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Showing papers by "University of Maryland, Baltimore County published in 2008"


Journal ArticleDOI
01 Jun 2008
TL;DR: This paper reports on the current state of the research on optimized node placement in WSNs, and categorizes the placement strategies into static and dynamic depending on whether the optimization is performed at the time of deployment or while the network is operational, respectively.
Abstract: The major challenge in designing wireless sensor networks (WSNs) is the support of the functional, such as data latency, and the non-functional, such as data integrity, requirements while coping with the computation, energy and communication constraints. Careful node placement can be a very effective optimization means for achieving the desired design goals. In this paper, we report on the current state of the research on optimized node placement in WSNs. We highlight the issues, identify the various objectives and enumerate the different models and formulations. We categorize the placement strategies into static and dynamic depending on whether the optimization is performed at the time of deployment or while the network is operational, respectively. We further classify the published techniques based on the role that the node plays in the network and the primary performance objective considered. The paper also highlights open problems in this area of research.

924 citations


Journal ArticleDOI
TL;DR: The prevailing paradigm in Internet privacy literature, treating privacy within a context merely of rights and violations, is inadequate for studying the Internet as a social realm as discussed by the authors, which is not the case in the real world.
Abstract: The prevailing paradigm in Internet privacy literature, treating privacy within a context merely of rights and violations, is inadequate for studying the Internet as a social realm. Following Goffm...

805 citations


Journal ArticleDOI
TL;DR: The 14‐mer peptide efficiently mimics the biotin acceptor function of the much larger protein domain normally recognized by BirA, and is identified as the minimum required sequence for biotinylation.
Abstract: The Escherichia coli biotin holoenzyme synthetase, BirA, catalyzes transfer of biotin to the epsilon amino group of a specific lysine residue of the biotin carboxyl carrier protein (BCCP) subunit of acetyl-CoA carboxylase. Sequences of naturally biotinylated substrates are highly conserved across evolutionary boundaries, and cross-species biotinylation has been demonstrated in several systems. To define the minimal substrate requirements in BirA-catalyzed biotinylation, we have measured the kinetics of modification of a 23-residue peptide previously identified by combinatorial methods. Although the sequence of the peptide bears little resemblance to the biotinylated sequence in BCCP, it is enzymatically biotinylated in vivo. Rates of biotin transfer to the 23-residue peptide are similar to those determined for BCCP. To further elucidate the sequence requirements for biotinylation, transient kinetic measurements were performed on a series of amino- and carboxy-terminal truncations of the 23-mer. The results, determined by stopped-flow fluorescence, allowed identification of a 14-residue peptide as the minimum required sequence. Additional support was obtained using matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF) mass spectrometric analysis of peptides that had been incubated with an excess of biotinyl-5'-adenylate intermediate and catalytic amounts of BirA. Results of these measurements indicate that while kinetically inactive truncations showed no significant shift in molecular mass to the values expected for biotinylated species, kinetically active truncations exhibited 100% biotinylation. The specificity constant (k(cat)/Km) governing BirA-catalyzed biotinylation of the 14-mer minimal substrate is similar to that determined for the natural substrate, BCCP. We conclude that the 14-mer peptide efficiently mimics the biotin acceptor function of the much larger protein domain normally recognized by BirA.

738 citations


Journal ArticleDOI
TL;DR: In this paper, the authors compare with ground-based AERONET observations of aerosol optical depth (AOD) to within expected accuracy more than 60% of the time over ocean and more than 72% over land.
Abstract: [1] The recently released Collection 5 Moderate Resolution Imaging Spectroradiometer (MODIS) aerosol products provide a consistent record of the Earth's aerosol system. Comparing with ground-based AERONET observations of aerosol optical depth (AOD) we find that Collection 5 MODIS aerosol products estimate AOD to within expected accuracy more than 60% of the time over ocean and more than 72% of the time over land. This is similar to previous results for ocean and better than the previous results for land. However, the new collection introduces a 0.015 offset between the Terra and Aqua global mean AOD over ocean, where none existed previously. Aqua conforms to previous values and expectations while Terra is higher than what had been expected. The cause of the offset is unknown, but changes to calibration are a possible explanation. Even though Terra's higher ocean AOD is unexpected and unexplained, we present climatological analyses of data from both sensors. We find that the multiannual global mean AOD at 550 nm over oceans is 0.13 for Aqua and 0.14 for Terra, and over land it is 0.19 in both Aqua and Terra. AOD in situations with 80% cloud fraction are twice the global mean values, although such situations occur only 2% of the time over ocean and less than 1% of the time over land. Aerosol particle size associated with these very cloudy situations does not show a drastic change over ocean, but does over land. Regionally, aerosol amounts vary from polluted areas such as east Asia and India, to the cleanest regions such as Australia and the northern continents. As AOD increases over maritime background conditions, fine mode aerosol dominates over dust over all oceans, except over the tropical Atlantic downwind of the Sahara and during some months over the Arabian Sea.

