Showing papers by "University of Illinois at Chicago published in 1994"

Gear geometry and applied theory

Abstract: This revised, expanded, edition covers the theory, design, geometry and manufacture of all types of gears and gear drives. This is an invaluable reference for designers, theoreticians, students, and manufacturers. This edition includes advances in gear theory, gear manufacturing, and computer simulation. Among the new topics are: 1. New geometry for modified spur and helical gears, face-gear drives, and cycloidal pumps. 2. New design approaches for one stage planetary gear trains and spiral bevel gear drives. 3. An enhanced approach for stress analysis of gear drives with FEM. 4. New methods of grinding face gear drives, generating double crowned pinions, and improved helical gear shaving. 5. Broad application of simulation of meshing and TCA. 6. New theories on the simulation of meshing for multi-body systems, detection of cases wherein the contact line on generating surfaces may have its own envelope, and detection and avoidance of singularities of generated surfaces.

Soy intake and cancer risk: A review of the in vitro and in vivo data

Abstract: International variations in cancer rates have been attributed, at least in part, to differences in dietary intake. Recently, it has been suggested that consumption of soyfoods may contribute to the relatively low rates of breast, colon, and prostate cancers in countries such as China and Japan. Soybeans contain a number of anticarcinogens, and a recent National Cancer Institute workshop recommended that the role of soyfoods in cancer prevention be investigated. In this review, the hypothesis that soy intake reduces cancer risk is considered by examining relevant in vitro, animal, and epidemiological data. Soybeans are a unique dietary source of the isoflavone genistein, which possesses weak estrogenic activity and has been shown to act in animal models as an antiestrogen. Genistein is also a specific inhibitor of protein tyrosine kinases; it also inhibits DNA topoisomerases and other critical enzymes involved in signal transduction. In vitro, genistein suppresses the growth of a wide range of can...

The X-ray crystal structure of the membrane protein prostaglandin H2 synthase-1.

Abstract: The three-dimensional structure of prostaglandin H2 synthase-1, an integral membrane protein, has been determined at 3.5 A resolution by X-ray crystallography. This bifunctional enzyme comprises three independent folding units: an epidermal growth factor domain, a membrane-binding motif and an enzymatic domain. Two adjacent but spatially distinct active sites were found for its haem-dependent peroxidase and cyclooxygenase activities. The cyclooxygenase active site is created by a long, hydrophobic channel that is the site of non-steroidal anti-inflammatory drug binding. The conformation of the membrane-binding motif strongly suggests that the enzyme integrates into only one leaflet of the lipid bilayer and is thus a monotopic membrane protein.

Efficacy of Divalproex vs Lithium and Placebo in the Treatment of Mania

Abstract: Objective. —To compare the effectiveness of divalproex sodium with that of lithium and placebo in patients with acute mania. Design. —Randomized, double-blind, parallel-group study of treatment outcomes in patients with manic-depressive illness. Patients. —A total of 179 hospitalized, acutely manic patients meeting the Research Diagnostic Criteria for manic disorder, approximately half of whom had been nonresponsive to lithium previously, were studied at nine university-affiliated hospitals. Interventions. —After a minimum 3-day washout period, random assignment for 21 days to divalproex, lithium, or placebo in a 2:1:2 ratio. Dosage of divalproex and lithium was increased if tolerated to a target concentration of 1041 μmol/L (150 μg/ mL) or 1.5 mmol/L (conventionally expressed as milliequivalents per liter), respectively. Main Outcome Measures. —Primary outcome measures were changes in the Mania Rating scale derived from the Schedule for Affective Disorders and Schizophrenia. Results. —Intent-to-treat analysis for efficacy was based on data from 68, 35, and 73 patients in the divalproex, lithium, and placebo groups, respectively. Groups were initially comparable except that all eight patients with four or more manic episodes in the previous year were in the divalproex group. In 30%, 33%, and 51% of the above groups, treatment was prematurely terminated due to lack of efficacy, with fewer premature terminations from divalproex than placebo (P=.017). The proportions of patients improving at least 50% were higher for divalproex and lithium groups than for the placebo group: 48% for divalproex (P=.004) and 49% for lithium (P=.025) vs 25% for placebo. Divalproex was as effective in rapid-cycling manic patients as in other patients. Conclusions. —Both divalproex and lithium were significantly more effective than placebo in reducing the symptoms of acute mania. The efficacy of divalproex appears to be independent of prior responsiveness to lithium. (JAMA. 1994;271:918-924)

Solar Engineering of Thermal Processes, 2nd ed.

