Showing papers by "Harvard University published in 2001"

The Colonial Origins of Comparative Development: An Empirical Investigation

Abstract: In Acemoglu, Johnson, and Robinson, henceforth AJR, (2001), we advanced the hypothesis that the mortality rates faced by Europeans in different parts of the world after 1500 affected their willingness to establish settlements and choice of colonization strategy. Places that were relatively healthy (for Europeans) were—when they fell under European control—more likely to receive better economic and political institutions. In contrast, places where European settlers were less likely to go were more likely to have “extractive” institutions imposed. We also posited that this early pattern of institutions has persisted over time and influences the extent and nature of institutions in the modern world. On this basis, we proposed using estimates of potential European settler mortality as an instrument for institutional variation in former European colonies today. Data on settlers themselves are unfortunately patchy—particularly because not many went to places they believed, with good reason, to be most unhealthy. We therefore followed the lead of Curtin (1989 and 1998) who compiled data on the death rates faced by European soldiers in various overseas postings. 1 Curtin’s data were based on pathbreaking data collection and statistical work initiated by the British military in the mid-nineteenth century. These data became part of the foundation of both contemporary thinking about public health (for soldiers and for civilians) and the life insurance industry (as actuaries and executives considered the

Alzheimer's Disease: Genes, Proteins, and Therapy

Abstract: Rapid progress in deciphering the biological mechanism of Alzheimer's disease (AD) has arisen from the application of molecular and cell biology to this complex disorder of the limbic and association cortices. In turn, new insights into fundamental aspects of protein biology have resulted from research on the disease. This beneficial interplay between basic and applied cell biology is well illustrated by advances in understanding the genotype-to-phenotype relationships of familial Alzheimer's disease. All four genes definitively linked to inherited forms of the disease to date have been shown to increase the production and/or deposition of amyloid β-protein in the brain. In particular, evidence that the presenilin proteins, mutations in which cause the most aggressive form of inherited AD, lead to altered intramembranous cleavage of the β-amyloid precursor protein by the protease called γ-secretase has spurred progress toward novel therapeutics. The finding that presenilin itself may be the long-sought γ-...

Nanowire Nanosensors for Highly Sensitive and Selective Detection of Biological and Chemical Species

Abstract: Boron-doped silicon nanowires (SiNWs) were used to create highly sensitive, real-time electrically based sensors for biological and chemical species. Amine- and oxide-functionalized SiNWs exhibit pH-dependent conductance that was linear over a large dynamic range and could be understood in terms of the change in surface charge during protonation and deprotonation. Biotin-modified SiNWs were used to detect streptavidin down to at least a picomolar concentration range. In addition, antigen-functionalized SiNWs show reversible antibody binding and concentration-dependent detection in real time. Lastly, detection of the reversible binding of the metabolic indicator Ca2+ was demonstrated. The small size and capability of these semiconductor nanowires for sensitive, label-free, real-time detection of a wide range of chemical and biological species could be exploited in array-based screening and in vivo diagnostics.

Insulin signalling and the regulation of glucose and lipid metabolism

Abstract: The epidemic of type 2 diabetes and impaired glucose tolerance is one of the main causes of morbidity and mortality worldwide. In both disorders, tissues such as muscle, fat and liver become less responsive or resistant to insulin. This state is also linked to other common health problems, such as obesity, polycystic ovarian disease, hyperlipidaemia, hypertension and atherosclerosis. The pathophysiology of insulin resistance involves a complex network of signalling pathways, activated by the insulin receptor, which regulates intermediary metabolism and its organization in cells. But recent studies have shown that numerous other hormones and signalling events attenuate insulin action, and are important in type 2 diabetes.

