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Showing papers by "University of Rochester published in 2004"


Journal ArticleDOI
TL;DR: The Infrared Array Camera (IRAC) is one of three focal plane instruments on the Spitzer Space Telescope as mentioned in this paper, which is a four-channel camera that obtains simultaneous broadband images at 3.6, 4.5, 5.8, and 8.0 m.
Abstract: The Infrared Array Camera (IRAC) is one of three focal plane instruments on the Spitzer Space Telescope. IRAC is a four-channel camera that obtains simultaneous broadband images at 3.6, 4.5, 5.8, and 8.0 � m. Two nearly adjacent 5A2 ; 5A2 fields of view in the focal plane are viewed by the four channels in pairs (3.6 and 5.8 � m; 4.5 and 8 � m). All four detector arrays in the camera are 256 ; 256 pixels in size, with the two shorter wavelength channels using InSb and the two longer wavelength channels using Si:As IBC detectors. IRAC is a powerful survey instrument because of its high sensitivity, large field of view, and four-color imaging. This paper summarizes the in-flight scientific, technical, and operational performance of IRAC.

3,567 citations


Journal Article
TL;DR: The second revision of the ILAR Taskforce on Classification of Childhood Arthritis (ILAR-JIA) was presented at the 2001 ILAR Workshop on Rheumatology as discussed by the authors.
Abstract: The primary aim of the International League of Associations for Rheumatology (ILAR) proposals for classification of juvenile idiopathic arthritis (JIA) is to delineate, for research purposes, relatively homogeneous, mutually exclusive categories of idiopathic childhood arthritis based on predominant clinical and laboratory features. As part of a continuing review process, the ILAR Taskforce on Classification of Childhood Arthritis met in Edmonton in 2001 to discuss modifications to the proposed JIA classification. Since the publication of the first revision of the original classification 1 , a number of descriptive studies using the new classification have been reported 2-11. The aims of this communication are 2-fold: to outline modifications to the revised classification proposed as a result of the Edmonton meeting, and to correct misconceptions highlighted by the published studies concerning the clinical use of the classification. The Edmonton Revision The changes embodied in the second revision of the classification are as follows: 1. Clarification of the definitions of each category. 2. Improvement in the congruity between inclusion and exclusion criteria. 3. Removal of the requirement that a dermatologist make the diagnosis of psoriasis. 4. Removal of the requirement that there be medical confirmation of HLA-B27 associated disease in a relative. 5. Reduction in the age for criterion " 3 " of enthesitis related arthritis, and exclusion " b " from 8 years to 6 years of age. 6. Improvement in the consistency of the structure. The impracticality of the requirement that a diagnosis of psoriasis be made by a dermatologist was recognized, and this requirement was modified so that the diagnosis of psori-asis could be made by a physician (not necessarily a dermatologist). Similarly, it is no longer required that there be medical confirmation of an HLA-B27 associated disease in a relative as contained in exclusion " c. " It is evident that it is very difficult to obtain a reliable history of psoriasis or an HLA-B27 associated disease in a second-degree relative. Therefore, a history of importance to the application of the criteria is restricted to the patient or a first-degree relative (parents or siblings) only. The study of Murray, et al 8 indicated that the HLA-B27 association is important in boys over the age of 6 years at onset of arthritis, and this age was substituted for 8 years in exclusion " b. " Discrepancies between inclusion and exclusion criteria were resolved, and the exclusions were identified by the letters …

3,201 citations


Journal ArticleDOI
TL;DR: Results reinforce the usefulness of a brief, easy to administer, patient-based index of asthma control.
Abstract: Background Asthma guidelines indicate that the goal of treatment should be optimum asthma control In a busy clinic practice with limited time and resources, there is need for a simple method for assessing asthma control with or without lung function testing Objectives The objective of this article was to describe the development of the Asthma Control Test (ACT), a patient-based tool for identifying patients with poorly controlled asthma Methods A 22-item survey was administered to 471 patients with asthma in the offices of asthma specialists The specialist's rating of asthma control after spirometry was also collected Stepwise regression methods were used to select a subset of items that showed the greatest discriminant validity in relation to the specialist's rating of asthma control Internal consistency reliability was computed, and discriminant validity tests were conducted for ACT scale scores The performance of ACT was investigated by using logistic regression methods and receiver operating characteristic analyses Results Five items were selected from regression analyses The internal consistency reliability of the 5-item ACT scale was 084 ACT scale scores discriminated between groups of patients differing in the specialist's rating of asthma control (F = 345, P P 1 (F = 43, P = 0052) As a screening tool, the overall agreement between ACT and the specialist's rating ranged from 71% to 78% depending on the cut points used, and the area under the receiver operating characteristic curve was 077 Conclusion Results reinforce the usefulness of a brief, easy to administer, patient-based index of asthma control

2,400 citations


Journal ArticleDOI
TL;DR: The study concludes that the central nervous system (CNS) can be targeted by airborne solid ultrafine particles and that the most likely mechanism is from deposits on the olfactory mucosa of the nasopharyngeal region of the respiratory tract and subsequent translocation via the Olfactory nerve.
Abstract: Ultrafine particles (UFP, particles <100 nm) are ubiquitous in ambient urban and indoor air from multiple sources and may contribute to adverse respiratory and cardiovascular effects of particulate...

