Rotational Defects Research Articles

Ab Initio Study of Phonon-Induced Dephasing of Electronic Excitations in Narrow Graphene Nanoribbons

Vibrational dephasing of the lowest energy electronic excitations in the perfect (16,16) graphene nanoribbon (GNR) and those with the C2-bond insertion and rotation defects is studied with ab initio molecular dynamics. Compared to single-walled carbon nanotubes (SWCNTs) of similar size, GNRs shows very different properties. The dephasing in the ideal GNR occurs twice faster than that in the SWCNTs. It is induced primarily by the 1300 cm (-1) disorder mode seen in bulk graphite rather than by the 1600 cm (-1) C-C stretching mode as in SWCNTs. In contrast to SWCNTs, defects exhibit weaker electron-phonon coupling compared to the ideal system. Therefore, defects should present much less of a practical problem in GNRs compared to SWCNTs. The predicted optical line widths can be tested experimentally.

Influence of grain boundary sliding on fracture toughness of nanocrystalline ceramics

A theoretical model is proposed describing a new physical microscopic mechanism of increased fracture toughness of nanocrystalline ceramics. According to this model, when a ceramic with a microcrack is deformed, intensive grain boundary sliding occurs near the crack tip under certain conditions. This sliding is accompanied by the formation of an array of disclination dipoles (rotational defects) producing elastic stresses. These stresses partially compensate the high local stresses concentrated near the microcrack tip and thereby hamper the microcrack growth. The proposed model is used to theoretically estimate the increase in the critical microcrack length (the length above which the catastrophic growth of microcracks occurs) caused by the formation of disclination dipoles during grain boundary sliding in nanoceramics. The increase in the critical microcrack length is a quantitative characteristic of the increased fracture toughness of nanoceramics.

Stress investigation on a Griffith crack initiated from an eccentric disclination in a cylinder

Disclinations are rotational line defects which may be introduced in metal wires during the manufacturing process. In this work, the relaxation of an eccentric (off-center) negative wedge disclination in a cylinder by nucleation of a Griffith crack is investigated. The nucleated crack is simulated with distributed edge dislocations. The stress intensity factors (SIFs) of the crack are evaluated by solving a set of singular integral equations. By enforcing the condition that the SIFs at the two crack tips should keep the same value in the nucleation process, the crack length growth on each side of the wedge disclination is determined. The critical disclination power and equilibrium crack lengths are then numerically determined. Some important characteristics of the Griffith crack nucleation are revealed. (1) The two tips of the nucleated Griffith crack grow asymmetrically when the disclination locates eccentrically. The tip closer to the cylinder edge travels a shorter length. This asymmetry is getting more severe as the normalized off-center distance increases. (2) The critical disclination power increases monotonically with the normalized off-center distance. (3) The normalized stable equilibrium crack length decreases as the normalized off-center distance increases while the normalized unstable equilibrium crack length shows an opposite dependence. The dependence of the critical disclination power and the equilibrium crack lengths on the disclination power and cylinder radius is also discussed in this work. It is believed that this work helps to predict the strength of disclinated metal wires at various length scales.

What are the interactions in quantum glasses?

The form of the low-temperature interactions between defects in neutral glassesis reconsidered. We analyze the case where the defects can be modeled eitheras simple two-level tunneling systems, or tunneling rotational impurities. Thecoupling to strain fields is determined up to second order in the displacementfield. It is shown that the linear coupling generates not only the usual1/r3 Ising-like interaction between the rotational tunneling defect modes, which causes them to freeze around atemperature TG, but also a random field term. At lower temperatures the inversion symmetric tunnelingmodes are still active—however, the coupling of these to the frozen rotationalmodes, now via the second-order coupling to phonons, generates another randomfield term acting on the inversion symmetric modes (as well as shorter-range1/r5 interactions between them). Detailed expressions for all these couplings are given.