716 citations


Journal ArticleDOI
TL;DR: It is shown that this population of immature myeloid cells induced by a given tumor share a common phenotype regardless of their in vivo location, and that Gr1highCD11bhighF4/80−CD80+IL4Rα+/−Arginase+ MDSC are induced by the proinflammatory proteins S100A8/A9.
Abstract: Chronic inflammation is a complex process that promotes carcinogenesis and tumor progression; however, the mechanisms by which specific inflammatory mediators contribute to tumor growth remain unclear. We and others recently demonstrated that the inflammatory mediators IL-1β, IL-6, and PGE2 induce accumulation of myeloid-derived suppressor cells (MDSC) in tumor-bearing individuals. MDSC impair tumor immunity and thereby facilitate carcinogenesis and tumor progression by inhibiting T and NK cell activation, and by polarizing immunity toward a tumor-promoting type 2 phenotype. We now show that this population of immature myeloid cells induced by a given tumor share a common phenotype regardless of their in vivo location (bone marrow, spleen, blood, or tumor site), and that Gr1highCD11bhighF4/80−CD80+IL4Rα+/−Arginase+ MDSC are induced by the proinflammatory proteins S100A8/A9. S100A8/A9 proteins bind to carboxylated N-glycans expressed on the receptor for advanced glycation end-products and other cell surface glycoprotein receptors on MDSC, signal through the NF-κB pathway, and promote MDSC migration. MDSC also synthesize and secrete S100A8/A9 proteins that accumulate in the serum of tumor-bearing mice, and in vivo blocking of S100A8/A9 binding to MDSC using an anti-carboxylated glycan Ab reduces MDSC levels in blood and secondary lymphoid organs in mice with metastatic disease. Therefore, the S100 family of inflammatory mediators serves as an autocrine feedback loop that sustains accumulation of MDSC. Since S100A8/A9 activation of MDSC is through the NF-κB signaling pathway, drugs that target this pathway may reduce MDSC levels and be useful therapeutic agents in conjunction with active immunotherapy in cancer patients.

677 citations


Journal ArticleDOI
TL;DR: In this article, the authors present empirical evidence from three surveys of local e-government in the United States to test whether these models are accurate or useful for understanding the actual development of eGovernment.
Abstract: Research into e-government is relatively new. Nevertheless, much contemporary thinking and writing about e-government is driven by normative models that appeared less than a decade ago. The authors present empirical evidence from three surveys of local e-government in the United States to test whether these models are accurate or useful for understanding the actual development of e-government. They find that local e-government is mainly informational, with a few transactions but virtually no indication of the high-level functions predicted in the models. Thus, the models do not accurately describe or predict the development of e-government, at least among American local governments. These models, though intellectually interesting, are purely speculative, having been developed without linkage to the literature about information technology and government. The authors offer grounded observations about e-government that will useful to scholars and practitioners alike.

553 citations


PatentDOI
TL;DR: It is shown that PI(4,5)P(2) binds directly to HIV-1 MA, inducing a conformational change that triggers myristate exposure and suggesting a potential mechanism for targeting Gag to membrane rafts.
Abstract: The present invention provides for testing methods to determine an effective testing agent that affects the activity of the HIV Gag protein at the plasma membrane of a cell, and specifically, effecting changes in the structural conformation of at least one fatty acid of PI(4,5)P 2 , a member of a family of differentially phosphorylated phosphatidylinositides, wherein inhibition of the extension of such fatty acid into the MA domain of the Gag protein reduces binding of Gag to the plasma membrane, thereby inhibiting virus particle assembly and subsequent replication of the HIV virus.

