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Showing papers by "Indiana University published in 2006"


Journal ArticleDOI
TL;DR: The authors provide a more complete conceptual model of entrepreneurial action that allows for examining entrepreneurial action at the individual level of analysis while remaining consistent with a rich legacy of system-level theories of the entrepreneur.
Abstract: By considering the amount of uncertainty perceived and the willingness to bear uncertainty concomitantly, we provide a more complete conceptual model of entrepreneurial action that allows for examination of entrepreneurial action at the individual level of analysis while remaining consistent with a rich legacy of system-level theories of the entrepreneur. Our model not only exposes limitations of existing theories of entrepreneurial action but also contributes to a deeper understanding of important conceptual issues, such as the nature of opportunity and the potential for philosophical reconciliation among entrepreneurship scholars.

2,347 citations


Journal ArticleDOI
21 Apr 2006-Science
TL;DR: It is shown that a flagellin-derived peptide induces a plant microRNA (miRNA) that negatively regulates messenger RNAs for the F-box auxin receptors TIR1, AFB2, and AFB3, implicating auxin in disease susceptibility and miRNA-mediated suppression of auxin signaling in resistance.
Abstract: Plants and animals activate defenses after perceiving pathogen-associated molecular patterns (PAMPs) such as bacterial flagellin. In Arabidopsis, perception of flagellin increases resistance to the bacterium Pseudomonas syringae, although the molecular mechanisms involved remain elusive. Here, we show that a flagellin-derived peptide induces a plant microRNA (miRNA) that negatively regulates messenger RNAs for the F-box auxin receptors TIR1, AFB2, and AFB3. Repression of auxin signaling restricts P. syringae growth, implicating auxin in disease susceptibility and miRNA-mediated suppression of auxin signaling in resistance.

1,770 citations


Journal ArticleDOI
TL;DR: In this article, the authors propose a more complete conceptual framework for analysis of SME credit availability issues, and emphasize a causal chain from policy to financial structures, which affect the feasibility and profitability of different lending technologies.
Abstract: We propose a more complete conceptual framework for analysis of SME credit availability issues. In this framework, lending technologies are the key conduit through which government policies and national financial structures affect credit availability. We emphasize a causal chain from policy to financial structures, which affect the feasibility and profitability of different lending technologies. These technologies, in turn, have important effects on SME credit availability. Financial structures include the presence of different financial institution types and the conditions under which they operate. Lending technologies include several transactions technologies plus relationship lending. We argue that the framework implicit in most of the literature is oversimplified, neglects key elements of the chain, and often yields misleading conclusions. A common oversimplification is the treatment of transactions technologies as a homogeneous group, unsuitable for serving informationally opaque SMEs, and a frequent misleading conclusion is that large institutions are disadvantaged in lending to opaque SMEs.

1,706 citations


Journal ArticleDOI
TL;DR: It is recommended that the term renal osteodystrophy be used exclusively to define alterations in bone morphology associated with CKD, and the term CKD-Mineral and Bone Disorder (CKD-MBD) be used to describe a broader clinical syndrome that develops as a systemic disorder of mineral and bone metabolism due to CKD.

1,698 citations


Journal ArticleDOI
TL;DR: In this article, the extent to which student engagement is associated with experimental and traditional measures of academic performance, whether the relationships between engagement and academic performance are conditional, and whether institutions differ in terms of their ability to convert student engagement into academic performance.
Abstract: This study examines (1) the extent to which student engagement is associated with experimental and traditional measures of academic performance, (2) whether the relationships between engagement and academic performance are conditional, and (3) whether institutions differ in terms of their ability to convert student engagement into academic performance. The sample consisted of 1058 students at 14 four-year colleges and universities that completed several instruments during 2002. Many measures of student engagement were linked positively with such desirable learning outcomes as critical thinking and grades, although most of the relationships were weak in strength. The results suggest that the lowest-ability students benefit more from engagement than classmates, first-year students and seniors convert different forms of engagement into academic achievement, and certain institutions more effectively convert student engagement into higher performance on critical thinking tests.

1,586 citations


Journal ArticleDOI
TL;DR: In this paper, the authors propose that hub firms orchestrate network activities to ensure the creation and extraction of value, without the benefit of hierarchical authority, and reject the view of network members as inert entities that merely respond to inducements and constraints arising from their network ties.
Abstract: Innovation networks can often be viewed as loosely coupled systems of autonomous firms. We propose that hub firms orchestrate network activities to ensure the creation and extraction of value, without the benefit of hierarchical authority. Orchestration comprises knowledge mobility, innovation appropriability, and network stability. We reject the view of network members as inert entities that merely respond to inducements and constraints arising from their network ties, and we embrace the essential player-structure duality present in networks.