Structure, optical properties and defects in nitride (III–V) nanoscale cage clusters

Density Functional Theory calculations are reported on cage structured BN, AlN, GaN and InN sub- and low nanosize stoichiometric clusters, including two octahedral families of T(d) and T(h) symmetry. The structures and energetics are determined, and we observe that BN clusters in particular show high stability with respect to the bulk phase. The cluster formation energy is demonstrated to include a constant term that we attribute to the curvature energy and the formation of six tetragonal defects. The (BN)(60) onion double-bubble structure was found to be particularly unstable. In contrast, similar or greater stability was found for double and single shell cages for the other nitrides. The optical absorption spectra have been first characterised by the one-electron Kohn-Sham orbital energies for all compounds, after which we concentrated on BN where we employed a recently developed Time Dependent Density Functional Theory approach. The one-electron band gaps do not show a strong and consistent size dependency, in disagreement with the predictions of quantum confinement theory. The density of excited bound states and absorption spectrum have been calculated for four smallest BN clusters within the first ionisation potential cut-off energy. The relative stability of different BN clusters has been further explored by studying principal point defects and their complexes including topological B-N bond rotational defects, vacancies, antisites and interstititials. The latter have the lowest energy of formation.

General Principles in the Surgical Treatment of Paralytic Strabismus

The surgical approach necessary to achieve the largest field of usable single binocular vision in patients with paralytic strabismus is one that has a greater effect in some directions of gaze than in others. Developing the appropriate “incomitant” strabismus surgery can be achieved by improving the ocular rotation of the involved eye(s), creating a matching rotation defect in the “normal” eye, and anticipating that surgery may create a new/different deviation (not present before the surgery) that can be used to surgeons' advantage. The severity of the limitation in ocular rotation will determine the amount and type of strengthening or weakening that will be necessary to the paralytic muscle and its yoke muscle.

Orientational isotopic effects in the thermal conductivity of CH4∕CD4 solid solutions

The thermal conductivity of (CH4)1−c(CD4)c solid solutions with c=0, 0.03, 0.065, 0.13, 0.22, 0.4, 0.78, and 1.0 is measured in the region of existence of three orientational phases: disordered (phase I), partially ordered (phase II), and completely ordered (phase III). The temperature range is 1.3–30K. It is shown that the thermal conductivity has different temperature dependences κ(T) in these phases. Its value increases with the degree of the orientational order in the phase. In phase I the thermal conductivity is independent of c and weakly dependent on T. The impurity effect in κ(T) is much stronger in the low-temperature part of phase II than in phase III. As the concentration c grows, the κ(T) curve of phase II approaches the dependence κ(T) typical of phase I. There is a hysteresis in the vicinity of the II↔III phase transition. In phase III the impurity effect in κ(T) can be considered as phonon scattering at rotational defects developing due to the difference between the moments of inertia of the CH4 and CD4 molecules. The obtained dependences of thermal conductivity on temperature and concentration can be explained qualitatively assuming that the dominant mechanism of phonon scattering is connected with the interaction of phonons with the rotational motion of the molecules in all of the three orientational phases of the CH4–CD4 system.

Kinematics, electromechanics, and kinetics of dielectric and piezoelectric crystals with lattice defects