548 citations


Journal ArticleDOI
TL;DR: It is especially found that non-users display an attitude towards social grooming that ranges from incredulous to hostile, which highlights the need to differentiate between the different modalities of Internet use.
Abstract: This paper explores the rapid adoption of online social network sites (also known as social networking sites) (SNSs) by students on a US college campus. Using quantitative (n = 713) and qualitative (n = 51) data based on a diverse sample of college students, demographic and other characteristics of SNS users and non-users are compared. Starting with the theoretical frameworks of Robin Dunbar and Erving Goffman, this paper situates SNS activity under two rubrics: (1) social grooming; and (2) presentation of the self. This study locates these sites within the emergence of social computing and makes a conceptual distinction between the expressive Internet, the Internet of social interactions, and the instrumental Internet, the Internet of airline tickets and weather forecasts. This paper compares and contrasts the user and non-user populations in terms of expressive and instrumental Internet use, social ties and attitudes toward social-grooming, privacy and efficiency. Two clusters are found to influence SNS...

481 citations


Journal ArticleDOI
TL;DR: A brief introduction to modern data assimilation methods in the Earth sciences, their applications, and pertinent research questions can be found in this article, where the authors point out examples of the assimilation of remotely sensed observations in land surface hydrology.

454 citations


Journal ArticleDOI
TL;DR: An examination of the ways that community psychology and allied disciplines can help increase the number and range of empowering settings, and enhance the community and societal impact of existing ones is examined.
Abstract: The pathways and processes through which empowering community settings influence their members, the surrounding community and the larger society are examined. To generate the proposed pathways and processes, a broad range of studies of community settings were reviewed, in the domains of adult well-being, positive youth development, locality development, and social change. A set of organizational characteristics and associated processes leading to member empowerment across domains were identified, as well as three pathways through which empowering settings in each domain contribute to community betterment and positive social change. The paper concludes with an examination of the ways that community psychology and allied disciplines can help increase the number and range of empowering settings, and enhance the community and societal impact of existing ones.

442 citations


Journal ArticleDOI
TL;DR: Several immune protumor effector mechanisms are upregulated by chronic inflammation, leading to the hypothesis that inflammation promotes carcinogenesis and tumor growth by altering the balance between protomor and antitumor immunity, thereby preventing the immune system from rejecting malignant cells, and providing a tumor-friendly environment for progressive disease.

Journal ArticleDOI
TL;DR: In this article, images and the radial profiles of the temperature, abundance, and brightness for 70 clusters of galaxies observed by XMM-Newton are presented along with a detailed discussion of the data reduction and analysis methods, including background modeling, which were used in the processing.
Abstract: Images and the radial profiles of the temperature, abundance, and brightness for 70 clusters of galaxies observed by XMM-Newton are presented along with a detailed discussion of the data reduction and analysis methods, including background modeling, which were used in the processing. Proper consideration of the various background components is vital to extend the reliable determination of cluster parameters to the largest possible cluster radii. The various components of the background including the quiescent particle background, cosmic diffuse emission, soft proton contamination, and solar wind charge exchange emission are discussed along with suggested means of their identification, filtering, and/or their modeling and subtraction. Every component is spectrally variable, sometimes significantly so, and all components except the cosmic background are temporally variable as well. The distributions of the events over the FOV vary between the components, and some distributions vary with energy. The scientific results from observations of low surface brightness objects and the diffuse background itself can be strongly affected by these background components and therefore great care should be taken in their consideration.

Journal ArticleDOI
TL;DR: In this paper, the temporal change in a Tasseled-cap "disturbance index" calculated from the early (~1990) and later (~2000) images was calculated.