2,237 citations


Journal ArticleDOI
TL;DR: Levitsky et al. as mentioned in this paper developed a framework for studying informal institutions and integrating them into comparative institutional analysis, based on a typology of four patterns of formal-informal institutional interaction: complementary, accommodating, competing, and substitutive.
Abstract: Mainstream comparative research on political institutions focuses primarily on formal rules. Yet in many contexts, informal institutions, ranging from bureaucratic and legislative norms to clientelism and patrimonialism, shape even more strongly political behavior and outcomes. Scholars who fail to consider these informal rules of the game risk missing many of the most important incentives and constraints that underlie political behavior. In this article we develop a framework for studying informal institutions and integrating them into comparative institutional analysis. The framework is based on a typology of four patterns of formal-informal institutional interaction: complementary, accommodating, competing, and substitutive. We then explore two issues largely ignored in the literature on this subject: the reasons and mechanisms behind the emergence of informal institutions, and the nature of their stability and change. Finally, we consider challenges in research on informal institutions, including issues of identification, measurement, and comparison.Gretchen Helmke's book Courts Under Constraints: Judges, Generals, and Presidents in Argentina, will be published by Cambridge University Press. Steven Levitsky is the author of Transforming Labor-Based Parties in Latin America: Argentine Peronism in Comparative Perspective and is currently writing a book on competitive authoritarian regimes in the post–Cold War era. The authors thank the Weatherhead Center for International Affairs at Harvard University and the Kellogg Institute for International Studies at the University of Notre Dame for generously sponsoring conferences on informal institutions. The authors also gratefully acknowledge comments from Jorge Dominguez, Anna Grzymala-Busse, Dennis Galvan, Goran Hyden, Jack Knight, Lisa Martin, Hillel Soifer, Benjamin Smith, Susan Stokes, Maria Victoria Murillo, and Kurt Weyland, as well as three anonymous reviewers and the editors of Perspectives on Politics.

2,220 citations



Journal ArticleDOI
TL;DR: A framework to handle semantic scene classification, where a natural scene may contain multiple objects such that the scene can be described by multiple class labels, is presented and appears to generalize to other classification problems of the same nature.

2,161 citations


Journal ArticleDOI
TL;DR: A major challenge for neuroscientists is to test ideas for how this might be achieved in populations of neurons experimentally, and so determine whether and how neurons code information about sensory uncertainty.

2,067 citations


Journal ArticleDOI
TL;DR: Patients with fistulizing Crohn's disease who have a response to induction therapy with inflIXimab have an increased likelihood of a sustained response over a 54-week period if infliximab treatment is continued every 8 weeks.
Abstract: BACKGROUND: Infliximab, a monoclonal antibody against tumor necrosis factor, is an effective maintenance therapy for patients with Crohn's disease without fistulas. It is not known whether infliximab is an effective maintenance therapy for patients with fistulas. METHODS: We performed a multicenter, double-blind, randomized, placebo-controlled trial to evaluate the efficacy of infliximab maintenance therapy in 306 adult patients with Crohn's disease and one or more draining abdominal or perianal fistulas of at least three months' duration. Patients received 5 mg of infliximab per kilogram of body weight intravenously on weeks 0, 2, and 6. A total of 195 patients who had a response at weeks 10 and 14 and 87 patients who had no response were then randomly assigned to receive placebo or 5 mg of infliximab per kilogram every eight weeks and to be followed to week 54. The primary analysis was the time to the loss of response among patients who had a response at week 14 and underwent randomization. RESULTS: The time to loss of response was significantly longer for patients who received infliximab maintenance therapy than for those who received placebo maintenance (more than 40 weeks vs. 14 weeks, P<0.001). At week 54, 19 percent of patients in the placebo maintenance group had a complete absence of draining fistulas, as compared with 36 percent of patients in the infliximab maintenance group (P=0.009). CONCLUSIONS: Patients with fistulizing Crohn's disease who have a response to induction therapy with infliximab have an increased likelihood of a sustained response over a 54-week period if infliximab treatment is continued every 8 weeks.