A mathematical framework is formulated to address the electromechanical behavior of dielectric and piezoelectric solids containing lattice imperfections. The macroscopic displacement gradient encompasses recoverable elasticity, deviatoric plasticity arising from dislocation glide, and volumetric deformation attributed to point vacancies in the crystal. A linear connection on the spatial manifold of deformed lattice vectors describes gradients of stretch and rotation at the microscale caused by continuous distributions of various classes of crystal defects. It is shown that parallel transport of a lattice director vector with respect to this connection about a closed loop yields a discontinuity with contributions from the torsion of the connection (physically, from dislocations) and its curvature (physically, from rotational defects such as domain walls, and from gradients in vacancy concentration). Classical balance laws of electrostatics and mass and momentum conservation are invoked. A free energy function dependent upon lattice distortion, polarization, temperature, and defect densities is suggested. Thermodynamically consistent kinetic relations for dislocation glide and vacancy diffusion are then derived, with the chemical potential for the latter depending upon defect density, electric potential, hydrostatic pressure, and vacancy energy. The theory also explicitly considers mass rearrangement at the free surface of the substance. Two forms of the contribution of vacancies to the free energy are investigated in detail: a logarithmic function common in chemical mixing theory, and a quadratic function analogous to the convex strain energy used in continuum elasticity theory. For the latter case, the analytical solution of the diffusion equation in one spatial dimension, at steady state, illustrates the effects of defect charge, defect energy, and mechanical stress on the distribution of vacancies in a dielectric thin film. A specific example is given of how compressive residual stresses observed in experiments may be correlated with the equilibrium concentration of vacancies within grains of a polycrystalline dielectric thin film, influencing its electrical performance.

Drosophila odz gene is required for multiple cell types in the compound retina

The Drosophila melanogaster pair-rule gene odz (odd Oz, or Ten-m) is expressed in distinct patterns in the larval eye imaginal disc. Its earliest eye expression occurs in ommatidial precursors starting from the posterior edge of the morphogenetic furrow. Loss of function of odz activity leads to visible light photoreceptor loss; R7 photoreceptor loss; ommatidial size, shape, and rotation defects; ommatidial disorder and fusions; interommatidial bristle defects; and ommatidial lens defects. The same effects are seen in odz eye mitotic clones, in odz-Ten-a transheterozygous combinations, and in eyes expressing an Odz-Dominant Negative transgene (Odz-DN). Effects of the same strength are also seen when the Odz-DN transgene is driven only in regions of scabrous expression, which overlaps the four columns of Odz expression clusters behind the furrow. Small odz mitotic clones suggest an odz role in cell proliferation or survival. Senseless is expressed in odz mutant clones, in a fairly ordered manner, indicating that Odz acts downstream of R8 specification. Disorder within each ommatidium in odz clones is accompanied by some loss of R7 precursors and visible photoreceptor precursor order.

LET-711, theCaenorhabditis elegansNOT1 Ortholog, Is Required for Spindle Positioning and Regulation of Microtubule Length in Embryos

Spindle positioning is essential for the segregation of cell fate determinants during asymmetric division, as well as for proper cellular arrangements during development. In Caenorhabditis elegans embryos, spindle positioning depends on interactions between the astral microtubules and the cell cortex. Here we show that let-711 is required for spindle positioning in the early embryo. Strong loss of let-711 function leads to sterility, whereas partial loss of function results in embryos with defects in the centration and rotation movements that position the first mitotic spindle. let-711 mutant embryos have longer microtubules that are more cold-stable than in wild type, a phenotype opposite to the short microtubule phenotype caused by mutations in the C. elegans XMAP215 homolog ZYG-9. Simultaneous reduction of both ZYG-9 and LET-711 can rescue the centration and rotation defects of both single mutants. let-711 mutant embryos also have larger than wild-type centrosomes at which higher levels of ZYG-9 accumulate compared with wild type. Molecular identification of LET-711 shows it to be an ortholog of NOT1, the core component of the CCR4/NOT complex, which plays roles in the negative regulation of gene expression at transcriptional and post-transcriptional levels in yeast, flies, and mammals. We therefore propose that LET-711 inhibits the expression of ZYG-9 and potentially other centrosome-associated proteins, in order to maintain normal centrosome size and microtubule dynamics during early embryonic divisions.

