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Ectopic lipids play a key role in numerous pathologies, including heart disease, stroke, and diabetes. Of all the lipids studied, perhaps the most well understood is cholesterol, a widely used clinical biomarker of cardiovascular disease and a target of pharmacological interventions (e.g., statins). Thousands of studies have interrogated the regulation and action of this disease-causing sterol. As a growing body of literature indicates, a new class of lipid-based therapies may be on the horizon. Ceramides are cholesterol-independent biomarkers of heart disease and diabetes in humans. Studies in rodents suggest that they are causative agents of disease, as lowering ceramides through genetic or pharmacological interventions prevents cardiovascular disease and diabetes. Herein, we discuss the evidence supporting the potential of therapeutics targeting ceramides to treat cardiometabolic disease, contrasting it with the robust datasets that drove the creation of cholesterol-lowering pharmaceuticals.

In this paper we present a series of results which show separations between the standard seeded model of self-assembly, Winfree's abstract Tile Assembly Model (aTAM), and the “seedless” 2-Handed Assembly Model (2HAM), which incorporates the dynamics of hierarchical self-assembly. In particular, we focus on the problem of self-assembling various shapes while minimizing the sizes of tile sets, or “programs”, in each of these models in order to compare and contrast the models. A high-level overview of a subset of these results was presented in a paper by the authors in STACS 2013, but in this version we expand and improve the set of results related to showing separations between the two models according to their abilities to self-assemble various shapes. We exhibit classes of finite shapes that can be self-assembled more efficiently in each model. We also demonstrate infinite shapes that can self-assemble in one model but not in the other, as well as a shape which cannot self-assemble in either model.

In this paper, we study the self-assembly of rectangles in a non-cooperative, 3D version of Winfree's abstract Tile Assembly Model. We prove two results. First, we give the full details for the proof of a general construction for the efficient self-assembly of thin rectangles that was first reported by Furcy, Summers and Wendlandt (2019). This construction is non-cooperative and “just-barely” 3D in the sense that it places tiles at most one step into the third dimension. Second, we give a non-cooperative, just-barely 3D optimal encoding construction that self-assembles the bits of a given binary string along the perimeter of a thin rectangle of constant height.

We update the Wood (2016) survey that gathered perceptions of accounting academics regarding the review and publication process to measure how perceptions have changed over the last five years. We find that academics generally perceive the overall process has not improved or has become worse since 2016. More specifically, we find that respondents think acceptance rates in elite journals should nearly double. Respondents believe reviewers focus too much on incremental contribution, rigor and method and that reviewers and editors give too little consideration for research that contributes to practice. Respondents believe that their institutions focus too much on publishing in top journals and that top journals are biased in that they give well-known researchers preferential treatment and favor certain topic areas and methodologies. The perceptions are largely the same across editors, reviewers, and the topic area and university ranking of respondents.

Sphingolipids are essential lipid components in the intestinal epithelial cells (IEC) along the intestinal tract. They play crucial roles in maintaining barrier integrity, regulating nutrient absorption, and acting as signaling molecules to regulate regeneration and differentiation of intestinal mucosa (Kurek et al., 2012). Ceramide is the central sphingolipid species and the precursor of all complex sphingolipids and other downstream simple intermediates like sphingosine (SPH), ceramide-1-phosphate (C-1-P), and sphingosine-1-phosphate (S-1-P). It is also a critical signaling molecule regulating numerous physiologic and pathologic processes. This review will summarize the metabolism of ceramides in the gut and their regulation in inflammatory bowel diseases and colorectal cancer.

The Mayo Clinic recently introduced a diagnostic test that quantifies plasma ceramides in order to identify patients at risk of major adverse cardiac events. By comparing recent discoveries about these biomarker ceramides with the exhaustive body of literature surrounding cholesterol, Summers aims to highlight important advances and critically needed areas of investigation on this exciting class of bioactive lipids.