Effects on Blood Pressure of Reduced Dietary Sodium and the Dietary Approaches to Stop Hypertension (DASH) Diet

Abstract: Background The effect of dietary composition on blood pressure is a subject of public health importance. We studied the effect of different levels of dietary sodium, in conjunction with the Dietary Approaches to Stop Hypertension (DASH) diet, which is rich in vegetables, fruits, and low-fat dairy products, in persons with and in those without hypertension. Methods A total of 412 participants were randomly assigned to eat either a control diet typical of intake in the United States or the DASH diet. Within the assigned diet, participants ate foods with high, intermediate, and low levels of sodium for 30 consecutive days each, in random order. Results Reducing the sodium intake from the high to the intermediate level reduced the systolic blood pressure by 2.1 mm Hg (P<0.001) during the control diet and by 1.3 mm Hg (P=0.03) during the DASH diet. Reducing the sodium intake from the intermediate to the low level caused additional reductions of 4.6 mm Hg during the control diet (P<0.001) and 1.7 mm Hg during t...

Estimating Wealth Effects Without Expenditure Data—Or Tears: An Application to Educational Enrollments in States of India

Abstract: This paper has an empirical and overtly methodological goal. The authors propose and defend a method for estimating the effect of household economic status on educational outcomes without direct survey information on income or expenditures. They construct an index based on indicators of household assets, solving the vexing problem of choosing the appropriate weights by allowing them to be determined by the statistical procedure of principal components. While the data for India cannot be used to compare alternative approaches they use data from Indonesia, Nepal, and Pakistan which have both expenditures and asset variables for the same households. With these data the authors show that not only is there a correspondence between a classification of households based on the asset index and consumption expenditures but also that the evidence is consistent with the asset index being a better proxy for predicting enrollments--apparently less subject to measurement error for this purpose--than consumption expenditures. The relationship between household wealth and educational enrollment of children can be estimated without expenditure data. A method for doing so - which uses an index based on household asset ownership indicators- is proposed and defended in this paper. In India, children from the wealthiest households are over 30 percentage points more likely to be in school than those from the poorest households.

Osteoporosis prevention, diagnosis, and therapy

Abstract: OBJECTIVES To clarify the factors associated with prevention, diagnosis, and treatment of osteoporosis, and to present the most recent information available in these areas. PARTICIPANTS From March 27-29, 2000, a nonfederal, nonadvocate, 13-member panel was convened, representing the fields of internal medicine, family and community medicine, endocrinology, epidemiology, orthopedic surgery, gerontology, rheumatology, obstetrics and gynecology, preventive medicine, and cell biology. Thirty-two experts from these fields presented data to the panel and an audience of 699. Primary sponsors were the National Institute of Arthritis and Musculoskeletal and Skin Diseases and the National Institutes of Health Office of Medical Applications of Research. EVIDENCE MEDLINE was searched for January 1995 through December 1999, and a bibliography of 2449 references provided to the panel. Experts prepared abstracts for presentations with relevant literature citations. Scientific evidence was given precedence over anecdotal experience. CONSENSUS PROCESS The panel, answering predefined questions, developed conclusions based on evidence presented in open forum and the literature. The panel composed a draft statement, which was read and circulated to the experts and the audience for public discussion. The panel resolved conflicts and released a revised statement at the end of the conference. The draft statement was posted on the Web on March 30, 2000, and updated with the panel's final revisions within a few weeks. CONCLUSIONS Though prevalent in white postmenopausal women, osteoporosis occurs in all populations and at all ages and has significant physical, psychosocial, and financial consequences. Risks for osteoporosis (reflected by low bone mineral density [BMD]) and for fracture overlap but are not identical. More attention should be paid to skeletal health in persons with conditions associated with secondary osteoporosis. Clinical risk factors have an important but poorly validated role in determining who should have BMD measurement, in assessing fracture risk, and in determining who should be treated. Adequate calcium and vitamin D intake is crucial to develop optimal peak bone mass and to preserve bone mass throughout life. Supplementation with these 2 nutrients may be necessary in persons not achieving recommended dietary intake. Gonadal steroids are important determinants of peak and lifetime bone mass in men, women, and children. Regular exercise, especially resistance and high-impact activities, contributes to development of high peak bone mass and may reduce risk of falls in older persons. Assessment of bone mass, identification of fracture risk, and determination of who should be treated are the optimal goals when evaluating patients for osteoporosis. Fracture prevention is the primary treatment goal for patients with osteoporosis. Several treatments have been shown to reduce the risk of osteoporotic fractures, including those that enhance bone mass and reduce the risk or consequences of falls. Adults with vertebral, rib, hip, or distal forearm fractures should be evaluated for osteoporosis and given appropriate therapy.

