.e. a hierarchical 2HDM scenario, taking into account the theoretical and experimental constraints. We provide benchmark planes to exploit the complementarity among these searches, analyzing their potential to probe the hierarchical 2HDM parameter space during LHC Run 2.
    • Application of distance sampling for assessing abundance and habitat relationships of a rare Sonoran Desert cactus

      Flesch, Aaron D.; Murray, Ian W.; Gicklhorn, Jeffrey M.; Powell, Brian F.; Univ Arizona, Sch Nat Resources & Environm (SPRINGER, 2019-11)
      Accurate abundance estimates of plant populations are fundamental to numerous ecological questions and for conservation. Estimating population parameters for rare or cryptic plant species, however, can be challenging and thus developing and testing new methods is useful. We assessed the efficacy of distance sampling for estimating abundance and habitat associations of the endangered Pima pineapple cactus (Coryphantha scheeri var. robustispina), a rare plant in the Sonoran Desert of southwestern North America that has traditionally been surveyed with census-based methods. Distance sampling (DS) involves measuring distances between focal objects and samples of lines or points, and modeling detection functions that adjust estimates for variation in detection probability (P). Although often used in animal systems, DS remains largely untested for plants. We encountered 105 live individuals along 36.9 km of transects in 11 study plots placed across much of the geographic range of the species, and estimated an average density of 1.47 individuals/ha (CV = 0.139). Compared to values from intensive censuses, density estimates from DS were underestimated by only 2.3% on average and highly correlated on the untransformed (r = 0.84) and logarithmic (r = 0.93) scales. Estimates of P averaged 0.49 and declined as soils became increasingly dominated by larger soil substrates, and somewhat with increasing vegetation volume and decreasing cactus height. Local densities increased with increasing slope and soil substrate size and decreased with increasing vegetation volume (P <= 0.024). Combined with careful survey design, DS offers an efficient method for estimating population parameters for uncommon and cryptic plants.
    • The art of co-production of knowledge in environmental sciences and management: lessons from international practice

      Djenontin, Ida Nadia S.; Meadow, Alison M.; Univ Arizona, Sch Geog & Dev; Univ Arizona, Inst Environm (SPRINGER, 2018-06)
      This review paper addresses the challenging question of "how to" design and implement co-production of knowledge in climate science and other environmental and agricultural sciences. Based on a grounded theory review of nine (9) published case studies of transdisciplinary and collaborative research projects, the paper offers a set of common themes regarding specific components and processes for the design, implementation, and achievement of co-production of knowledge work, which represent the "Modus Operandi" of knowledge co-production. The analysis focuses on practical methodological guidance based on lessons from how different research teams have approached the challenges of complex collaborative research. We begin by identifying broad factors or actions that inhibit or facilitate the process, then highlight specific practices associated with co-production of knowledge and necessary competencies for undertaking co-production. We provide insights on issues such as the integration of social and professional cultures, gender and social equity, and power dynamics, and illustrate the different ways in which researchers have addressed these issues. By exploring the specific practices involved in knowledge co-production, this paper provides guidance to researchers on how to navigate different possibilities of the process of conducting transdisciplinary and co-production of knowledge research projects that best fit their research context, stakeholder needs, and research team capacities.
    • ATLAS b-jet identification performance and efficiency measurement with t(t)over-bar events in pp collisions at root s=13 TeV

      Berlendis, S; Cheu, E; Delitzsch, C M; Johns, K A; Jones, S; Lampl, W; LeBlanc, M; Leone, R; Loch, P; Rutherfoord, J P; et al. (SPRINGER, 2019-11-25)
      The algorithms used by the ATLAS Collaboration during Run 2 of the Large Hadron Collider to identify jets containing b-hadrons are presented. The performance of the algorithms is evaluated in the simulation and the efficiency with which these algorithms identify jets containing b-hadrons is measured in collision data. The measurement uses a likelihood-based method in a sample highly enriched in t (t) over bar events. The topology of the t -> Wb decays is exploited to simultaneously measure both the jet flavour composition of the sample and the efficiency in a transverse momentum range from 20 to 600 GeV. The efficiency measurement is subsequently compared with that predicted by the simulation. The data used in this measurement, corresponding to a total integrated luminosity of 80.5 fb(-1), were collected in proton-proton collisions during the years 2015-2017 at a centre-of-mass energy root s = 13 TeV. By simultaneously extracting both the efficiency and jet flavour composition, this measurement significantly improves the precision compared to previous results, with uncertainties ranging from 1 to 8% depending on the jet transverse momentum.
    • Bacterial Rhizoplane Colonization Patterns of Buchloe dactyloides Growing in Metalliferous Mine Tailings Reflect Plant Status and Biogeochemical Conditions