Journal ArticleDOI
TL;DR: This paper examined the response of Arctic gas and aerosol concentrations to perturbations in pollutant emissions from Europe, East and South Asia, and North America using re-sults from a coordinated model intercomparison.
Abstract: We examine the response of Arctic gas and aerosol concentrations to perturbations in pollutant emissions from Europe, East and South Asia, and North America using re- sults from a coordinated model intercomparison. These sen- sitivities to regional emissions (mixing ratio change per unit emission) vary widely across models and species. Intermodel differences are systematic, however, so that the relative im- portance of different regions is robust. North America con- tributes the most to Arctic ozone pollution. For aerosols

Journal ArticleDOI
TL;DR: Results of mixed-effects regression models revealed a prospective decline on tests of verbal learning, nonverbal memory, working memory, and a cognitive screening measure among those with increasing levels of pulse pressure and persons with higher baseline pulse wave velocity.
Abstract: Pulse pressure and pulse wave velocity, markers of arterial stiffness, have been associated with stroke, dementia, and lowered levels of cognitive function. Here we examine longitudinal relations of pulse pressure and pulse wave velocity to multiple domains of cognitive function among nondemented, stroke-free persons. Up to 1749 participants from the Baltimore Longitudinal Study of Aging completed tests of verbal and nonverbal memory, attention, perceptuo-motor speed, confrontation naming, executive functions, and cognitive screening measures, as well as concurrent sphygmomanometric assessment of blood pressure (for derivation of pulse pressure) on 1 to 8 occasions over 14 years. A subset of ≤582 participants also underwent a single baseline assessment of pulse wave velocity and cognitive assessment on 1 to 6 occasions over 11 years. Results of mixed-effects regression models revealed a prospective decline on tests of verbal learning, nonverbal memory, working memory, and a cognitive screening measure among those with increasing levels of pulse pressure ( P P

Journal ArticleDOI
TL;DR: In this paper, the authors assimilated GRACE-derived monthly terrestrial water storage (TWS) anomalies for each of the four major subbasins of the Mississippi into the Catchment Land Surface Model (CLSM) using an ensemble Kalman smoother from January 2003 to May 2006.
Abstract: Assimilation of data from the Gravity Recovery and Climate Experiment (GRACE) system of satellites yielded improved simulation of water storage and fluxes in the Mississippi River basin, as evaluated against independent measurements. The authors assimilated GRACE-derived monthly terrestrial water storage (TWS) anomalies for each of the four major subbasins of the Mississippi into the Catchment Land Surface Model (CLSM) using an ensemble Kalman smoother from January 2003 to May 2006. Compared with the open-loop CLSM simulation, assimilation estimates of groundwater variability exhibited enhanced skill with respect to measured groundwater in all four subbasins. Assimilation also significantly increased the correlation between simulated TWS and gauged river flow for all four subbasins and for the Mississippi River itself. In addition, model performance was evaluated for eight smaller watersheds within the Mississippi basin, all of which are smaller than the scale of GRACE observations. In seven of e...

Journal ArticleDOI
15 Aug 2008-Science
TL;DR: Focusing on the Amazon, it is shown how a feedback between the optical properties of aerosols and the cloud fraction can modify the aerosol forcing, changing the total radiative energy and redistributing it over the atmospheric column.
Abstract: The effect of anthropogenic aerosols on clouds is one of the most important and least understood aspects of human-induced climate change. Small changes in the amount of cloud coverage can produce a climate forcing equivalent in magnitude and opposite in sign to that caused by anthropogenic greenhouse gases, and changes in cloud height can shift the effect of clouds from cooling to warming. Focusing on the Amazon, we show a smooth transition between two opposing effects of aerosols on clouds: the microphysical and the radiative. We show how a feedback between the optical properties of aerosols and the cloud fraction can modify the aerosol forcing, changing the total radiative energy and redistributing it over the atmospheric column.

