Research papers

Click Chemistry: Diverse Chemical Function from a Few Good Reactions

Hartmuth C. Kolb, M. G. Finn, K. Barry Sharpless

Examination of nature's favorite molecules reveals a striking preference for making carbon–heteroatom bonds over carbon–carbon bonds—surely no surprise given that carbon dioxide is nature's starting material and that most reactions are performed in water. Nucleic acids, proteins, and polysaccharides are condensation polymers of small subunits stitched together by carbon–heteroatom bonds. Even the 35 or so building blocks from which these crucial molecules are made each contain, at most, six contiguous C−C bonds, except for the three aromatic amino acids. Taking our cue from nature's approach, we address here the development of a set of powerful, highly reliable, and selective reactions for the rapid synthesis of useful new compounds and combinatorial libraries through heteroatom links (C−X−C), an approach we call “click chemistry”. Click chemistry is at once defined, enabled, and constrained by a handful of nearly perfect “spring-loaded” reactions. The stringent criteria for a process to earn click chemistry status are described along with examples of the molecular frameworks that are easily made using this spartan, but powerful, synthetic strategy.

Hydrogels for Tissue Engineering

Kuen Yong Lee, David Mooney

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTHydrogels for Tissue EngineeringKuen Yong Lee and David J. MooneyView Author Information Departments of Biologic & Materials Sciences, Chemical Engineering, and Biomedical Engineering, University of Michigan, Ann Arbor, Michigan 48109 Cite this: Chem. Rev. 2001, 101, 7, 1869–1880Publication Date (Web):May 31, 2001Publication History Received15 November 2000Published online31 May 2001Published inissue 1 July 2001https://pubs.acs.org/doi/10.1021/cr000108xhttps://doi.org/10.1021/cr000108xresearch-articleACS PublicationsCopyright © 2001 American Chemical SocietyRequest reuse permissionsArticle Views48495Altmetric-Citations4364LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose SUBJECTS:Anatomy,Biopolymers,Hydrogels,Peptides and proteins,Regenerative medicine Get e-Alerts

Modeling the Shape of the Scene: A Holistic Representation of the Spatial Envelope

Aude Oliva, Antonio Torralba

A new mathematical model for relative quantification in real-time RT-PCR

Michael W. Pfaffl

Use of the real-time polymerase chain reaction (PCR) to amplify cDNA products reverse transcribed from mRNA is on the way to becoming a routine tool in molecular biology to study low abundance gene expression. Real-time PCR is easy to perform, provides the necessary accuracy and produces reliable as well as rapid quantification results. But accurate quantification of nucleic acids requires a reproducible methodology and an adequate mathematical model for data analysis. This study enters into the particular topics of the relative quantification in real-time RT-PCR of a target gene transcript in comparison to a reference gene transcript. Therefore, a new mathematical model is presented. The relative expression ratio is calculated only from the real-time PCR efficiencies and the crossing point deviation of an unknown sample versus a control. This model needs no calibration curve. Control levels were included in the model to standardise each reaction run with respect to RNA integrity, sample loading and inter-PCR variations. High accuracy and reproducibility (<2.5% variation) were reached in LightCycler PCR using the established mathematical model.

Sustainability Science

Robert W. Kates, William C. Clark, Robert W. Corell, Jermaine Hall, Carlo Jaeger, Ian Lowe, James J. McCarthy, Hans Joachim …

Meeting fundamental human needs while preserving Earth's life support systems will require an accelerated transition toward sustainability. A new field of sustainability science is emerging that seeks to understand the fundamental character of interactions between nature and society and to encourage those interactions along more sustainable trajectories. Such an integrated, place-based science will require new research strategies and institutional innovations to enable them especially in developing countries still separated by deepening divides from mainstream science. Sustainability science needs to be widely discussed in the scientific community, reconnected to the political agenda for sustainable development, and become a major focus for research.

