University of Toledo

In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. For example, a key point that needs to be emphasized is thatthere is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process versus those that measure flux through the autophagy pathway (i.e., the completeprocess including the amount and rate of cargo sequestered and degraded). In particular, a block in macroautophagy that results in autophagosome accumulation must be differentiated from stimuli that increase autophagic activity, defined as increasedautophagy induction coupled with increased delivery to, and degradation within, lysosomes (inmost higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in manycases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. It is worth emphasizing here that lysosomal digestion is a stage of autophagy and evaluating its competence is a crucial part of the evaluation of autophagic flux, or complete autophagy. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as forreviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multipleassays to monitor autophagy. Along these lines, because of the potential for pleiotropic effects due to blocking autophagy through genetic manipulation, it is imperative to target by gene knockout or RNA interference more than one autophagyrelated protein. In addition, some individual Atg proteins, or groups of proteins, are involved in other cellular pathways implying that not all Atg proteins can be used as a specific marker for an autophagic process. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular assays, we hope to encourage technical innovation in the field.

In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.

OBJECTIVE: The 1980 American College of Rheumatology (ACR) classification criteria for systemic sclerosis (SSc) lack sensitivity for early SSc and limited cutaneous SSc. The present work, by a joint committee of the ACR and the European League Against Rheumatism (EULAR), was undertaken for the purpose of developing new classification criteria for SSc. METHODS: Using consensus methods, 23 candidate items were arranged in a multicriteria additive point system with a threshold to classify cases as SSc. The classification system was reduced by clustering items and simplifying weights. The system was tested by 1) determining specificity and sensitivity in SSc cases and controls with scleroderma-like disorders, and 2) validating against the combined view of a group of experts on a set of cases with or without SSc. RESULTS: It was determined that skin thickening of the fingers extending proximal to the metacarpophalangeal joints is sufficient for the patient to be classified as having SSc; if that is not present, 7 additive items apply, with varying weights for each: skin thickening of the fingers, fingertip lesions, telangiectasia, abnormal nailfold capillaries, interstitial lung disease or pulmonary arterial hypertension, Raynaud's phenomenon, and SSc-related autoantibodies. Sensitivity and specificity in the validation sample were, respectively, 0.91 and 0.92 for the new classification criteria and 0.75 and 0.72 for the 1980 ACR classification criteria. All selected cases were classified in accordance with consensus-based expert opinion. All cases classified as SSc according to the 1980 ACR criteria were classified as SSc with the new criteria, and several additional cases were now considered to be SSc. CONCLUSION: The ACR/EULAR classification criteria for SSc performed better than the 1980 ACR criteria for SSc and should allow for more patients to be classified correctly as having the disease.

In this study, we developed a typology of deviant workplace behaviors using multidimensional scaling techniques. Results suggest that deviant workplace behaviors vary along two dimensions: minor versus serious, and interpersonal versus organizational. On the basis of these two dimensions, employee deviance appears to fall into four distinct categories: production deviance, property deviance, political deviance, and personal aggression. Theoretical and empirical implications are discussed.

The purpose of this research was to develop broad, theoretically derived measure(s) of deviant behavior in the workplace. Two scales were developed: a 12-item scale of organizational deviance (deviant behaviors directly harmful to the organization) and a 7-item scale of interpersonal deviance (deviant behaviors directly harmful to other individuals within the organization). These scales were found to have internal reliabilities of .81 and .78, respectively. Confirmatory factor analysis verified that a 2-factor structure had acceptable fit. Preliminary evidence of construct validity is also provided. The implications of this instrument for future empirical research on workplace deviance are discussed.

Thin-film solar cells based on Methylammonium triiodideplumbate (CH3NH3PbI3) halide perovskites have recently shown remarkable performance. First-principle calculations show that CH3NH3PbI3 has unusual defect physics: (i) Different from common p-type thin-film solar cell absorbers, it exhibits flexible conductivity from good p-type, intrinsic to good n-type depending on the growth conditions; (ii) Dominant intrinsic defects create only shallow levels, which partially explain the long electron-hole diffusion length and high open-circuit voltage in solar cell. The unusual defect properties can be attributed to the strong Pb lone-pair s orbital and I p orbital antibonding coupling and the high ionicity of CH3NH3PbI3.