2,006 citations


Journal ArticleDOI
TL;DR: A multisite effort by the Treatment Fidelity Workgroup of the National Institutes of Health Behavior Change Consortium to identify treatment fidelity concepts and strategies in health behavior intervention research is described.
Abstract: Treatment fidelity refers to the methodological strategies used to monitor and enhance the reliability and validity of behavioral interventions. This article describes a multisite effort by the Treatment Fidelity Workgroup of the National Institutes of Health Behavior Change Consortium (BCC) to identify treatment fidelity concepts and strategies in health behavior intervention research. The work group reviewed treatment fidelity practices in the research literature, identified techniques used within the BCC, and developed recommendations for incorporating these practices more consistently. The recommendations cover study design, provider training, treatment delivery, treatment receipt, and enactment of treatment skills. Funding agencies, reviewers, and journal editors are encouraged to make treatment fidelity a standard part of the conduct and evaluation of health behavior intervention research.

1,987 citations


Journal ArticleDOI
TL;DR: In patients with severe, nonischemic dilated cardiomyopathy who were treated with ACE inhibitors and beta-blockers, the implantation of a cardioverter-defibrillator significantly reduced the risk of sudden death from arrhythmia and was associated with a nonsignificant reduction in the riskof death from any cause.
Abstract: background Patients with nonischemic dilated cardiomyopathy are at substantial risk for sudden death from cardiac causes. However, the value of prophylactic implantation of an implantable cardioverter–defibrillator (ICD) to prevent sudden death in such patients is unknown. methods We enrolled 458 patients with nonischemic dilated cardiomyopathy, a left ventricular ejection fraction of less than 36 percent, and premature ventricular complexes or nonsustained ventricular tachycardia. A total of 229 patients were randomly assigned to receive standard medical therapy, and 229 to receive standard medical therapy plus a single-chamber ICD. results Patients were followed for a mean (±SD) of 29.0±14.4 months. The mean left ventricular ejection fraction was 21 percent. The vast majority of patients were treated with angiotensin-converting–enzyme (ACE) inhibitors (86 percent) and beta-blockers (85 percent). There were 68 deaths: 28 in the ICD group, as compared with 40 in the standard-therapy group (hazard ratio, 0.65; 95 percent confidence interval, 0.40 to 1.06; P=0.08). The mortality rate at two years was 14.1 percent in the standard-therapy group (annual mortality rate, 7 percent) and 7.9 percent in the ICD group. There were 17 sudden deaths from arrhythmia: 3 in the ICD group, as compared with 14 in the standardtherapy group (hazard ratio, 0.20; 95 percent confidence interval, 0.06 to 0.71; P=0.006). conclusions In patients with severe, nonischemic dilated cardiomyopathy who were treated with ACE inhibitors and beta-blockers, the implantation of a cardioverter–defibrillator significantly reduced the risk of sudden death from arrhythmia and was associated with a nonsignificant reduction in the risk of death from any cause.

Journal ArticleDOI
TL;DR: In this paper, the authors tested a self-determination theory based model in which employees' autonomous causality orientation and their perceptions of their managers' autonomy support independently predicted satisfaction of the employees' intrinsic needs for competence, autonomy, and relatedness, which in turn predicted their performance evaluations and psychological adjustment.
Abstract: Studies in 2 work organizations tested a self-determination theory based model in which employees’ autonomous causality orientation and their perceptions of their managers’ autonomy support independently predicted satisfaction of the employees’ intrinsic needs for competence, autonomy, and relatedness, which in turn predicted their performance evaluations and psychological adjustment. Path analysis indicated that the self-determination theory model fit the data very well and that alternative models did not provide any advantage.