Abstract: The updated fourth edition of the "bible" of solar energy theory and applications Over several editions, Solar Engineering of Thermal Processes has become a classic solar engineering text and reference. This revised Fourth Edition offers current coverage of solar energy theory, systems design, and applications in different market sectors along with an emphasis on solar system design and analysis using simulations to help readers translate theory into practice. An important resource for students of solar engineering, solar energy, and alternative energy as well as professionals working in the power and energy industry or related fields, Solar Engineering of Thermal Processes, Fourth Edition features: Increased coverage of leading-edge topics such as photovoltaics and the design of solar cells and heatersA brand-new chapter on applying CombiSys (a readymade TRNSYS simulation program available for free download) to simulate a solar heated house with solar- heated domestic hot waterAdditional simulation problems available through a companion websiteAn extensive array of homework problems and exercises

Synonymous codon usage in Drosophila melanogaster: natural selection and translational accuracy.

Abstract: I present evidence that natural selection biases synonymous codon usage to enhance the accuracy of protein synthesis in Drosophila melanogaster. Since the fitness cost of a translational misincorporation will depend on how the amino acid substitution affects protein function, selection for translational accuracy predicts an association between codon usage in DNA and functional constraint at the protein level. The frequency of preferred codons is significantly higher at codons conserved for amino acids than at nonconserved codons in 38 genes compared between D. melanogaster and Drosophila virilis or Drosophila pseudoobscura (Z = 5.93, P

Neighborhood disadvantage, stressful life events, and adjustment in urban elementary-school children.

Abstract: Assessed the occurrence of three types of stressful life events among African- American and Hispanic children living in urban neighborhoods, and examined the concurrent and prospective relations between stressful life events and adjustment. Younger children and children living in the most disadvantaged neighborhoods experienced more stressful life events. Stressful life events were significantly related to higher concurrent levels of aggression and predicted increases in aggression P year later. Life transitions and exposure to violence predicted concurrent aggression, but circumscribed events served as the strongest predictor of aggression 1 year later. Total number of stressful events and exposure to violence significantly interacted with neighborhood disadvantage, such that effects were only apparent under conditions of high neighborhood disadvantage.

Nitric oxide synthase inhibition and cerebrovascular regulation.

Abstract: There is increasing evidence that nitric oxide (NO) is an important molecular messenger involved in a wide variety of biological processes. Recent data suggest that NO is also involved in the regulation of the cerebral circulation. Thus, NO participants in the maintenance of resting cerebrovascular tone and may play an important role in selected vasodilator responses of the cerebral circulation. Furthermore, evidence has been presented suggesting that NO participates in the mechanisms of cerebral ischemic damage. Despite the widespread attention that NO has captured in recent years and the large number of studies that have been published on the subject, there is considerable controversy regarding the role of this agent in cerebrovascular regulation and in ischemic damage. In this paper the results of investigations on NO and the cerebral circulation are reviewed and the evidence for and against a role of NO is critically examined.

A random-effects ordinal regression model for multilevel analysis.

Abstract: A random-effects ordinal regression model is proposed for analysis of clustered or longitudinal ordinal response data. This model is developed for both the probit and logistic response functions. The threshold concept is used, in which it is assumed that the observed ordered category is determined by the value of a latent unobservable continuous response that follows a linear regression model incorporating random effects. A maximum marginal likelihood (MML) solution is described using Gauss-Hermite quadrature to numerically integrate over the distribution of random effects. An analysis of a dataset where students are clustered or nested within classrooms is used to illustrate features of random-effects analysis of clustered ordinal data, while an analysis of a longitudinal dataset where psychiatric patients are repeatedly rated as to their severity is used to illustrate features of the random-effects approach for longitudinal ordinal data.

Structural determinants for activation of the alpha-subunit of a heterotrimeric G protein.

Abstract: The 1.8 A crystal structure of transducin α-GDP, when compared to that of the activated complex with GTP-γS, reveals the nature of the conformational changes that occur on activation of a heterotrimeric G-protein α-subunit. Structural changes initiated by direct contacts with the terminal phosphate of GTP propagate to regions that have been implicated in effector activation. The changes are distinct from those observed in other members of the GTPase superfamily.