Extracellular enzymes are the proximate agents of organic matter decomposition and measures of these activities can be used as indicators of microbial nutrient demand. We conducted a global-scale meta-analysis of the seven-most widely measured soil enzyme activities, using data from 40 ecosystems. The activities of beta-1,4-glucosidase, cellobiohydrolase, beta-1,4-N-acetylglucosaminidase and phosphatase g(-1) soil increased with organic matter concentration; leucine aminopeptidase, phenol oxidase and peroxidase activities showed no relationship. All activities were significantly related to soil pH. Specific activities, i.e. activity g(-1) soil organic matter, also varied in relation to soil pH for all enzymes. Relationships with mean annual temperature (MAT) and precipitation (MAP) were generally weak. For hydrolases, ratios of specific C, N and P acquisition activities converged on 1 : 1 : 1 but across ecosystems, the ratio of C : P acquisition was inversely related to MAP and MAT while the ratio of C : N acquisition increased with MAP. Oxidative activities were more variable than hydrolytic activities and increased with soil pH. Our analyses indicate that the enzymatic potential for hydrolyzing the labile components of soil organic matter is tied to substrate availability, soil pH and the stoichiometry of microbial nutrient demand. The enzymatic potential for oxidizing the recalcitrant fractions of soil organic material, which is a proximate control on soil organic matter accumulation, is most strongly related to soil pH. These trends provide insight into the biogeochemical processes that create global patterns in ecological stoichiometry and organic matter storage.

We present a set of evolving guidelines for reviewing qualitative research, to serve four functions: to contribute to the process of legitimizing qualitative research; to ensure more appropriate and valid scientific reviews of qualitative manuscripts, theses, and dissertations; to encourage better quality control in qualitative research through better self- and other-monitoring; and to encourage further developments in approach and method. Building on a review of existing principles of good practice in qualitative research, we used an iterative process of revision and feedback from colleagues who engage in qualitative research, resulting in a set of seven guidelines common to both qualitative and quantitative research and seven guidelines especially pertinent to qualitative investigations in psychology and related social sciences. The Evolving Guidelines are subject to continuing revision and should not be used in a rigid manner, in order to avoid stifling creativity in this rapidly evolving, rich research tradition.

This article contrasts traditional versus end-user computing environments and reports on the development of an instrument which merges ease of use and information product items to measure the satisfaction of users who directly interact with the computer for a specific application. Using a survey of 618 end users, the researchers conducted a factor analysis and modified the instrument. The results suggest a 12-item instrument that measures five components of end-user satisfaction — content, accuracy, format, ease of use, and timeliness. Evidence of the instrument’s discriminant validity is presented. Reliability and validity is assessed by nature and type of application. Finally, standards for evaluating end-user applications are presented, and the instrument’s usefulness for achieving more precision in research questions is explored.

Halide perovskites solar cells have the potential to exhibit higher energy conversion efficiencies with ultrathin films than conventional thin-film solar cells based on CdTe, CuInSe2 , and Cu2 ZnSnSe4 . The superior solar-cell performance of halide perovskites may originate from its high optical absorption, comparable electron and hole effective mass, and electrically clean defect properties, including point defects and grain boundaries.

The research reported in this paper studies the phenomenon of technostress, that is, stress experienced by end users of Information and Communication Technologies (ICTs), and examines its influence on their job satisfaction, commitment to the organization, and intention to stay. Drawing from the Transaction-Based Model of stress and prior research on the effects of ICTs on end users, we first conceptually build a nomological net for technostress to understand the influence of technostress on three variables relating to end users of ICTs: job satisfaction, and organizational and continuance commitment. Because there are no prior instruments to measure constructs related to technostress, we develop and empirically validate two second order constructs: technostress creators (i.e., factors that create stress from the use of ICTs) and technostress inhibitors (i.e., organizational mechanisms that reduce stress from the use of ICTs). We test our conceptual model using data from the responses of 608 end users of ICTs from multiple organizations to a survey questionnaire. Our results, based on structural equation modeling (SEM), show that technostress creators decrease job satisfaction, leading to decreased organizational and continuance commitment, while Technostress inhibitors increase job satisfaction and organizational and continuance commitment. We also find that age, gender, education, and computer confidence influence technostress. The implications of these results and future research directions are discussed.

Abstract— A modification to Brown and Miller's critical plane approach is proposed to predict multiaxial fatigue life under both in‐phase and out‐of‐phase loading conditions. The components of this modified parameter consist of the maximum shear strain amplitude and the maximum normal stress on the maximum shear strain amplitude plane. Additional cyclic hardening developed during out‐of‐phase loading is included in the normal stress term. Also, the mathematical formulation of this new parameter is such that variable amplitude loading can be accommodated. Experimental results from tubular specimens made of 1045 HR steel under in‐phase and 90° out‐of‐phase axial‐torsional straining using both sinusoidal and trapezoidal wave forms were correlated within a factor of about two employing this approach. Available Inconel 718 axial‐torsional data including mean strain histories were also satisfactorily correlated using the aforementioned parameter.