Proceedings ArticleDOI
25 Mar 2008
TL;DR: This paper examines the communication patterns of millions of mobile phone users, allowing it to study the underlying social network in a large-scale communication network and proposes a spreading activation-based technique that predicts potential churners by examining the current set of churners and their underlyingsocial network.
Abstract: Social Network Analysis has emerged as a key paradigm in modern sociology, technology, and information sciences. The paradigm stems from the view that the attributes of an individual in a network are less important than their ties (relationships) with other individuals in the network. Exploring the nature and strength of these ties can help understand the structure and dynamics of social networks and explain real-world phenomena, ranging from organizational efficiency to the spread of information and disease.In this paper, we examine the communication patterns of millions of mobile phone users, allowing us to study the underlying social network in a large-scale communication network. Our primary goal is to address the role of social ties in the formation and growth of groups, or communities, in a mobile network. In particular, we study the 'evolution of churners in an operator's network spanning over a period of four months. Our analysis explores the propensity of a subscriber to churn out of a service provider's network depending on the number of ties (friends) that have already churned. Based on our findings, we propose a spreading activation-based technique that predicts potential churners by examining the current set of churners and their underlying social network. The efficiency of the prediction is expressed as a lift curve, which indicates the fraction of all churners that can be caught when a certain fraction of subscribers were contacted.

Journal ArticleDOI
TL;DR: The results from the Baltimore Ecosystem Study, part of the Long Term Ecological Research Network, expose new assumptions and test existing assumptions about urban ecosystems and suggest a broader range of structural and functional relationships than is often assumed for urban ecological systems.
Abstract: The emerging discipline of urban ecology is shifting focus from ecological processes embedded within cities to integrative studies of large urban areas as biophysical-social complexes. Yet this discipline lacks a theory. Results from the Baltimore Ecosystem Study, part of the Long Term Ecological Research Network, expose new assumptions and test existing assumptions about urban ecosystems. The findings suggest a broader range of structural and functional relationships than is often assumed for urban ecological systems. We address the relationships between social status and awareness of environmental problems, and between race and environmental hazard. We present patterns of species diversity, riparian function, and stream nitrate loading. In addition, we probe the suitability of land-use models, the diversity of soils, and the potential for urban carbon sequestration. Finally, we illustrate lags between social patterns and vegetation, the biogeochemistry of lawns, ecosystem nutrient retention, and social-biophysical feedbacks. These results suggest a framework for a theory of urban ecosystems.

Journal ArticleDOI
TL;DR: Results from the global Web survey of IT departments in 2005 and 2007 suggest that, although the overall project failure rate is high, word of a software crisis is exaggerated.
Abstract: Results from our global Web survey of IT departments in 2005 and 2007 suggest that, although the overall project failure rate is high, word of a software crisis is exaggerated.

Journal ArticleDOI
TL;DR: There are a number of strong measures for assessing children's pain, which allows professionals options to meet their particular needs and future directions in pain assessment are identified, such as highlighting culture and the impact of pain on functioning.
Abstract: Objective To conduct an evidence-based review of pediatric pain measures. Methods Seventeen measures were examined, spanning pain intensity self-report, questionnaires and diaries, and behavioral observations. Measures were classified as “Well-established,” “Approaching well-established,” or “Promising” according to established criteria. Information was highlighted to help professionals evaluate the instruments for particular purposes (e.g., research, clinical work). Results Eleven measures met criteria for “Well-established,” six “Approaching well-established,” and zero were classified as “Promising.” Conclusions There are a number of strong measures for assessing children's pain, which allows professionals options to meet their particular needs. Future directions in pain assessment are identified, such as highlighting culture and the impact of pain on functioning. This review examines the research and characteristics of some of the commonly used pain tools in hopes that the reader will be able to use this evidence-based approach and the information in future selection of assessment devices for pediatric pain.

Journal ArticleDOI
TL;DR: In this paper, the first 9 months of data of the Swift BAT survey of AGN in the 14-195 keV band were analyzed and a power law was fit to the logN - log S distribution, and the slope was found to be 1.42+/-0.26.
Abstract: We present the results1 of the analysis of the first 9 months of data of the Swift BAT survey of AGN in the 14-195 keV band. Using archival X-ray data or follow-up Swift XRT observations, we have identified 129 (103 AGN) of 130 objects detected at [b] > 15deg and with significance > 4.8-delta. One source remains unidentified. These same X-ray data have allowed measurement of the X-ray properties of the objects. We fit a power law to the logN - log S distribution, and find the slope to be 1.42+/-0.14. Characterizing the differential luminosity function data as a broken power law, we find a break luminosity logL*(ergs/s)= 43.85+/-0.26. We obtain a mean photon index 1.98 in the 14-195 keV band, with an rms spread of 0.27. Integration of our luminosity function gives a local volume density of AGN above 10(exp 41) erg/s of 2.4x10(exp -3) Mpc(sup -3), which is about 10% of the total luminous local galaxy density above M* = -19.75. We have obtained X-ray spectra from the literature and from Swift XRT follow-up observations. These show that the distribution of log nH is essentially flat from nH = 10(exp 20)/sq cm to 10(exp 24)/sq cm, with 50% of the objects having column densities of less than 10(exp 22)/sq cm. BAT Seyfert galaxies have a median redshift of 0.03, a maximum log luminosity of 45.1, and approximately half have log nH > 22.