1,470 citations


Journal ArticleDOI
20 Dec 2006-JAMA
TL;DR: Cognitive training resulted in improved cognitive abilities specific to the abilities trained that continued 5 years after the initiation of the intervention, and booster training for the speed of processing group showed a significant effect on the performance-based functional measure of everyday speed ofprocessing.
Abstract: ContextCognitive training has been shown to improve cognitive abilities in older adults but the effects of cognitive training on everyday function have not been demonstrated.ObjectiveTo determine the effects of cognitive training on daily function and durability of training on cognitive abilities.Design, Setting, and ParticipantsFive-year follow-up of a randomized controlled single-blind trial with 4 treatment groups. A volunteer sample of 2832 persons (mean age, 73.6 years; 26% black), living independently in 6 US cities, was recruited from senior housing, community centers, and hospitals and clinics. The study was conducted between April 1998 and December 2004. Five-year follow-up was completed in 67% of the sample.InterventionsTen-session training for memory (verbal episodic memory), reasoning (inductive reasoning), or speed of processing (visual search and identification); 4-session booster training at 11 and 35 months after training in a random sample of those who completed training.Main Outcome MeasuresSelf-reported and performance-based measures of daily function and cognitive abilities.ResultsThe reasoning group reported significantly less difficulty in the instrumental activities of daily living (IADL) than the control group (effect size, 0.29; 99% confidence interval [CI], 0.03-0.55). Neither speed of processing training (effect size, 0.26; 99% CI, −0.002 to 0.51) nor memory training (effect size, 0.20; 99% CI, −0.06 to 0.46) had a significant effect on IADL. The booster training for the speed of processing group, but not for the other 2 groups, showed a significant effect on the performance-based functional measure of everyday speed of processing (effect size, 0.30; 99% CI, 0.08-0.52). No booster effects were seen for any of the groups for everyday problem-solving or self-reported difficulty in IADL. Each intervention maintained effects on its specific targeted cognitive ability through 5 years (memory: effect size, 0.23 [99% CI, 0.11-0.35]; reasoning: effect size, 0.26 [99% CI, 0.17-0.35]; speed of processing: effect size, 0.76 [99% CI, 0.62-0.90]). Booster training produced additional improvement with the reasoning intervention for reasoning performance (effect size, 0.28; 99% CI, 0.12-0.43) and the speed of processing intervention for speed of processing performance (effect size, 0.85; 99% CI, 0.61-1.09).ConclusionsReasoning training resulted in less functional decline in self-reported IADL. Compared with the control group, cognitive training resulted in improved cognitive abilities specific to the abilities trained that continued 5 years after the initiation of the intervention.Trial Registrationclinicaltrials.gov Identifier: NCT00298558

1,356 citations


Journal ArticleDOI
TL;DR: While many of the genes induced by eIF2 phosphorylation are shared between different environmental stresses, eIF1 kinases function in conjunction with other stress-response pathways, such as those regulated by mitogen-activated protein kinases, to elicit gene expression programmes that are tailored for the specific stress condition.
Abstract: In response to environmental stresses, a family of protein kinases phosphorylate eIF2 (eukaryotic initiation factor 2) to alleviate cellular injury or alternatively induce apoptosis. Phosphorylation of eIF2 reduces global translation, allowing cells to conserve resources and to initiate a reconfiguration of gene expression to effectively manage stress conditions. Accompanying this general protein synthesis control, eIF2 phosphorylation induces translation of specific mRNAs, such as that encoding the bZIP (basic leucine zipper) transcriptional regulator ATF4 (activating transcription factor 4). ATF4 also enhances the expression of additional transcription factors, ATF3 and CHOP (CCAAT/enhancer-binding protein homologous protein)/GADD153 (growth arrest and DNA-damage-inducible protein), that assist in the regulation of genes involved in metabolism, the redox status of the cells and apoptosis. Reduced translation by eIF2 phosphorylation can also lead to activation of stress-related transcription factors, such as NF-kappaB (nuclear factor kappaB), by lowering the steady-state levels of short-lived regulatory proteins such as IkappaB (inhibitor of NF-kappaB). While many of the genes induced by eIF2 phosphorylation are shared between different environmental stresses, eIF2 kinases function in conjunction with other stress-response pathways, such as those regulated by mitogen-activated protein kinases, to elicit gene expression programmes that are tailored for the specific stress condition. Loss of eIF2 kinase pathways can have important health consequences. Mice devoid of the eIF2 kinase GCN2 [general control non-derepressible-2 or EIF2AK4 (eIF2alpha kinase 4)] show sensitivity to nutritional deficiencies and aberrant eating behaviours, and deletion of PEK [pancreatic eIF2alpha kinase or PERK (RNA-dependent protein kinase-like endoplasmic reticulum kinase) or EIF2AK3] leads to neonatal insulin-dependent diabetes, epiphyseal dysplasia and hepatic and renal complications.

