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In the December 2000 issue of the Journal of Abnormal Child Psychology, we published a set of papers presenting secondary analyses of the Multimodal Treatment Study of ADHD (MTA), and R. A. Barkley (2000) provided a commentary. A critique of the design of the study (MTA Cooperative Group, 1999) was presented based on a theoretical perspective of a "behavioral inhibition" deficit that has been hypothesized as the core deficit of ADHD (R. A. Barkley, 1997). The commentary questioned the design and analysis of the MTA in terms of (1) the empirical criteria for selection of components of behavioral (Beh) intervention, (2) the effectiveness of the Beh intervention, (3) the methods for analyses at the group and individual level, (4) implications of the MTA findings for clinical practice, (5) the role of genetics in response to treatment, and (6) the lack of a nontreatment control group. In this response, we relate the content of the papers to the commentary, (1) by reviewing the selection criteria for the Beh treatment, as outlined by K. C. Wells, W. E. Pelham, et al. (2000), (2) by addressing the myth that the MTA Beh treatment was ineffective (Pelham, 1999), (3) by describing the use of analyses at the level of the individual participant, as presented by J. S. March et al. (2000) and W. E. Pelham et al. (2000) as well as elsewhere by J. M. Swanson et al. (2001) and C. K. Conners et al. (2001), (4) by relating some of the suggestions from the secondary analyses about clinically relevant factors such as comorbidity (as presented by J. S. March et al., 2000) and family and parental characteristics (as presented by B. Hoza et al., 2000, S. P. Hinshaw et al., 2000, and K. C. Wells, J. N. Epstein, et al., 2000), (5) by discussing the statistical concept of heritability and the lack of a significant difference in the presence of ADHD symptoms in parents of the MTA families compared to parents in the classmate-control families (as presented by J. N. Epstein, et al., 2000), and (6) by acknowledging that an ethically necessary weakness of the MTA design is that it did not include a no-treatment control group. We discuss the use of secondary analyses to suggest how, when, and for what subgroups effectiveness of the Beh treatment may have been manifested. Finally, we invite others to use the large and rich data set that will soon be available in the public domain, to perform secondary analyses to mine the meaning of the MTA and to evaluate theories of ADHD and response to treatments. [ABSTRACT FROM AUTHOR]

The jamming transition is an important feature of granular materials, with prior work showing an excess of low-frequency modes in the granular analog to the density of states, the granular density of modes. In this work, we present an experimental method for acoustically measuring the granular density of modes using a single impact event to excite vibrational modes in an experimental, three-dimensional, granular material. We test three different granular materials, all of which are composed of spherical beads. The first two systems are monodisperse collections of either 6 mm or 8 mm diameter beads. The third system is a bidisperse mixture of the previous two bead sizes. During data collection, the particles are confined to a box; on top of this box, and resting on the granular material, is a light, rigid sheet onto which pressure can be applied to the system. To excite the material, a steel impactor ball is dropped on top of the system. The response of the granular material to the impact pulse is recorded by piezoelectric sensors buried throughout the material, and the density of modes is computed from the spectrum of the velocity autocorrelation of these sensors. Our measurements of the density of modes show more low-frequency modes at low pressure, consistent with previous experimental and numerical results, as well as several low-frequency peaks in the density of modes that shift with applied pressure. Our method represents an experimentally simple technique for investigating the granular density of modes and may increase the accessibility and number of such measurements.

Developing quantitative methods for characterizing structural properties of force chains in densely packed granular media is an important step toward understanding or predicting large-scale physical properties of a packing. A promising framework in which to develop such methods is network science, which can be used to translate particle locations and force contacts into a graph in which particles are represented by nodes and forces between particles are represented by weighted edges. Recent work applying network-based community-detection techniques to extract force chains opens the door to developing statistics of force-chain structure, with the goal of identifying geometric and topological differences across packings, and providing a foundation on which to build predictions of bulk material properties from mesoscale network features. Here we discuss a trio of related but fundamentally distinct measurements of the mesoscale structure of force chains in two-dimensional (2D) packings, including a statistic derived using tools from algebraic topology, which together provide a tool set for the analysis of force chain architecture. We demonstrate the utility of this tool set by detecting variations in force-chain architecture with pressure. Collectively, these techniques can be generalized to 3D packings, and to the assessment of continuous deformations of packings under stress or strain.

Force chains form heterogeneous physical structures that can constrain the mechanical stability and acoustic transmission of granular media. However, despite their relevance for predicting bulk properties of materials, there is no agreement on a quantitative description of force chains. Consequently, it is difficult to compare the force-chain structures in different materials or experimental conditions. To address this challenge, we treat granular materials as spatially-embedded networks in which the nodes (particles) are connected by weighted edges that represent contact forces. We use techniques from community detection, which is a type of clustering, to find sets of closely connected particles. By using a geographical null model that is constrained by the particles' contact network, we extract chain-like structures that are reminiscent of force chains. We propose three diagnostics to measure these chain-like structures, and we demonstrate the utility of these diagnostics for identifying and characterizing classes of force-chain network architectures in various materials. To illustrate our methods, we describe how force-chain architecture depends on pressure for two very different types of packings: (1) ones derived from laboratory experiments and (2) ones derived from idealized, numerically-generated frictionless packings. By resolving individual force chains, we quantify statistical properties of force-chain shape and strength, which are potentially crucial diagnostics of bulk properties (including material stability). These methods facilitate quantitative comparisons between different particulate systems, regardless of whether they are measured experimentally or numerically.