Journal ArticleDOI
TL;DR: The clinical data suggest that levodopa either slows the progression of Parkinson's disease or has a prolonged effect on the symptoms of the disease, and the neuroimaging data suggest either thatlevodopa accelerates the loss of nigrostriatal dopamine nerve terminals or that its pharmacologic effects modify the dopamine transporter.
Abstract: background Despite the known benefit of levodopa in reducing the symptoms of Parkinson’s disease, concern has been expressed that its use might hasten neurodegeneration. This study assessed the effect of levodopa on the rate of progression of Parkinson’s disease. methods In this randomized, double-blind, placebo-controlled trial, we evaluated 361 patients with early Parkinson’s disease who were assigned to receive carbidopa–levodopa at a daily dose of 37.5 and 150 mg, 75 and 300 mg, or 150 and 600 mg, respectively, or a matching placebo for a period of 40 weeks, and then to undergo withdrawal of treatment for 2 weeks. The primary outcome was a change in scores on the Unified Parkinson’s Disease Rating Scale (UPDRS) between baseline and 42 weeks. Neuroimaging studies of 142 subjects were performed at baseline and at week 40 to assess striatal dopamine-transporter density with the use of iodine-123–labeled 2- b -carboxymethoxy3- b -(4-iodophenyl)tropane ([ 123 I] b -CIT) uptake. results The severity of parkinsonism increased more in the placebo group than in all the groups receiving levodopa: the mean difference between the total score on the UPDRS at baseline and at 42 weeks was 7.8 units in the placebo group, 1.9 units in the group receiving levodopa at a dose of 150 mg daily, 1.9 in those receiving 300 mg daily, and i1.4 in those receiving 600 mg daily (P<0.001). In contrast, in a substudy of 116 patients the mean percent decline in the [ 123 I] b -CIT uptake was significantly greater with levodopa than placebo (–6 percent among those receiving levodopa at 150 mg daily, –4 percent in those receiving it at 300 mg daily, and –7.2 percent among those receiving it at 600 mg daily, as compared with –1.4 percent among those receiving placebo; 19 patients with no dopaminergic deficits on the baseline scans were excluded from the analysis) (P=0.036). The subjects receiving the highest dose of levodopa had significantly more dyskinesia, hypertonia, infection, headache, and nausea than those receiving placebo. conclusions The clinical data suggest that levodopa either slows the progression of Parkinson’s disease or has a prolonged effect on the symptoms of the disease. In contrast, the neuroimaging data suggest either that levodopa accelerates the loss of nigrostriatal dopamine nerve terminals or that its pharmacologic effects modify the dopamine transporter. The potential long-term effects of levodopa on Parkinson’s disease remain uncertain.

Journal ArticleDOI
TL;DR: The Infrared Spectrograph (IRS) as discussed by the authors is one of the three science instruments on the Spitzer Space Telescope and is optimized to take full advantage of the very low background in the space environment.
Abstract: The Infrared Spectrograph (IRS) is one of three science instruments on the Spitzer Space Telescope .T he IRS comprises four separate spectrograph modules covering the wavelength range from 5.3 to 38 � m with spectral resolutions, R ¼ k=� k � 90 and 600, and it was optimized to take full advantage of the very low background in the space environment. The IRS is performing at or better than the prelaunch predictions. An autonomous target acquisition capability enables the IRS to locate the mid-infrared centroid of a source, providing the information so that the spacecraft can accurately offset that centroid to a selected slit. This feature is particularly useful when taking spectra of sources with poorly known coordinates. An automated data-reduction pipeline has been developed at the Spitzer Science Center. Subject headingg infrared: general — instrumentation: spectrographs — space vehicles: instruments

Journal ArticleDOI
TL;DR: AR remains important in the development and progression of prostate cancer and the inhibition of AR activity through mechanisms in addition to androgen ablation, such as modulation of signal transduction pathways, may delay prostate cancer progression.
Abstract: The normal development and maintenance of the prostate is dependent on androgen acting through the androgen receptor (AR). AR remains important in the development and progression of prostate cancer. AR expression is maintained throughout prostate cancer progression, and the majority of androgen-independent or hormone refractory prostate cancers express AR. Mutation of AR, especially mutations that result in a relaxation of AR ligand specificity, may contribute to the progression of prostate cancer and the failure of endocrine therapy by allowing AR transcriptional activation in response to antiandrogens or other endogenous hormones. Similarly, alterations in the relative expression of AR coregulators have been found to occur with prostate cancer progression and may contribute to differences in AR ligand specificity or transcriptional activity. Prostate cancer progression is also associated with increased growth factor production and an altered response to growth factors by prostate cancer cells. The kinase signal transduction cascades initiated by mitogenic growth factors modulate the transcriptional activity of AR and the interaction between AR and AR coactivators. The inhibition of AR activity through mechanisms in addition to androgen ablation, such as modulation of signal transduction pathways, may delay prostate cancer progression.

Journal ArticleDOI
TL;DR: It is shown that under the influence of pure vacuum noise two entangled qubits become completely disentangled in a finite-time, and in a specific example the time to be given by ln((2+sqrt[2] / 2) times the usual spontaneous lifetime).
Abstract: We show that under the influence of pure vacuum noise two entangled qubits become completely disentangled in a finite-time, and in a specific example we find the time to be given by ln((2+sqrt[2] / 2) times the usual spontaneous lifetime.