1,291 citations


Journal ArticleDOI
TL;DR: In this paper, the electronic states of narrow graphene ribbons with zigzag and armchair edges were analyzed using the Dirac equation with appropriate boundary conditions, showing that the boundary condition allows a particlelike and a hole-like band with evanescent wave functions confined to the surfaces, which continuously turn into zero energy surface states as the width gets large.
Abstract: We study the electronic states of narrow graphene ribbons (``nanoribbons'') with zigzag and armchair edges. The finite width of these systems breaks the spectrum into an infinite set of bands, which we demonstrate can be quantitatively understood using the Dirac equation with appropriate boundary conditions. For the zigzag nanoribbon we demonstrate that the boundary condition allows a particlelike and a holelike band with evanescent wave functions confined to the surfaces, which continuously turn into the well-known zero energy surface states as the width gets large. For armchair edges, we show that the boundary condition leads to admixing of valley states, and the band structure is metallic when the width of the sample in lattice constant units has the form $3M+1$, with $M$ an integer, and insulating otherwise. A comparison of the wave functions and energies from tight-binding calculations and solutions of the Dirac equations yields quantitative agreement for all but the narrowest ribbons.

1,244 citations


Journal ArticleDOI
TL;DR: The GAIT trial as discussed by the authors evaluated the efficacy and safety of glucosamine and chondroitin sulfate as a treatment for knee pain from osteoarthritis in 1583 patients.
Abstract: Background Glucosamine and chondroitin sulfate are used to treat osteoarthritis. The multicenter, double-blind, placebo- and celecoxib-controlled Glucosamine/chondroitin Arthritis Intervention Trial (GAIT) evaluated their efficacy and safety as a treatment for knee pain from osteoarthritis. Methods We randomly assigned 1583 patients with symptomatic knee osteoarthritis to receive 1500 mg of glucosamine daily, 1200 mg of chondroitin sulfate daily, both glucosamine and chondroitin sulfate, 200 mg of celecoxib daily, or placebo for 24 weeks. Up to 4000 mg of acetaminophen daily was allowed as rescue analgesia. Assignment was stratified according to the severity of knee pain (mild [N=1229] vs. moderate to severe [N=354]). The primary outcome measure was a 20 percent decrease in knee pain from baseline to week 24. Results The mean age of the patients was 59 years, and 64 percent were women. Overall, glucosamine and chondroitin sulfate were not significantly better than placebo in reducing knee pain by 20 perce...

1,199 citations


Journal ArticleDOI
TL;DR: The authors examined the effects of three strategic process variables (strategic decision-making participativeness, strategy formation mode, and strategic learning from failure) on the entrepreneur's success and failure.
Abstract: This research examined the effects of three strategic process variables—strategic decision–making participativeness, strategy formation mode, and strategic learning from failure—on the entrepreneur...

Journal ArticleDOI
TL;DR: Hahn et al. as mentioned in this paper presented CAFE (Computational Analysis of gene Family Evolution), a tool for the statistical analysis of the evolution of the size of gene families.
Abstract: Summary: We present CAFE (Computational Analysis of gene Family Evolution), a tool for the statistical analysis of the evolution of the size of gene families. It uses a stochastic birth and death process to model the evolution of gene family sizes over a phylogeny. For a specified phylogenetic tree, and given the gene family sizes in the extant species, CAFE can estimate the global birth and death rate of gene families, infer the most likely gene family size at all internal nodes, identify gene families that have accelerated rates of gain and loss (quantified by a p-value) and identify which branches cause the p-value to be small for significant families. Availability: Software is available from http://www.bio.indiana.edu/~hahnlab/Software.html Contact: mwh@indiana.edu

Journal ArticleDOI
TL;DR: The molecular mechanisms by which bone adapts to loading and repairs damage are starting to become clear, and have implications for bone health, disease, and the feasibility of living in weightless environments (e.g., spaceflight).
Abstract: Bone is a dynamic tissue that is constantly renewed. The cell populations that participate in this process--the osteoblasts and osteoclasts--are derived from different progenitor pools that are under distinct molecular control mechanisms. Together, these cells form temporary anatomical structures, called basic multicellular units, that execute bone remodeling. A number of stimuli affect bone turnover, including hormones, cytokines, and mechanical stimuli. All of these factors affect the amount and quality of the tissue produced. Mechanical loading is a particularly potent stimulus for bone cells, which improves bone strength and inhibits bone loss with age. Like other materials, bone accumulates damage from loading, but, unlike engineering materials, bone is capable of self-repair. The molecular mechanisms by which bone adapts to loading and repairs damage are starting to become clear. Many of these processes have implications for bone health, disease, and the feasibility of living in weightless environments (e.g., spaceflight).