Granular media, whose features range from the particle scale to the force-chain scale and the bulk scale, are usually modeled as either particulate or continuum materials. In contrast with each of these approaches, network representations are natural for the simultaneous examination of microscopic, mesoscopic, and macroscopic features. In this paper, we treat granular materials as spatially embedded networks in which the nodes (particles) are connected by weighted edges obtained from contact forces. We test a variety of network measures to determine their utility in helping to describe sound propagation in granular networks and find that network diagnostics can be used to probe particle-, curve-, domain-, and system-scale structures in granular media. In particular, diagnostics of mesoscale network structure are reproducible across experiments, are correlated with sound propagation in this medium, and can be used to identify potentially interesting size scales. We also demonstrate that the sensitivity of network diagnostics depends on the phase of sound propagation. In the injection phase, the signal propagates systemically, as indicated by correlations with the network diagnostic of global efficiency. In the scattering phase, however, the signal is better predicted by mesoscale community structure, suggesting that the acoustic signal scatters over local geographic neighborhoods. Collectively, our results demonstrate how the force network of a granular system is imprinted on transmitted waves.

Identifying and characterizing protein interactions are fundamental steps toward understanding and modeling biological networks. Methods that detect protein interactions in intact cells rather than buffered solutions are likely more relevant to natural systems since molecular crowding events in the cytosol can influence the diffusion and reactivity of individual proteins. One in vivo, imaging-based method relies on the colocalization of two proteins of interest fused to DivIVA, a cell division protein from Bacillus subtilis, and green fluorescent protein (GFP). We have modified this imaging-based assay to facilitate rapid cloning by constructing new vectors encoding N- and C-terminal DivIVA or GFP molecular tag fusions based on site-specific recombination technology. The sensitivity of the assay was defined using a well-characterized protein interaction system involving the eukaryotic nuclear import receptor subunit, Importin alpha (Imp alpha), and variant nuclear localization signals (NLS) representing a range of binding affinities. These data demonstrate that the modified colocalization assay is sensitive enough to detect protein interactions with K(d) values that span over four orders of magnitude (1 nM to 15 microM). Lastly, this assay was used to confirm numerous protein interactions identified from mass spectrometry-based analyses of affinity isolates as part of an interactome mapping project in Rhodopseudomonas palustris.

Elucidation of protein-protein interactions can provide new knowledge on protein function. Enrichments of affinity-tagged (or "bait") proteins with interaction partners generally include background, nonspecific protein artifacts. Furthermore, in vivo bait expression may introduce additional artifacts arising from altered physiology or metabolism. In this study, we compared these effects for chromosome and plasmid encoding strategies for bait proteins in two microbes: Escherichia coli and Rhodopseudomonas palustris. Differential metabolic labeling of strains expressing bait protein relative to the wild-type strain in each species allowed comparison by liquid chromatography tandem mass spectrometry (LC-MS-MS). At the local level of the protein complex, authentic interacting proteins of RNA polymerase (RNAP) were successfully discerned from artifactual proteins by the isotopic differentiation of interactions as random or targeted (I-DIRT, Tackett, A. J.; et al. J. Proteome Res. 2005, 4, 1752-1756). To investigate global effects of bait protein production, we compared proteomes from strains harboring a plasmid encoding an affinity-tagged subunit (RpoA) of RNAP with the corresponding wild-type strains. The RpoA abundance ratios of 0.8 for R. palustris and 1.7 for E. coli in plasmid strains versus wild-type indicated only slightly altered expression. While most other proteins also showed no appreciable difference in abundance, several that did show altered levels were involved in amino acid metabolism. Measurements at both local and global levels proved useful for evaluating in vitro and in vivo artifacts of plasmid-encoding strategies for bait protein expression.

One of the most promising methods for large-scale studies of protein interactions is isolation of an affinity-tagged protein with its in vivo interaction partners, followed by mass spectrometric identification of the copurified proteins. Previous studies have generated affinity-tagged proteins using genetic tools or cloning systems that are specific to a particular organism. To enable protein-protein interaction studies across a wider range of Gram-negative bacteria, we have developed a methodology based on expression of affinity-tagged "bait" proteins from a medium copy-number plasmid. This construct is based on a broad-host-range vector backbone (pBBR1MCS5). The vector has been modified to incorporate the Gateway DEST vector recombination region, to facilitate cloning and expression of fusion proteins bearing a variety of affinity, fluorescent, or other tags. We demonstrate this methodology by characterizing interactions among subunits of the DNA-dependent RNA polymerase complex in two metabolically versatile Gram-negative microbial species of environmental interest, Rhodopseudomonas palustris CGA010 and Shewanella oneidensis MR-1. Results compared favorably with those for both plasmid and chromosomally encoded affinity-tagged fusion proteins expressed in a model organism, Escherichia coli.

