Packing structures and transitions in liquids and solids.

Classification of potential energy minima-mechanically stable molecular packings-offers a unifying principle for understanding condensed phase properties. This approach permits identification of an inherent structure in liquids that is normally obscured by thermal motions. Melting and freezing occur through characteristic sequences of molecular packings, and a defect-softening phenomenon underlies the fact that they are thermodynamically first order. The topological distribution of feasible transitions between contiguous potential minima explains glass transitions and associated relaxation behavior.

Object-based attentional selection--grouped arrays or spatially invariant representations?: comment on vecera and Farah (1994).

S. P. Vecera and M. J. Farah (1994) have addressed the issue of whether visual attention selects objects or locations. They obtained data that they interpreted as evidence for attentional selection of objects from an internal spatially invariant representation. A. F. Kramer, T. A. Weber, and S. E. Watson question this interpretation on both theoretical and empirical grounds. First, the authors suggest that there are other interpretations of the Vecera and Farah data that are consistent with location-mediated selection of objects. Second, they provide data, using the displays employed by Vecera and Farah in conjunction with a postdisplay probe technique, that suggests that attention is directed to the locations of the target objects. The implications of the results for space and object-based attentional selection are discussed.

Influence of case type, word frequency, and exposure duration on visual word recognition.

The authors report 4 lexical decision experiments in which case type, word frequency, and exposure duration were varied. These data indicated that there is a larger mixed-case disadvantage for nonwords than for words for longer duration presentations of targets. However, when targets were presented for 100 ms (followed by a postdisplay pattern mask), a larger mixed-case disadvantage occurred for words than for nonwords. For word frequency, the data from Experiments 1, 2, and 3 revealed a slightly larger mixed- case disadvantage for higher frequency words than for lower frequency words. (There was additivity between word frequency and case type for experiment 4.) These results are consistent with a holistically biased, hybrid model of visual word recognition but inconsistent with analytically biased, hybrid models of word recognition, such as the process model (Besner & Johnston, 1989) and the interactive-activation model (McClelland & Rumelhart, 1981).

Word frequency effects at brief exposure durations: comment on Paap and Johansen (1994).

K. R. Paap and L. S. Johansen (1994) proposed that word frequency effects do not occur on a lexical decision task (LDT) when postmasked target exposure duration is sufficiently brief because such a task prevents verification--their hypothesized locus of the word frequency effect. In making this assertion, they proposed that the activation interpretation of A. R. Dobbs, A. Friedman, and J. Lloyd (1985) and of P. A. Allen, M. McNeal, and D. Kvak (1992) was flawed. However, evidence that Paap and Johansen's conclusions were wrong and that their experimental design contained flaws is provided here. In Experiment 1 of the present study, word frequency effects were evident on an LDT at the 75% accuracy level proposed by Paap and Johansen as being sufficiently low to prevent verification. In Experiment 2 the mental lexica of participants from the same population as that used for Experiment 1 contained very-low-frequency words. Thus, the present results are consistent with an activation locus.

Object-based attentional selection and aging.

The authors conducted 2 studies to examine potential age-related differences in object-based attentional selection. Participants were briefly presented with pairs of wrenches and were asked to make 1 response if both target properties (i.e., an open end and a hexagonal end) were present and another response if only a single target property was present in the display. The critical manipulation was whether the target properties were present on 1 wrench or distributed between 2 wrenches. Space-based models of selective attention predict no difference in performance between these conditions. However, object-based attentional selection models predict better performance when both target properties appear on a single object. The results from both of the studies were consistent with object-based models of attentional selection. Furthermore, both young and old adults showed similar performance effects, suggesting the object-based attentional selection is insensitive to normal aging.

On mental multiplication and age.

In 2 experiments, younger and older adults were presented with simple multiplication problems (e.g., 4 x 7 = 28 and 5 x 3 = 10) for their timed, true or false judgments. All of the effects typically obtained in basic research on mental arithmetic were obtained, that is, reaction time (a) increased with the size of the problem, (b) was slowed for answers deviating only a small amount from the correct value, and (c) was slowed when related (e.g., 7 x 4 = 21) versus unrelated (e.g., 7 x 4 = 18) answers were presented. Older adults were slower in their judgments. Most important, age did not interact significantly with problem size or split size. The authors suggest that elderly adults' central processes, such as memory retrieval and decision making, did not demonstrate the typical age deficit because of the skilled nature of these processes in simple arithmetic.

Influence of age and processing stage on visual word recognition.