HIFα Targeted for VHL-Mediated Destruction by Proline Hydroxylation: Implications for O2 Sensing

Abstract: HIF (hypoxia-inducible factor) is a transcription factor that plays a pivotal role in cellular adaptation to changes in oxygen availability. In the presence of oxygen, HIF is targeted for destruction by an E3 ubiquitin ligase containing the von Hippel-Lindau tumor suppressor protein (pVHL). We found that human pVHL binds to a short HIF-derived peptide when a conserved proline residue at the core of this peptide is hydroxylated. Because proline hydroxylation requires molecular oxygen and Fe(2+), this protein modification may play a key role in mammalian oxygen sensing.

Effect of parathyroid hormone (1-34) on fractures and bone mineral density in postmenopausal women with osteoporosis.

Abstract: Background Once-daily injections of parathyroid hormone or its amino-terminal fragments increase bone formation and bone mass without causing hypercalcemia, but their effects on fractures are unknown. Methods We randomly assigned 1637 postmenopausal women with prior vertebral fractures to receive 20 or 40 μg of parathyroid hormone (1-34) or placebo, administered subcutaneously by the women daily. We obtained vertebral radiographs at base line and at the end of the study (median duration of observation, 21 months) and performed serial measurements of bone mass by dual-energy x-ray absorptiometry. Results New vertebral fractures occurred in 14 percent of the women in the placebo group and in 5 percent and 4 percent, respectively, of the women in the 20-μg and 40-μg parathyroid hormone groups; the respective relative risks of fracture in the 20-μg and 40-μg groups, as compared with the placebo group, were 0.35 and 0.31 (95 percent confidence intervals, 0.22 to 0.55 and 0.19 to 0.50). New nonvertebral fragili...

Minimum information about a microarray experiment (MIAME)-toward standards for microarray data.

Abstract: Microarray analysis has become a widely used tool for the generation of gene expression data on a genomic scale. Although many significant results have been derived from microarray studies, one limitation has been the lack of standards for presenting and exchanging such data. Here we present a proposal, the Minimum Information About a Microarray Experiment (MIAME), that describes the minimum information required to ensure that microarray data can be easily interpreted and that results derived from its analysis can be independently verified. The ultimate goal of this work is to establish a standard for recording and reporting microarray-based gene expression data, which will in turn facilitate the establishment of databases and public repositories and enable the development of data analysis tools. With respect to MIAME, we concentrate on defining the content and structure of the necessary information rather than the technical format for capturing it.

Strategy and the Internet.

Abstract: Many of the pioneers of Internet business, both dot-coms and established companies, have competed in ways that violate nearly every precept of good strategy. Rather than focus on profits, they have chased customers indiscriminately through discounting, channel incentives, and advertising. Rather than concentrate on delivering value that earns an attractive price from customers, they have pursued indirect revenues such as advertising and click-through fees. Rather than make trade-offs, they have rushed to offer every conceivable product or service. It did not have to be this way--and it does not have to be in the future. When it comes to reinforcing a distinctive strategy, Michael Porter argues, the Internet provides a better technological platform than previous generations of IT. Gaining competitive advantage does not require a radically new approach to business; it requires building on the proven principles of effective strategy. Porter argues that, contrary to recent thought, the Internet is not disruptive to most existing industries and established companies. It rarely nullifies important sources of competitive advantage in an industry; it often makes them even more valuable. And as all companies embrace Internet technology, the Internet itself will be neutralized as a source of advantage. Robust competitive advantages will arise instead from traditional strengths such as unique products, proprietary content, and distinctive physical activities. Internet technology may be able to fortify those advantages, but it is unlikely to supplant them. Porter debunks such Internet myths as first-mover advantage, the power of virtual companies, and the multiplying rewards of network effects. He disentangles the distorted signals from the marketplace, explains why the Internet complements rather than cannibalizes existing ways of doing business, and outlines strategic imperatives for dot-coms and traditional companies.