Journal ArticleDOI
TL;DR: A dynamic programming algorithm for prediction of RNA secondary structure has been revised to accommodate folding constraints determined by chemical modification and to include free energy increments for coaxial stacking of helices when they are either adjacent or separated by a single mismatch.
Abstract: A dynamic programming algorithm for prediction of RNA secondary structure has been revised to accommodate folding constraints determined by chemical modification and to include free energy increments for coaxial stacking of helices when they are either adjacent or separated by a single mismatch. Furthermore, free energy parameters are revised to account for recent experimental results for terminal mismatches and hairpin, bulge, internal, and multibranch loops. To demonstrate the applicability of this method, in vivo modification was performed on 5S rRNA in both Escherichia coli and Candida albicans with 1-cyclohexyl-3-(2-morpholinoethyl) carbodiimide metho-p-toluene sulfonate, dimethyl sulfate, and kethoxal. The percentage of known base pairs in the predicted structure increased from 26.3% to 86.8% for the E. coli sequence by using modification constraints. For C. albicans, the accuracy remained 87.5% both with and without modification data. On average, for these sequences and a set of 14 sequences with known secondary structure and chemical modification data taken from the literature, accuracy improves from 67% to 76%. This enhancement primarily reflects improvement for three sequences that are predicted with <40% accuracy on the basis of energetics alone. For these sequences, inclusion of chemical modification constraints improves the average accuracy from 28% to 78%. For the 11 sequences with <6% pseudoknotted base pairs, structures predicted with constraints from chemical modification contain on average 84% of known canonical base pairs.

Journal ArticleDOI
TL;DR: Three field experiments with high school and college students tested the self-determination theory hypotheses that intrinsic (vs. extrinsic) goals and autonomy-supportive learning climates would improve students' learning, performance, and persistence.
Abstract: Three field experiments with high school and college students tested the self-determination theory (E. L. Deci & R. M. Ryan, 2000) hypotheses that intrinsic (vs. extrinsic) goals and autonomy-supportive (vs. controlling) learning climates would improve students' learning, performance, and persistence. The learning of text material or physical exercises was framed in terms of intrinsic (community, personal growth, health) versus extrinsic (money, image) goals, which were presented in an autonomy-supportive versus controlling manner. Analyses of variance confirmed that both experimentally manipulated variables yielded main effects on depth of processing, test performance, and persistence (all ps <.001), and an interaction resulted in synergistically high deep processing and test performance (but not persistence) when both intrinsic goals and autonomy support were present. Effects were significantly mediated by autonomous motivation.

Journal ArticleDOI
TL;DR: The length of survival among patients with follicular lymphoma correlates with the molecular features of nonmalignant immune cells present in the tumor at diagnosis.
Abstract: background Patients with follicular lymphoma may survive for periods of less than 1 year to more than 20 years after diagnosis. We used gene-expression profiles of tumor-biopsy specimens obtained at diagnosis to develop a molecular predictor of the length of survival. methods Gene-expression profiling was performed on 191 biopsy specimens obtained from patients with untreated follicular lymphoma. Supervised methods were used to discover expression patterns associated with the length of survival in a training set of 95 specimens. A molecular predictor of survival was constructed from these genes and validated in an independent test set of 96 specimens. results Individual genes that predicted the length of survival were grouped into gene-expression signatures on the basis of their expression in the training set, and two such signatures were used to construct a survival predictor. The two signatures allowed patients with specimens in the test set to be divided into four quartiles with widely disparate median lengths of survival (13.6, 11.1, 10.8, and 3.9 years), independently of clinical prognostic variables. Flow cytometry showed that these signatures reflected gene expression by nonmalignant tumor-infiltrating immune cells. conclusions The length of survival among patients with follicular lymphoma correlates with the molecular features of nonmalignant immune cells present in the tumor at diagnosis.

Book ChapterDOI
01 Jan 2004
TL;DR: In this paper, both intrinsic motivation and integrated extrinsic motivation can be facilitated in homes, schools, workplace, athletic fields, and clinical settings that are interpersonally supportive, where people's perspectives are acknowledged and they are encouraged to experiment, allowed to try their own solutions to problems, provided with choice and responded to when they initiate.
Abstract: Self-determination in human behavior is based in autonomous motivation, which encompasses both intrinsic motivation and integrated extrinsic motivation . Intrinsic motivation involves doing an activity without the necessity of external prompts or rewards because it is interesting and satisfies the basic psychological needs for competence, autonomy, and relatedness. Extrinsic motivation involves doing an activity because it leads to some separate outcome such as a reward, approval from others, or the avoidance of punishment. Intrinsic motivation is invariantly autonomous, but extrinsic motivation varies in its degree of autonomy. Extrinsic motivation becomes autonomous through the processes of internalization and integration. Both intrinsic motivation and integrated extrinsic motivation can be facilitated in homes, schools, workplace, athletic fields, and clinical settings that are interpersonally supportive—that is, where people's perspectives are acknowledged and they are encouraged to experiment, allowed to try their own solutions to problems, provided with choice, and responded to when they initiate. Under such supportive conditions individuals are more engaged and persistent, perform more effectively, and display higher levels of psychological health and well-being.