Objective Aging and weight gain lead to a decline in brown and beige adipocyte functionality that exacerbates obesity and insulin resistance. We sought to determine whether sphingolipids, such as ceramides, a class of lipid metabolites that accumulate in aging and overnutrition, are sufficient or necessary for the metabolic impairment of these thermogenic adipocytes. Methods We generated new mouse models allowing for the conditional ablation of genes required for ceramide synthesis (i.e., serine palmitoyltransferase subunit 2, Sptlc2) or degradation (i.e., acid ceramidase 1, Asah1) from mature, thermogenic adipocytes (i.e., from cells expressing uncoupling protein-1). Mice underwent a comprehensive suite of phenotyping protocols to assess energy expenditure and glucose and lipid homeostasis. Complementary studies were conducted in primary brown adipocytes to dissect the mechanisms controlling ceramide synthesis or action. Results Depletion of Sptlc2 increased energy expenditure, improved glucose homeostasis, and prevented diet-induced obesity. Conversely, depletion of Asah1 led to ceramide accumulation, diminution of energy expenditure, and exacerbation of insulin resistance and obesity. Mechanistically, ceramides slowed lipolysis, inhibited glucose uptake, and decreased mitochondrial respiration. Moreover, β-adrenergic receptor agonists, which activate thermogenesis in brown adipocytes, decreased transcription of enzymes required for ceramide synthesis. Conclusions These studies support our hypothesis that ceramides are necessary and sufficient for the impairment in thermogenic adipocyte function that accompanies obesity. Moreover, they suggest that implementation of therapeutic strategies to block ceramide synthesis in thermogenic adipocytes may serve as a means of improving adipose health and combating obesity and cardiometabolic disease., Highlights • β-Adrenergic agonists lower ceramide levels in brown adipocytes by decreasing expression of Sptlc2 and CerS6. • Selective inhibition of ceramide synthesis in UCP1+ cells confers resistance to obesity and increases energy expenditure. • Selectively inducing ceramide accumulation in UCP1+ cells impairs thermogenesis to exacerbate obesity and insulin resistance. • Brown adipocyte ceramides alter mitochondrial ultrastructure and activity and influences rates of fatty acid uptake.

The accumulation of sphingolipids in obesity leads to impairments in insulin sensitivity and mitochondrial metabolism, but the precise species driving these defects is unclear. We have modeled these obesity-induced effects in cultured C2C12 myotubes, using BSA-conjugated palmitate to increase synthesis of endogenous sphingolipids and to inhibit insulin signaling and oxidative phosphorylation. Palmitate (a) induced the accumulation of sphingomyelin (SM) precursors such as sphinganine, dihydroceramide, and ceramide; (b) inhibited insulin stimulation of a central modulator of anabolic metabolism, Akt/PKB; (c) inhibited insulin-stimulated glycogen synthesis; and (d) decreased oxygen consumption and ATP synthesis. Under these conditions, palmitate failed to alter levels of SMs, which are the most abundant sphingolipids, suggesting that they are not the primary intermediates accounting for the deleterious palmitate effects. Treating cells with a pharmacological inhibitor of SM synthase or using CRISPR to knock out the Sms2 gene recapitulated the palmitate effects by inducing the accumulation of SM precursors and impairing insulin signaling and mitochondrial metabolism. To profile the sphingolipids that accumulate in obesity, we performed lipidomics on quadriceps muscles from obese mice with impaired glucose tolerance. Like the cultured myotubes, these tissues accumulated ceramides but not SMs. Collectively, these data suggest that SM precursors such as ceramides, rather than SMs, are likely nutritional antagonists of metabolic function in skeletal muscle.

The relevance of academic accounting research to practice has been frequently discussed in the accounting academy, yet very little data has been put forth in these discussions. We create relevance of accounting research (ROAR) scores by asking accounting professionals to read and evaluate the titles and abstracts of every article published in 12 leading accounting journals for the years 2016 to 2018, inclusive. These scores allow for an evidence-based evaluation and discussion of how academic accounting research is perceived by accounting professionals. The scores also allow us to identify the articles, authors, journals, and accounting topic areas that are perceived to be more relevant to accounting practice. By continuing to produce these scores in perpetuity, we expect this data to help academics and professionals better identify and utilize research relevant to the accounting profession.

Auditors increasingly employ technologies to improve audit quality. Using a design science approach, we examine whether using drones and automated counting software can improve audit quality and thereby improve financial reporting. We assess three dimensions of audit quality—efficiency, effectiveness, and quality of audit documentation. We provide evidence that auditors can perform inventory counts with these technologies much more efficiently than they can with manual techniques, decreasing count time in our study from 681 hours to 19 hours. At the same time, auditors can maintain or improve audit effectiveness with these technologies, decreasing error rates in our study from 0.15% to 0.03%, while providing higher-quality audit documentation. Interviews with national-level partners and audit standard setters highlight impediments to adopting these technologies, including firm concerns about being first movers combined with inability of standard setters to provide guidance at a pace that matches the pace of technological development. Collectively, our results suggest that technology-enabled inventory audits can improve audit quality, and further regulatory guidance on using such technologies would enhance adoption.

We extend prior accounting education research by ranking accounting education publications based on citation counts. We collect publications in two accounting education specialty journals, Issues in Accounting Education and Journal of Accounting Education , and 11 other high-quality journals included in the Summers and Wood (2015a) database. We aggregate rankings by institution and by individuals for both traditional publications (including “instructional-resource” papers that are not case-based) and cased-based publications. We also provide citation-based benchmarking data for accounting education scholarship. We present our results in time windows of the most recent 6 years (i.e., 2008–2013, inclusive), 12 years (i.e., 2002–2013, inclusive), and since 1990 to show changes in citation-based rankings over time. These rankings allow institutions and individuals who specialize and excel in accounting education publications to track and to receive recognition for their performance.