Prothèses totales de hanche après échec de fixation de fractures per et sous-trochantériennes chez les sujets âgés

Purpose of the study Most pertrochanteric fractures can be successfully fixed with osteosynthesis. Osteosynthesis fails however is a small number of patients who require re-operation for implantation of a total hip prosthesis. This situation occurs in particular when the material has penetrated the acetabulum and in elderly subjects. Although this type of arthroplasty is routine practice, few series have been reported. We present here outcome and complications of total hip arthroplasty after failure of per- and subtrochanteric fracture fixation. Material and methods Between 1990 and 2000, twenty patients aged 79 years on average (range 62-78 years) underwent revision for total hip arthroplasty after failure of osteosynthesis for fracture of the upper femur. A gliding THS had been used for fixation in 18 patients, a plate in one and a Gamma nail in one. Osteosynthesis failure was related to early disassembly in ten patients, pseudarthrosis in eight and malunion in two. Revision was performed via a posterolateral approach in all cases. A standard total hip prosthesis was used in 16 patients, a longer femoral stem was required in four. Femoral components were cemented in 18 patients and non-cemented in two. The cup was a standard cemented cup in 12, retaining and cemented in eight. Results Mean operative time and blood loss were greater than in first-intention arthroplasties. All patients had lost their independence prior to the revision procedure. Despite their age, all recovered independence after a stay in rehabilitation. Most still required crutches. Use of a retaining cup enabled avoiding dislocation in all cases. For those who did not have a retaining cup, dislocation was the most frequent complication (3/12). The difficulties observed were: 1) elimination of associated infection before surgery; many of these elderly subjects had altered ESR and CRP values for various reasons; 2) abnormal position of the trochanteric mass because of a rotation defect; 3) malunion of the upper femur in the frontal or sagittal planes; 4) more or less easily achieved positioning of the femoral piece on the calcar; 5) difficult intraoperative identification of limb length due to loss of usual landmarks on the lesser and greater trochanter; 6) removal of fracture screws which sometimes required use of a trephine and bridging the last screw hole with a longer centromedullary stem. The most frequent postoperative orthopedic problems were leg length discrepancy (1-2 cm for eight patients), gluteus medius insufficiency, limping and pain at palpation of the trochanteric area. Discussion Despite the difficult technique and the potential complications which are more important than for first-intention arthroplasties, this series demonstrates that total hip prosthesis is a reliable solution for treating fixation failures of the upper femur.

Rotation of the Myocardial Wall of the Outflow Tract Is Implicated in the Normal Positioning of the Great Arteries

Congenital heart defects frequently involve a failure of outflow tract (OFT) formation during development. We analyzed the remodeling of the OFT, using the y96-Myf5-nlacZ-16 transgene, which marks a subpopulation of myocardial cells of the pulmonary trunk. Expression analyses of reporter transcript and protein suggest that the myocardial wall of the OFT rotates before and during the formation of the great arteries. Rotational movement was confirmed by Di-I injection experiments with cultured embryos. We subsequently examined the expression of the transgene in mouse models for OFT defects. In hearts with persistent truncus arteriosus (PTA), double outlet right ventricle (DORV), or transposition of the great arteries, rotation of the myocardial wall of the OFT is arrested or fails to initiate. This is observed in Splotch (Pax3) mutants with PTA or DORV and may be a result of defects in neural crest migration, known to affect OFT septation. However, in Pitx2deltac mutant embryos, where cardiac neural crest cells are present in the heart, PTA and DORV are again associated with a rotation defect. This is also seen in Pitx2deltac mutants, which have transposition of the great arteries. Because Pitx2c is involved in left-right signaling, these results suggest that embryonic laterality affects rotation of the myocardial wall during OFT maturation. We propose that failure of normal rotation of OFT myocardium may underlie major forms of congenital heart disease.