Long-Term Use of a Left Ventricular Assist Device for End-Stage Heart Failure

Abstract: Background Implantable left ventricular assist devices have benefited patients with end-stage heart failure as a bridge to cardiac transplantation, but their long-term use for the purpose of enhancing survival and the quality of life has not been evaluated. Methods We randomly assigned 129 patients with end-stage heart failure who were ineligible for cardiac transplantation to receive a left ventricular assist device (68 patients) or optimal medical management (61). All patients had symptoms of New York Heart Association class IV heart failure. Results Kaplan–Meier survival analysis showed a reduction of 48 percent in the risk of death from any cause in the group that received left ventricular assist devices as compared with the medical-therapy group (relative risk, 0.52; 95 percent confidence interval, 0.34 to 0.78; P=0.001). The rates of survival at one year were 52 percent in the device group and 25 percent in the medical-therapy group (P=0.002), and the rates at two years were 23 percent and 8 percent...

Testing the number of components in a normal mixture

Abstract: We demonstrate that, under a theorem proposed by Vuong, the likelihood ratio statistic based on the Kullback-Leibler information criterion of the null hypothesis that a random sample is drawn from a k 0 -component normal mixture distribution against the alternative hypothesis that the sample is drawn from a k 1 -component normal mixture distribution is asymptotically distributed as a weighted sum of independent chi-squared random variables with one degree of freedom, under general regularity conditions. We report simulation studies of two cases where we are testing a single normal versus a two-component normal mixture and a two-component normal mixture versus a three-component normal mixture. An empirical adjustment to the likelihood ratio statistic is proposed that appears to improve the rate of convergence to the limiting distribution.

A clearer vision for in vivo imaging.

Abstract: Progress continues in the development of smaller, more penetrable probes for biological imaging.

Final Results from the Hubble Space Telescope Key Project to Measure the Hubble Constant

Abstract: We present here the final results of the Hubble Space Telescope (HST) Key Project to measure the Hubble constant. We summarize our method, the results, and the uncertainties, tabulate our revised distances, and give the implications of these results for cosmology. Our results are based on a Cepheid calibration of several secondary distance methods applied over the range of about 60-400 Mpc. The analysis presented here benefits from a number of recent improvements and refinements, including (1) a larger LMC Cepheid sample to define the fiducial period-luminosity (PL) relations, (2) a more recent HST Wide Field and Planetary Camera 2 (WFPC2) photometric calibration, (3) a correction for Cepheid metallicity, and (4) a correction for incompleteness bias in the observed Cepheid PL samples. We adopt a distance modulus to the LMC (relative to which the more distant galaxies are measured) of μ0 = 18.50 ± 0.10 mag, or 50 kpc. New, revised distances are given for the 18 spiral galaxies for which Cepheids have been discovered as part of the Key Project, as well as for 13 additional galaxies with published Cepheid data. The new calibration results in a Cepheid distance to NGC 4258 in better agreement with the maser distance to this galaxy. Based on these revised Cepheid distances, we find values (in km s-1 Mpc-1) of H0 = 71 ± 2 ± 6 (systematic) (Type Ia supernovae), H0 = 71 ± 3 ± 7 (Tully-Fisher relation), H0 = 70 ± 5 ± 6 (surface brightness fluctuations), H0 = 72 ± 9 ± 7 (Type II supernovae), and H0 = 82 ± 6 ± 9 (fundamental plane). We combine these results for the different methods with three different weighting schemes, and find good agreement and consistency with H0 = 72 ± 8 km s-1 Mpc-1. Finally, we compare these results with other, global methods for measuring H0.

Mammalian Mitogen-Activated Protein Kinase Signal Transduction Pathways Activated by Stress and Inflammation

Abstract: The molecular details of mammalian stress-activated signal transduction pathways have only begun to be dissected. This, despite the fact that the impact of these pathways on the pathology of chroni...