Based on empirical survey data, this paper uses concepts from sociotechnical theory and role theory to explore the effects of stress created by information and computer technology (ICT)—that is, "technostress"—on role stress and on individual productivity. We first explain different ways in which ICTs can create stress in users and identify factors that create technostress. We next propose three hypotheses: (1) technostress is inversely related to individual productivity, (2) role stress is inversely related to individual productivity, and (3) technostress is directly related to role stress. We then use structural equation modeling on survey data from ICT users in 223 organizations to test the hypotheses. The results show support for them. Theoretically, the paper contributes in three ways. First, the different dimensions of technostress identified here add to existing concepts on stress experienced by individuals in organizations. Second, by showing that technostress inversely affects productivity, the paper reinforces that failure to manage the effects of ICT-induced stress can offset expected increases in productivity. Third, validation of the positive relationship between technostress and role stress adds a new conceptual thread to literature analyzing the relationship between technology and organizational roles and structure. In the practical domain, the paper proposes a diagnostic tool to evaluate the extent to which technostress is present in an organization and suggests that the adverse effects of technostress can be partly countered by strategies that reduce role conflict and role overload.

CONTEXT: Although low levels of high-density lipoprotein cholesterol (HDL-C) increase risk for coronary disease, no data exist regarding potential benefits of administration of HDL-C or an HDL mimetic. ApoA-I Milano is a variant of apolipoprotein A-I identified in individuals in rural Italy who exhibit very low levels of HDL. Infusion of recombinant ApoA-I Milano-phospholipid complexes produces rapid regression of atherosclerosis in animal models. OBJECTIVE: We assessed the effect of intravenous recombinant ApoA-I Milano/phospholipid complexes (ETC-216) on atheroma burden in patients with acute coronary syndromes (ACS). DESIGN: The study was a double-blind, randomized, placebo-controlled multicenter pilot trial comparing the effect of ETC-216 or placebo on coronary atheroma burden measured by intravascular ultrasound (IVUS). SETTING: Ten community and tertiary care hospitals in the United States. PATIENTS: Between November 2001 and March 2003, 123 patients aged 38 to 82 years consented, 57 were randomly assigned, and 47 completed the protocol. INTERVENTIONS: In a ratio of 1:2:2, patients received 5 weekly infusions of placebo or ETC-216 at 15 mg/kg or 45 mg/kg. Intravascular ultrasound was performed within 2 weeks following ACS and repeated after 5 weekly treatments. MAIN OUTCOME MEASURES: The primary efficacy parameter was the change in percent atheroma volume (follow-up minus baseline) in the combined ETC-216 cohort. Prespecified secondary efficacy measures included the change in total atheroma volume and average maximal atheroma thickness. RESULTS: The mean (SD) percent atheroma volume decreased by -1.06% (3.17%) in the combined ETC-216 group (median, -0.81%; 95% confidence interval [CI], -1.53% to -0.34%; P =.02 compared with baseline). In the placebo group, mean (SD) percent atheroma volume increased by 0.14% (3.09%; median, 0.03%; 95% CI, -1.11% to 1.43%; P =.97 compared with baseline). The absolute reduction in atheroma volume in the combined treatment groups was -14.1 mm3 or a 4.2% decrease from baseline (P<.001). CONCLUSIONS: A recombinant ApoA-I Milano/phospholipid complex (ETC-216) administered intravenously for 5 doses at weekly intervals produced significant regression of coronary atherosclerosis as measured by IVUS. Although promising, these results require confirmation in larger clinical trials with morbidity and mortality end points.

Multiple exciton generation (MEG) is a process that can occur in semiconductor nanocrystals, or quantum dots (QDs), whereby absorption of a photon bearing at least twice the bandgap energy produces two or more electron-hole pairs. Here, we report on photocurrent enhancement arising from MEG in lead selenide (PbSe) QD-based solar cells, as manifested by an external quantum efficiency (the spectrally resolved ratio of collected charge carriers to incident photons) that peaked at 114 ± 1% in the best device measured. The associated internal quantum efficiency (corrected for reflection and absorption losses) was 130%. We compare our results with transient absorption measurements of MEG in isolated PbSe QDs and find reasonable agreement. Our findings demonstrate that MEG charge carriers can be collected in suitably designed QD solar cells, providing ample incentive to better understand MEG within isolated and coupled QDs as a research path to enhancing the efficiency of solar light harvesting technologies.