Sphingolipid synthesis involves a highly conserved biosynthetic pathway that produces fundamental precursors of complex sphingolipids. The final reaction involves the insertion of a double bond into dihydroceramides to generate the more abundant ceramides, which are converted to sphingomyelins and glucosylceramides/gangliosides by the addition of polar head groups. Although ceramides have long been known to mediate cellular stress responses, the dihydroceramides that are transiently produced during de novo sphingolipid synthesis were deemed inert. Evidence published in the last few years suggests that these dihydroceramides accumulate to a far greater extent in tissues than previously thought. Moreover, they have biological functions that are distinct and non-overlapping with those of the more prevalent ceramides. Roles are being uncovered in autophagy, hypoxia, and cellular proliferation, and the lipids are now implicated in the etiology, treatment, and/or diagnosis of diabetes, cancer, ischemia/reperfusion injury, and neurodegenerative diseases. This minireview summarizes recent findings on this emerging class of bioactive lipids.

Summary Inhibition of ceramide synthesis prevents diabetes, steatosis, and cardiovascular disease in rodents. Six different ceramide synthases (CerS) that differ in tissue distribution and substrate specificity account for the diversity in acyl-chain composition of distinct ceramide species. Haploinsufficiency for ceramide synthase 2 (CerS2), the dominant isoform in the liver that preferentially makes very-long-chain (C22/C24/C24:1) ceramides, led to compensatory increases in long-chain C16-ceramides and conferred susceptibility to diet-induced steatohepatitis and insulin resistance. Mechanistic studies revealed that these metabolic effects were likely due to impaired β-oxidation resulting from inactivation of electron transport chain components. Inhibiting global ceramide synthesis negated the effects of CerS2 haploinsufficiency in vivo, and increasing C16-ceramides by overexpressing CerS6 recapitulated the phenotype in isolated, primary hepatocytes. Collectively, these studies reveal that altering sphingolipid acylation patterns impacts hepatic steatosis and insulin sensitivity and identify CerS6 as a possible therapeutic target for treating metabolic diseases associated with obesity.

In obesity and dyslipidemia, the oversupply of fat to tissues not suited for lipid storage induces cellular dysfunction that underlies diabetes and cardiovascular disease (i.e., lipotoxicity). Of the myriad lipids that accrue under these conditions, sphingolipids such as ceramide or its metabolites are amongst the most deleterious because they disrupt insulin sensitivity, pancreatic β cell function, vascular reactivity, and mitochondrial metabolism. Remarkably, inhibiting ceramide biosynthesis or catalyzing ceramide degradation in rodents ameliorates many metabolic disorders including diabetes, cardiomyopathy, insulin resistance, atherosclerosis, and steatohepatitis. Herein we discuss and critically assess studies that identify sphingolipids as major contributors to the tissue dysfunction underlying metabolic pathologies, highlighting the need to further decipher the full array of benefits elicited by ceramide depletion.

The recent implementation of genomic and lipidomic approaches has produced a large body of evidence implicating the sphingolipid ceramide in a diverse range of physiological processes and as a critical modulator of cellular stress. In this review, we discuss from a historical perspective the most important discoveries produced over the last decade supporting a role for ceramide and its metabolites in the pathogenesis of insulin resistance and other obesity-associated metabolic diseases. Moreover, we describe how a ceramide-centric view of insulin resistance might be reconciled in the context of other prominent models of nutrient-induced insulin resistance.

We survey some recent results related to the self-assembly of infinite structures in Winfree’s abstract Tile Assembly Model. These results include impossibility results, as well as the construction of novel tile assembly systems that produce computationally interesting shapes and patterns. Several open questions are also presented and motivated.

Summary: Autophagy is a homeostatic cellular process involved in the degradation of long-lived or damaged cellular components. The role of autophagy in adipogenesis is well recognized, but its role in mature adipocyte function is largely unknown. We show that the autophagy proteins Atg3 and Atg16L1 are required for proper mitochondrial function in mature adipocytes. In contrast to previous studies, we found that post-developmental ablation of autophagy causes peripheral insulin resistance independently of diet or adiposity. Finally, lack of adipocyte autophagy reveals cross talk between fat and liver, mediated by lipid peroxide-induced Nrf2 signaling. Our data reveal a role for autophagy in preventing lipid peroxide formation and its transfer in insulin-sensitive peripheral tissues. : Cai et al. describe how lack of autophagy in mature adipocytes causes insulin resistance with no change in body weight. Adipocytes lacking Atg3 or Atg16L1 accumulate dysfunctional mitochondria and have increased lipid peroxidation and Nrf2 and keap1 activation. This study reveals a role for lipid peroxides and Nrf2 signaling in an adipose-liver crosstalk. Keywords: autophagy, adipocytes, insulin resistance, inflammation, mitochondria, lipid peroxide, adipose tissue, adiponectin