Journal ArticleDOI
TL;DR: Higher adolescent-reported depressive symptoms, lower parent-reported externalizing symptoms, and higher frequencies of NSSI predicted weaker suicidal ideation remission slopes, which underscore the need for more longitudinal research on the course of adolescent suicidality.
Abstract: Remarkably little is known regarding the temporal course of adolescent suicidal ideation and behavior, the prediction of suicidal attempts from changes in suicidal ideation, or the prediction of suicidal attempts after accounting for suicidal ideation as a predictor. A sample of 143 adolescents 12-15 years old was assessed during psychiatric inpatient hospitalization and again at 3, 6, 9, 15, and 18 months postdischarge through a series of structured interviews and parent- and adolescent-reported instruments. Symptoms of depression, posttraumatic stress disorder, externalizing psychopathology, hopelessness, and engagement in several forms of self-injurious/suicidal behaviors (i.e., suicide threats/gestures, plans, nonsuicidal self-injury [NSSI]) were assessed. Latent growth curve analyses revealed a period of suicidal ideation remission between baseline and 6 months following discharge, as well as a subtle period of suicidal ideation reemergence between 9 and 18 months postdischarge. Changes in suicidal ideation predicted suicide attempts. After accounting for the effects of suicidal ideation, baseline suicide threats/gestures also predicted future suicide attempts. Higher adolescent-reported depressive symptoms, lower parent-reported externalizing symptoms, and higher frequencies of NSSI predicted weaker suicidal ideation remission slopes. Findings underscore the need for more longitudinal research on the course of adolescent suicidality.

Journal ArticleDOI
TL;DR: In this paper, an ensemble of aircraft, satellite, sonde, and surface observations for April-May 2006 (NASA/INTEX-B aircraft campaign) were used to better understand the mechanisms for transpacific ozone pollution and its implications for North American air quality.
Abstract: We use an ensemble of aircraft, satellite, sonde, and surface observations for April–May 2006 (NASA/INTEX-B aircraft campaign) to better understand the mechanisms for transpacific ozone pollution and its implications for North American air quality The observations are interpreted with a global 3-D chemical transport model (GEOS-Chem) OMI NO2 satellite observations constrain Asian anthropogenic NOx emissions and indicate a factor of 2 increase from 2000 to 2006 in China Satellite observations of CO from AIRS and TES indicate two major events of Asian transpacific pollution during INTEX-B Correlation between TES CO and ozone observations shows evidence for transpacific ozone pollution The semi-permanent Pacific High and Aleutian Low cause splitting of transpacific pollution plumes over the Northeast Pacific The northern branch circulates around the Aleutian Low and has little impact on North America The southern branch circulates around the Pacific High and some of that air impacts western North America Both aircraft measurements and model results show sustained ozone production driven by peroxyacetylnitrate (PAN) decomposition in the southern branch, roughly doubling the transpacific influence from ozone produced in the Asian boundary layer Model simulation of ozone observations at Mt Bachelor Observatory in Oregon (27 km altitude) indicates a mean Asian ozone pollution contribution of 9±3 ppbv to the mean observed concentration of 54 ppbv, reflecting mostly an enhancement in background ozone rather than episodic Asian plumes Asian pollution enhanced surface ozone concentrations by 5–7 ppbv over western North America in spring 2006 The 2000–2006 rise in Asian anthropogenic emissions increased this influence by 1–2 ppbv

