Showing papers by "Dartmouth College published in 2000"

How do glucocorticoids influence stress responses? Integrating permissive, suppressive, stimulatory, and preparative actions.

Abstract: The secretion of glucocorticoids (GCs) is a classic endocrine response to stress. Despite that, it remains controversial as to what purpose GCs serve at such times. One view, stretching back to the time of Hans Selye, posits that GCs help mediate the ongoing or pending stress response, either via basal levels of GCs permitting other facets of the stress response to emerge efficaciously, and/or by stress levels of GCs actively stimulating the stress response. In contrast, a revisionist viewpoint posits that GCs suppress the stress response, preventing it from being pathologically overactivated. In this review, we consider recent findings regarding GC action and, based on them, generate criteria for determining whether a particular GC action permits, stimulates, or suppresses an ongoing stressresponse or, as an additional category, is preparative for a subsequent stressor. We apply these GC actions to the realms of cardiovascular function, fluid volume and hemorrhage, immunity and inflammation, metabolism, neurobiology, and reproductive physiology. We find that GC actions fall into markedly different categories, depending on the physiological endpoint in question, with evidence for mediating effects in some cases, and suppressive or preparative in others. We then attempt to assimilate these heterogeneous GC actions into a physiological whole. (Endocrine Reviews 21: 55‐ 89, 2000)

Knowledge flows within multinational corporations

Abstract: Pursuing a nodal (i.e., subsidiary) level of analysis, this paper advances and tests an overarching theoretical framework pertaining to intracorporate knowledge transfers within multinational corporations (MNCs). We predicted that (i) knowledge outflows from a subsidiary would be positively associated with value of the subsidiary’s knowledge stock, its motivational disposition to share knowledge, and the richness of transmission channels; and (ii) knowledge inflows into a subsidiary would be positively associated with richness of transmission channels, motivational disposition to acquire knowledge, and the capacity to absorb the incoming knowledge. These predictions were tested empirically with data from 374 subsidiaries within 75 MNCs headquartered in the U.S., Europe, and Japan. Except for our predictions regarding the impact of source unit's motivational disposition on knowledge outflows, the data provide either full or partial support to all of the other elements of our theoretical framework. Copyright © 2000 John Wiley & Sons, Ltd.

Biofilm Formation as Microbial Development

Abstract: ▪ Abstract Biofilms can be defined as communities of microorganisms attached to a surface. It is clear that microorganisms undergo profound changes during their transition from planktonic (free-swimming) organisms to cells that are part of a complex, surface-attached community. These changes are reflected in the new phenotypic characteristics developed by biofilm bacteria and occur in response to a variety of environmental signals. Recent genetic and molecular approaches used to study bacterial and fungal biofilms have identified genes and regulatory circuits important for initial cell-surface interactions, biofilm maturation, and the return of biofilm microorganisms to a planktonic mode of growth. Studies to date suggest that the planktonic-biofilm transition is a complex and highly regulated process. The results reviewed in this article indicate that the formation of biofilms serves as a new model system for the study of microbial development.

Microbial Biofilms: from Ecology to Molecular Genetics

Abstract: Biofilms are complex communities of microorganisms attached to surfaces or associated with interfaces. Despite the focus of modern microbiology research on pure culture, planktonic (free-swimming) bacteria, it is now widely recognized that most bacteria found in natural, clinical, and industrial settings persist in association with surfaces. Furthermore, these microbial communities are often composed of multiple species that interact with each other and their environment. The determination of biofilm architecture, particularly the spatial arrangement of microcolonies (clusters of cells) relative to one another, has profound implications for the function of these complex communities. Numerous new experimental approaches and methodologies have been developed in order to explore metabolic interactions, phylogenetic groupings, and competition among members of the biofilm. To complement this broad view of biofilm ecology, individual organisms have been studied using molecular genetics in order to identify the genes required for biofilm development and to dissect the regulatory pathways that control the plankton-to-biofilm transition. These molecular genetic studies have led to the emergence of the concept of biofilm formation as a novel system for the study of bacterial development. The recent explosion in the field of biofilm research has led to exciting progress in the development of new technologies for studying these communities, advanced our understanding of the ecological significance of surface-attached bacteria, and provided new insights into the molecular genetic basis of biofilm development.