The accumulation of fat in tissues not suited for lipid storage has deleterious consequences on organ function, leading to cellular damage that underlies diabetes, heart disease, and hypertension. To combat these lipotoxic events, several therapeutics improve insulin sensitivity and/or ameliorate features of metabolic disease by limiting the inappropriate deposition of fat in peripheral tissues (i.e. thiazolidinediones, metformin, and statins). Recent advances in genomics and lipidomics have accelerated progress towards understanding the pathogenic events associated with the excessive production, underutilization, or inefficient storage of fat. Herein we review studies applying pharmacological or genetic strategies to manipulate the expression or activity of enzymes controlling lipid deposition, in order to gain a clearer understanding of the molecular mechanisms by which fatty acids contribute to metabolic disease.

Winfree (1998) showed that discrete Sierpinski triangles can self-assemble in the Tile Assembly Model. A striking molecular realization of this self-assembly, using DNA tiles a few nanometers long and verifying the results by atomic-force microscopy, was achieved by Rothemund, Papadakis, and Winfree (2004).Precisely speaking, the above self-assemblies tile completely filled-in, two-dimensional regions of the plane, with labeled subsets of these tiles representing discrete Sierpinski triangles. This paper addresses the more challenging problem of the strict self-assembly of discrete Sierpinski triangles, i.e., the task of tiling a discrete Sierpinski triangle and nothing else.We first prove that the standard discrete Sierpinski triangle cannot strictly self-assemble in the Tile Assembly Model. We then define the fibered Sierpinski triangle, a discrete Sierpinski triangle with the same fractal dimension as the standard one but with thin fibers that can carry data, and show that the fibered Sierpinski triangle strictly self-assembles in the Tile Assembly Model. In contrast with the simple XOR algorithm of the earlier, non-strict self-assemblies, our strict self-assembly algorithm makes extensive, recursive use of optimal counters, coupled with measured delay and corner-turning operations. We verify our strict self-assembly using the local determinism method of Soloveichik and Winfree (2007).

Hindlimb unweighting (HLU) in rats mimics the fluid shift experienced by astronauts and may serve as a model for ground-based orthostatic hypotension. It has been shown that the abdominal aorta of HLU rats exhibits a deficit in contractile response to adrenergic agonists. The hypothesis of the present study was that decreased activity in the RhoA/Rho-kinase pathway could contribute to that deficit. Wistar rats were subjected to 20 days of HLU treatment. Abdominal aorta rings from HLU and control rats were suspended in baths for measurement of contraction. Concentration response curves were obtained to the alpha adrenergic agonist, phenylephrine and the thromboxane-mimetic, U46619. HLU treatment caused decreased contraction in response to both. The Rho-kinase inhibitor, Y27632, caused a reduction in the phenylephrine-induced contraction in control, but not HLU aorta. Other rings were frozen after stimulation 1 μM U46619 or phenylephrine. Western analysis revealed a decreased expression of RhoA, but increased expression of both Rho kinase and MYPT1, the regulatory subunit of myosin light chain (MLC) phosphatase. MYPT1 and MLC phosphorylation was decreased by HLU in phenylephrine stimulated aorta. Decreased activity in the RhoA/Rho-kinase pathway may be involved in the decreased contraction seen in the HLU abdominal aorta.

One key reason companies implement internal controls is to reduce the likelihood of unethical behavior. Yet, research on ego depletion from psychology suggests that some controls may cause reductions in employees’ self-control, which could lead to increases in unethical behavior. Therefore, this study examines how different types of controls — namely preventive, detective with immediate feedback, and detective with delayed feedback — impact self-control and ethical judgments. Based on the results of three different experiments with 462 participants, we find no significant relation between self-control and the types of internal controls tested. Furthermore, we find that the types of controls tested have no effect on ethical judgments or ethical ideology. Thus, our results suggest that controls in general and some types of internal controls do not differentially impact self-control.

Electronic commerce can be defined as the conduct of commerce in goods and services, with the assistance of telecommunications and telecommunications-based tools. The economic growth potential of e-commerce is extraordinary-but so are the challenges that lie on the path toward success. One of the more pressing challenges is how to ensure the integrity and reliability of the transaction process: key aspects being fair-exchange and atomicity assurance. This paper delineates an extended fair-exchange standard, which includes atomicity assurance, intended for a wide audience including e-commerce designers, managers, users, and auditors. We demonstrate how such a standard prevents or mitigates important e-commerce concerns. To bridge theory with practice, we illustrate how the application of model checking can be used to verify the correctness of the implementation of e-commerce protocols to prevent the failure of such protocols when unforeseen circumstances occur.