Chemistry with ADF

G. te Velde, F. Matthias Bickelhaupt, Evert Jan Baerends, Célia Fonseca Guerra, S. J. A. van Gisbergen, J. G. Snijders, Tom …

Abstract We present the theoretical and technical foundations of the Amsterdam Density Functional (ADF) program with a survey of the characteristics of the code (numerical integration, density fitting for the Coulomb potential, and STO basis functions). Recent developments enhance the efficiency of ADF (e.g., parallelization, near order‐N scaling, QM/MM) and its functionality (e.g., NMR chemical shifts, COSMO solvent effects, ZORA relativistic method, excitation energies, frequency‐dependent (hyper)polarizabilities, atomic VDD charges). In the Applications section we discuss the physical model of the electronic structure and the chemical bond, i.e., the Kohn–Sham molecular orbital (MO) theory, and illustrate the power of the Kohn–Sham MO model in conjunction with the ADF‐typical fragment approach to quantitatively understand and predict chemical phenomena. We review the “Activation‐strain TS interaction” (ATS) model of chemical reactivity as a conceptual framework for understanding how activation barriers of various types of (competing) reaction mechanisms arise and how they may be controlled, for example, in organic chemistry or homogeneous catalysis. Finally, we include a brief discussion of exemplary applications in the field of biochemistry (structure and bonding of DNA) and of time‐dependent density functional theory (TDDFT) to indicate how this development further reinforces the ADF tools for the analysis of chemical phenomena. © 2001 John Wiley &amp; Sons, Inc. J Comput Chem 22: 931–967, 2001

Coupling an Advanced Land Surface–Hydrology Model with the Penn State–NCAR MM5 Modeling System. Part I: Model Implementation and Sensitivity

Fei Chen, Jimy Dudhia

This paper addresses and documents a number of issues related to the implementation of an advanced land surface–hydrology model in the Penn State–NCAR fifth-generation Mesoscale Model (MM5). The concept adopted here is that the land surface model should be able to provide not only reasonable diurnal variations of surface heat fluxes as surface boundary conditions for coupled models, but also correct seasonal evolutions of soil moisture in the context of a long-term data assimilation system. In a similar way to that in which the modified Oregon State University land surface model (LSM) has been used in the NCEP global and regional forecast models, it is implemented in MM5 to facilitate the initialization of soil moisture. Also, 1-km resolution vegetation and soil texture maps are introduced in the coupled MM5–LSM system to help identify vegetation/water/soil characteristics at fine scales and capture the feedback of these land surface forcings. A monthly varying climatological 0.15° × 0.15° green vegetation fraction is utilized to represent the annual control of vegetation on the surface evaporation. Specification of various vegetation and soil parameters is discussed, and the available water capacity in the LSM is extended to account for subgrid-scale heterogeneity. The coupling of the LSM to MM5 is also sensitive to the treatment of the surface layer, especially the calculation of the roughness length for heat/moisture. Including the effect of the molecular sublayer can improve the simulation of surface heat flux. It is shown that the soil thermal and hydraulic conductivities and the surface energy balance are very sensitive to soil moisture changes. Hence, it is necessary to establish an appropriate soil moisture data assimilation system to improve the soil moisture initialization at fine scales.

Progress in invasion biology: predicting invaders

Cynthia S. Kolar, David M. Lodge

High-energy-physics event generation with Pythia 6.1

Torbjörn Sjöstrand, P. Edén, Christer Friberg, Leif Lönnblad, Gabriela Miu, S. Mrenna, E. Norrbin

Frailty in Older Adults: Evidence for a Phenotype

Linda P. Fried, Catherine M. Tangen, Jeremy Walston, Anne B. Newman, Calvin H. Hirsch, John S. Gottdiener, Teresa E. Seeman,…