Indium phosphide nanowires as building blocks for nanoscale electronic and optoelectronic devices

Abstract: Nanowires and nanotubes carry charge and excitons efficiently, and are therefore potentially ideal building blocks for nanoscale electronics and optoelectronics. Carbon nanotubes have already been exploited in devices such as field-effect and single-electron transistors, but the practical utility of nanotube components for building electronic circuits is limited, as it is not yet possible to selectively grow semiconducting or metallic nanotubes. Here we report the assembly of functional nanoscale devices from indium phosphide nanowires, the electrical properties of which are controlled by selective doping. Gate-voltage-dependent transport measurements demonstrate that the nanowires can be predictably synthesized as either n- or p-type. These doped nanowires function as nanoscale field-effect transistors, and can be assembled into crossed-wire p-n junctions that exhibit rectifying behaviour. Significantly, the p-n junctions emit light strongly and are perhaps the smallest light-emitting diodes that have yet been made. Finally, we show that electric-field-directed assembly can be used to create highly integrated device arrays from nanowire building blocks.

FLUXNET: A New Tool to Study the Temporal and Spatial Variability of Ecosystem-Scale Carbon Dioxide, Water Vapor, and Energy Flux Densities

Abstract: FLUXNET is a global network of micrometeorological flux measurement sites that measure the exchanges of carbon dioxide, water vapor, and energy between the biosphere and atmosphere. At present over 140 sites are operating on a long-term and continuous basis. Vegetation under study includes temperate conifer and broadleaved (deciduous and evergreen) forests, tropical and boreal forests, crops, grasslands, chaparral, wetlands, and tundra. Sites exist on five continents and their latitudinal distribution ranges from 70°N to 30°S. FLUXNET has several primary functions. First, it provides infrastructure for compiling, archiving, and distributing carbon, water, and energy flux measurement, and meteorological, plant, and soil data to the science community. (Data and site information are available online at the FLUXNET Web site, http://www-eosdis.ornl.gov/FLUXNET/.) Second, the project supports calibration and flux intercomparison activities. This activity ensures that data from the regional networks are intercomparable. And third, FLUXNET supports the synthesis, discussion, and communication of ideas and data by supporting project scientists, workshops, and visiting scientists. The overarching goal is to provide information for validating computations of net primary productivity, evaporation, and energy absorption that are being generated by sensors mounted on the NASA Terra satellite. Data being compiled by FLUXNET are being used to quantify and compare magnitudes and dynamics of annual ecosystem carbon and water balances, to quantify the response of stand-scale carbon dioxide and water vapor flux densities to controlling biotic and abiotic factors, and to validate a hierarchy of soil–plant–atmosphere trace gas exchange models. Findings so far include 1) net CO 2 exchange of temperate broadleaved forests increases by about 5.7 g C m −2 day −1 for each additional day that the growing season is extended; 2) the sensitivity of net ecosystem CO 2 exchange to sunlight doubles if the sky is cloudy rather than clear; 3) the spectrum of CO 2 flux density exhibits peaks at timescales of days, weeks, and years, and a spectral gap exists at the month timescale; 4) the optimal temperature of net CO 2 exchange varies with mean summer temperature; and 5) stand age affects carbon dioxide and water vapor flux densities.

Functional nanoscale electronic devices assembled using silicon nanowire building blocks.

Abstract: Because semiconductor nanowires can transport electrons and holes, they could function as building blocks for nanoscale electronics assembled without the need for complex and costly fabrication facilities. Boron- and phosphorous-doped silicon nanowires were used as building blocks to assemble three types of semiconductor nanodevices. Passive diode structures consisting of crossed p- and n-type nanowires exhibit rectifying transport similar to planar p-n junctions. Active bipolar transistors, consisting of heavily and lightly n-doped nanowires crossing a common p-type wire base, exhibit common base and emitter current gains as large as 0.94 and 16, respectively. In addition, p- and n-type nanowires have been used to assemble complementary inverter-like structures. The facile assembly of key electronic device elements from well-defined nanoscale building blocks may represent a step toward a "bottom-up" paradigm for electronics manufacturing.