Recent studies indicate that insulin resistance and type 2 diabetes result from the accumulation of lipids in tissues not suited for fat storage, such as skeletal muscle and the liver. To elucidate the mechanisms linking exogenous fats to the inhibition of insulin action, we evaluated the effects of free fatty acids (FFAs) on insulin signal transduction in cultured C2C12 myotubes. As we described previously (Chavez, J. A., and Summers, S. A. (2003) Arch. Biochem. Biophys. 419, 101-109), long-chain saturated FFAs inhibited insulin stimulation of Akt/protein kinase B, a central regulator of glucose uptake and anabolic metabolism. Moreover, these FFAs stimulated the de novo synthesis of ceramide and sphingosine, two sphingolipids shown previously to inhibit insulin action. To determine the contribution of either sphingolipid in FFA-dependent inhibition of insulin action, we generated C2C12 myotubes that constitutively overexpress acid ceramidase (AC), an enzyme that catalyzes the lysosomal conversion of ceramide to sphingosine. AC overexpression negated the inhibitory effects of saturated FFAs on insulin signaling while blocking their stimulation of ceramide accumulation. By contrast, AC overexpression stimulated the accrual of sphingosine. These results support a role for aberrant accumulation of ceramide, but not sphingosine, in the inhibition of muscle insulin sensitivity by exogenous FFAs.

Use of the Internet for electronic business has the potential to revolutionize the way many businesses are conducted. Yet, several businesses have fallen victim to problems in information systems that facilitate e-Business. These problems are characterized by uncertainties due to system complexity, rapid development, interconnectivity, and a lack of familiarity with the new technologically based economy. This paper demonstrates how model checking can aid in the design and assurance of e-Business processes in environments characterized by distributed processing, parallelism, concurrency, communication uncertainties, and continuous operations.

The sphingolipid ceramide negatively regulates insulin action by inhibiting Akt/protein kinase B (PKB), a serine/threonine kinase that is a central regulator of glucose uptake and anabolic metabolism. Despite considerable attention, the molecular mechanism accounting for this action of ceramide has remained both elusive and controversial. Herein we utilized deletion constructs encoding two different functional domains of Akt/PKB to identify which region of the enzyme conferred responsiveness to ceramide. Surprisingly the findings obtained with these separate domains reveal that ceramide blocks insulin stimulation of Akt/PKB by two independent mechanisms. First, using the isolated pleckstrin homology domain, we found that ceramide specifically blocks the translocation of Akt/PKB, but not its upstream activator phosphoinositide-dependent kinase-1, to the plasma membrane. Second, using a construct lacking this pleckstrin homology domain, which does not require translocation for activation, we found that ceramide stimulates the dephosphorylation of Akt/PKB by protein phosphatase 2A. Collectively these findings identify at least two independent mechanisms by which excessive ceramide accumulation in peripheral tissues could contribute to the development of insulin resistance. Moreover the results obtained provide a unifying theory to account for the numerous dissenting reports investigating the actions of ceramide toward Akt/PKB.

A strong correlation between intramyocellular lipid concentrations and the severity of insulin resistance has fueled speculation that lipid oversupply to skeletal muscle, fat, or liver may desensitize these tissues to the anabolic effects of insulin. To identify free fatty acids (FFAs) capable of inhibiting insulin action, we treated 3T3-L1 adipocytes or C2C12 myotubes with either the saturated FFA palmitate (C16:0) or the monounsaturated FFA oleate (C18:1), which were shown previously to be the most prevalent FFAs in rat soleus and gastrocnemius muscles. In C2C12 myotubes, palmitate, but not oleate, inhibited insulin-stimulation of glycogen synthesis, as well as its activation of Akt/Protein Kinase B (PKB), an obligate intermediate in the regulation of anabolic metabolism. Palmitate also induced the accrual of ceramide and diacylglycerol (DAG), two lipid metabolites that have been shown to inhibit insulin signaling in cultured cells and to accumulate in insulin resistant tissues. Interestingly, in 3T3-L1 adipocytes, neither palmitate nor oleate inhibited glycogen synthesis or Akt/PKB activation, nor did they induce ceramide or DAG synthesis. Using myotubes, we also tested whether other saturated fatty acids blocked insulin signaling while promoting ceramide and DAG accumulation. The long-chain fatty acids stearate (18:0), arachidate (20:0), and lignocerate (24:0) reproduced palmitate's effects on these events, while saturated fatty acids with shorter hydrocarbon chains [i.e., laurate (12:0) and myristate (14:0)] failed to induce ceramide accumulation or inhibit Akt/PKB activation. Collectively these findings implicate excess delivery of long-chain fatty acids in the development of insulin resistance resulting from lipid oversupply to skeletal muscle.