BACKGROUND: Frailty is considered highly prevalent in old age and to confer high risk for falls, disability, hospitalization, and mortality. Frailty has been considered synonymous with disability, comorbidity, and other characteristics, but it is recognized that it may have a biologic basis and be a distinct clinical syndrome. A standardized definition has not yet been established. METHODS: To develop and operationalize a phenotype of frailty in older adults and assess concurrent and predictive validity, the study used data from the Cardiovascular Health Study. Participants were 5,317 men and women 65 years and older (4,735 from an original cohort recruited in 1989-90 and 582 from an African American cohort recruited in 1992-93). Both cohorts received almost identical baseline evaluations and 7 and 4 years of follow-up, respectively, with annual examinations and surveillance for outcomes including incident disease, hospitalization, falls, disability, and mortality. RESULTS: Frailty was defined as a clinical syndrome in which three or more of the following criteria were present: unintentional weight loss (10 lbs in past year), self-reported exhaustion, weakness (grip strength), slow walking speed, and low physical activity. The overall prevalence of frailty in this community-dwelling population was 6.9%; it increased with age and was greater in women than men. Four-year incidence was 7.2%. Frailty was associated with being African American, having lower education and income, poorer health, and having higher rates of comorbid chronic diseases and disability. There was overlap, but not concordance, in the cooccurrence of frailty, comorbidity, and disability. This frailty phenotype was independently predictive (over 3 years) of incident falls, worsening mobility or ADL disability, hospitalization, and death, with hazard ratios ranging from 1.82 to 4.46, unadjusted, and 1.29-2.24, adjusted for a number of health, disease, and social characteristics predictive of 5-year mortality. Intermediate frailty status, as indicated by the presence of one or two criteria, showed intermediate risk of these outcomes as well as increased risk of becoming frail over 3-4 years of follow-up (odds ratios for incident frailty = 4.51 unadjusted and 2.63 adjusted for covariates, compared to those with no frailty criteria at baseline). CONCLUSIONS: This study provides a potential standardized definition for frailty in community-dwelling older adults and offers concurrent and predictive validity for the definition. It also finds that there is an intermediate stage identifying those at high risk of frailty. Finally, it provides evidence that frailty is not synonymous with either comorbidity or disability, but comorbidity is an etiologic risk factor for, and disability is an outcome of, frailty. This provides a potential basis for clinical assessment for those who are frail or at risk, and for future research to develop interventions for frailty based on a standardized ascertainment of frailty.

The Five Factor Model and impulsivity: using a structural model of personality to understand impulsivity

Stephen P. Whiteside, Donald R. Lynam

Computational modelling of visual attention

Laurent Itti, Christof Koch

Regression Modeling Strategies

Frank E. Harrell

PAST: PALEONTOLOGICAL STATISTICAL SOFTWARE PACKAGE FOR EDUCATION AND DATA ANALYSIS

Øyvind Hammer, David A. T. Harper, Paul D. Ryan

A comprehensive, but simple-to-use software package for executing a range of standard numerical analysis and operations used in quantitative paleontology has been developed. The program, called PAST (PAleontological STatistics), runs on standard Windows computers and is available free of charge. PAST integrates spreadsheet-type data entry with univariate and multivariate statistics, curve fitting, timeseries analysis, data plotting, and simple phylogenetic analysis. Many of the functions are specific to paleontology and ecology, and these functions are not found in standard, more extensive, statistical packages. PAST also includes fourteen case studies (data files and exercises) illustrating use of the program for paleontological problems, making it a complete educational package for courses in quantitative methods.

Structural equation modeling with AMOS: basic concepts, applications, and programming

Barbara M. Byrne

Contents: Part I: Introduction. Structural Equation Models: The Basics. Using the EQS Program. Part II: Single-Group Analyses. Application 1: Testing for the Factorial Validity of a Theoretical Construct (First-Order CFA Model). Application 2: Testing for the Factorial Validity of Scores From a Measuring Instrument (First-Order CFA Model). Application 3: Testing for the Factorial Validity of Scores from a Measuring Instrument (Second-Order CFA Model). Application 4: Testing for the Validity of a Causal Structure. Part III: Multiple-Group Analyses. Application 5: Testing for the Factorial Invariance of a Measuring Instrument. Application 6: Testing for the Invariance of a Causal Structure. Application 7: Testing for Latent Mean Differences (First-Order CFA Model). Application 8: Testing for Latent Mean Differences (Second-Order CFA Model). Part IV: Other Important Topics. Application 9: Testing for Construct Validity: The Multitrait-Multimethod Model. Application 10: Testing for Change Over Time: The Latent Growth Curve Model. Application 11: Testing for Within- and Between-Level Variance: The Multilevel Model.