Journal ArticleDOI
TL;DR: It is suggested that growth velocity during an ELBW infant’s NICU hospitalization exerts a significant, and possibly independent, effect on neurodevelopmental and growth outcomes at 18 to 22 months’ corrected age.
Abstract: OBJECTIVES. The objectives of this study were to assess whether (1) in-hospital growth velocity is predictive of neurodevelopmental and growth outcomes at 18 to 22 months’ corrected age among extremely low birth weight (ELBW) infants and (2) in-hospital growth velocity contributes to these outcomes after controlling for confounding demographic and clinical variables. METHODS. Infants 501 to 1000 g birth weight from a multicenter cohort study were divided into quartiles of in-hospital growth velocity rates. Variables considered for the logistic-regression models included gender, race, gestational age, small for gestational age, mother’s education, severe intraventricular hemorrhage, periventricular leukomalacia, age at regaining birth weight, necrotizing enterocolitis, late-onset infection, bronchopulmonary dysplasia, postnatal steroid therapy for pulmonary disease, and center. RESULTS. Of the 600 discharged infants, 495 (83%) were evaluated at 18 to 22 months’ corrected age. As the rate of weight gain increased between quartile 1 and quartile 4, from 12.0 to 21.2 g/kg per day, the incidence of cerebral palsy, Bayley II Mental Developmental Index (MDI) CONCLUSIONS. These analyses suggest that growth velocity during an ELBW infant’s NICU hospitalization exerts a significant, and possibly independent, effect on neurodevelopmental and growth outcomes at 18 to 22 months’ corrected age.

Journal ArticleDOI
TL;DR: A stochastic computational framework for the forecast of global epidemics that considers the complete worldwide air travel infrastructure complemented with census population data and defines a set of quantitative measures able to characterize the level of heterogeneity and predictability of the epidemic pattern.
Abstract: The systematic study of large-scale networks has unveiled the ubiquitous presence of connectivity patterns characterized by large-scale heterogeneities and unbounded statistical fluctuations. These features affect dramatically the behavior of the diffusion processes occurring on networks, determining the ensuing statistical properties of their evolution pattern and dynamics. In this article, we present a stochastic computational framework for the forecast of global epidemics that considers the complete worldwide air travel infrastructure complemented with census population data. We address two basic issues in global epidemic modeling: (i) we study the role of the large scale properties of the airline transportation network in determining the global diffusion pattern of emerging diseases; and (ii) we evaluate the reliability of forecasts and outbreak scenarios with respect to the intrinsic stochasticity of disease transmission and traffic flows. To address these issues we define a set of quantitative measures able to characterize the level of heterogeneity and predictability of the epidemic pattern. These measures may be used for the analysis of containment policies and epidemic risk assessment.

Journal ArticleDOI
TL;DR: The authors argue that public managers should look inside the "black box" of collaboration processes and find a complex construct of five variable dimensions: governance, administration, organizational autonomy, mutuality, and norms.
Abstract: Social science research contains a wealth of knowledge for people seeking to understand collaboration processes. The authors argue that public managers should look inside the “black box” of collaboration processes. Inside, they will find a complex construct of five variable dimensions: governance, administration, organizational autonomy, mutuality, and norms. Public managers must know these five dimensions and manage them intentionally in order to collaborate effectively.

Journal ArticleDOI
Dengsheng Lu1
TL;DR: In this article, a review of previous research on remote sensing-based biomass estimation approaches and a discussion of existing issues influencing biomass estimation are valuable for further improving biomass estimation performance, especially in those study areas with complex forest stand structures and environmental conditions.
Abstract: Remotely sensed data have become the primary source for biomass estimation. A summary of previous research on remote sensing‐based biomass estimation approaches and a discussion of existing issues influencing biomass estimation are valuable for further improving biomass estimation performance. The literature review has demonstrated that biomass estimation remains a challenging task, especially in those study areas with complex forest stand structures and environmental conditions. Either optical sensor data or radar data are more suitable for forest sites with relatively simple forest stand structure than the sites with complex biophysical environments. A combination of spectral responses and image textures improves biomass estimation performance. More research is needed to focus on the integration of optical and radar data, the use of multi‐source data, and the selection of suitable variables and algorithms for biomass estimation at different scales. Understanding and identifying major uncertainties cause...