A geometric framework for the kinematics of crystals with defects

Presented is a general theoretical framework capable of describing the finite deformation kinematics of several classes of defects prevalent in metallic crystals. Our treatment relies upon powerful tools from differential geometry, including linear connections and covariant differentiation, torsion, curvature and anholonomic spaces. A length scale dependent, three-term multiplicative decomposition of the deformation gradient is suggested, with terms representing recoverable elasticity, residual lattice deformation due to defect fields, and plastic deformation resulting from defect fluxes. Also proposed is an additional micromorphic variable representing additional degrees-of-freedom associated with rotational lattice defects (i.e. disclinations), point defects, and most generally, Somigliana dislocations. We illustrate how particular implementations of our general framework encompass notable theories from the literature and classify particular versions of the framework via geometric terminology.

Effects of dimethylsulphoxide on mice arsenite-induced dysmorphogenesis in embryo culture and cytotoxicity in embryo cells

Dimethylsulphoxide (DMSO) is a widely used vehicle for water insoluble compounds in experimental studies. Nevertheless, little is known about its potential impact on dysmorphogenesis caused by reactive oxygen species (ROS). In order to evaluate if DMSO at concentrations used as vehicle can alter in vitro sodium arsenite (Asi) teratogenicity and cytotoxicity, mouse embryos with 4–5 somites were grown for 48 h in Asi 0.4 and 4 μM, with and without 0.1% DMSO (v/v). Also embryonic mesenchymal cell were cultured, using mesenchymal mouse embryo cells obtained from gestation day 11 and treated with DMSO 0.1%, 0.2% and 0.5% (v/v) 15 min before Asi was added at final concentrations of 0.4 and 4 μM. Cytotoxicity and intracellular ROS production, were evaluated with MTT and 5-(and-6)-chloromethyl-2′,7′-dichlorodihydrofluorescein diacetate, acetyl ester (CM-H 2DCFDA), respectively. Results indicated that Asi produced growth retardation and abnormal development. Main malformations involved neural tube closure defects, abnormal rotation and optic vesicle defects among others. Co-treatment with DMSO partially reduced neural tube defects as well as facial dysmophology. Asi reduced cell viability inversely to the level of ROS production, and DMSO returned cellular viability to control values by reducing ROS intracellular production. In summary, the protective effect observed for DMSO appeared to reflect free radical scavenger properties, though other mechanisms independent to ROS production may have also been involved.

17β‐ and 17α‐estradiol are non‐competitive inhibitors of dopamine uptake: implications for Parkinson's disease models and therapeutics

AbstractDespite compelling literature documenting the cyto‐ and neuro‐protective activities of various estrogens in a wide variety of cell and animal models, several large clinical trials of hormone replacement therapies have failed to detect such beneficial responses in humans. To some degree, this failure stems from profound hormonal responses that counterbalance the protective effects. This limitation could be circumvented by the development of less hormonally active estrogen analogs that retain the cytoprotective activities of the parental hormones. For example, 17α‐estradiol (17α‐E2) is at least 200‐fold less active than 17β‐estradiol (17β‐E2) as a transactivating hormone, yet it is equipotent as a cytoprotectant in many cell types exposed to a variety of stressors, such as amyloid toxicity, serum withdrawal, oxidative stress, and glutamate excitotoxicity. Both estradiol isomers stabilize mitochondrial function under pathogenic conditions, and both have shown efficacy in animal models of stroke. The results for models of Parkinson's disease differ, and 17β‐E2, but not 17α‐E2, has been reported previously to provide neuroprotection against MPTP toxicity. However, such findings must be regarded in light of reports that 17β‐E2 impedes cellular uptake of MPTP by the dopamine transporter (DAT), thereby forestalling development of the lesion rather than providing authentic cytoprotection. We report here that both 17α‐E2 and 17β‐E2 show classical, non‐competitive, inhibition of dopamine uptake by the human DAT (hDAT) transfected into Ltk− mouse fibroblasts, HEK293 human embryonic kidney cells, and SH‐SY5Y human neuroblastoma cells. IC50 values vary slightly with cell type, but are 400 and 70 nM for 17α‐E2 and 17β‐E2, respectively, in SH‐SY5Y cells. We also evaluated 17α‐E2 in the 6‐OH‐dopamine (6‐OHDA) model of PD, where toxin uptake occurs via the DAT. In these studies, treatment with estrogen was delayed for 6 hr after unilateral intrastriatal 6‐OHDA injection to allow for toxin uptake. After 6 hr, a loading dose of 17α‐E2 (100 µg/kg in sesame oil) was injected s.c., accompanied by implanting of a sustained release silastic device. After 21 days, animals treated with 17α‐E2 showed significant improvements in both gait asymmetry and apo‐morphine induced rotational defects. These positive results encourage evaluation of 17α‐E2 in a host of neurodegenerative diseases. Drug Dev. Res. 66:160–171, 2006. © 2006 Wiley‐Liss, Inc.