From a literature survey, 86 chemicals are tabulated that have been evaluated in 121 assays for their clastogenic effects in Zea mays. Eighty-one of the 86 chemicals are reported as giving a positive reaction (i.e. causing chromosome aberrations). Of these, 36 are reported positive with a dose response. In addition, 32 assays have been recorded for 7 types of radiation, all of which reacted positively. The results of 126 assays with 63 chemicals and 12 types of radiation tested for the inductions of gene mutations are tabulated, as well as 63 chemicals and/or radiation in combined treatments. Three studies reported positive results for mutations on Zea mays seed sent on space flights. The Zea mays (2n=20) assay is a very good plant bioassay for assessing chromosome damage both in mitosis and meiosis and for somatic mutations induced by chemicals and radiations. The carcinogenicity and Salmonella assays correlate in all cases. The maize bioassay has been shown to be as sensitive and as specific an assay as other plant genotoxicity assays, such as Hordeum vulgare, Vicia faba, Crepis capillaris, Pisum sativum, Lycopersicon esculentum and Allium cepa and should be considered in further studies in assessing clastogenicity. Tests using Zea mays can be made for a spectrum of mutant phenotypes of which many are identifiable in young seedlings.

Photosynthetic reaction centers are integral plant membrane protein complexes and molecular photovoltaic structures. We report here that addition of Photosystem I (PSI)-proteoliposomes to retinoblastoma cells imparts photosensitivity to these mammalian cells, as demonstrated by light-induced movement of calcium ions. Control experiments with liposomes lacking PSI demonstrated no photosensitivity. The data demonstrate that PSI, a nanoscale molecular photovoltaic structure extracted from plants, can impart a photoresponse to mammalian cells in vitro.

From a literature survey, 21 chemicals are tabulated that have been evaluated in 39 assays for their clastogenic effects in Lycopersicon. Nineteen of the 21 chemicals are reported as giving a positive reaction (i.e. causing chromosome aberrations). Of these, five are reported positive with a dose response. In addition, 23 assays have been recorded for six types of radiation, all of which reacted positively. The results of 102 assays with 32 chemicals and seven types of radiation tested for the induction of gene mutations are tabulated, as well as 20 chemicals and/or radiation in combined treatments. The Lycopersicon esculentum (2n=24) assay is a very good plant bioassay for assessing chromosome damage both in mitosis and meiosis and for somatic mutations induced by chemicals and radiations. The Lycopersicon bioassay has been shown to be as sensitive and as specific an assay as other plant genotoxicity assays, such as Hordeum vulgare, Vicia faba, Crepis capillaris, Pisum sativum and Allium cepa and should be considered in further studies in assessing clastogenicity. Tests using L. esculentum can be made for a spectrum of mutant phenotypes of which many are identifiable in young seedlings.

From a literature survey, 117 chemicals are tabulated that have been assayed in 179 assays for their clastogenic effects in Pisum. Of the 117 chemicals that have been assayed, 65 are reported at giving a positive reaction (i.e. causing chromosome aberrations), 30 positive with a dose response, five borderline positive. Seventeen chemicals gave a negative response. Eighty-one percent of the chemicals gave a definite positive response. A c-mitotic effect was detected from treatment with 17 chemicals. In addition to the above tabulation of chemicals, 39 chemicals have been reported with an antimitotic effect. Thirteen assays have been recorded for five types of radiation, which with the exception of ultrasound reacted positively. The results of assays with 38 chemicals and/or radiations in combined treatments, as well as 15 chemicals and three types of radiations that induce somatic mutations are tabulated. The Pisum sativum (2n=14) bioassay has been shown to be a very good plant bioassay for assessing chromosome damage both in mitosis and meiosis for somatic mutations induced by chemicals, radiations, and environmental pollutants. For some chemicals, the Pisum assay is not as sensitive in assessing clastogenicity as the Allium assay, although this should be considered in relative terms. Pisum fulvum (2n=14) has been used in clastogenic studies also, but to a much lesser extent.

Crepis capillaris (2n=6) is an excellent plant for the assay of chromosome aberrations after chemical treatment. C. tectorum (2n=8) has been used also in mutagenic studies, but to a much lesser extent. A protocol has been given for using root tips to study the cytological endpoints, such as chromosome breaks and exchanges, which follow the testing of chemicals in somatic cells. Meiotic endpoints have not been used in C. capillaris for testing potential chemical mutagens but should be considered, especially a meiotic micronucleus assay. From a literature survey, 81 chemicals are tabulated that have been assayed in 162 Crepis assays for their clastogenic effects. Of the 162 assays that have been carried out, 40 are reported at giving a positive reaction (i.e., causing chromosome aberrations), 97 positive and with a dose response, 7 borderline positive, and 17 negative. Eighty-five percent of the chemicals gave a definite positive response. Assays for one chemical gave contrary results, and were not included in the above tabulation. The Crepis bioassay has been shown to be an excellent plant bioassay for assessing chromosome damage induced by chemicals and environmental pollutants., (Copyright 1998 Elsevier Science B.V. All rights reserved.)