Testing Tradeoff and Pecking Order Predictions About Dividends and Debt

Abstract: Confirming predictions shared by the tradeoff and pecking order models, more profitable firms and firms with fewer investments have higher dividend payouts. Confirming the pecking order model but contradicting the tradeoff model, more profitable firms are less levered. Firms with more investments have less market leverage, which is consistent with the tradeoff model and a complex pecking order model. Firms with more investments have lower long-term dividend payouts, but dividends do not vary to accommodate short-term variation in investment. As the pecking order model predicts, short-term variation in investment and earnings is mostly absorbed by debt.

Disappearing Dividends: Changing Firm Characteristics or Lower Propensity to Pay?

Abstract: The percent of firms paying cash dividends falls from 66.5 in 1978 to 20.8 in 1999. The decline is due in part to the changing characteristics of publicly traded firms. Fed by new lists, the population of publicly traded firms tilts increasingly toward small firms with low profitability and strong growth opportunities characteristics typical of firms that have never paid dividends. More interesting, we also show that controlling for characteristics, firms become less likely to pay dividends. This lower propensity to pay is at least as important as changing characteristics in the declining incidence of dividend payers.

Plants and Productivity in International Trade

Abstract: We reconcile international trade theory with findings of enormous plant-level heterogeneity in exporting and productivity. Our model extends basic Ricardian theory to accommodate many countries, geographic barriers, and imperfect competition. Fitting the model to bilateral trade among the United States and its 46 major trade partners, we see how well it can explain basic facts about U.S. plants: (i) productivity dispersion, (ii) the productivity advantage of exporters, (iii) the small fraction who export, (iv) the small fraction of revenues from exporting among those that do, and (v) the much larger size of exporters. We pick up all these basic qualitative features, and go quite far in matching them quantitatively. We examine counterfactuals to assess the impact of various global shifts on productivity, plant entry and exit, and labor turnover in U.S. manufacturing.

Cerebral specialization and interhemispheric communication: does the corpus callosum enable the human condition?

Abstract: Summary The surgical disconnection of the cerebral hemispheres half-brain. By having the callosum serve as the great communication link between redundant systems, a precreates an extraordinary opportunity to study basic existing system could be jettisoned as new functions neurological mechanisms: the organization of the sensory developed in one hemisphere, while the other hemisphere and motors systems, the cortical representation of the could continue to perform the previous functions for both perceptual and cognitive processes, the lateralization of half-brains. Split-brain studies have also revealed the function, and, perhaps most importantly, how the divided complex mosaic of mental processes that participate in brain yields clues to the nature of conscious experience. human cognition. And yet, even though each cerebral Studies of split-brain patients over the last 40 years hemisphere has its own set of capacities, with the left have resulted in numerous insights into the processes of hemisphere specialized for language and speech and perception, attention, memory, language and reasoning major problem-solving capacities and the right abilities. When the constellation of findings is considered hemisphere specialized for tasks such as facial recognition as a whole, one sees the cortical arena as a patchwork of and attentional monitoring, we all have the subjective specialized processes. When this is considered in the light experience of feeling totally integrated. Indeed, even of new studies on the lateralization of functions, it becomes though many of these functions have an automatic quality reasonable to suppose that the corpus callosum has to them and are carried out by the brain prior to our enabled the development of the many specialized systems conscious awareness of them, our subjective belief and by allowing the reworking of existing cortical areas feeling is that we are in charge of our actions. These while preserving existing functions. Thus, while language phenomena appear to be related to our left hemisphere’s emerged in the left hemisphere at the cost of pre-existing interpreter, a device that allows us to construct theories perceptual systems, the critical features of the bilaterally about the relationship between perceived events, actions and feelings. present perceptual system were spared in the opposite

Self-Regulatory Failure: A Resource-Depletion Approach

Abstract: Three studies were conducted to test the behavioral consequences of effortful self-regulation. Individuals with chronic inhibitions about eating were exposed to situations varying in level of self-regulatory demand. Subsequently, participants' ability to self-regulate was measured. Two studies manipulated self-regulatory demand by exposing participants to good-tasting snack foods, whereas a third study required participants to control their emotional expressions. As hypothesized, exerting self-control during the first task led to decrements in self-control on a subsequent task. Moreover, these effects were not due to changes in affective state and occurred only when self-control was required in the first task. These findings are explained in terms of depletion of self-regulatory resources, which impairs successful volitional control.

