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Showing papers by "University of Utah published in 2002"


Journal ArticleDOI
Robert H. Waterston1, Kerstin Lindblad-Toh2, Ewan Birney, Jane Rogers3  +219 moreInstitutions (26)
05 Dec 2002-Nature
TL;DR: The results of an international collaboration to produce a high-quality draft sequence of the mouse genome are reported and an initial comparative analysis of the Mouse and human genomes is presented, describing some of the insights that can be gleaned from the two sequences.
Abstract: The sequence of the mouse genome is a key informational tool for understanding the contents of the human genome and a key experimental tool for biomedical research. Here, we report the results of an international collaboration to produce a high-quality draft sequence of the mouse genome. We also present an initial comparative analysis of the mouse and human genomes, describing some of the insights that can be gleaned from the two sequences. We discuss topics including the analysis of the evolutionary forces shaping the size, structure and sequence of the genomes; the conservation of large-scale synteny across most of the genomes; the much lower extent of sequence orthology covering less than half of the genomes; the proportions of the genomes under selection; the number of protein-coding genes; the expansion of gene families related to reproduction and immunity; the evolution of proteins; and the identification of intraspecies polymorphism.

6,643 citations


Journal ArticleDOI
TL;DR: A primer pair is presented that eliminates the problem of presumed impossible to measure telomeres in vertebrate DNA by PCR amplification with oligonucleotide primers designed to hybridize to the TTAGGG and CCCTAA repeats, allowing simple and rapid measurement of telomere length in a closed tube, fluorescence-based assay.
Abstract: It has long been presumed impossible to measure telomeres in vertebrate DNA by PCR amplification with oligonucleotide primers designed to hybridize to the TTAGGG and CCCTAA repeats, because only primer dimer-derived products are expected. Here we present a primer pair that eliminates this problem, allowing simple and rapid measurement of telomeres in a closed tube, fluorescence-based assay. This assay will facilitate investigations of the biology of telomeres and the roles they play in the molecular pathophysiology of diseases and aging.

3,014 citations


MonographDOI
06 May 2002
TL;DR: Some of the greatest scientists including Poisson, Faraday, Maxwell, Rayleigh, and Einstein have contributed to the theory of composite materials Mathematically, it is the study of partial differential equations with rapid oscillations in their coefficients Although extensively studied for more than a hundred years, an explosion of ideas in the last five decades has dramatically increased our understanding of the relationship between the properties of the constituent materials, the underlying microstructure of a composite, and the overall effective moduli which govern the macroscopic behavior as mentioned in this paper.
Abstract: Some of the greatest scientists including Poisson, Faraday, Maxwell, Rayleigh, and Einstein have contributed to the theory of composite materials Mathematically, it is the study of partial differential equations with rapid oscillations in their coefficients Although extensively studied for more than a hundred years, an explosion of ideas in the last five decades (and particularly in the last three decades) has dramatically increased our understanding of the relationship between the properties of the constituent materials, the underlying microstructure of a composite, and the overall effective (electrical, thermal, elastic) moduli which govern the macroscopic behavior This renaissance has been fueled by the technological need for improving our knowledge base of composites, by the advance of the underlying mathematical theory of homogenization, by the discovery of new variational principles, by the recognition of how important the subject is to solving structural optimization problems, and by the realization of the connection with the mathematical problem of quasiconvexification This 2002 book surveys these exciting developments at the frontier of mathematics

2,455 citations


Journal ArticleDOI
TL;DR: It is timely to summarize the polymeric systems that undergo sol-gel transitions, particularly due to temperature, with emphasis on the underlying transition mechanisms and potential delivery aspects.

2,048 citations


Journal ArticleDOI
TL;DR: Application of resilience using an educational and practical framework provides a means for connecting with and nurturing a client's resilience, which is the force that drives a person to grow through adversity and disruptions.
Abstract: Resiliency and resilience theory is presented as three waves of resiliency inquiry. The identification of resilient qualities was the first wave characterized through phenomenological identification of developmental assets and protective factors. The second wave described resilience as a disruptive and reintegrative process for accessing resilient qualities. The third wave exemplified the postmodern and multidisciplinary view of resilience, which is the force that drives a person to grow through adversity and disruptions. Application of resilience using an educational and practical framework provides a means for connecting with and nurturing a client's resilience. Practical paradigms of resiliency that empower client control and choice are suggested.