Myc-mediated apoptosis requires wild-type p53 in a manner independent of cell cycle arrest and the ability of p53 to induce p21waf1/cip1.

Abstract: Deregulated expression of the c-myc proto-oncogene can lead to apoptosis under certain physiological conditions. By introducing a conditionally active Myc allele into primary embryo fibroblasts null for p53, and into fibroblasts without endogenous p53 expression but ectopically expressing a temperature-sensitive p53 allele, we show that expression of wild-type p53 is required for susceptibility to Myc-mediated apoptosis. Although ectopic expression of wild-type p53 blocked cells in the G1 phase of the cell cycle, G1 arrest by isoleucine starvation, in a manner independent of p53, did not confer susceptibility to apoptosis. Thus, growth arrest per se is not sufficient to induce Myc-mediated apoptosis; instead, a property intrinsic to p53 is specifically required. Moreover, apoptosis did not require induction of p53 target proteins, including the cyclin-dependent kinase inhibitor p21waf1/cip1. Therefore, the role of p53 in apoptosis may be distinct from its role in cell cycle arrest.

GTPase Mechanism of Gproteins From the 1.7-A Crystal Structure of Transducin alpha-GDP-AIF-4

Abstract: ALUMINIUM fluoride (A1F−4) activates members of the hetero-trimeric G-protein (Gαβγ) family1,2 by binding to inactive Gα·GDP near the site occupied by the γ-phosphate in Gα·GTP (ref. 3). Here we describe the crystal structure of transducin a o GDP acti-vated with aluminium fluoride (Gtα·GDP·A1F−4·H·O) at 1.7 A, a resolution sufficient to establish the coordination geometry of the bound aluminium fluoride as well as the extensive network of direct and water-mediated interactions that stabilize it. These observations are derived from three independent representations in the asymmetric unit, eliminating any chance of drawing conclu-sions based on stereochemistry imposed by crystal packing. Surprisingly, aluminium fluoride activates Gα·GDP by binding with a geometry resembling a pentavalent intermediate for GTP hydrolysis. The stabilizing interactions involve not only residues that interact with the y-phosphate in Gtα·GTPγS, but also conserved residues essential for GTPase activity. Thus the Gtα·GDP·AIF−4·H2O structure provides new insight into the mechanism of GTP hydrolysis.

Constraints on hydrothermal heat flux through the oceanic lithosphere from global heat flow

Abstract: A significant discrepancy exists between the heat flow measured at the seafloor and the higher values predicted by thermal models of the cooling lithosphere. This discrepancy is generally interpreted as indicating that the upper oceanic crust is cooled significantly by hydrothermal circulation. The magnitude of this heat flow discrepancy is the primary datum used to estimate the volume of hydrothermal flow, and the variation in the discrepancy with lithospheric age is the primary constraint on how the hydrothermal flux is divided between near-ridge and off-ridge environments. The resulting estimates are important for investigation of both the thermal structure of the lithosphere and the chemistry of the oceans. We reevaluate the magnitude and age variation of the discrepancy using a global heat flow data set substantially larger than in earlier studies, and the GDHI (Global Depth and Heat Flow) model that better predicts the heat flow. We estimate that of the predicted global oceanic heat flux of 32 x 10(exp 12) W, 34% (11 x 10(exp 12) W) occurs by hydrothermal flow. Approximately 30% of the hydrothermal heat flux occurs in crust younger than 1 Ma, so the majority of this flux is off-ridge. These hydrothermal heat flux estimates are upper bounds, because heat flow measurements require sediment at the site and so are made preferentially at topographic lows, where heat flow may be depressed. Because the water temperature for the near-ridge flow exceeds that for the off-ridge flow, the near-ridge water flow will be even a smaller fraction of the total water flow. As a result, in estimating fluxes from geochemical data, use of the high water temperatures appropriate for the ridge axis may significantly overestimate the heat flux for an assumed water flux or underestimate the water flux for an assumed heat flux. Our data also permit improved estimates of the 'sealing' age, defined as the age where the observed heat flow approximately equals that predicted, suggesting that hydrothermal heat transfer has largely ceased. Although earlier studies suggested major differences in sealing ages for different ocean basins, we find that the sealing ages for the Atlantic, Pacific, and Indian oceans are similar and consistent with the sealing age for the entire data set, 65 +/- 10 Ma. The previous inference of a young (approximately 20 Ma) sealing age for the Pacific appears to have biased downward several previous estimates of the global hydrothermal flux. The heat flow data also provide indirect evidence for the mechanism by which the hydrothermal heat flux becomes small, which has often been ascribed to isolation of the igneous crust from seawater due to the hydraulic conductivity of the intervening sediment. We find, however, that even the least sedimented sites show the systematic increase of the ratio of observed to predicted heat flow with age, although the more sedimented sites have a younger sealing age. Moreover, the heat flow discrepancy persists at heavily sedimented sites until approximately 50 Ma. It thus appears that approximately 100-200 m of sediment is neither necessary nor sufficient to stop hydrothermal heat transfer. We therefore conclude that the age of the crust is the primary control on the fraction of heat transported by hydrothermal flow and that sediment thickness has a lesser effect. This inference is consistent with models in which hydrothermal flow decreases with age due to reduced crustal porosity and hence permeability.