Fractal stream chemistry and its implications for contaminant transport in catchments

Abstract: The time it takes for rainfall to travel through a catchment and reach the stream is a fundamental hydraulic parameter that controls the retention of soluble contaminants and thus the downstream consequences of pollution episodes. Catchments with short flushing times will deliver brief, intense contaminant pulses to downstream waters, whereas catchments with longer flushing times will deliver less intense but more sustained contaminant fluxes. Here we analyse detailed time series of chloride, a natural tracer, in both rainfall and runoff from headwater catchments at Plynlimon, Wales. We show that, although the chloride concentrations in rainfall have a white noise spectrum, the chloride concentrations in streamflow exhibit fractal 1/f scaling over three orders of magnitude. The fractal fluctuations in tracer concentrations indicate that these catchments do not have characteristic flushing times. Instead, their travel times follow an approximate power-law distribution implying that they will retain a long chemical memory of past inputs. Contaminants will initially be flushed rapidly, but then low-level contamination will be delivered to streams for a surprisingly long time.

Pilus retraction powers bacterial twitching motility.

Abstract: Twitching and social gliding motility allow many Gram negative bacteria to crawl along surfaces, and are implicated in a wide range of biological functions1. Type IV pili (Tfp) are required for twitching and social gliding, but the mechanism by which these filaments promote motility has remained enigmatic1,2,3,4. Here we use laser tweezers5 to show that Tfp forcefully retract. Neisseria gonorrhoeae cells that produce Tfp actively crawl on a glass surface and form adherent microcolonies. When laser tweezers are used to place and hold cells near a microcolony, retractile forces pull the cells toward the microcolony. In quantitative experiments, the Tfp of immobilized bacteria bind to latex beads and retract, pulling beads from the tweezers at forces that can exceed 80 pN. Episodes of retraction terminate with release or breakage of the Tfp tether. Both motility and retraction mediated by Tfp occur at about 1 µm s-1 and require protein synthesis and function of the PilT protein. Our experiments establish that Tfp filaments retract, generate substantial force and directly mediate cell movement.

A clinical prototype for active microwave imaging of the breast

Abstract: Despite its recognized value in detecting and characterizing breast disease, X-ray mammography has important limitations that motivate the quest for alternatives to augment the diagnostic tools that are currently available to the radiologist. The rationale for pursuing electromagnetic methods is strong given the data in the literature, which show that the electromagnetic properties of breast malignancy are significantly different than normal in the high megahertz to low gigahertz spectral range, microwave illumination can effectively penetrate the breast at these frequencies, and the breast is a small readily accessible tissue volume, making it an ideal site for deploying advanced near-field imaging concepts that exploit model-based image reconstruction methodology. In this paper a clinical prototype of a microwave imaging system, which actively illuminates the breast with a 16-element transceiving monopole antenna array in the 300-1000 MHz range, is reported. Microwave exams have been delivered to five women through a water-coupled interface to the pendant breast with the participant positioned prone on an examination table. This configuration has been found to be a practical, comfortable approach to microwave breast imaging. Sessions lasted 10-15 min per breast and included full tomographic data acquisition at seven different array heights beginning at the chest wall and moving anteriorly toward the nipple for seven different frequencies at each array position. This clinical experience appears to be the first report of active near-field microwave imaging of the breast and is certainly the first attempt to exploit model-based image reconstructions from in vivo breast data in order to convert the measured microwave signals into spatial maps of electrical permittivity and conductivity. While clearly preliminary, the results are encouraging and have supplied some interesting findings. Specifically, it appears that the average relative permittivity of the breast as a whole correlates with radiologic breast density categorization and may be considerably higher than previously published values, which have been based on ex vivo tissue specimens.