Journal ArticleDOI
TL;DR: It is found that single- and double-stranded oligonucleotides have different propensities to adsorb on gold nanoparticles in colloidal solution and this observation is used to design a hybridization assay based on color changes associated with gold aggregation.
Abstract: We find that single- and double-stranded oligonucleotides have different propensities to adsorb on gold nanoparticles in colloidal solution. We use this observation to design a hybridization assay based on color changes associated with gold aggregation. Because the underlying adsorption mechanism is electrostatic, no covalent functionalization of the gold, the probe, or the target DNA is required. Hybridization conditions can be optimized because it is completely separated from the detection step. The assay is complete within 5 min, and <100 femtomoles of target produces color changes observable without instrumentation. Single-base-pair mismatches are easily detected.

Journal ArticleDOI
TL;DR: The value of the biopsychosocial model has not been in the discovery of new scientific laws, as the term “new paradigm” would suggest, but rather in guiding parsimonious application of medical knowledge to the needs of each patient.
Abstract: The biopsychosocial model is both a philosophy of clinical care and a practical clinical guide. Philosophically, it is a way of understanding how suffering, disease, and illness are affected by multiple levels of organization, from the societal to the molecular. At the practical level, it is a way of understanding the patient’s subjective experience as an essential contributor to accurate diagnosis, health outcomes, and humane care. In this article, we defend the biopsychosocial model as a necessary contribution to the scientific clinical method, while suggesting 3 clarifications: (1) the relationship between mental and physical aspects of health is complex—subjective experience depends on but is not reducible to laws of physiology; (2) models of circular causality must be tempered by linear approximations when considering treatment options; and (3) promoting a more participatory clinician-patient relationship is in keeping with current Western cultural tendencies, but may not be universally accepted. We propose a biopsychosocial-oriented clinical practice whose pillars include (1) self-awareness; (2) active cultivation of trust; (3) an emotional style characterized by empathic curiosity; (4) self-calibration as a way to reduce bias; (5) educating the emotions to assist with diagnosis and forming therapeutic relationships; (6) using informed intuition; and (7) communicating clinical evidence to foster dialogue, not just the mechanical application of protocol. In conclusion, the value of the biopsychosocial model has not been in the discovery of new scientific laws, as the term “new paradigm” would suggest, but rather in guiding parsimonious application of medical knowledge to the needs of each patient.

Journal ArticleDOI
TL;DR: The acquisition and loss of mRNA-associated proteins accompanies the transition from the pioneer round to subsequent rounds of translation, and from translational competence to substrate for nonsense-mediated mRNA decay.
Abstract: Studies of nonsense-mediated mRNA decay in mammalian cells have proffered unforeseen insights into changes in mRNA–protein interactions throughout the lifetime of an mRNA. Remarkably, mRNA acquires a complex of proteins at each exon–exon junction during pre-mRNA splicing that influences the subsequent steps of mRNA translation and nonsense-mediated mRNA decay. Complex-loaded mRNA is thought to undergo a pioneer round of translation when still bound by cap-binding proteins CBP80 and CBP20 and poly(A)-binding protein 2. The acquisition and loss of mRNA-associated proteins accompanies the transition from the pioneer round to subsequent rounds of translation, and from translational competence to substrate for nonsense-mediated mRNA decay.

Posted Content
TL;DR: In this article, the authors find that shocks to trend growth rather than transitory fluctuations around a stable trend are the primary source of fluctuations in emerging markets, and the key features of emerging market business cycles are then shown to be consistent with this underlying income process in an otherwise standard equilibrium model.
Abstract: Emerging market business cycles exhibit strongly countercyclical current accounts, consumption volatility that exceeds income volatility, and “sudden stops†in capital inflows. These features contrast with developed small open economies. Nevertheless, we show that a standard model characterizes both types of markets. Motivated by the frequent policy regime switches observed in emerging markets, our premise is that these economies are subject to substantial volatility in trend growth. Our methodology exploits the information in consumption and net exports to identify the persistence of productivity. We find that shocks to trend growth—rather than transitory fluctuations around a stable trend—are the primary source of fluctuations in emerging markets. The key features of emerging market business cycles are then shown to be consistent with this underlying income process in an otherwise standard equilibrium model.