1,979 citations


Journal ArticleDOI
TL;DR: This committee presents one key recommendation for community action to accompany the four recommendations for individual choices to reduce cancer risk, recognizing that a supportive social environment is indispensable if individuals at all levels of society are to have genuine opportunities to choose healthy behaviors.
Abstract: The American Cancer Society (ACS) publishes Nutrition and Physical Activity Guidelines to serve as a foundation for its communication, policy, and community strategies and ultimately, to affect dietary and physical activity patterns among Americans. These Guidelines, published every 5 years, are developed by a national panel of experts in cancer research, prevention, epidemiology, public health, and policy, and as such, they represent the most current scientific evidence related to dietary and activity patterns and cancer risk. The ACS Guidelines include recommendations for individual choices regarding diet and physical activity patterns, but those choices occur within a community context that either facilitates or interferes with healthy behaviors. Community efforts are essential to create a social environment that promotes healthy food choices and physical activity. Therefore, this committee presents one key recommendation for community action to accompany the four recommendations for individual choices to reduce cancer risk. This recommendation for community action recognizes that a supportive social environment is indispensable if individuals at all levels of society are to have genuine opportunities to choose healthy behaviors. The ACS Guidelines are consistent with guidelines from the American Heart Association and the American Diabetes Association for the prevention of coronary heart disease and diabetes, as well as for general health promotion, as defined by the Department of Health and Human Services' 2005 Dietary Guidelines for Americans.

1,957 citations


Journal ArticleDOI
TL;DR: CloudSat as discussed by the authors is a satellite experiment designed to measure the vertical structure of clouds from space, and once launched, CloudSat will orbit in formation as part of a constellation of satellites (the A-Train) that includes NASA's Aqua and Aura satellites, a NASA-CNES lidar satellite (CALIPSO), and a CNES satellite carrying a polarimeter (PARASOL).
Abstract: CloudSat is a satellite experiment designed to measure the vertical structure of clouds from space. The expected launch of CloudSat is planned for 2004, and once launched, CloudSat will orbit in formation as part of a constellation of satellites (the A-Train) that includes NASA's Aqua and Aura satellites, a NASA–CNES lidar satellite (CALIPSO), and a CNES satellite carrying a polarimeter (PARASOL). A unique feature that CloudSat brings to this constellation is the ability to fly a precise orbit enabling the fields of view of the CloudSat radar to be overlapped with the CALIPSO lidar footprint and the other measurements of the constellation. The precision and near simultaneity of this overlap creates a unique multisatellite observing system for studying the atmospheric processes essential to the hydrological cycle. The vertical profiles of cloud properties provided by CloudSat on the global scale fill a critical gap in the investigation of feedback mechanisms linking clouds to climate. Measuring these profi...