Long-distance quantum communication with atomic ensembles and linear optics

Abstract: Quantum communication holds promise for absolutely secure transmission of secret messages and the faithful transfer of unknown quantum states. Photonic channels appear to be very attractive for the physical implementation of quantum communication. However, owing to losses and decoherence in the channel, the communication fidelity decreases exponentially with the channel length. Here we describe a scheme that allows the implementation of robust quantum communication over long lossy channels. The scheme involves laser manipulation of atomic ensembles, beam splitters, and single-photon detectors with moderate efficiencies, and is therefore compatible with current experimental technology. We show that the communication efficiency scales polynomially with the channel length, and hence the scheme should be operable over very long distances.

Varieties of Capitalism

Abstract: Scholarship on varieties of capitalism (VofC) explores the ways in which the institutions structuring the political economy affect patterns of economic performance or policy making and the distribution of well-being. Contesting the claim that there is one best route to superior economic performance, a number of schemas have been proposed to explain why countries have often been able to secure substantial rates of growth in different ways, often with relatively egalitarian distributions of income. Prominent among them is a VofC analysis focused on the developed democracies that distinguishes liberal and coordinated market economies according to the ways in which firms coordinate their endeavors. On the basis of institutional complementarities among subspheres of the political economy, it suggests that the institutional structure of the political economy confers comparative institutional advantages, notably for radical and incremental innovation, which explains why economies have not converged in the context of globalization. Although this framework is contested, it has inspired new research on many subjects, including the basis for innovation, the determinants of social policy, the grounds for international negotiation, and the character of institutional change. In this issue area, there is promising terrain for further research into the origins of varieties of capitalism, the factors that drive institutional change in the political economy, how institutional arrangements in the subspheres of the political economy interact with one another, the normative underlay for capitalism, and the effects of varieties of capitalism on multiple dimensions of well-being. Keywords: capitalism; political economy; globalization; politics; institutional change; economic growth; macroeconomics; innovation; complementarities; social policy

Social ties and mental health.

Abstract: It is generally agreed that social ties play a beneficial role in the maintenance of psychological well-being. In this targeted review, we highlight four sets of insights that emerge from the literature on social ties and mental health outcomes (defined as stress reactions, psychological well-being, and psychological distress, including depressive symptoms and anxiety). First, the pathways by which social networks and social supports influence mental health can be described by two alternative (although not mutually exclusive) causal models—the main effect model and the stress-buffering model. Second, the protective effects of social ties on mental health are not uniform across groups in society. Gender differences in support derived from social network participation may partly account for the higher prevalence of psychological distress among women compared to men. Social connections may paradoxically increase levels of mental illness symptoms among women with low resources, especially if such connections entail role strain associated with obligations to provide social support to others. Third, egocentric networks are nested within a broader structure of social relationships. The notion of social capital embraces the embeddedness of individual social ties within the broader social structure. Fourth, despite some successes reported in social support interventions to enhance mental health, further work is needed to deepen our understanding of the design, timing, and dose of interventions that work, as well as the characteristics of individuals who benefit the most.

Hepatitis C Virus Infection

Abstract: Hepatitis C virus (HCV) infects an estimated 170 million persons worldwide and thus represents a viral pandemic, one that is five times as widespread as infection with the human immunodeficiency virus type 1 (HIV-1). The institution of blood-screening measures in developed countries has decreased the risk of transfusion-associated hepatitis to a negligible level, but new cases continue to occur mainly as a result of injection-drug use and, to a lesser degree, through other means of percutaneous or mucous-membrane exposure. Progression to chronic disease occurs in the majority of HCV-infected persons, and infection with the virus has become the main indication . . .