Product sequencing: co-evolution of knowledge, capabilities and products

Abstract: This article provides a conceptual model that explains how the coevolution of organizational knowledge, capabilities, and products over long time spans can result in competitive advantage through innovation and strategic linkage of products at a point in time and over time. At the heart of the model are sequences of products within and across markets, supported by an underlying system of knowledge and systems of learning. This dynamic model brings the importance of the products themselves, supported by vertical chains of activities, into the analysis of resource and knowledge-based competitive advantage. The model also suggests that we can think about the evolution of firms, and by implication the evolution of industries, not only in terms of knowledge and capabilities, but also in terms of vertical chains and products. Short company histories illustrate the workings of the model. Copyright © 2000 John Wiley & Sons, Ltd.

Do the Rich Save More

Abstract: The question of whether higher–lifetime income households save a larger fraction of their income was the subject of much debate in the 1950s and 1960s, and while not resolved, it remains central to the evaluation of tax and macroeconomic policies. We resolve this long‐standing question using new empirical methods applied to the Panel Study of Income Dynamics, the Survey of Consumer Finances, and the Consumer Expenditure Survey. We find a strong positive relationship between saving rates and lifetime income and a weaker but still positive relationship between the marginal propensity to save and lifetime income. There is little support for theories that seek to explain these positive correlations by relying solely on time preference rates, nonhomothetic preferences, or variations in Social Security benefits. There is more support for models emphasizing uncertainty with respect to income and health expenses, bequest motives, and asset‐based means testing or behavioral factors causing minimal saving rates amo...

Eugene: A conceptual manual

Abstract: The study of international relations using quantitative analysis relies, in part, on the availability of comprehensive and easily manipulable data sets. To execute large‐n statistical tests of hypotheses, data must be available on the variables of interest, and those data must be manipulated into a suitable format to allow the inclusion of appropriate control variables as well as variables of central theoretical interest This paper introduces software designed to eliminate many of the difficulties commonly involved in constructing large international relations data sets, and with the unavailability of data on expected utility theories of war. In order to solve these two problems, we developed EUGene (the Expected Utility Generation and Data Management Program). EUGene is a stand‐alone Microsoft Windows based program for the construction of annual data sets for use in quantitative studies of international relations. It generates data for variables necessary to incorporate key variables from implementations...

Definitive hematopoietic stem cells first develop within the major arterial regions of the mouse embryo

Abstract: The aorta–gonad–mesonephros (AGM) region is a potent hematopoietic site within the mammalian embryo body, and the first place from which hematopoietic stem cells (HSCs) emerge. Within the complex embryonic vascular, excretory and reproductive tissues of the AGM region, the precise location of HSC development is unknown. To determine where HSCs develop, we subdissected the AGM into aorta and urogenital ridge segments and transplanted the cells into irradiated adult recipients. We demonstrate that HSCs first appear in the dorsal aorta area. Furthermore, we show that vitelline and umbilical arteries contain high frequencies of HSCs coincident with HSC appearance in the AGM. While later in development and after organ explant culture we find HSCs in the urogenital ridges, our results strongly suggest that the major arteries of the embryo are the most important sites from which definitive HSCs first emerge.

Interleukin‐1 induction of collagenase 3 (matrix metalloproteinase 13) gene expression in chondrocytes requires p38, c‐jun N‐terminal kinase, and nuclear factor κB: Differential regulation of collagenase 1 and collagenase 3

Abstract: Objective To examine the mechanism of interleukin-1 (IL-1)–induced collagenase 3 (matrix metalloproteinase 13 [MMP-13]) gene expression in cultured chondrocytes for the purpose of better understanding how the gene is induced in these cells, and how it contributes to cartilage degradation in osteoarthritis. Methods The transcriptional and posttranscriptional responses of the MMP-13 gene to IL-1 were assessed first. Then, direct inhibitors of mitogen-activated protein kinase (MAPK) signaling pathways and a constitutive repressor of nuclear factor κB (NF-κB) were used to assess the role of each pathway in IL-1–mediated induction of MMP-13. Results We found that IL-1 induction of MMP-13 requires p38 activity, c-Jun N-terminal kinase (JNK) activity and NF-κB translocation. These results suggest that both NF-κB and activator protein 1 transcription factors are necessary for IL-1 induction of MMP-13. We also compared the signaling pathways necessary for IL-1 to stimulate collagenase 1 (MMP-1) in articular chondrocytes and chondrosarcoma cells and found that IL-1 induction of MMP-1 requires different pathways from those required by MMP-13. In chondrosarcoma cells, MMP-1 induction depends on p38 and MEK (an MAPK kinase of the extracellular signal–regulated kinase pathway) and does not require JNK or NF-κB. In articular chondrocytes, inhibition of MEK had no effect, while inhibition of p38 gave variable results. Conclusion These studies demonstrate, for the first time, that p38, JNK, and NF-κB are required for IL-1 induction of MMP-13. The results also highlight the differential requirements for signaling pathways in the induction of MMP-1 and MMP-13. Additionally, they demonstrate that induction of MMP-1 by IL-1 in chondrocytic cells depends on unique combinations of signaling pathways that are cell type–specific.