The rotational spectra of the 7 19 1, 6 19 1, and 7 2 vibrational states of nitric acid

The rotational spectra of the first three vibrational states of nitric acid above 1000 cm −1, 7 19 1, 6 19 1, and 7 2, have been measured and analyzed. The 7 2 state, along with the previously published 7 1 state, show the rotational and centrifugal distortional constants have a near linear dependence on the υ 7 vibrational quantum number. Large changes for several centrifugal distortion constants of the υ 7 = n series of states are attributed to a c-type Coriolis resonance manifold between the ν 7 and ν 6 vibrational modes and the Hamiltonian reduction and representation used to fit the spectra. The 7 19 1 and 6 19 1 states have torsional splittings of 12.361(8) and 22.47(1) MHz, respectively. These splittings are large compared to 2.340(8) MHz of the 9 1 state and can be explained by a ∼1–2% mixing through anharmonic Fermi resonances with the 9 3 state, which has a large torsional splitting of ∼1760 MHz. The millimeter/submillimeter-wave spectrum of each state was fit separately to the experimental uncertainty of the measurements. The resultant rotational constants, distortional constants and inertial defects agree well with DFT calculations.

Modeling dislocations and disclinations with finite micropolar elastoplasticity

Aspects of a constitutive model for characterizing crystalline metals containing a distribution of dislocation and disclination defects are presented. Kinematics, balance laws, and general kinetic relations are developed – from the perspective of multiscale volume averaging – upon examination of a deforming crystalline element containing a distribution of displacement discontinuities in the form of translational and rotational lattice defects, i.e., dislocations and disclinations. The macroscopic kinematic description is characterized by a three-term multiplicative decomposition of the deformation gradient. The micro-level description follows from an additive decomposition of an affine connection into contributions from populations of dislocations and disclinations to the distortion of the lattice directors. Standard balance equations apply at the macroscopic scale, while momentum balances reminiscent of those encountered in micropolar elasticity (i.e., couple stress theory) are imposed at the micro-level on first and second order moment stresses associated with geometrically necessary defects. Thermodynamic restrictions are presented, and general features of kinetic relations are postulated for time rates of inelastic deformations and internal variables. Micropolar rotations are incorporated to capture physics that geometrically necessary dislocations stemming from first order gradients of elastic or plastic parts of the total deformation gradient may alone be unable to reflect, including evolution of defect substructure at multiple length scales and incompatible lattice misorientation gradients arising in ductile single crystals subjected to nominally homogeneous deformation.

Genetic regions that interact with loss- and gain-of-function phenotypes of deltex implicate novel genes in Drosophila Notch signaling