Multiple studies suggest that lipid oversupply to skeletal muscle contributes to the development of insulin resistance, perhaps by promoting the accumulation of lipid metabolites capable of inhibiting signal transduction. Herein we demonstrate that exposing muscle cells to particular saturated free fatty acids (FFAs), but not mono-unsaturated FFAs, inhibits insulin stimulation of Akt/protein kinase B, a serine/threonine kinase that is a central mediator of insulin-stimulated anabolic metabolism. These saturated FFAs concomitantly induced the accumulation of ceramide and diacylglycerol, two products of fatty acyl-CoA that have been shown to accumulate in insulin-resistant tissues and to inhibit early steps in insulin signaling. Preventing de novo ceramide synthesis negated the antagonistic effect of saturated FFAs toward Akt/protein kinase B. Moreover, inducing ceramide buildup recapitulated and augmented the inhibitory effect of saturated FFAs. By contrast, diacylglycerol proved dispensable for these FFA effects. Collectively these results identify ceramide as a necessary and sufficient intermediate linking saturated fats to the inhibition of insulin signaling.

Academic research has a role in advancing and enlightening society in broad areas of study. Many forces interact to influence the directions, topics, and methodologies used in research. In this paper, we explore and discuss the relationships between the top general-interest and specialist accounting journals. We test whether top journals (e.g., “Top 3” or “Top 6”), relative to a set of high-quality but specialist journals, (1) are perceived to be general in what they will consider publishing, (2) have historically published diverse sets of articles, (3) have editorial board members with diverse sets of interests and skills, and (4) publish the most highly cited articles by topic area and methodology. The results suggest that some of the top journals are not as general as their mission statements suggest and that they do not publish the most highly cited articles in some topic areas and methodologies. These results may help institutions consider whether “counting” only the top journals is an appropriate measure for judging faculty scholarship. The results suggest that counting articles in the traditional top journals alone will be problematic if institutions want to promote research in a broad range of accounting topics and issues in the profession.

The current studies investigated the contribution of phosphatidylinositol 3-kinase (PI3-kinase) isoforms to insulin-stimulated glucose uptake and glucose transporter 4 (GLUT4) translocation. Experiments involving the microinjection of antibodies specific for the p110 catalytic subunit of class I PI3-kinases demonstrated an absolute requirement for this form of the enzyme in GLUT4 translocation. This finding was confirmed by the demonstration that the PI3-kinase antagonist wortmannin inhibits GLUT4 and insulin-responsive aminopeptidase translocation with a dose response identical to that required to inhibit another class I PI3-kinase-dependent event, activation of pp70 S6-kinase. Interestingly, wortmannin inhibited insulin-stimulated glucose uptake at much lower doses, suggesting the existence of a second, higher affinity target of the drug. Subsequent removal of wortmannin from the media shifted this dose-response curve to one resembling that for GLUT4 translocation and pp70 S6-kinase. This is consistent with the lower affinity target being p110, which is irreversibly inhibited by wortmannin. Wortmannin did not reduce glucose uptake in cells stably expressing Myr-Akt, which constitutively induced GLUT4 translocation to the plasma membrane; this demonstrates that wortmannin does not inhibit the transporters directly. In addition to elucidating a second wortmannin-sensitive pathway in 3T3-L1 adipocytes, these studies suggest that the presence of GLUT4 on the plasma membrane is not sufficient for activation of glucose uptake.

To characterize the contribution of glycogen synthase kinase 3beta (GSK3beta) inactivation to insulin-stimulated glucose metabolism, wild-type (WT-GSK), catalytically inactive (KM-GSK), and uninhibitable (S9A-GSK) forms of GSK3beta were expressed in insulin-responsive 3T3-L1 adipocytes using adenovirus technology. WT-GSK, but not KM-GSK, reduced basal and insulin-stimulated glycogen synthase activity without affecting the -fold stimulation of the enzyme by insulin. S9A-GSK similarly decreased cellular glycogen synthase activity, but also partially blocked insulin stimulation of the enzyme. S9A-GSK expression also markedly inhibited insulin stimulation of IRS-1-associated phosphatidylinositol 3-kinase activity, but only weakly inhibited insulin-stimulated Akt/PKB phosphorylation and glucose uptake, with no effect on GLUT4 translocation. To further evaluate the role of GSK3beta in insulin signaling, the GSK3beta inhibitor lithium was used to mimic the consequences of insulin-stimulated GSK3beta inactivation. Although lithium stimulated the incorporation of glucose into glycogen and glycogen synthase enzyme activity, the inhibitor was without effect on GLUT4 translocation and pp70 S6 kinase. Lithium stimulation of glycogen synthesis was insensitive to wortmannin, which is consistent with its acting directly on GSK3beta downstream of phosphatidylinositol 3-kinase. These data support the hypothesis that GSK3beta contributes to insulin regulation of glycogen synthesis, but is not responsible for the increase in glucose transport.