Journal ArticleDOI
TL;DR: Breast cancer cells with CD44+/CD24- subpopulation express higher levels of proinvasive genes and have highly invasive properties, however, this phenotype is not sufficient to predict capacity for pulmonary metastasis.
Abstract: A subpopulation (CD44+/CD24-) of breast cancer cells has been reported to have stem/progenitor cell properties. The aim of this study was to investigate whether this subpopulation of cancer cells has the unique ability to invade, home, and proliferate at sites of metastasis. CD44 and CD24 expression was determined by flow cytometry. Northern blotting was used to determine the expression of proinvasive and 'bone and lung metastasis signature' genes. A matrigel invasion assay and intracardiac inoculation into nude mice were used to evaluate invasion, and homing and proliferation at sites of metastasis, respectively. Five among 13 breast cancer cell lines examined (MDA-MB-231, MDA-MB-436, Hs578T, SUM1315, and HBL-100) contained a higher percentage (>30%) of CD44+/CD24- cells. Cell lines with high CD44+/CD24- cell numbers express basal/mesenchymal or myoepithelial but not luminal markers. Expression levels of proinvasive genes (IL-1α, IL-6, IL-8, and urokinase plasminogen activator [UPA]) were higher in cell lines with a significant CD44+/CD24- population than in other cell lines. Among the CD44+/CD24--positive cell lines, MDA-MB-231 has the unique property of expressing a broad range of genes that favor bone and lung metastasis. Consistent with previous studies in nude mice, cell lines with CD44+/CD24- subpopulation were more invasive than other cell lines. However, only a subset of CD44+/CD24--positive cell lines was able to home and proliferate in lungs. Breast cancer cells with CD44+/CD24- subpopulation express higher levels of proinvasive genes and have highly invasive properties. However, this phenotype is not sufficient to predict capacity for pulmonary metastasis.

Journal ArticleDOI
TL;DR: In countries with a weak legal system and a high level of corruption, it has been shown that political connections are valuable to a corporation as mentioned in this paper, which is also true in the U.S., which has well-developed financial markets as well as a strong legal system.
Abstract: In countries with a weak legal system and a high level of corruption it has been shown that political connections are valuable to a corporation. This paper explores whether political connections are also important in the U.S., which has well-developed financial markets as well as a strong legal system. The paper uses an original hand-collected data set on the political connections of board members of S&P 500 companies to sort companies into those connected to the Republican Party and those connected to the Democratic Party. An analysis of the stock price response to the announcement of the board nomination of a politically connected director shows a positive abnormal stock return. The paper also analyses the stock price response to the Republican win in the 2000 Presidential Election and finds that companies connected to the Republican Party increase in value while companies connected to the Democratic Party decrease in value. The results further suggest that these effects are more pronounced for larger corporations. Finally, the paper controls for political donations by corporations prior to the 2000 election and finds that, unlike board connections, donations do not predict industry-adjusted abnormal post-election returns.

Journal ArticleDOI
TL;DR: This paper found that organizational change in government agencies has not induced a high volume of articles that explicitly address the topic in public administration journals, but that there are prominent exceptions to this observation (e.g., Bryson and Anderson 2000; Chackerian and Mavima 2000; Mani 1995; Wise 2002 ).
Abstract: C an governmental organizations change? Reform initiatives have swept through governments in the United States and overseas, again and again bringing news about eff orts to reinvent, transform, or reform government agencies ( Barzelay 2001; Kettl 2000; Pollitt and Bouckaert 2000; Stillman 1999 ). Curiously, however, this recurrent theme of change in government agencies has not induced a high volume of articles that explicitly address the topic in public administration journals. # ere are prominent exceptions to this observation (e.g., Bryson and Anderson 2000; Chackerian and Mavima 2000; Mani 1995; Wise 2002 ) and journal articles about topics related to organizational change (e.g., Berman and Wang 2000; Brudney and Wright 2002; Hood and Peters 2004 ). Articles reporting research and theory with titles containing “ organizational change ” and with that theme as a focal topic, however, appear with much less regularity in public administration journals than in research journals focusing on general management and organization theory.