Journal ArticleDOI
Gary A. Churchill, David C. Airey1, Hooman Allayee2, Joe M. Angel3, Alan D. Attie4, Jackson Beatty5, Willam D. Beavis6, John K. Belknap7, Beth Bennett8, Wade H. Berrettini9, André Bleich10, Molly A. Bogue, Karl W. Broman11, Kari J. Buck12, Edward S. Buckler13, Margit Burmeister14, Elissa J. Chesler15, James M. Cheverud16, Steven J. Clapcote17, Melloni N. Cook18, Roger D. Cox19, John C. Crabbe12, Wim E. Crusio20, Ariel Darvasi21, Christian F. Deschepper22, Rebecca W. Doerge23, Charles R. Farber24, Jiri Forejt25, Daniel Gaile26, Steven J. Garlow27, Hartmut Geiger28, Howard K. Gershenfeld29, Terry Gordon30, Jing Gu15, Weikuan Gu15, Gerald de Haan31, Nancy L. Hayes32, Craig Heller33, Heinz Himmelbauer34, Robert Hitzemann12, Kent W. Hunter35, Hui-Chen Hsu36, Fuad A. Iraqi37, Boris Ivandic38, Howard J. Jacob39, Ritsert C. Jansen31, Karl J. Jepsen40, Dabney K. Johnson41, Thomas E. Johnson8, Gerd Kempermann42, Christina Kendziorski4, Malak Kotb15, R. Frank Kooy43, Bastien Llamas22, Frank Lammert44, J. M. Lassalle45, Pedro R. Lowenstein5, Lu Lu15, Aldons J. Lusis5, Kenneth F. Manly15, Ralph S. Marcucio46, Doug Matthews18, Juan F. Medrano24, Darla R. Miller41, Guy Mittleman18, Beverly A. Mock35, Jeffrey S. Mogil47, Xavier Montagutelli48, Grant Morahan49, David G. Morris50, Richard Mott51, Joseph H. Nadeau52, Hiroki Nagase53, Richard S. Nowakowski32, Bruce F. O'Hara54, Alexander V. Osadchuk, Grier P. Page36, Beverly Paigen, Kenneth Paigen, Abraham A. Palmer, Huei Ju Pan, Leena Peltonen-Palotie5, Leena Peltonen-Palotie55, Jeremy L. Peirce15, Daniel Pomp56, Michal Pravenec25, Daniel R. Prows28, Zonghua Qi1, Roger H. Reeves11, John C. Roder17, Glenn D. Rosen57, Eric E. Schadt58, Leonard C. Schalkwyk59, Ze'ev Seltzer17, Kazuhiro Shimomura60, Siming Shou61, Mikko J. Sillanpää55, Linda D. Siracusa62, Hans-Willem Snoeck40, Jimmy L. Spearow24, Karen L. Svenson, Lisa M. Tarantino63, David W. Threadgill64, Linda A. Toth65, William Valdar51, Fernando Pardo-Manuel de Villena64, Craig H Warden24, Steve Whatley59, Robert W. Williams15, Tom Wiltshire63, Nengjun Yi36, Dabao Zhang66, Min Zhang13, Fei Zou64 
Vanderbilt University1, University of Southern California2, University of Texas MD Anderson Cancer Center3, University of Wisconsin-Madison4, University of California, Los Angeles5, National Center for Genome Resources6, Portland VA Medical Center7, University of Colorado Boulder8, University of Pennsylvania9, Hannover Medical School10, Johns Hopkins University11, Oregon Health & Science University12, Cornell University13, University of Michigan14, University of Tennessee Health Science Center15, Washington University in St. Louis16, University of Toronto17, University of Memphis18, Medical Research Council19, University of Massachusetts Medical School20, Hebrew University of Jerusalem21, Université de Montréal22, Purdue University23, University of California, Davis24, Academy of Sciences of the Czech Republic25, University at Buffalo26, Emory University27, University of Cincinnati28, University of Texas Southwestern Medical Center29, New York University30, University of Groningen31, Rutgers University32, Stanford University33, Max Planck Society34, National Institutes of Health35, University of Alabama at Birmingham36, International Livestock Research Institute37, Heidelberg University38, Medical College of Wisconsin39, Icahn School of Medicine at Mount Sinai40, Oak Ridge National Laboratory41, Charité42, University of Antwerp43, RWTH Aachen University44, Paul Sabatier University45, University of California, San Francisco46, McGill University47, Pasteur Institute48, University of Western Australia49, Yale University50, University of Oxford51, Case Western Reserve University52, Roswell Park Cancer Institute53, University of Kentucky54, University of Helsinki55, University of Nebraska–Lincoln56, Harvard University57, Merck & Co.58, King's College London59, Northwestern University60, Shriners Hospitals for Children61, Thomas Jefferson University62, Novartis63, University of North Carolina at Chapel Hill64, Southern Illinois University Carbondale65, University of Rochester66
TL;DR: The Collaborative Cross will provide a common reference panel specifically designed for the integrative analysis of complex systems and will change the way the authors approach human health and disease.
Abstract: The goal of the Complex Trait Consortium is to promote the development of resources that can be used to understand, treat and ultimately prevent pervasive human diseases. Existing and proposed mouse resources that are optimized to study the actions of isolated genetic loci on a fixed background are less effective for studying intact polygenic networks and interactions among genes, environments, pathogens and other factors. The Collaborative Cross will provide a common reference panel specifically designed for the integrative analysis of complex systems and will change the way we approach human health and disease.

