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Notes: This Article attempts to explain the views about business of Brandeis and Holmes. The Article analyses why their economic thinking differed as it did; to what extent it comports with a modern understanding of economics; and how Holmes and Brandeis could have been such close allies when their economic theories differed as fundamentally as they did. Finally, the Article addresses the consequences and current significance of, if any, the theories of Brandeis and Holmes, with particular though not exclusive reference on the one hand to antitrust law and on the other hand to the current crisis of corporate governance.

Notes: Patent-holding pharmaceutical companies are shown to be imperfectly able to charge differential prices for AIDS drugs due to the potential for black market exchange. Thus, greater segmentation in the international market through additional barriers to smuggling would induce firms to charge lower prices for AIDS drugs in poorer countries. Without these additional barriers, widespread drug distribution through mandated lower prices or weakened patent protection in the developing world would result in smuggling, undercutting demand in developed markets and reducing firms' research incentives. By contrast, further market segmentation would allow policy makers to go beyond the induced price cuts and remove patent protection in many markets where the benefits to increased distribution would likely outweigh the losses to research incentives.

Notes: 1. Our objectives were to examine small-scale patterns in oviposition and genetic relatedness in a population of the stream-dwelling caddis Plectrocnemia conspersa and, in particular, to look for any evidence of the spatial proximity of close kin and, therefore, ‘patchy recruitment’.2. In order to examine the distribution of related larvae at the beginning of the aquatic phase, we searched the stream for egg masses. Spatially and temporally structured samples of larvae were then collected from the stream over four sample dates within one generation. The genetic relatedness of these field-collected larvae, estimated using six polymorphic microsatellite loci, was subsequently compared with that of larvae reared from individual egg masses in the laboratory.3. Egg masses were laid in clusters or ‘hot spots’ along the stream. The mean relatedness coefficient within reared egg masses ranged from 0.327 to 0.525, and differed significantly from that estimated for the population as a whole (0.070), indicating that the markers were sufficiently powerful to identify groups of siblings. Each egg mass was likely to be the progeny of one father, although the possibility of a small contribution from a second male could not be excluded for a few masses.4. Mean relatedness within the spatially structured groups of larvae in the stream, even those in close proximity to each other, did not differ from the background population level estimate, suggesting that siblings disperse away from each other very quickly and that kin structure does not persist over time.5. Changes in spatial genetic structure late in the larval life indicated that neighbouring larvae were less closely related than the population overall, possibly suggesting some direct or indirect means of avoiding kin when approaching the onset of pupation.6. Our counts of egg masses suggested that survival through the egg stage and early larval life was apparently very high (〉50%) for a non-social insect, and may be a consequence of the colonial net that is briefly occupied by first instar larvae.7. The number of egg masses laid in the stream (approximately 400 in the sample year), the lack of a spatial genetic structure showing evidence of families even early in larval life, and the high survival of eggs and early instar larvae, all refute the ‘patchy recruitment hypothesis’ for this species.

Notes: Summary:  A combination of approaches – gene mapping, biomarker analysis, and studies of signal transduction – has helped to clarify the mechanisms of age-related change in mouse immune status and the implications of immune aging for late-life disease. Mapping studies have documented multiple quantitative trait loci (QTL) that influence the levels of age-sensitive T-cell subsets. Some of these QTL have effects that are demonstrable in young-adult mice (8 months of age) and others demonstrable only in middle-aged mice (18 months). Biomarker studies show that T-cell subset levels measured at 8 or 18 months are significant predictors of lifespan for mice dying of lymphoma, fibrosarcoma, mammary adenocarcinoma, or all causes combined. Mice whose immune systems resemble that of young animals, i.e. with low levels of CD4+ and CD8+ memory T cells and relatively high levels of CD4+ T cells, tend to outlive their siblings with the opposite subset pattern. Biochemical analyses show that T cells from aged mice show defects in the activation process within a few minutes of encountering a stimulus and that the defects precede the recognition by the T-cell receptor of agonist peptides on the antigen-presenting cell. Defective assembly of cytoskeletal fibers and hyperglycosylation of T-cell surface glycoproteins contribute to the immunodeficiency state, and indeed treatment with a sialylglycoprotein endopeptidase can restore full function to CD4+ T cells from aged donors in vitro.

Notes: abstract After showing that authenticity is socially constructed rather than an attribute of that which is called authentic, we examine the authenticity work involved in claiming authenticity and discuss the processes of authentication. We then explore the situations in which the quest for authenticity makes for change and conclude by showing that the salience of authenticity can change.