The authors used a lexical-decision task in 3 different experiments to examine whether age differences in word recognition were consistent across processing stage. In all experiments, word frequency and length were manipulated. In Experiments 1 and 2, encoding difficulty was varied, and in Experiment 3, response selection difficulty was varied. In all 3 experiments, there were no age differences for word frequency. However, in Experiments 1 and 2, older adults showed a larger decrement for encoding. In Experiment 3, age differences were larger when response selection load increased. These results suggest that age differences in word recognition occur because older adults exhibit primarily peripheral-rather than central-processing decrements. The implications of these data for generalized and localized slowing models are discussed.

Selective processing of superimposed objects: an electrophysiological analysis of object-based attentional selection.

We investigated whether object-based attentional selection occurs from grouped-array or spatially-invariant representations. Subjects were presented with colored objects and asked to judge whether a particular color/shape conjunction was present, regardless of whether the color and shape were part of a single object (same-object condition) or occurred on two different objects (different-object condition). RTs and accuracies were recorded for subjects judgments. ERP components, in particular the P1 and N1, were elicited both from the presentation of the target objects and from a post-display probe that was employed as an index of spatial attention. Consistent with predictions of object-based selection models, RTs and accuracies were faster on same than on different object trials. N1s elicited by the target objects and P1s elicited by the post-display probes discriminated between same and different object trials when the two target objects were superimposed. These data are consistent with the proposal that object-based selection is spatially mediated, even in the case of partially overlapping objects. The data are discussed in terms of space- and object-based models of visual selective attention.

Hypnotic susceptibility, imaging ability, and the detection of embedded words within letters.

Two experiments were conducted to determine the role of hypnotic susceptibility level (high or low) and imaging ability (vivid or poor) in the performance of a visual search for words embedded within matrices of letters. In Experiment 1, subjects searched for target words from a list; however, distractor words were also embedded in the matrices. Results indicated that subjects judged both high in hypnotic susceptibility and vivid in imaging ability demonstrated the fastest search speed with a greater percentage of target words found. These subjects also made fewer false alarm errors (locating distractor words not on the target list). The poorest performance was exhibited by subjects judged both low in hypnotic susceptibility and poor in imaging ability. The amount of variance accounted for by hypnotic susceptibility and imaging ability was approximately equal for each dependent measure. In Experiment 2, when subjects searched for target words from a list without distractor words embedded in matrices, similar results to those reported for Experiment 1 were produced, except that the percentage of words found was equivalent across groups. This was attributed to the elimination of potential false alarm errors. The results are explained in terms of the use of either a holistic or a detail strategy in the performance of a visual search.

The C-terminus of p63 contains multiple regulatory elements with different functions.

The transcription factor p63 is expressed as at least six different isoforms, of which two have been assigned critical biological roles within ectodermal development and skin stem cell biology on the one hand and supervision of the genetic stability of oocytes on the other hand. These two isoforms contain a C-terminal inhibitory domain that negatively regulates their transcriptional activity. This inhibitory domain contains two individual components: one that uses an internal binding mechanism to interact with and mask the transactivation domain and one that is based on sumoylation. We have carried out an extensive alanine scanning study to identify critical regions within the inhibitory domain. These experiments show that a stretch of ∼13 amino acids is crucial for the binding function. Further, investigation of transcriptional activity and the intracellular level of mutants that cannot be sumoylated suggests that sumoylation reduces the concentration of p63. We therefore propose that the inhibitory function of the C-terminal domain is in part due to direct inhibition of the transcriptional activity of the protein and in part due to indirect inhibition by controlling the concentration of p63.

Conformational stability and activity of p73 require a second helix in the tetramerization domain.

p73 and p63, the two ancestral members of the p53 family, are involved in neurogenesis, epithelial stem cell maintenance and quality control of female germ cells. The highly conserved oligomerization domain (OD) of tumor suppressor p53 is essential for its biological functions, and its structure was believed to be the prototype for all three proteins. However, we report that the ODs of p73 and p63 differ from the OD of p53 by containing an additional alpha-helix that is not present in the structure of the p53 OD. Deletion of this helix causes a dissociation of the OD into dimers; it also causes conformational instability and reduces the transcriptional activity of p73. Moreover, we show that ODs of p73 and p63 strongly interact and that a large number of different heterotetramers are supported by the additional helix. Detailed analysis shows that the heterotetramer consisting of two homodimers is thermodynamically more stable than the two homotetramers. No heterooligomerization between p53 and the p73/p63 subfamily was observed, supporting the notion of functional orthogonality within the p53 family.

Adult age differences in attention: filtering or selection?