1,929 citations


Journal ArticleDOI
Bruce L. Wilkoff1, James R. Cook, Andrew E. Epstein2, Leon Greene, Alfred P. Hallstrom, Henry H. Hsia, Steven P. Kutalek, Arjun Sharma, Brian Blatt, Barry Karas, James Kirchhoffer, Deborah Warwick, Mary Duquette, Jean Provencher, Maureen Redmond, John M. Herre, Robert S. Bernstein, Linette R. Klevan, Kathleen D. Barackman, Jennine Zumbuhl, Mina K. Chung1, Fredrick J. Jaeger1, David O. Martin1, Andrea Natale1, Walid Saliba1, Robert A. Schweikert1, Mark Niebauer1, Patrick J. Tchou1, Raquel Rozich1, Marc Roelke, Constantinos A. Costeas, Donald G. Rubenstein, Scott Ruffo, Kelly Kumar, Elizabeth McCarthy, Valerie Pastore, Mark S. Wathen3, Jeffrey N. Rottman3, Mark Anderson3, John T. Lee3, Katherine T. Murray3, Dan M. Roden3, Nancy Conners3, Sandy Saunders3, Gearoid P. O'Neill4, Anne Skadsen4, Shelley Allen4, Ellie Vierra4, Stephen Greer, Jeffrey Neuhauser, Pam Myers, Celeste Lee, Terri Moore, Richard C. Klein5, Roger A. Freedman5, Geri Wadsworth5, Sharon M. Dailey2, G. Neal Kay2, Vance J. Plumb2, Rosemary S. Bubien2, Linda W. Kay2, Candace M. Nasser2, Jane E. Slabaugh2, Robert B. Leman6, Jenifer L. Lake6, Julie Clark6, Elizabeth Clarke6, Laura Finklea6, John C. Love7, Charles M. Carpenter7, Andrew Corsello7, Joel E. Cutler7, Susan BosworthFarrell7, Gregory Michaud8, Alfred E. Buxton8, Kristin E. Ellison8, Frederic Christian8, Malcolm Kirk8, Pamela L. Corcoran8, Stephen T. Rothbart9, Roy B. Sauberman9, Jennifer McCarthy9, Mary Ellen Page9, Jonathan S. Steinberg, Frederick Ehlert, Bengt Herweg, Margot Vloka, Ammy Malinay, Edith Menchavez, Michael Rome, Kathy Marks, Alison Swarens, Maribel Hernandez, Roger A. Marinchak, Douglas Esberg, John Finkle, Glenn Harper, Peter R. Kowey, Colin Movsowitz 
25 Dec 2002-JAMA
TL;DR: For patients with standard indications for ICD therapy, no indication for cardiac pacing, and an LVEF of 40% or less, dual-chamber pacing offers no clinical advantage over ventricular backup pacing and may be detrimental by increasing the combined end point of death or hospitalization for heart failure.
Abstract: CONTEXT: Implantable cardioverter defibrillator (ICD) therapy with backup ventricular pacing increases survival in patients with life-threatening ventricular arrhythmias. Most currently implanted ICD devices provide dual-chamber pacing therapy. The most common comorbid cause for mortality in this population is congestive heart failure. OBJECTIVE: To determine the efficacy of dual-chamber pacing compared with backup ventricular pacing in patients with standard indications for ICD implantation but without indications for antibradycardia pacing. DESIGN: The Dual Chamber and VVI Implantable Defibrillator (DAVID) Trial, a single-blind, parallel-group, randomized clinical trial. SETTING AND PARTICIPANTS: A total of 506 patients with indications for ICD therapy were enrolled between October 2000 and September 2002 at 37 US centers. All patients had a left ventricular ejection fraction (LVEF) of 40% or less, no indication for antibradycardia pacemaker therapy, and no persistent atrial arrhythmias. INTERVENTIONS: All patients had an ICD with dual-chamber, rate-responsive pacing capability implanted. Patients were randomly assigned to have the ICDs programmed to ventricular backup pacing at 40/min (VVI-40; n = 256) or dual-chamber rate-responsive pacing at 70/min (DDDR-70; n = 250). Maximal tolerated medical therapy for left ventricular dysfunction, including angiotensin-converting enzyme inhibitors and beta-blockers, was prescribed to all patients. MAIN OUTCOME MEASURE: Composite end point of time to death or first hospitalization for congestive heart failure. RESULTS: One-year survival free of the composite end point was 83.9% for patients treated with VVI-40 compared with 73.3% for patients treated with DDDR-70 (relative hazard, 1.61; 95% confidence interval [CI], 1.06-2.44). The components of the composite end point, mortality of 6.5% for VVI-40 vs 10.1% for DDDR-70 (relative hazard, 1.61; 95% CI, 0.84-3.09) and hospitalization for congestive heart failure of 13.3% for VVI-40 vs 22.6% for DDDR-70 (relative hazard, 1.54; 95% CI, 0.97-2.46), also trended in favor of VVI-40 programming. CONCLUSION: For patients with standard indications for ICD therapy, no indication for cardiac pacing, and an LVEF of 40% or less, dual-chamber pacing offers no clinical advantage over ventricular backup pacing and may be detrimental by increasing the combined end point of death or hospitalization for heart failure.

1,922 citations


Proceedings ArticleDOI
01 Jul 2002
TL;DR: The work presented in this paper leverages the time-tested techniques of photographic practice to develop a new tone reproduction operator and uses and extends the techniques developed by Ansel Adams to deal with digital images.
Abstract: A classic photographic task is the mapping of the potentially high dynamic range of real world luminances to the low dynamic range of the photographic print. This tone reproduction problem is also faced by computer graphics practitioners who map digital images to a low dynamic range print or screen. The work presented in this paper leverages the time-tested techniques of photographic practice to develop a new tone reproduction operator. In particular, we use and extend the techniques developed by Ansel Adams to deal with digital images. The resulting algorithm is simple and produces good results for a wide variety of images.

1,708 citations


Journal ArticleDOI
TL;DR: Patients undergoing hemodialysis thrice weekly appear to have no major benefit from a higher dialysis dose than that recommended by current U.S. guidelines or from the use of a high-flux membrane.
Abstract: Background The effects of the dose of dialysis and the level of flux of the dialyzer membrane on mortality and morbidity among patients undergoing maintenance hemodialysis are uncertain. Methods We undertook a randomized clinical trial in 1846 patients undergoing thrice-weekly dialysis, using a two-by-two factorial design to assign patients randomly to a standard or high dose of dialysis and to a low-flux or high-flux dialyzer. Results In the standard-dose group, the mean (±SD) urea-reduction ratio was 66.3±2.5 percent, the single-pool Kt/V was 1.32±0.09, and the equilibrated Kt/V was 1.16±0.08; in the high-dose group, the values were 75.2±2.5 percent, 1.71±0.11, and 1.53±0.09, respectively. Flux, estimated on the basis of beta2-microglobulin clearance, was 3±7 ml per minute in the low-flux group and 34±11 ml per minute in the high-flux group. The primary outcome, death from any cause, was not significantly influenced by the dose or flux assignment: the relative risk of death in the high-dose group as com...