Oxidants, oxidative stress and the biology of ageing

Toren Finkel, Nikki J. Holbrook

The "What" and "Why" of Goal Pursuits: Human Needs and the Self-Determination of Behavior

Edward L. Deci, Richard M. Ryan

Self-determination theory (SDT) maintains that an understanding of human motivation requires a consideration of innate psychological needs for competence, autonomy, and relatedness. We discuss the SDT concept of needs as it relates to previous need theories, emphasizing that needs specify the necessary conditions for psychological growth, integrity, and well-being. This concept of needs leads to the hypotheses that different regulatory processes underlying goal pursuits are differentially associated with effective functioning and well-being and also that different goal contents have different relations to the quality of behavior and mental health, specifically because different regulatory processes and different goal contents are associated with differing degrees of need satisfaction. Social contexts and individual differences that support satisfaction of the basic needs facilitate natural growth processes including intrinsically motivated behavior and integration of extrinsic motivations, whereas those that forestall autonomy, competence, or relatedness are associated with poorer motivation, performance, and well-being. We also discuss the relation of the psychological needs to cultural values, evolutionary processes, and other contemporary motivation theories.

The Biology of Soft Shores and Estuaries

Alec Brown

"The Biology of Soft Shores and Estuaries." African Zoology, 35(2), pp. 302–303

Oxford Advanced Learner's Dictionary of Current English.

Albert Sydney Hornby

Oxford advanced learner's dictionary of current English , Oxford advanced learner's dictionary of current English , مرکز فناوری اطلاعات و اطلاع رسانی کشاورزی

Climate Extremes: Observations, Modeling, and Impacts

David R. Easterling, Gerald A. Meehl, Camille Parmesan, Stanley A. Changnon, Thomas R. Karl, Linda O. Mearns

One of the major concerns with a potential change in climate is that an increase in extreme events will occur. Results of observational studies suggest that in many areas that have been analyzed, changes in total precipitation are amplified at the tails, and changes in some temperature extremes have been observed. Model output has been analyzed that shows changes in extreme events for future climates, such as increases in extreme high temperatures, decreases in extreme low temperatures, and increases in intense precipitation events. In addition, the societal infrastructure is becoming more sensitive to weather and climate extremes, which would be exacerbated by climate change. In wild plants and animals, climate-induced extinctions, distributional and phenological changes, and species' range shifts are being documented at an increasing rate. Several apparently gradual biological changes are linked to responses to extreme weather and climate events.

Marginal Structural Models and Causal Inference in Epidemiology

James M. Robins, Miguel A. Hernán, Babette Brumback

In observational studies with exposures or treatments that vary over time, standard approaches for adjustment of confounding are biased when there exist time-dependent confounders that are also affected by previous treatment. This paper introduces marginal structural models, a new class of causal models that allow for improved adjustment of confounding in those situations. The parameters of a marginal structural model can be consistently estimated using a new class of estimators, the inverse-probability-of-treatment weighted estimators.

Competing models of entrepreneurial intentions

Norris Krueger, Michael D. Reilly, Alan L. Carsrud

Multiagent Systems : A Modern Approach to Distributed Artificial Intelligence

Gerhard Weiß

From the Publisher: This is the first comprehensive introduction to multiagent systems and contemporary distributed artificial intelligence. The book provides detailed coverage of basic topics as well as several closely related ones and is suitable as a textbook. The book can be used for teaching as well as self-study, and it is designed to meet the needs of both researchers and practitioners. In view of the interdisciplinary nature of the field, it will be a useful reference not only for computer scientists and engineers, but for social scientists and management and organization scientists as well.

Constrained model predictive control: Stability and optimality

D.Q. Mayne, James B. Rawlings, Christopher V. Rao, P.O.M. Scokaert