We examined the effect of target letter redundancy for target-only (TO) and target-plus-noise (TPN) trials on a visual search, divided attention task where target letters were presented in one or two corners of a two-corner display. Half of the two-letter displays also included a noise letter. In both Experiment 1 (two-choice vs go/no-go) and Experiment 2 (all go/no-go), older adults showed larger redundancy gains than did young adults, and this effect did not interact with task type or visual similarity. However, for the "no-go" trials in both experiments, there were no age differences in overall errors. These results suggest that there are age differences in the activation of selective attention rather than age differences in inhibitory control. In Experiment 2, young adults under lower-luminance presentation conditions (18 cd/m2) showed a smaller redundancy gain than did older adults under higher-luminance presentation conditions (40 cd/m2). These results provided further support of the age differences in activation interpretation, as well as indicating that older adults' larger redundancy gain was not due to an age decrement in retinal illuminance.

Age differences in letter and color matching: selective attention or internal noise?

We tested healthy young and older adults on a letter-matching task that varied letter identity and letter color (Experiment 1) and on a color matching task that varied letter color and letter identity (Experiment 2). The goal of this investigation was to empirically disentangle the theoretical concepts of internal noise and selective attention. The results from Experiment 1 indicated that both young and older adults exhibited "fast-same" effects for reaction time and "false-different" effects for errors, and older adults exhibited a relatively larger "false-different" effect. However, letter color did not affect performance. The data from Experiment 2 indicated that older adults, compared with young adults, evidenced greater interference from "different-similar" letter pairs than "different-dissimilar" letter pairs even though the task was color matching. These data suggest that older adults evidenced greater levels of internal noise, and that this factor may modulate age differences in selective attention.

Caveats when considering ketogenic diets for the treatment of pyruvate dehydrogenase complex deficiency.

OBJECTIVES: We conducted a critical assessment of the use of diets high in fat and low in carbohydrate ("ketogenic") in the treatment of children with congenital lactic acidosis caused by mutations in the mitochondrial pyruvate dehydrogenase complex (PDC). STUDY DESIGN: The dietary composition of 18 subjects (11 from literature sources and 7 previously unpublished cases) was analyzed for nutrient composition. The biochemical and clinical responses to a long-term ketogenic regimen were also evaluated. RESULTS: There was lack of uniformity in the proportion of fat calories administered and in the fatty acid composition of the diets. Ketogenic diets are also generally high in protein, compared with the recommended dietary allowance for age. Patient response to these regimens also varied considerably. CONCLUSIONS: Although ketogenic diets have become the standard of care for the treatment of PDC deficiency, data to support their use are based on a few uncontrolled case reports in which dietary composition varied widely. Furthermore, there are several theoretical reasons for concern about the long-term safety of high-fat, low-carbohydrate diets. A controlled, prospective evaluation of the risks and benefits of these regimens for patients with PDC deficiency is required to establish rational nutritional guidelines.

Influence of response selection and noise similarity on age differences in the redundancy gain.

We examined the impact of target redundancy for target-plus-noise (TPN) and target-only (TO) trials. Experiment 1 manipulated response selection load (two-choice vs go/no-go) and Experiment 2 (all two-choice) varied noise redundancy (single or cumulative noise letters) on a visual search, divided attention task in which target letters were presented in one, two, or three corners of a four-corner display. Half of the trials also included noise letters. For Experiment 1, there was a definite redundancy gain for TO trials. Furthermore, older adults, relative to young adults, evidenced an even larger redundancy gain for TO trials than for TPN trials, although response selection load did not interact with age. These results are consistent with the notion that older adults exhibit a processing resources decrement. For Experiment 2, older adults evidenced a relatively larger redundancy gain for TPN trials than for TO trials, and this was especially the case for TPN trials in which all nontarget locations were filled with noise letters. Experiment 2 results are consistent with the notion that older adults also exhibit a selective attention decrement.

Functional loss of ABCA1 in mice causes severe placental malformation, aberrant lipid distribution, and kidney glomerulonephritis as well as high-density lipoprotein cholesterol deficiency.

Tangier disease (TD) and familial HDL deficiency (FHA) have recently been linked to mutations in the human ATP-binding cassette transporter 1 (hABCA1), a member of the ABC superfamily. Both diseases are characterized by the lowering or lack of high-density lipoprotein cholesterol (HDL-C) and low serum cholesterol. The murine ABCA1-/- phenotype corroborates the human TD linkage to ABCA1. Similar to TD in humans, HDL-C is virtually absent in ABCA1-/- mice accompanied by a reduction in serum cholesterol and lipid deposition in various tissues. In addition, the placenta of ABCA1-/- mice is malformed, resulting in severe embryo growth retardation, fetal loss, and neonatal death. The basis for these defects appears to be altered steroidogenesis, a direct result of the lack of HDL-C. By 6 months of age, ABCA1-/- animals develop membranoproliferative glomerulonephritis due to deposition of immunocomplexes followed by cardiomegaly with ventricular dilation and hypertrophy, ultimately succumbing to congestive heart failure. This murine model of TD will be very useful in the study of lipid metabolism, renal inflammation, and cardiovascular disease and may reveal previously unsuspected relationships between them.