Journal ArticleDOI
TL;DR: Two studies showed that communicating personal positive events with others was associated with increased daily positive affect and well-being, above and beyond the impact of the positive event itself and other daily events.
Abstract: Four studies examined the intrapersonal and interpersonal consequences of seeking out others when good things happen (i.e., capitalization). Two studies showed that communicating personal positive events with others was associated with increased daily positive affect and well-being, above and beyond the impact of the positive event itself and other daily events. Moreover, when others were perceived to respond actively and constructively (and not passively or destructively) to capitalization attempts, the benefits were further enhanced. Two studies found that close relationships in which one's partner typically responds to capitalization attempts enthusiastically were associated with higher relationship well-being (e.g., intimacy, daily marital satisfaction). The results are discussed in terms of the theoretical and empirical importance of understanding how people "cope" with positive events, cultivate positive emotions, and enhance social bonds.

Journal ArticleDOI
TL;DR: The proposed parallel algorithm retains the ability to explore multiple peaks in the posterior distribution of trees while maintaining a fast execution time, and performance results indicate nearly linear speed improvement in both programming models for small and large data sets.
Abstract: Motivation: Bayesian estimation of phylogeny is based on the posterior probability distribution of trees. Currently, the only numerical method that can effectively approximate posterior probabilities of trees is Markov chain Monte Carlo (MCMC). Standard implementations of MCMC can be prone to entrapment in local optima. Metropolis coupled MCMC [(MC)3], a variant of MCMC, allows multiple peaks in the landscape of trees to be more readily explored, but at the cost of increased execution time. Results: This paper presents a parallel algorithm for (MC)3. The proposed parallel algorithm retains the ability to explore multiple peaks in the posterior distribution of trees while maintaining a fast execution time. The algorithm has been implemented using two popular parallel programming models: message passing and shared memory. Performance results indicate nearly linear speed improvement in both programming models for small and large data sets. Availability: MrBayes v3.0 is available at http://morphbank.ebc.uu.se/mrbayes/

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TL;DR: It is shown that BLyS can sustain PC survival in vitro, and this survival can be further enhanced by interleukin 6, and selective up-regulation of Mcl-1 in PCs byBLyS suggests that this α-apoptotic gene product may play an important role in PC survival.
Abstract: Long-lived humoral immunity is manifested by the ability of bone marrow plasma cells (PCs) to survive for extended periods of time. Recent studies have underscored the importance of BLyS and APRIL as factors that can support the survival of B lineage lymphocytes. We show that BLyS can sustain PC survival in vitro, and this survival can be further enhanced by interleukin 6. Selective up-regulation of Mcl-1 in PCs by BLyS suggests that this α-apoptotic gene product may play an important role in PC survival. Blockade of BLyS, via transmembrane activator and cyclophilin ligand interactor–immunoglobulin treatment, inhibited PC survival in vitro and in vivo. Heightened expression of B cell maturation antigen (BCMA), and lowered expression of transmembrane activator and cyclophilin ligand interactor and BAFF receptor in PCs relative to resting B cells suggests a vital role of BCMA in PC survival. Affirmation of the importance of BCMA in PC survival was provided by studies in BCMA−/− mice in which the survival of long-lived bone marrow PCs was impaired compared with wild-type controls. These findings offer new insights into the molecular basis for the long-term survival of PCs.

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TL;DR: An expert panel from multiple disciplines developed definitions for rhinosinusitis and outlined strategies for design of clinical trials and reached consensus on definitions and strategies for clinical research on acute presumed bacterial rhinosineitis, chronic rhinosinitis with polyposis, and classic allergic fungal rhinusitis.
Abstract: Background There is a need for more research on all forms of rhinosinusitis. Progress in this area has been hampered by a lack of consensus definitions and the limited number of published clinical trials. Objectives To develop consensus definitions for rhinosinusitis and outline strategies useful in clinical trials. Methods Five national societies, The American Academy of Allergy, Asthma and Immunology; The American Academy of Otolaryngic Allergy; The American Academy of Otolaryngology Head and Neck Surgery; The American College of Allergy, Asthma and Immunology; and the American Rhinologic Society formed an expert panel from multiple disciplines. Over two days, the panel developed definitions for rhinosinusitis and outlined strategies for design of clinical trials. Results Committee members agreed to adopt the term "rhinosinusitis" and reached consensus on definitions and strategies for clinical research on acute presumed bacterial rhinosinusitis, chronic rhinosinusitis without polyposis, chronic rhinosinusitis with polyposis, and classic allergic fungal rhinosinusitis. Symptom and objective criteria, measures for monitoring research progress, and use of symptom scoring tools, quality-of-life instruments, radiologic studies, and rhinoscopic assessment were outlined for each condition. Conclusion The recommendations from this conference should improve accuracy of clinical diagnosis and serve as a starting point for design of rhinosinusitis clinical trials.