Sphingolipids have garnered attention for their role in insulin resistance and lipotoxic cell death. Aberrant accumulation of ceramides correlates with hepatic insulin resistance and steatosis. To further investigate the tissue-specific effects of local changes in ceramidase activity, we have developed transgenic mice inducibly expressing acid ceramidase, to trigger the deacylation of ceramides. This represents the first inducible genetic model that acutely manipulates ceramides in adult mouse tissues. Hepatic overexpression of acid ceramidase prevents hepatic steatosis and prompts improvements in insulin action in liver and adipose tissue. Conversely, overexpression of acid ceramidase within adipose tissue prevents hepatic steatosis and insulin resistance. Induction of ceramidase activity in either tissue promotes a lowering of hepatic ceramides and reduced activation of the ceramide-activated protein kinase C isoform PKC-zeta. These observations suggest the existence of a rapidly acting "crosstalk" between liver and adipose tissue sphingolipids, critically regulating glucose metabolism and hepatic lipid uptake.

Akt is a serine/threonine kinase that requires a functional phosphatidylinositol 3-kinase to be stimulated by insulin and other growth factors. When directed to membranes by the addition of a src myristoylation sequence, Akt becomes constitutively active. In the present study, a conditionally active version of Akt was constructed by fusing the Akt containing the myristoylation sequence to the hormone binding domain of a mutant murine estrogen receptor that selectively binds 4-hydroxytamoxifen. The chimeric protein was expressed in NIH3T3 cells and was shown to be stimulated by hormone treatment 17-fold after only a 20-min treatment. This hormone treatment also stimulated an approximate 3-fold increase in the phosphorylation of the chimeric protein and a shift in its migration on SDS gels. Activation of this conditionally active Akt resulted in the rapid stimulation of the 70-kDa S6 kinase. This conditionally active Akt was also found to rapidly stimulate in these cells the phosphorylation of properties of PHAS-I, a key protein in the regulation of protein synthesis. The conditionally active Akt, when expressed in 3T3-L1 adipocytes, was also stimulated, although its rate and extent of activation was less then in the NIH3T3 cells. Its stimulation was shown to be capable of inducing glucose uptake into adipocytes by stimulating translocation of the insulin-responsive glucose transporter GLUT4 to the plasma membrane.

Polyoma middle T antigen (PMT) was originally identified as the tumorigenic component of the polyomavirus genome. To investigate whether the serine/threonine kinase Akt/PKB, which is the proto-oncogene transduced by the transforming AKT8 retrovirus, is activated by PMT, 3T3-L1 fibroblasts were stably transfected with wild type PMT. PMT expression accelerated glucose transport and increased phosphorylation of p70 S6-kinase and MAPK. PMT expression also stimulated Akt kinase activity 7 fold as compared to untreated, mock infected cells. This stimulation rivaled that obtained following insulin treatment of both mock and PMT infected cells. Akt activation and phosphorylation were eliminated in a PMT mutant incapable of interacting with PI3-kinase, but not one which does not interact with Shc, and correlated closely to the amount of PI3-kinase activity in anti-phosphotyrosine immunoprecipitates. These results indicate that the PI3-kinase pathway is requisite, but the Shc pathway is dispensable, for Akt activation. The studies further suggest that Akt may participate in PMT and PI3-kinase's regulation of cellular transformation and tumorigenesis.

We extend prior accounting education research by ranking accounting education publications based on citation counts. We collect publications in two accounting education specialty journals, Issues in Accounting Education and Journal of Accounting Education, and 11 other high-quality journals included in the Summers and Wood (2015a) database. We aggregate rankings by institution and by individuals for both traditional publications (including “instructional-resource” papers that are not case-based) and cased-based publications. We also provide citation-based benchmarking data for accounting education scholarship. We present our results in time windows of the most recent 6 years (i.e., 2008-2013, inclusive), 12 years (i.e., 2002-2013, inclusive), and since 1990 to show changes in citation-based rankings over time. These rankings allow institutions and individuals who specialize and excel in accounting education publications to track and to receive recognition for their performance.

This study creates citation-based rankings for accounting institutions by topical areas (AIS, audit, financial, managerial, tax, and other) and methodologies (archival, analytical, experimental, and other) extending prior count-based ranking studies that disaggregate rankings by topic and methodology. We report separate rankings for different year windows (previous six years, 12 years, and since 1990) and only give institutions credit for authors who currently work for the institution. We show that disaggregated citation-based rankings are important as the correlations for some topic areas and methodologies with an overall ranking are modest. We also show that the correlation for citation-based and count-based rankings can differ significantly in some situations suggesting the importance of considering both types of rankings in decision making. Data Availability: Requests for data may be made to the authors.