      Honeker, Linnea K; Neilson, Julia W; Root, Robert A; Gil-Loaiza, Juliana; Chorover, Jon; Maier, Raina M; Univ Arizona, Dept Soil Water & Environm Sci (SPRINGER, 2017-11)
      Plant establishment during phytostabilization of legacy mine tailings in semiarid regions is challenging due to low pH, low organic carbon, low nutrients, and high toxic metal(loid) concentrations. Plant-associated bacterial communities are particularly important under these harsh conditions because of their beneficial services to plants. We hypothesize that bacterial colonization profiles on rhizoplane surfaces reflect deterministic processes that are governed by plant health and the root environment. The aim of this study was to identify associations between bacterial colonization patterns on buffalo grass (Buchloe dactyloides) rhizoplanes and both plant status (leaf chlorophyll and plant cover) and substrate biogeochemistry (pH, electrical conductivity, total organic carbon, total nitrogen, and rhizosphere microbial community). Buffalo grass plants from mesocosm- and field-scale phytostabilization trials conducted with tailings from the Iron King Mine and Humboldt Smelter Superfund Site in Dewey-Humboldt, Arizona, were analyzed. These tailings are extremely acidic and have arsenic and lead concentrations of 2-4 g kg-1 substrate. Bacterial communities on rhizoplanes and in rhizosphere-associated substrate were characterized using fluorescence in situ hybridization and 16S rRNA gene amplicon sequencing, respectively. The results indicated that the metabolic status of rhizoplane bacterial colonizers is significantly related to plant health. Principal component analysis revealed that root-surface Alphaproteobacteria relative abundance was associated most strongly with substrate pH and Gammaproteobacteria relative abundance associated strongly with substrate pH and plant cover. These factors also affected the phylogenetic profiles of the associated rhizosphere communities. In summary, rhizoplane bacterial colonization patterns are plant specific and influenced by plant status and rhizosphere biogeochemical conditions.
    • Balancing the learning ability and memory demand of a perceptron-based dynamically trainable neural network

      Richter, Edward; Valancius, Spencer; McClanahan, Josiah; Mixter, John; Akoglu, Ali; Univ Arizona, Dept Elect & Comp Engn (SPRINGER, 2018-07)
      Artificial neural networks (ANNs) have become a popular means of solving complex problems in prediction-based applications such as image and natural language processing. Two challenges prominent in the neural network domain are the practicality of hardware implementation and dynamically training the network. In this study, we address these challenges with a development methodology that balances the hardware footprint and the quality of the ANN. We use the well-known perceptron-based branch prediction problem as a case study for demonstrating this methodology. This problem is perfect to analyze dynamic hardware implementations of ANNs because it exists in hardware and trains dynamically. Using our hierarchical configuration search space exploration, we show that we can decrease the memory footprint of a standard perceptron-based branch predictor by 2.3 with only a 0.6% decrease in prediction accuracy.
    • Behavioral pharmacology of the mixed-action delta-selective opioid receptor agonist BBI-11008: studies on acute, inflammatory and neuropathic pain, respiration, and drug self-administration

      Stevenson, Glenn W; Giuvelis, Denise; Cormier, James; Cone, Katherine; Atherton, Phillip; Krivitsky, Rebecca; Warner, Emily; St Laurent, Brooke; Dutra, Julio; Bidlack, Jean M; et al. (SPRINGER, 2020-01-07)
      BBI-11008 had a 78-fold greater affinity for the delta opioid receptor than the mu receptor, and there was no binding to the kappa opioid receptor. BBI-11008 (3.2-100; 10-32 mg kg-1, i.v.) and morphine (1-10; 1-3.2 mg kg-1, i.v.) produced antinociceptive and anti-allodynic effects in assays of acute thermal nociception and complete Freund's adjuvant (CFA)-induced inflammatory pain, with BBI-11008 being less potent than morphine in both assays. BBI-11008 (1-18 mg kg-1, i.v.) had similar efficacy to gabapentin (10-56 mg kg-1, i.v.) in a spinal nerve ligation (SNL) model of neuropathic pain. In the respiration assay, with increasing %CO2 exposure, BBI-11008 produced an initial increase (32 mg kg-1, s.c.) and then decrease (56 mg kg-1, s.c.) in minute volume (MV) whereas morphine (3.2-32 mg kg-1, s.c.) produced dose-dependent decreases in MV. In the drug self-administration procedure, BBI-11008 did not maintain self-administration at any dose tested.
    • Best practices for Electronically Activated Recorder (EAR) research: A practical guide to coding and processing EAR data