Logistic Regression in Rare Events Data

Abstract: We study rare events data, binary dependent variables with dozens to thousands of times fewer ones (events, such as wars, vetoes, cases of political activism, or epidemiological infections) than zeros (“nonevents”). In many literatures, these variables have proven difficult to explain and predict, a problem that seems to have at least two sources. First, popular statistical procedures, such as logistic regression, can sharply underestimate the probability of rare events. We recommend corrections that outperform existing methods and change the estimates of absolute and relative risks by as much as some estimated effects reported in the literature. Second, commonly used data collection strategies are grossly inefficient for rare events data. The fear of collecting data with too few events has led to data collections with huge numbers of observations but relatively few, and poorly measured, explanatory variables, such as in international conflict data with more than a quarter-million dyads, only a few of which are at war. As it turns out, more efficient sampling designs exist for making valid inferences, such as sampling all available events (e.g., wars) and a tiny fraction of nonevents (peace). This enables scholars to save as much as 99% of their (nonfixed) data collection costs or to collect much more meaningful explanatory variables. We provide methods that link these two results, enabling both types of corrections to work simultaneously, and software that implements the methods developed.

A cellular function for the RNA-interference enzyme Dicer in the maturation of the let-7 small temporal RNA.

Abstract: The 21-nucleotide small temporal RNA (stRNA) let-7 regulates developmental timing in Caenorhabditis elegans and probably in other bilateral animals We present in vivo and in vitro evidence that in Drosophila melanogaster a developmentally regulated precursor RNA is cleaved by an RNA interference-like mechanism to produce mature let-7 stRNA Targeted destruction in cultured human cells of the messenger RNA encoding the enzyme Dicer, which acts in the RNA interference pathway, leads to accumulation of the let-7 precursor Thus, the RNA interference and stRNA pathways intersect Both pathways require the RNA-processing enzyme Dicer to produce the active small-RNA component that represses gene expression

Digital Divide: Civic Engagement, Information Poverty, and the Internet Worldwide

Abstract: From the Publisher: Digital Divide examines access and use of the Internet in 179 nations world-wide. A global divide is evident between industrialized and developing societies. A social divide is apparent between rich and poor within each nation. Within the online community, evidence for a democratic divide is emerging between those who do and do not use Internet resources to engage and participate in public life. Part I outlines the theoretical debate between cyber-optimists who see the Internet as the great leveler. Part II examines the virtual political system and the way that representative institutions have responded to new opportunities on the Internet. Part III analyzes how the public has responded to these opportunities in Europe and the United States and develops the civic engagement model to explain patterns of participation via the Internet.

PD-L2 is a second ligand for PD-1 and inhibits T cell activation

Abstract: Programmed death I (PD-I)-deficient mice develop a variety of autoimmune-like diseases, which suggests that this immunoinhibitory receptor plays an important role in tolerance. We identify here PD-1 ligand 2 (PD-L2) as a second ligand for PD-1 and compare the function and expression of PD-L1 and PD-L2. Engagement of PD-1 by PD-L2 dramatically inhibits T cell receptor (TCR)-mediated proliferation and cytokine production by CD4+ T cells. At low antigen concentrations, PD-L2-PD-1 interactions inhibit strong B7-CD28 signals. In contrast, at high antigen concentrations, PD-L2-PD-1 interactions reduce cytokine production but do not inhibit T cell proliferation. PD-L-PD-1 interactions lead to cell cycle arrest in G0/G1 but do not increase cell death. In addition, ligation of PD-1 + TCR leads to rapid phosphorylation of SHP-2, as compared to TCR ligation alone. PD-L expression was up-regulated on antigen-presenting cells by interferon gamma treatment and was also present on some normal tissues and tumor cell lines. Taken together, these studies show overlapping functions of PD-L1 and PD-L2 and indicate a key role for the PD-L-PD-1 pathway in regulatingT cell responses.

Soft Lithography in Biology and Biochemistry

Abstract: ▪ Abstract Soft lithography, a set of techniques for microfabrication, is based on printing and molding using elastomeric stamps with the patterns of interest in bas-relief. As a technique for fabricating microstructures for biological applications, soft lithography overcomes many of the shortcomings of photolithography. In particular, soft lithography offers the ability to control the molecular structure of surfaces and to pattern the complex molecules relevant to biology, to fabricate channel structures appropriate for microfluidics, and to pattern and manipulate cells. For the relatively large feature sizes used in biology (≥50 μm), production of prototype patterns and structures is convenient, inexpensive, and rapid. Self-assembled monolayers of alkanethiolates on gold are particularly easy to pattern by soft lithography, and they provide exquisite control over surface biochemistry.