Business trends show that more and more employees are creating shadow IT systems — IT systems that are not sanctioned or monitored by the IT department. This paper examines how the use of shadow IT in product costing impacts managers’ perceptions of information credibility and managerial decision-making. Using two experiments, we find that participants view information from shadow IT systems as less credible and they are less impacted by and less willing to rely on costing reports produced from shadow IT systems versus non-shadow IT systems. We also find that although participants are concerned about the credibility of shadow IT systems, they are unlikely to find simple mathematical errors embedded in shadow IT costing reports. This suggests that although concerned about shadow IT systems, managers still do not exercise sufficient care in evaluating reports created using these systems. The results of our study should prove informative as shadow systems become more prevalent in organizations.

This paper examines factors that influence job applicants’ willingness to apply for positions in internal auditing. We predict and find evidence that job applicants are dissuaded from applying for internal audit positions. In two separate experiments involving participants at seven universities, we discover that this phenomenon is most prevalent for applicants with business experience. Experienced applicants are 20 and 33 percent less willing to apply for a position if it is labeled as “internal audit” versus “accounting” in the two experiments, respectively. In addition, we find that the only experimental condition that increases interest in applying for an internal audit position for experienced applicants occurs when the position advertises the combination of (1) a short stint in internal auditing and then a move from internal audit into a management position and (2) work primarily related to consulting services rather than assurance services. As a potential explanation for these findings, we find evidence that participants believe other business professionals have negative stereotypes of internal auditing — which likely dissuade potential job applicants from applying to work in internal audit. The results should prove informative to practitioners, internal audit professional organizations, and business professionals concerned with high quality corporate governance.

Prior academic and practitioner literature argues that the ethical tone at the top of an organization is a key factor in establishing an effective internal control environment. Drawing on self-concept maintenance theory and in-group bias theory, we predict that entry-level staff auditors will disregard a company’s ethical standards unless they observe a strong ethical tone from both their partner (tone at the top) and their supervising senior (tone at the bottom). Also, we predict that staff auditors will be more influenced by the tone of their supervising senior than the partner when these two individuals provide conflicting tones. In a 2 x 2 experiment that manipulates the tone set by a staff auditor’s supervising senior and engagement partner, we provide evidence consistent with our expectations. Further analyses suggest that participants made less ethical decisions because they were less likely to view the situation as an ethical dilemma when either the senior or partner exhibited low tone. The results of this study emphasize that tone at the top is not, by itself, sufficient to produce ethical decision making; organizations must strive to foster a strong ethical tone throughout the entire organization, especially at lower levels of the organization.

Previous rankings of accounting literature have largely ignored the subtopic of accounting education research. Given the important role that rankings play in creating incentives and benchmarks, ranking education research may improve both the quality and quantity of research in this subtopic. This paper ranks academic institutions and individual accounting researchers based on their production of accounting education research. We show that the correlation between education research rankings and singular, non-education research rankings is very low (i.e., ranges from 0.20 to 0.31), emphasizing the importance of considering education rankings separately from other topical areas in accounting research. We also provide evidence of the institutional factors that contribute to producing accounting education research and when professors produce this type of research in their careers. These findings will likely be of interest to current faculty, administrators, and industry leaders as they make decisions based on accounting education research.

SYNOPSIS: This paper presents rankings of accounting doctoral programs based on the research productivity of each institution’s graduates in the years immediately following their graduation. We use two time periods for analysis: the first three years after graduation and the first six years after graduation. We extend previous doctoral program ranking literature by expanding rankings of accounting doctoral programs with specific rankings for topical areas (accounting information systems [AIS], audit, financial, managerial, and tax) and methodologies (analytical, archival, and experimental). We show that rankings for topical and methodological areas differ significantly from rankings produced using methodologies that create a singular doctoral program ranking. These results emphasize the importance of considering topical and methodological areas when assessing doctoral program research strengths. These rankings should be of value to Ph.D. program applicants, administrators of academic programs, and industry—such as administrators of programs like the Accounting Doctoral Scholars program, KPMG Ph.D. Project, and prospective Ph.D. students.

In the current global economy, the survival of insurance companies depends on its ability to respond to the customer demands, which are settlements of the insurance claims. All insurance companies face the conflicting goals of settling claims quickly and authenticating the claims. The increasing cost of human experts in fraud detection has led many companies to develop expert systems, which respond to the needs of the companies in a cost effective and efficient way. It has been observed that the opportunity exists for claim adjustors to settle insurance claims in favor of the claimants simply by colluding with the claimant and sacrificing the monetary interest of the insurers. This use of experts in claim settlement leaves room for subjective judgment and the use of discretion while finalizing a claim. In this paper, we develop a fuzzy logic based expert system that can evaluate and identify the elements of fraud involved in insurance claims settlement. It helps to decide if the claims settled are genuine or their exists an element of fraud which needs substantive testing by an auditor. The proposed methodology has been illustrated with an example that tends to model insurance claims in general. The main contributions of this paper are the 'index of ambiguity' and the fuzzy-logic based methodology to detect an element of fraud in the previously settled insurance claims.