Journal ArticleDOI
TL;DR: The presented analysis enables the measurement of the rich-club ordering and its relation with the function and dynamics of networks in examples drawn from the biological, social and technological domains.
Abstract: Uncovering the hidden regularities and organizational principles of networks arising in physical systems ranging from the molecular level to the scale of large communication infrastructures is the key issue in understanding their fabric and dynamical properties1,2,3,4,5. The ‘rich-club’ phenomenon refers to the tendency of nodes with high centrality, the dominant elements of the system, to form tightly interconnected communities, and it is one of the crucial properties accounting for the formation of dominant communities in both computer and social sciences4,5,6,7,8. Here, we provide the analytical expression and the correct null models that allow for a quantitative discussion of the rich-club phenomenon. The presented analysis enables the measurement of the rich-club ordering and its relation with the function and dynamics of networks in examples drawn from the biological, social and technological domains.

Journal ArticleDOI
TL;DR: A review of the literature on collaborative public management by synthesizing what we know from recent research and what we’ve known for quite some time is presented in this article, which addresses the prevalence of collaboration, the components of emerging collaborative structures, the types of skills that are unique to collaborative management, and the effects of collaboration.
Abstract: Collaborative public management research is flourishing. A great deal of attention is being paid to the process and impact of collaboration in the public sector, and the results are promising. This article reviews the literature on collaborative public management by synthesizing what we know from recent research and what we’ve known for quite some time. It addresses the prevalence of collaboration (both recently and historically), the components of emerging collaborative structures, the types of skills that are unique to collaborative management, and the effects of collaboration. Collaborative public management research offers a set of findings that contribute to an emerging knowledge base that supplements established public management theory.

Journal ArticleDOI
TL;DR: A novel transgenic mouse model on a C57BL/6J genetic background that coexpresses KM670/671NL mutated amyloid precursor protein and L166P mutated presenilin 1 under the control of a neuron‐specific Thy1 promoter element (APPPS1 mice) is generated, well suited for studying therapeutic strategies and the pathomechanism of amyloidsosis by cross‐breeding to other genetically engineered mouse models.
Abstract: We have generated a novel transgenic mouse model on a C57BL/6J genetic background that coexpresses KM670/671NL mutated amyloid precursor protein and L166P mutated presenilin 1 under the control of a neuron-specific Thy1 promoter element (APPPS1 mice). Cerebral amyloidosis starts at 6–8 weeks and the ratio of human amyloid (A)β42 to Aβ40 is 1.5 and 5 in pre-depositing and amyloid-depositing mice, respectively. Consistent with this ratio, extensive congophilic parenchymal amyloid but minimal amyloid angiopathy is observed. Amyloid-associated pathologies include dystrophic synaptic boutons, hyperphosphorylated tau-positive neuritic structures and robust gliosis, with neocortical microglia number increasing threefold from 1 to 8 months of age. Global neocortical neuron loss is not apparent up to 8 months of age, but local neuron loss in the dentate gyrus is observed. Because of the early onset of amyloid lesions, the defined genetic background of the model and the facile breeding characteristics, APPPS1 mice are well suited for studying therapeutic strategies and the pathomechanism of amyloidosis by cross-breeding to other genetically engineered mouse models.

Journal ArticleDOI
TL;DR: The VSL2 predictors are applicable to disordered regions of any length and can accurately identify the short dis ordered regions that are often misclassified by the previous disorder predictors.
Abstract: Due to the functional importance of intrinsically disordered proteins or protein regions, prediction of intrinsic protein disorder from amino acid sequence has become an area of active research as witnessed in the 6th experiment on Critical Assessment of Techniques for Protein Structure Prediction (CASP6). Since the initial work by Romero et al. (Identifying disordered regions in proteins from amino acid sequences, IEEE Int. Conf. Neural Netw., 1997), our group has developed several predictors optimized for long disordered regions (>30 residues) with prediction accuracy exceeding 85%. However, these predictors are less successful on short disordered regions (≤30 residues). A probable cause is a length-dependent amino acid compositions and sequence properties of disordered regions. We proposed two new predictor models, VSL2-M1 and VSL2-M2, to address this length-dependency problem in prediction of intrinsic protein disorder. These two predictors are similar to the original VSL1 predictor used in the CASP6 experiment. In both models, two specialized predictors were first built and optimized for short (≤30 residues) and long disordered regions (>30 residues), respectively. A meta predictor was then trained to integrate the specialized predictors into the final predictor model. As the 10-fold cross-validation results showed, the VSL2 predictors achieved well-balanced prediction accuracies of 81% on both short and long disordered regions. Comparisons over the VSL2 training dataset via 10-fold cross-validation and a blind-test set of unrelated recent PDB chains indicated that VSL2 predictors were significantly more accurate than several existing predictors of intrinsic protein disorder. The VSL2 predictors are applicable to disordered regions of any length and can accurately identify the short disordered regions that are often misclassified by our previous disorder predictors. The success of the VSL2 predictors further confirmed the previously observed differences in amino acid compositions and sequence properties between short and long disordered regions, and justified our approaches for modelling short and long disordered regions separately. The VSL2 predictors are freely accessible for non-commercial use at http://www.ist.temple.edu/disprot/predictorVSL2.php