The Notch signaling pathway is an evolutionarily conserved mechanism that regulates many cell fate decisions. The deltex (dx) gene encodes an E3-ubiquitin ligase that binds to the intracellular domain of the Notch protein and regulates Notch signaling in a positive manner. However, it is still not clear how Dx does this. We generated a transgenic line, GMR-dx, which overexpresses dx in the developing Drosophila eye disc. The GMR-dx line showed a rough-eye phenotype, specific transformation of a photoreceptor cell (R3 to R4), and a rotation defect in the ommatidia. This phenotype was suppressed in combination with a dx loss-of-function mutant, indicating that it was due to a dx gain-of-function. We previously reported that overexpression of Dx results in the stabilization of Notch in late endosomes. Here, we found that three motifs in Dx, a region that binds to Notch, a proline-rich motif and a RING-H2 finger, were required for this stabilization, although the relative activity of these variants in this assay did not always correspond to the severity of the rough-eye phenotype. In an attempt to identify novel genes of the Notch pathway, we tested a large collection of chromosomal deficiencies for the ability to modify the eye phenotypes of the GMR-dx line. Twelve genomic segments that enhanced the rough-eye phenotype of GMR-dx were identified. To evaluate the specificity of these interactions, we then determined whether the deletions also interacted with the wing phenotypes associated with a loss-of-function mutation of dx, dx24. Analyses based on whole-genome information allowed us to conclude that we have identified two novel loci that probably include uncharacterized genes involved in Dx-mediated Notch signaling.

Fine structures of zeolite-Linde-L (LTL): surface structures, growth unit and defects.

High-resolution electron microscopy (HREM) has been used to image the surface structure of nano- and micrometer-sized synthetic crystals of zeolite-Linde-L (LTL). Columnar holes and rotational, nano-sized, wheel-like defects were observed within the crystals, where the hole has a minimum size equal to that of the rotational defect. Predictions of surface structure from atomistic computer simulation concur with the observations from HREM and provide insight into the crystal growth mechanism of perfect and defective LTL. Analysis of the energetics of the formation of rotational defect structures reveals that the driving force for defect creation is thermodynamic and furthermore, the rotational defects could be created in high concentrations. Formation of a columnar hole is found to be slightly energetically unfavourable and therefore we speculate that the incidence of both rotational and nano-sized vacancy defects is strongly dependent on kinetic factors and reaction conditions. The morphology of nano- and microcrystalline LTL is contradistinct and we use insights from simulation to propose an explanation of the disparity in crystal shape.

Developmental toxicity of mixtures: the water disinfection by-products dichloro-, dibromo- and bromochloro acetic acid in rat embryo culture

The chlorination of drinking water results in production of numerous disinfection by-products (DBPs). One of the important classes of DBPs is the haloacetic acids. We have previously shown that the haloacetic acids (HAs), dichloro (DCA), dibromo (DBA) and bromochloro (BCA) acetic acid are developmentally toxic in mouse whole embryo culture. Human exposure to these contaminants in drinking water would involve simultaneous exposure to all three HAs. This study explores the question of developmental toxicity interactions between these compounds. Gestational day (GD) 9.5 rat embryos were exposed to various concentrations of the three HAs (singly or in combination) for 48 h and then evaluated for dysmorphology. The embryonic effects from exposure to the single compounds and mixtures were evaluated using developmental score (DEVSC) as the parameter of comparison. Concentrations of individual compounds and mixtures were chosen (based on a dose-additivity model) which were predicted to produce scores 10 or 20% lower than control levels. Evaluations were performed on all possible combinations of the three HAs. The HAs were dysmorphogenic and resulted in primarily rotation and heart defects and to a lesser extent prosencephalic, visceral arch, and eye defects. The percent anomalies in the rat were comparable to those previously published for the mouse at comparable toxicant concentration. There was a low incidence of neural tube defects in the rat following exposure to the HAs. The rat neural tube appeared less sensitive to the HAs than did the mouse resulting in a higher rate of neural tube dysmorphology in the mouse. Following exposures to BCA and DBA, alone and in combination, there was a significant incidence of delayed embryonic caudal development with apparent normal development anterior to the second visceral arch. The developmental scores for embryos exposed to combinations of the three compounds, when compared to scores for embryos exposed to the single compounds, indicated that the dose-additivity model adequately predicted the observed toxicity and that the developmental toxicity of these water disinfection by-products appears to be additive in whole embryo culture (WEC).