Journal ArticleDOI
TL;DR: The design and basic operation of the microscale manifestation of a cell culture analog system that achieves approximate physiological liquid‐to‐cell ratio and hydrodynamic shear stress while replicating the liquid residence time parameters in the PBPK model is described.
Abstract: Whole animal testing is an essential part in evaluating the toxicological and pharmacological profiles of chemicals and pharmaceuticals, but these experiments are expensive and cumbersome. A cell culture analog (CCA) system, when used in conjunction with a physiologically based pharmacokinetic (PBPK) model, provides an in vitro supplement to animal studies and the possibility of a human surrogate for predicting human response in clinical trials. A PBPK model mathematically simulates animal metabolism by modeling the absorption, distribution, metabolism, and elimination kinetics of a chemical in interconnected tissue compartments. A CCA uses mammalian cells cultured in interconnected chambers to physically represent the corresponding PBPK. These compartments are connected by recirculating tissue culture medium that acts as a blood surrogate. The purpose of this article is to describe the design and basic operation of the microscale manifestation of such a system. Microscale CCAs offer the potential for inexpensive, relatively high throughput evaluation of chemicals while minimizing demand for reagents and cells. Using microfabrication technology, a three-chamber ("lung"-"liver"-"other") microscale cell culture analog (microCCA) device was fabricated on a 1 in. (2.54 cm) square silicon chip. With a design flow rate of 1.76 microL/min, this microCCA device achieves approximate physiological liquid-to-cell ratio and hydrodynamic shear stress while replicating the liquid residence time parameters in the PBPK model. A dissolved oxygen sensor based on collision quenching of a fluorescent ruthenium complex by oxygen molecules was integrated into the system, demonstrating the potential to integrate real-time sensors into such devices.

Journal ArticleDOI
TL;DR: This work generates mutations in the single Drosophila melanogaster Vps34 orthologue, causing cell-autonomous disruption of autophagosome/autolysosome formation in larval fat body cells, and shows that TOR/Atg1 signaling regulates the starvation-induced recruitment of PI(3)P to nascent autophagy.
Abstract: Degradation of cytoplasmic components by autophagy requires the class III phosphatidylinositol 3 (PI(3))-kinase Vps34, but the mechanisms by which this kinase and its lipid product PI(3) phosphate (PI(3)P) promote autophagy are unclear. In mammalian cells, Vps34, with the proautophagic tumor suppressors Beclin1/Atg6, Bif-1, and UVRAG, forms a multiprotein complex that initiates autophagosome formation. Distinct Vps34 complexes also regulate endocytic processes that are critical for late-stage autophagosome-lysosome fusion. In contrast, Vps34 may also transduce activating nutrient signals to mammalian target of rapamycin (TOR), a negative regulator of autophagy. To determine potential in vivo functions of Vps34, we generated mutations in the single Drosophila melanogaster Vps34 orthologue, causing cell-autonomous disruption of autophagosome/autolysosome formation in larval fat body cells. Endocytosis is also disrupted in Vps34(-/-) animals, but we demonstrate that this does not account for their autophagy defect. Unexpectedly, TOR signaling is unaffected in Vps34 mutants, indicating that Vps34 does not act upstream of TOR in this system. Instead, we show that TOR/Atg1 signaling regulates the starvation-induced recruitment of PI(3)P to nascent autophagosomes. Our results suggest that Vps34 is regulated by TOR-dependent nutrient signals directly at sites of autophagosome formation.

Journal ArticleDOI
TL;DR: In this paper, the Murchison meteorite was analyzed and the carbon isotope ratios for uracil and xanthine of δ13C = + 4.5 and + 3.7, respectively, indicated a non-terrestrial origin for these compounds.