      Kaplan, Deanna M; Rentscher, Kelly E; Lim, Maximilian; Reyes, Ramon; Keating, Dylan; Romero, Jennifer; Shah, Anisha; Smith, Aaren D; York, Kylee A; Milek, Anne; et al. (SPRINGER, 2020-01-02)
      Since its introduction in 2001, the Electronically Activated Recorder (EAR) method has become an established and broadly used tool for the naturalistic observation of daily social behavior in clinical, health, personality, and social science research. Previous treatments of the method have focused primarily on its measurement approach (relative to other ecological assessment methods), research design considerations (e.g., sampling schemes, privacy considerations), and the properties of its data (i.e., reliability, validity, and added measurement value). However, the evolved procedures and practices related to arguably one of the most critical parts of EAR research-the coding process that converts the sampled raw ambient sounds into quantitative behavioral data for statistical analysis-so far have largely been communicated informally between EAR researchers. This article documents "best practices" for processing EAR data, which have been tested and refined in our research over the years. Our aim is to provide practical information on important topics such as the development of a coding system, the training and supervision of EAR coders, EAR data preparation and database optimization, the troubleshooting of common coding challenges, and coding considerations specific to diverse populations.
    • Buffelgrass invasion and glyphosate effects on desert soil microbiome communities

      Gornish, Elise S.; Franklin, Kim; Rowe, Julia; Barberán, Albert; Univ Arizona, Sch Nat Resources & Environm; Univ Arizona, Dept Environm Sci (SPRINGER, 2020-05-04)
      Buffelgrass (Cenchus ciliaris) is a drought-tolerant invasive grass in the Americas and Australia that significantly impacts native plant communities and ecosystems. Despite the clear need to develop a comprehensive understanding of how buffelgrass is able to invade and rapidly establish in arid ecosystems, there is still a lack of knowledge as to if and how this weed might change the soil microbiome in a way that affects its dominance in the presence of management. We investigated the effect of buffelgrass on soil microbial communities in areas that have either been exposed to or not exposed to glyphosate in Saguaro National Park, Arizona USA. We found that buffelgrass roots in invaded areas are surrounded by a distinct soil community that includes a greater number of nitrifiers than in uninvaded soil. We also observed increases in arbuscular mycorrhizal fungi, ectomycorrhizal fungi and methanotrophs with buffelgrass invasion compared to uninvaded soil. Finally, we found no evidence of glyphosate effects on the soil microbiome. Overall, our study results suggest that buffelgrass can escape the limitation of nutrient availability in arid ecosystems by directly or indirectly modifying the soil microbiome. The competitive dominance of buffelgrass in arid systems might be indirectly enhanced by nitrifiers and fungal symbionts, which are often involved in rapid biomass accumulation. This work highlights the importance of soil microbiome considerations in weed science research.
    • Building the local food movement in Chiapas, Mexico: rationales, benefits, and limitations

      Bellante, Laurel; Univ Arizona, Sch Geog & Dev (SPRINGER, 2016-05-18)
      Alternative food networks (AFNs) have become a common response to the socioecological injustices generated by the industrialized food system. Using a political ecology framework, this paper evaluates the emergence of an AFN in Chiapas, Mexico. While the Mexican context presents a particular set of challenges, the case study also reveals the strength the alternative food movement derives from a diverse network of actors committed to building a “community economy” that reasserts the multifunctional values of organic agriculture and local commodity chains. Nonetheless, just as the AFN functions as an important livelihood strategy for otherwise disenfranchised producers it simultaneously encounters similar limitations as those observed in other market-driven approaches to sustainable food governance.
    • C-infinity Smoothing for Weak Solutions of the Inhomogeneous Landau Equation