[1] We upscaled FLUXNET observations of carbon dioxide, water, and energy fluxes to the global scale using the machine learning technique, model tree ensembles (MTE). We trained MTE to predict site-level gross primary productivity (GPP), terrestrial ecosystem respiration (TER), net ecosystem exchange (NEE), latent energy (LE), and sensible heat (H) based on remote sensing indices, climate and meteorological data, and information on land use. We applied the trained MTEs to generate global flux fields at a 0.5° × 0.5° spatial resolution and a monthly temporal resolution from 1982 to 2008. Cross-validation analyses revealed good performance of MTE in predicting among-site flux variability with modeling efficiencies (MEf) between 0.64 and 0.84, except for NEE (MEf = 0.32). Performance was also good for predicting seasonal patterns (MEf between 0.84 and 0.89, except for NEE (0.64)). By comparison, predictions of monthly anomalies were not as strong (MEf between 0.29 and 0.52). Improved accounting of disturbance and lagged environmental effects, along with improved characterization of errors in the training data set, would contribute most to further reducing uncertainties. Our global estimates of LE (158 ± 7 J × 1018 yr−1), H (164 ± 15 J × 1018 yr−1), and GPP (119 ± 6 Pg C yr−1) were similar to independent estimates. Our global TER estimate (96 ± 6 Pg C yr−1) was likely underestimated by 5–10%. Hot spot regions of interannual variability in carbon fluxes occurred in semiarid to semihumid regions and were controlled by moisture supply. Overall, GPP was more important to interannual variability in NEE than TER. Our empirically derived fluxes may be used for calibration and evaluation of land surface process models and for exploratory and diagnostic assessments of the biosphere.

In 2011, Lake Erie experienced the largest harmful algal bloom in its recorded history, with a peak intensity over three times greater than any previously observed bloom. Here we show that long-term trends in agricultural practices are consistent with increasing phosphorus loading to the western basin of the lake, and that these trends, coupled with meteorological conditions in spring 2011, produced record-breaking nutrient loads. An extended period of weak lake circulation then led to abnormally long residence times that incubated the bloom, and warm and quiescent conditions after bloom onset allowed algae to remain near the top of the water column and prevented flushing of nutrients from the system. We further find that all of these factors are consistent with expected future conditions. If a scientifically guided management plan to mitigate these impacts is not implemented, we can therefore expect this bloom to be a harbinger of future blooms in Lake Erie.

First-principles calculations help to understand the fundamental mechanisms of the emerging perovskite solar cells and guide further developments.

The dimensionality of the user satisfaction construct is an important theoretical issue that has received considerable attention. Focusing on end users who directly interact with application software, Doll and Torkzadeah (1988) develop a 12-item application specific instrument for providing an overall assessment of end-user computing satisfaction (EUCS). They also contend that EUCS is comprised of five component measures (content, accuracy, format, ease of use, timeliness) that explain the construct and permit more precision in formulating and testing research hypotheses. The acceptance of the EUCS as a standardized instrument requires confirmation that it explains and measures the user satisfaction construct.Based on a sample of 409 respondents from 18 organizations, this research uses confirmatory factor analysis (LISREL) to test alternative models of underlying factor structure and assess the reliability and validity of factors and items. Without respecifying the model, the results provide some support for Doll and Torkzadeh's proposed model of the five first-order factors and one second-order (higher-order) factor. Thus the evidence supports the use of: (1) the 12-item instrument as an overall measure of EUCS; and (2) the five component factors for explaining the EUCS construct.

Abstract: Although forest edges have been studied extensively as an important consequence of fragmentation, a unifying theory of edge influence has yet to be developed. Our objective was to take steps toward the development of such a theory by (1) synthesizing the current knowledge of patterns of forest structure and composition at anthropogenically created forest edges, (2) developing hypotheses about the magnitude and distance of edge influence that consider the ecological processes influencing these patterns, and (3) identifying needs for future research. We compiled data from 44 published studies on edge influence on forest structure and composition in boreal, temperate, and tropical forests. Abiotic and biotic gradients near created forest edges generate a set of primary responses to edge creation. Indirect effects from these primary responses and the original edge gradient perpetuate edge influence, leading to secondary responses. Further changes in vegetation affect the edge environment, resulting in ongoing edge dynamics. We suggest that the magnitude and distance of edge influence are a direct function of the contrast in structure and composition between adjacent communities on either side of the edge. Local factors such as climate, edge characteristics, stand attributes, and biotic factors affect patch contrast. Regional factors define the context within which to assess the ecological significance of edge influence (the degree to which the edge habitat differs from interior forest habitat). Our hypotheses will help predict edge influence on structure and composition in forested ecosystems, an important consideration for conservation. For future research on forest edges in fragmented landscapes, we encourage the testing of our hypotheses, the use of standardized methodology, complete descriptions of study sites, studies on other types of edges, synthesis of edge influence on different components of the ecosystem, and investigations of edges in a landscape context.