Differential influence of parental smoking and friends' smoking on adolescent initiation and escalation of smoking.

Abstract: Smoking-related behaviors and attitudes of significant others (especially friends and parents) are among the most consistent predictors of adolescent smoking. However, theorists remain divided on whether the behaviors of significant others influence adolescent smoking directly or indirectly, and the relative influence of parental and peer smoking on adolescents' own smoking is still a matter of debate. In addition, little research has examined the role of significant others' behavior on different stages of smoking onset. In particular, not much information is available regarding gender and ethnic differences in social influences on smoking behavior. We use structural equation modeling to address these issues. Different theoretical perspectives from cognitive-affective theories (Ajzen 1985; Ajzen and Fishbein 1980) and social learning theories (Akers et al. 1979; Bandura 1969, 1982, 1986) have been integrated into a structural model of smoking influence. The results show that friends' smoking affects adolescent initiation into smoking both directly and indirectly, whereas parental smoking influences smoking initiation only indirectly. The data also show that friends' and parents' smoking affect smoking escalation only indirectly. In general, friends' smoking has a stronger effect on adolescents' smoking behavior, particularly on initiation. Multiple group comparisons of the structural models predicting smoking initiation among males and females reveal that parental approval of smoking plays a significant mediating role for females, but not for males. Comparisons of Whites, Blacks, Hispanics, and other ethnic groups reveal that there are some significant differences in the pathways of friends' influences among the four groups.

Plane curves associated to character varieties of 3-manifolds.

Abstract: Consider a compact 3-manifold M with boundary consisting of a single torus. The papers [CS1, CS2, CGLS] discuss the variety of characters of SL2(C) representations of zl(M), and some of the ways in which the topological structure of M is reflected in the algebraic geometry of the character variety. We will describe in this paper a certain affine algebraic curve DM which is naturally associated to the character variety of M. A basis B = {~, 9.1/} for the peripheral subgroup of M determines an embedding P8 of DM into C* x C* with coordinates l and m. The closure in C 2 of ps(DM) is a plane algebraic curve and therefore is defined by a polynomial AM,n0, m) that, after certain normalizations, is uniquely determined up to multiplication by constants. The polynomial AM, B is effectively computable and is an invariant of the manifold M together with the choice of basis B. The results in this paper describe how geometric properties of the character variety, and hence topological properties of M, are reflected by the polynomial AM, B. In the case that M is the complement of a knot K in a homology 3-sphere we may take the basis B to consist of the longitude and meridian of K. With the usual orientation conventions this basis is well-defined modulo the involution which inverts both the longitude and meridian. It will follow from the construction of DM that if the basis B' is obtained from B by inverting both generators then the regular maps PB and PB, have the same image. Thus Ar:= AM, s = AM, B, is an invariant of the knot. The polynomial AM, B displays, in a striking way, information about the incompressible surfaces in M. This involves the Newton polygon of AM.B,

Development of aspirin resistance in persons with previous ischemic stroke.