      Henderson, Christopher; Snelson, Stanley; Univ Arizona, Dept Math (SPRINGER, 2019-11-06)
      We consider the spatially inhomogeneous Landau equation with initial data that is bounded by a Gaussian in the velocity variable. In the case of moderately soft potentials, we show that weak solutions immediately become smooth, and remain smooth as long as the mass, energy, and entropy densities remain under control. For very soft potentials, we obtain the same conclusion with the additional assumption that a sufficiently high moment of the solution in the velocity variable remains bounded. Our proof relies on the iteration of local Schauder-type estimates.
    • Caffeine inhibits PI3K and mTORC2 in Dictyostelium and differentially affects multiple other cAMP chemoattractant signaling effectors

      Tariqul Islam, A F M; Scavello, Margarethakay; Lotfi, Pouya; Daniel, Dustin; Haldeman, Pearce; Charest, Pascale G; Univ Arizona, Dept Chem & Biochem; Univ Arizona, Dept Basic Med Sci (SPRINGER, 2019-07-01)
      Caffeine is commonly used in Dictyostelium to inhibit the synthesis of the chemoattractant cAMP and, therefore, its secretion and the autocrine stimulation of cells, in order to prevent its interference with the study of chemoattractant-induced responses. However, the mechanism through which caffeine inhibits cAMP synthesis in Dictyostelium has not been characterized. Here, we report the effects of caffeine on the cAMP chemoattractant signaling network. We found that caffeine inhibits phosphatidylinositol 3-kinase (PI3K) and mechanistic target of rapamycin complex 2 (mTORC2). Both PI3K and mTORC2 are essential for the chemoattractant-stimulated cAMP production, thereby providing a mechanism for the caffeine-mediated inhibition of cAMP synthesis. Our results also reveal that caffeine treatment of cells leads to an increase in cAMP-induced RasG and Rap1 activation, and inhibition of the PKA, cGMP, MyoII, and ERK1 responses. Finally, we observed that caffeine has opposite effects on F-actin and ERK2 depending on the assay and Dictyostelium strain used, respectively. Altogether, our findings reveal that caffeine considerably affects the cAMP-induced chemotactic signaling pathways in Dictyostelium, most likely acting through multiple targets that include PI3K and mTORC2.
    • Carfilzomib combined with suberanilohydroxamic acid (SAHA) synergistically promotes endoplasmic reticulum stress in non-small cell lung cancer cell lines.

      Hanke, Neale T; Garland, Linda L; Baker, Amanda F; Univ Arizona, Ctr Canc, Coll Med, Tucson, AZ 85721 USA (SPRINGER, 2016-03-01)
      The endoplasmic reticulum (ER) stress response is a therapeutic target for pharmacologic intervention in cancer cells. We hypothesized that combining carfilzomib (CFZ), a proteasome inhibitor, and vorinostat (SAHA), a histone deacetylase (HDAC) inhibitor, would synergistically activate ER stress in non-small cell lung cancer (NSCLC) cell lines, resulting in enhanced anti-tumor activity. Five NSCLC cell lines were treated with CFZ, SAHA, or the combination and cell proliferation measured using the MTT assay. Calcusyn software was utilized to determine the combination index as a measure of synergy. Cell viability and cytotoxicity were measured using trypan blue exclusion, CellTiter, and CytoTox assays. Western blot was used to measure markers of apoptosis, ER stress, and oxidative stress-related proteins. Reactive oxygen species (ROS) was measured using the fluorophore CM-H2DCFDA. Synergistic activity was observed for all cell lines following 48 and 72 h of combined treatment. H520 and A549 cell lines were used to assess viability and apoptosis. In both cell lines, increased death and cleaved caspase-3 were observed following combination treatment as compared with single-agent treatments. Combination therapy was associated with upregulation of ER stress-regulated proteins including activating transcription factor 4, GRP78/BiP, and C/EBP homologous protein. Both cell lines also showed increased ROS and the oxidative stress-related protein, heat shock protein 70. Combining proteasome inhibition with HDAC inhibition enhances ER stress, which may contribute to the synergistic anticancer activity observed in NSCLC cell lines. Further preclinical and clinical studies of CFZ + SAHA in NSCLC are warranted.