Journal ArticleDOI
28 Mar 2008-Science
TL;DR: In this article, the authors reported the detection of magnetar-like x-ray bursts from the young pulsar PSR J1846-0258, at the center of the supernova remnant Kes 75.
Abstract: We report the detection of magnetar-like x-ray bursts from the young pulsar PSR J1846-0258, at the center of the supernova remnant Kes 75. This pulsar, long thought to be exclusively rotation-powered, has an inferred surface dipolar magnetic field of 4.9deg 10(exp 13) gauss, which is higher than those of the vast majority of rotation-powered pulsars, but lower than those of the approximately 12 previously identified magnetars. The bursts were accompanied by a sudden flux increase and an unprecedented change in timing behavior. These phenomena lower the magnetic and rotational thresholds associated with magnetar-like behavior and suggest that in neutron stars there exists a continuum of magnetic activity that increases with inferred magnetic field strength.

Journal ArticleDOI
TL;DR: Findings show that RAGE, carboxylated glycans and S100A8/A9 play essential roles in tumor–stromal interactions, leading to inflammation-associated colon carcinogenesis.
Abstract: Patients with inflammatory bowel diseases are at increased risk for colorectal cancer, but the molecular mechanisms linking inflammation and cancer are not well defined. We earlier showed that carboxylated N-glycans expressed on receptor for advanced glycation end products (RAGE) and other glycoproteins mediate colitis through activation of nuclear factor kappa B (NF-κB). Because NF-κB signaling plays a critical role in the molecular pathogenesis of colitis-associated cancer (CAC), we reasoned that carboxylated glycans, RAGE and its ligands might promote CAC. Carboxylated glycans are expressed on a subpopulation of RAGE on colon cancer cells and mediate S100A8/A9 binding to RAGE. Colon tumor cells express binding sites for S100A8/A9 and binding leads to activation of NF-κB and tumor cell proliferation. Binding, downstream signaling and tumor cell proliferation are blocked by mAbGB3.1, an anti-carboxylate glycan antibody, and by anti-RAGE. In human colon tumor tissues and in a mouse model of CAC, we found that myeloid progenitors expressing S100A8 and S100A9 infiltrate regions of dysplasia and adenoma. mAbGB3.1 administration markedly reduces chronic inflammation and tumorigenesis in the mouse model of CAC and RAGE-deficient mice are resistant to the onset of CAC. These findings show that RAGE, carboxylated glycans and S100A8/A9 play essential roles in tumor–stromal interactions, leading to inflammation-associated colon carcinogenesis.

Journal ArticleDOI
TL;DR: In this paper, the authors developed an empirical algorithm to retrieve surface ocean colored dissolved organic matter (CDOM) and dissolved organic carbon (DOC) from NASA's MODIS-Aqua and SeaWiFS satellite sensors and investigate the processes that influence the distributions of CDOM and DOC.
Abstract: [1] Oceanographic cruises were conducted within the U.S. Middle Atlantic Bight (MAB) to collect field measurements to develop algorithms to retrieve surface ocean colored dissolved organic matter (CDOM) and dissolved organic carbon (DOC) from NASA's MODIS-Aqua and SeaWiFS satellite sensors and to investigate the processes that influence the distributions of CDOM and DOC. In order to develop empirical algorithms for CDOM and DOC, the CDOM absorption coefficient (aCDOM) was correlated with in situ remote sensing reflectance band ratios, and DOC was then derived from aCDOM through the aCDOM to DOC relationships. Our validation analyses demonstrate successful retrieval of DOC and CDOM using MODIS and SeaWiFS with mean absolute percent differences from field measurements of 9.3 ± 7.3% for DOC, 19 ± 14% for aCDOM(355), 15.5 ± 12% for aCDOM(443), and 8.6 ± 4.9% for the CDOM spectral slope. To our knowledge, the algorithms presented here represent the first validated algorithms for satellite retrieval of aCDOM, DOC, and CDOM spectral slope in the coastal ocean. Satellite imagery demonstrates the importance of riverine/estuarine discharge from Chesapeake Bay and Delaware Bay to the export of CDOM and DOC to the coastal ocean. Between spring and summer, photooxidation has a significant impact on CDOM distributions resulting in a pronounced decrease in aCDOM between the midshelf and continental slope region of the MAB. The satellite-derived DOC products demonstrate the net ecosystem production of DOC of 12 to 34 μmol C L−1 between spring and summer. The aCDOM algorithms presented here are applicable to other coastal regions and can also be used to retrieve DOC using region-specific aCDOM to DOC relationships.