Abstract: Background and Purpose The ex vivo effect of aspirin (ASA) on platelet aggregation, the platelet component of thrombosis, was studied at repeated intervals in a cohort of patients taking aspirin for recurrent ischemic stroke prevention to define the maintenance of efficacy over time. Methods We administered increasing doses of aspirin (from 325 to 1300 mg/d) to patients with previous ischemic stroke and determined the extent of inhibition of platelet aggregation after 2 weeks and thereafter at approximately 6-month intervals. Results Over 33 months, 306 patients had platelet aggregation studies performed to define their initial response to ASA therapy. Of these, 228 had complete and 78 had partial inhibition of platelet aggregation at initial testing. To date, 119 of those who had complete inhibition and 52 who had partial inhibition have undergone repeat testing at least once. At repeat testing 39 of the 119 (32.7%) with complete inhibition at initial testing had lost part of the antiplatelet effect of ASA and

The Na-K-Cl cotransporters

Abstract: The Na-K-Cl cotransporters are a class of membrane proteins that transport Na, K, and Cl ions into and out of cells in an electrically neutral manner, in most cases with a stoichiometry of 1Na:1K:2...

The limits of anchoring

Abstract: Anchoring and adjustment is a pervasive bias in which decision makers are influenced by random or uninformative numbers or starting points. As a means of understanding this effect, we explore two limits on anchoring. In Experiments 1 and 2, implausibly extreme anchors had a proportionally smaller effect than anchors close to the expected value of the lotteries evaluated. In Experiments 2 and 3, anchoring occurred only if the anchor and preference judgment were expressed on the same scale. Incompatible anchors and response modes resulted in no anchoring bias. A confirmatory search mechanism is proposed to account for these results.

An Experimental Study of Inbreeding Depression in a Natural Habitat

Abstract: Inbreeding is known to lead to decreased survival and reproduction in captive populations of animals. It is also important to know whether inbreeding has deleterious effects in natural habitats. An estimate was made of the effects of inbreeding in white-footed mice, Peromyscus leucopus noveboracensis, derived from a wild population. This study demonstrates that inbreeding had a significant detrimental effect on the survivorship of mice reintroduced into a natural habitat. This effect was more severe than the effect observed in laboratory studies of the population.

The DNA-binding specificity of the hepatocyte nuclear factor 3/forkhead domain is influenced by amino-acid residues adjacent to the recognition helix.

Abstract: Three distinct hepatocyte nuclear factor 3 (HNF-3) proteins (HNF-3 alpha, -3 beta, and -3 gamma) are known to regulate the transcription of liver-specific genes. The HNF-3 proteins bind to DNA as a monomer through a modified helix-turn-helix, known as the winged helix motif, which is also utilized by a number of developmental regulators, including the Drosophila homeotic forkhead (fkh) protein. We have previously described the isolation, from rodent tissue, of an extensive family of tissue-specific HNF-3/fkh homolog (HFH) genes sharing homology in their winged helix motifs. In this report, we have determined the preferred DNA-binding consensus sequence for the HNF-3 beta protein as well as for two divergent family members, HFH-1 and HFH-2. We show that these HNF-3/fkh proteins bind to distinct DNA sites and that the specificity of protein recognition is dependent on subtle nucleotide alterations in the site. The HNF-3, HFH-1, and HFH-2 consensus binding sequences were also used to search DNA regulatory regions to identify potential target genes. Furthermore, an analysis of the DNA-binding properties of a series of HFH-1/HNF-3 beta protein chimeras has allowed us to identify a 20-amino-acid region, located adjacent to the DNA recognition helix, which contributes to DNA-binding specificity. These sequences are not involved in base-specific contacts and include residues which diverge within the HNF-3/fkh family. Replacement of this 20-amino-acid region in HNF-3 beta with corresponding residues from HFH-1 enabled the HNF-3 beta recognition helix to bind only HFH-1-specific DNA-binding sites. We propose a model in which this 20-amino-acid flanking region influences the DNA-binding properties of the recognition helix.

Role of alginate lyase in cell detachment of Pseudomonas aeruginosa.