Journal ArticleDOI
07 Dec 2006-Nature
TL;DR: High-resolution carbon isotope and sulphur isotope records from the Huqf Supergroup, Sultanate of Oman, that cover most of the Ediacaran period indicate that the ocean became increasingly oxygenated after the end of the Marinoan glaciation and allow us to identify three distinct stages of oxidation.
Abstract: Oxygenation of the Earth's surface is thought to have occurred in two main steps. The first, about 2,300 million years ago, saw a significant increase in atmospheric and surface ocean oxygen levels and has been widely studied. Much less is known about the second step, which took place around 800–540 million years ago and appears to have been associated with the evolution of complex animals. Now carbon and sulphur isotope records from sediments in the Sultanate of Oman have been used to construct a record of the amount of oxygen in the ocean during the Ediacaran period (635–542 million years ago). The data suggest that there were three distinct stages of oxidation within this period: the second stage involved an increase in oxygen in the deep ocean and appears to have been associated with the evolution of complex animals. Reconstruction of the amount of oxygen in the ocean during the Ediacaran period using carbon- and sulphur-isotope records identifies three distinct stages of oxidation over this interval. Complex animals may have evolved during the second stage, indicating that this event may have played a key role in the evolution of eukaryotic organisms. Oxygenation of the Earth’s surface is increasingly thought to have occurred in two steps. The first step, which occurred ∼2,300 million years (Myr) ago, involved a significant increase in atmospheric oxygen concentrations and oxygenation of the surface ocean1,2. A further increase in atmospheric oxygen appears to have taken place during the late Neoproterozoic period3,4 (∼800–542 Myr ago). This increase may have stimulated the evolution of macroscopic multicellular animals and the subsequent radiation of calcified invertebrates4,5, and may have led to oxygenation of the deep ocean6. However, the nature and timing of Neoproterozoic oxidation remain uncertain. Here we present high-resolution carbon isotope and sulphur isotope records from the Huqf Supergroup, Sultanate of Oman, that cover most of the Ediacaran period (∼635 to ∼548 Myr ago). These records indicate that the ocean became increasingly oxygenated after the end of the Marinoan glaciation, and they allow us to identify three distinct stages of oxidation. When considered in the context of other records from this period7,8,9,10,11,12,13,14,15, our data indicate that certain groups of eukaryotic organisms appeared and diversified during the second and third stages of oxygenation. The second stage corresponds with the Shuram excursion in the carbon isotope record16 and seems to have involved the oxidation of a large reservoir of organic carbon suspended in the deep ocean6, indicating that this event may have had a key role in the evolution of eukaryotic organisms. Our data thus provide new insights into the oxygenation of the Ediacaran ocean and the stepwise restructuring of the carbon6,16,17 and sulphur cycles3,18,19 that occurred during this significant period of Earth’s history.

Journal ArticleDOI
TL;DR: In this paper, the effects of globalization on the resilience, vulnerability, and adaptability of coupled human-environment systems (SESs) have been discussed, and the authors argue that socioeconomic resilience regularly substitutes for biophysical resilience in SESs with consequences that are often unforeseen.
Abstract: We argue that globalization is a central feature of coupled human–environment systems or, as we call them, socio-ecological systems (SESs). In this article, we focus on the effects of globalization on the resilience, vulnerability, and adaptability of these systems. We begin with a brief discussion of key terms, arguing that socio-economic resilience regularly substitutes for biophysical resilience in SESs with consequences that are often unforeseen. A discussion of several mega-trends (e.g. the rise of mega-cities, the demand for hydrocarbons, the revolution in information technologies) underpins our argument. We then proceed to identify key analytical dimensions of globalization, including rising connectedness, increased speed, spatial stretching, and declining diversity. We show how each of these phenomena can cut both ways in terms of impacts on the resilience and vulnerability of SESs. A particularly important insight flowing from this analysis centers on the reversal of the usual conditions in which large-scale things are slow and durable while small-scale things are fast and ephemeral. The fact that SESs are reflexive can lead either to initiatives aimed at avoiding or mitigating the dangers of globalization or to positive feedback processes that intensify the impacts of globalization. In the concluding section, we argue for sustained empirical research regarding these concerns and make suggestions about ways to enhance the incentives for individual researchers to work on these matters.