Notes: We describe large scale ab initio quantum chemical and mixed quantum mechanics/molecular mechanics (QM/MM) methods for studying enzymatic reactions. First, technical aspects of the methodology are reviewed, including the hybrid density functional theory (DFT) methods that are typically employed for the QM aspect of the calculations, and various approaches to defining the interface between the QM and MM regions in QM/MM approaches. The modeling of the enzymatic catalytic cycle for three examplesĐ??methane monooxygenase, cytochrome P450, and triose phosphate isomeraseĐ??are discussed in some depth, followed by a brief summary of other systems that have been investigated by ab initio methods over the past several years. Finally, a discussion of the qualitative and quantitative conclusions concerning enzymatic catalysis that are available from modern ab initio approaches is presented, followed by a conclusion briefly summarizing future prospects.

Notes: Research on interest groups today neglects the important task of analyzing historical patterns and secular, long-term changes. We note critical measurement errors in how contemporary political science has assessed the origins and development of interest group politics in the United States. Interest group scholars lack the reliable longitudinal data available to such fields as electoral or congressional studies. We suggest multidimensional means of recovering the "lost years" of interest group research, compensating for the absence of comprehensive and systematic data on U.S. organized interests before the 1960s. In order to generate empirical and theoretical insights that are not constrained by a particular historical context, we propose a conceptual framework for studying "interest group systems" across time. We also examine the rich possibilities of investigating the interest group and party systems as interacting and autonomous vehicles of representation in American political development. Only by broadening the time horizons of research will scholars be able to develop reliable insights about patterns and transformations of American interest group politics.

Notes: A new approach for pulse labelling of plants using the short-lived positron emitting radioisotope carbon-11 (half-life: 20.4 min) as 11CO2 is reported together with its application to measuring [11C]isoprene emissions from intact leaves capturing information associated with: (1) rate of emission; (2) the relative contribution of recently fixed carbon to isoprene biosynthesis; and (3) the transit time for tracer movement through the leaf and biochemical pathways associated with isoprene biosynthesis. This approach was applied to study the response of certain Populus species to exogenous treatments of jasmonic acid (JA), a plant hormone implicated in signal transduction linked to defence response against herbivory. Twelve hours after treatment of single intact leaves of aspen (Populus tremuloides) with a 1 m m JA spray, isoprene emissions from those leaves increased 1.5 times the controls from 35.4 ± 2.2 to 53.1 ± 4.8 nmol m−2 s−1. [11C]Isoprene emissions from the same leaves, reflecting the isoprene that was derived from recently fixed carbon, increased much more, to 2.2 times the controls. This increase coincided with a change in emitted [11C]isoprene from 0.31 to 0.68% of 11C fixed in the leaf tissue, while the tracer transit time remained constant at 12.5 min. These results suggest that JA had no effect on enzyme kinetics involved in isoprene biosynthesis, but did impact the source of recent carbon feeding that pathway. Studies with poplar (Populus nigra clone NC 5271) showed similar trends in systemic emissions (from an untreated leaf on the same plant).

Notes: We have investigated the effect of JNK1 ko, JNK2 ko, JNK3 ko, JNK2+3 ko and c-JunAA mutation on neuronal survival in adult transgenic mice following ischemia, 6-hydroxydopamine induced neurotoxicity, axon transection and kainic acid induced excitotoxicity. Deletion of JNK isoforms indicated the compartment-specific expression of JNK isoforms with 46-kDa JNK1 as the main phosphorylated JNK isoform. Permanent occlusion of the MCA significantly enlarged the infarct area in JNK1 ko, which showed an increased expression of JNK3 in the penumbra. Survival of dopaminergic neurons in the substantia nigra compacta (SNC) following intrastriatal injection of 6-hydroxydopamine was transiently improved in JNK3 ko and c-JunAA mice after 7 days, but not 60 days. Following transection of the medial forebrain bundle, however, JNK3 ko conferred persisting neuroprotection of axotomised SNC neurons. None of the JNK ko and c-JunAA mutation affected the survival of facial motoneurons following peripheral axotomy when investigated after 90 days. Finally, we determined the impact of JNK ko on the survival of animals and the degeneration of hippocampal neurons following kainic acid. JNK3 ko mice were substantially resistant against and survived kainic acid-induced seizures. JNK3 ko and JNK1 ko showed a nonsignificant tendency for decreased or increased death of hippocampal neurons, respectively. Surprisingly, the deletion of a single JNK isoform did not attenuate the immunocytochemical signal of phosphorylated c-Jun irrespective on the experimental set-up. This comprehensive study provides novel insights into the context-dependent physiological and pathological functions of JNK isoforms.