Abstract: The exopolysaccharide alginate of Pseudomonas aeruginosa was shown to be important in determining the degree of cell detachment from an agar surface. Nonmucoid strain 8822 gave rise to 50-fold more sloughed cells than mucoid strains 8821 and 8830. Alginate anchors the bacteria to the agar surface, thereby influencing the extent of detachment. The role of the P. aeruginosa alginate lyase in the process of cell sloughing was investigated. Increased expression of the alginate lyase in mucoid strain 8830 led to alginate degradation and increased cell detachment. Similar effects were seen both when the alginate lyase was induced at the initial stage of cell inoculation and when it was induced at a later stage of growth. It appears that high-molecular-weight alginate polymers are required to efficiently retain the bacteria within the growth film. When expressed from a regulated promoter, the alginate lyase can induce enhanced sloughing of cells because of degradation of the alginate. This suggests a possible role for the lyase in the development of bacterial growth films. Images

Quantitative studies of endothelial cell adhesion. Directional remodeling of focal adhesion sites in response to flow forces.

Abstract: Focal adhesion sites were observed in cultured endothelial cells by tandem scanning confocal microscopy and digitized image analysis, techniques that provide real-time images of adhesion site area and topography in living cells. Image subtraction demonstrated that in the presence of unidirectional steady laminar flow (shear stress [tau] = 10 dyn/cm2) a substantial fraction of focal adhesion sites remodeled in the direction of flow. In contrast, focal adhesions of control (no flow) cells remodeled without preferred direction. In confluent monolayers subjected to shear stresses of 10 dyn/cm2, cells began to realign in the direction of flow after 7-9 h. This was accompanied by redistribution of intracellular stress fibers, alignment of individual focal adhesion sites, and the coalescence of smaller sites resulting in fewer, but larger, focal adhesions per cell. Cell adhesion, repeatedly calculated in the same cells as a function of the areas of focal contact and the separation distances between membrane and substratum, varied by < 10% during both short (30 min), or prolonged (< or = 24 h), periods of exposure to flow. Consistent with these measurements, the gains and losses of focal adhesion area as each site remodeled were approximately equivalent. When the glass substratum was coated with gelatin, rates of remodeling were inhibited by 47% during flow (tau = 10 dyn/cm2). These studies: (a) reveal the dynamic nature of focal adhesion; (b) demonstrate that these sites at the ablumenal endothelial membrane are both acutely and chronically responsive to frictional shear stress forces applied to the opposite (lumenal) cell surface; and (c) suggest that components of the focal adhesion complex may be mechanically responsive elements coupled to the cytoskeleton.

Biological applications of atomic force microscopy

Abstract: The newly developed atomic force microscope (AFM) provides a unique window to the microworld of cells, subcellular structures, and biomolecules. The AFM can image the three-dimensional structure of biological specimens in a physiological environment. This enables real-time biochemical and physiological processes to be monitored at a resolution similar to that obtained for the electron microscope. The process of image acquisition is such that the AFM can also measure forces at the molecular level. In addition, the AFM can interact with the sample, thereby manipulating the molecules in a defined manner--nanomanipulation! The AFM has been used to image living cells and the underlying cytoskeleton, chromatin and plasmids, ion channels, and a variety of membranes. Dynamic processes such as crystal growth and the polymerization of fibrinogen and physicochemical properties such as elasticity and viscosity in living cells have been studied. Nanomanipulations, including dissection of DNA, plasma membranes, and cells, and transfer of synthetic structures have been achieved. This review describes the operating principles, accomplishments, and the future promise of the AFM.

Resistance to arsenic compounds in microorganisms

Abstract: Arsenic ions, frequently present as environmental pollutants, are very toxic for most microorganisms. Some microbial strains possess genetic determinants that confer resistance. In bacteria, these determinants are often found on plasmids, which has facilitated their study at the molecular level. Bacterial plasmids conferring arsenic resistance encode specific efflux pumps able to extrude arsenic from the cell cytoplasm thus lowering the intracellular concentration of the toxic ions. In Gram-negative bacteria, the efflux pump consists of a two-component ATPase complex. ArsA is the ATPase subunit and is associated with an integral membrane subunit, ArsB. Arsenate is enzymatically reduced to arsenite (the substrate of ArsB and the activator of ArsA) by the small cytoplasmic ArsC polypeptide. In Gram-positive bacteria, comparable arsB and arsC genes (and proteins) are found, but arsA is missing. In addition to the wide spread plasmid arsenic resistance determinant, a few bacteria confer resistance to arsenite with a separate determinant for enzymatic oxidation of more-toxic arsenite to less-toxic arsenate. In contrast to the detailed information on the mechanisms of arsenic resistance in bacteria, little work has been reported on this subject in algae and fungi.