Maternal thyroid deficiency and pregnancy complications: implications for population screening.

Abstract: Objective—To examine the relation between certain pregnancy complications and thyroid stimulating hormone (TSH) measurements in a cohort of pregnant women. Methods—TSH was measured in sera obtained from women during the second trimester as part of routine prenatal care. Information was then collected about vaginal bleeding, premature delivery, low birthweight, abruptio placentae, pregnancy induced hypertension, need for cesarean section, low Apgar scores, and fetal and neonatal death. Results—Among 9403 women with singleton pregnancies,TSH measurements were 6 mU/l or greater in 209 (2.2%).The rate of fetal death was significantly higher in those pregnancies (3.8%) than in the women with TSH less than 6 mU/l (0.9%, odds ratio 4.4, 95% confidence interval 1.9‐9.5). Other pregnancy complications did not occur more frequently Conclusion—From the second trimester onward, the major adverse obstetrical outcome associated with raised TSH in the general population is an increased rate of fetal death. If thyroid replacement treatment avoided this problem this would be another reason to consider population screening. (J Med Screen 2000;7:127‐130)

Chemoprevention of Cancer

Abstract: In this short article, we review the conceptual basis for chemoprevention of cancer, the proven clinical efficacy of this concept, and current trends to develop new chemopreventive agents based on understanding of their mechanisms of action. Four classes of new agents, namely selective inhibitors of cyclooxygenase-2, selective estrogen receptor modulators, rexinoids (retinoids that bind selectively to the receptors known as RXRs) and ligands for the peroxisome proliferator-activated receptor-gamma are discussed in detail. The importance of developing totally new classes of chemopreventive agents is stressed, with particular emphasis on the potential usefulness of new synthetic triterpenoids derived from naturally occurring molecules.

Product Sequencing: Co-Evolution of Knowledge, Capabilities and Products

Abstract: This paper provides a conceptual model that explains how organizational knowledge, capabilities, and products co-evolve over long time spans, and how this can result in competitive advantage through innovation and strategic linkage of products at a point in time and over time.

Government Ownership Of Banks

Abstract: In this paper, we investigate a neglected aspect of financial systems of many countries around the world: government ownership of banks. We assemble data which establish four findings. First, government ownership of banks is large and pervasive around the world. Second, such ownership is particularly significant in countries with low levels of per capita income, underdeveloped financial systems, interventionist and inefficient governments, and poor protection of property rights. Third, government ownership of banks is associated with slower subsequent financial development. Finally, government ownership of banks is associated with lower subsequent growth of per capita income, and in particular with lower growth of productivity rather than slower factor accumulation. This evidence is inconsistent with optimistic "development" theories of government ownership of banks common in the 1960s, but supports the more "political" theories of the effects of government ownership of firms.

Peer Effects with Random Assignment: Results for Dartmouth Roommates

Abstract: This paper uses a unique data set to measure peer effects among college roommates. Freshman year roommates and dormmates are randomly assigned at Dartmouth College. I find that peers have an impact on grade point average and on decisions to join social groups such as fraternities. Residential peer effects are markedly absent in other major life decisions such as choice of college major. Peer effects in GPA occur at the individual room level whereas peer effects in fraternity membership occur both at the room level and the entire dorm level. Overall, the data provide strong evidence for the existence of peer effects in student outcomes.