Journal ArticleDOI
TL;DR: It is concluded that species introductions generally alter plants' interactions with enemies, mutualists and competitors, and that there is increasing evidence that these altered interactions jointly influence the success of introduced populations.
Abstract: Introduced plant populations lose interactions with enemies, mutualists and competitors from their native ranges, and gain interactions with new species, under new abiotic conditions. From a biogeographical perspective, differences in the assemblage of interacting species, as well as in abiotic conditions, may explain the demographic success of the introduced plant populations relative to conspecifics in their native range. Within invaded communities, the new interactions and conditions experienced by the invader may influence both its demographic success and its effects on native biodiversity. Here, we examine indirect effects involving enemies, mutualists and competitors of introduced plants, and effects of abiotic conditions on biotic interactions. We then synthesize ideas building on Darwin’s idea that the kinds of new interactions gained by an introduced population will depend on its relatedness to native populations. This yields a heuristic framework to explain how biotic interactions and abiotic conditions influence invader success. We conclude that species introductions generally alter plants interactions with enemies, mutualists and competitors, and that there is increasing evidence that these altered interactions jointly influence the success of introduced populations. Ecology Letters (2006) 9: 726‐740

Journal ArticleDOI
10 May 2006-JAMA
TL;DR: In this article, the authors evaluated the effectiveness of a collaborative care model to improve the quality of care for patients with Alzheimer disease and found that the intervention patients were more likely to receive cholinesterase inhibitors (79.8% vs 55.1%) and antidepressants (45.2% vs 27.5%).
Abstract: ContextMost older adults with dementia will be cared for by primary care physicians, but the primary care practice environment presents important challenges to providing quality care.ObjectiveTo test the effectiveness of a collaborative care model to improve the quality of care for patients with Alzheimer disease.Design, Setting, and PatientsControlled clinical trial of 153 older adults with Alzheimer disease and their caregivers who were randomized by physician to receive collaborative care management (n = 84) or augmented usual care (n = 69) at primary care practices within 2 US university-affiliated health care systems from January 2002 through August 2004. Eligible patients (identified via screening or medical record) met diagnostic criteria for Alzheimer disease and had a self-identified caregiver.InterventionIntervention patients received 1 year of care management by an interdisciplinary team led by an advanced practice nurse working with the patient's family caregiver and integrated within primary care. The team used standard protocols to initiate treatment and identify, monitor, and treat behavioral and psychological symptoms of dementia, stressing nonpharmacological management.Main Outcome MeasuresNeuropsychiatric Inventory (NPI) administered at baseline and at 6, 12, and 18 months. Secondary outcomes included the Cornell Scale for Depression in Dementia (CSDD), cognition, activities of daily living, resource use, and caregiver's depression severity.ResultsInitiated by caregivers' reports, 89% of intervention patients triggered at least 1 protocol for behavioral and psychological symptoms of dementia with a mean of 4 per patient from a total of 8 possible protocols. Intervention patients were more likely to receive cholinesterase inhibitors (79.8% vs 55.1%; P = .002) and antidepressants (45.2% vs 27.5%; P = .03). Intervention patients had significantly fewer behavioral and psychological symptoms of dementia as measured by the total NPI score at 12 months (mean difference, −5.6; P = .01) and at 18 months (mean difference, −5.4; P = .01). Intervention caregivers also reported significant improvements in distress as measured by the caregiver NPI at 12 months; at 18 months, caregivers showed improvement in depression as measured by the Patient Health Questionnaire-9. No group differences were found on the CSDD, cognition, activities of daily living, or on rates of hospitalization, nursing home placement, or death.ConclusionsCollaborative care for the treatment of Alzheimer disease resulted in significant improvement in the quality of care and in behavioral and psychological symptoms of dementia among primary care patients and their caregivers. These improvements were achieved without significantly increasing the use of antipsychotics or sedative-hypnotics.Trial Registrationclinicaltrials.gov Identifier: NCT00246896

Journal ArticleDOI
TL;DR: In this article, the requirements for reactive oxygen species (ROS) generation in epithelial cells were delineated and structural requirements for ROS generation by Nox4 were identified. But, they did not identify the protein p22phox on internal membranes, where ROS generation occurs.