1,670 citations


Journal ArticleDOI
TL;DR: Using the directional-bonding methodology, this work has synthesized high-symmetry ensembles resembling the Platonic solids and the Archimedean solids, as well as other cages, like trigonal bipyramids, adamantanoids, and trigonal prisms.
Abstract: We provide a summary of our results in three-dimensional, coordination-driven self-assembly based on the directional-bonding methodology, in which the stoichiometric mixing of complementary building blocks, with appropriate, predefined geometries, leads to targeted, nanoscopic cages. Using this motif, we have synthesized high-symmetry ensembles resembling the Platonic solids, such as dodecahedra, and the Archimedean solids, such as truncated tetrahedra and cuboctahedra, as well as other cages, like trigonal bipyramids, adamantanoids, and trigonal prisms. The synthesis and characterization of these compounds is discussed, as is some host-guest chemistry.

Journal ArticleDOI
TL;DR: In this article, the authors examined the relationship between the cost of equity capital and levels of annual report and timely disclosure and investor relations activities and concluded that aggregating across different disclosure types results in a loss of information.
Abstract: This paper examines the association between the cost of equity capital and levels of annual report and timely disclosure, and investor relations activities. We estimate the cost of equity capital using the classic dividend discount model. We find that the cost of equity capital decreases in the annual report disclosure level but increases in the level of timely disclosures. The latter result is contrary to theory but is consistent with managers’ claims that greater timely disclosures may increase the cost of equity capital, possibly through increased stock price volatility. We find no association between the cost of equity capital and the level of investor relations activities. We conclude that aggregating across different disclosure types results in a loss of information. Failing to include all disclosure types in regression analyses may lead to a correlated omitted variable bias and erroneous conclusions.

Journal ArticleDOI
TL;DR: Bilateral prophylactic oophorectomy reduces the risk of coelomic epithelial cancer and breast cancer in women with BRCA1 or BRCa2 mutations.
Abstract: Background Data concerning the efficacy of bilateral prophylactic oophorectomy for reducing the risk of gynecologic cancer in women with BRCA1 or BRCA2 mutations are limited. We investigated whether this procedure reduces the risk of cancers of the coelomic epithelium and breast in women who carry such mutations. Methods A total of 551 women with disease-associated germ-line BRCA1 or BRCA2 mutations were identified from registries and studied for the occurrence of ovarian and breast cancer. We determined the incidence of ovarian cancer in 259 women who had undergone bilateral prophylactic oophorectomy and in 292 matched controls who had not undergone the procedure. In a subgroup of 241 women with no history of breast cancer or prophylactic mastectomy, the incidence of breast cancer was determined in 99 women who had undergone bilateral prophylactic oophorectomy and in 142 matched controls. The length of postoperative follow-up for both groups was at least eight years. Results Six women who underwent proph...

Journal ArticleDOI
09 Dec 2002
TL;DR: The overall design and implementation of Netbed is presented and its ability to improve experimental automation and efficiency is demonstrated, leading to new methods of experimentation, including automated parameter-space studies within emulation and straightforward comparisons of simulated, emulated, and wide-area scenarios.
Abstract: Three experimental environments traditionally support network and distributed systems research: network emulators, network simulators, and live networks. The continued use of multiple approaches highlights both the value and inadequacy of each. Netbed, a descendant of Emulab, provides an experimentation facility that integrates these approaches, allowing researchers to configure and access networks composed of emulated, simulated, and wide-area nodes and links. Netbed's primary goals are ease of use, control, and realism, achieved through consistent use of virtualization and abstraction.By providing operating system-like services, such as resource allocation and scheduling, and by virtualizing heterogeneous resources, Netbed acts as a virtual machine for network experimentation. This paper presents Netbed's overall design and implementation and demonstrates its ability to improve experimental automation and efficiency. These, in turn, lead to new methods of experimentation, including automated parameter-space studies within emulation and straightforward comparisons of simulated, emulated, and wide-area scenarios.

Journal ArticleDOI
TL;DR: In this article, the authors compare and contrast the experiences of Chicana/Chicano students through a Eurocentric and a critical raced-gendered epistemological perspective and demonstrate that each perspective holds vastly different views of what counts as knowledge, specifically regarding language, culture, and commitment to communities.
Abstract: For too long, the histories, experiences, cultures, and languages of students of color have been devalued, misinterpreted, or omitted within formal educational settings. In this article, the author uses critical race theory (CRT) and Latina/Latino critical theory (LatCrit) to demonstrate how critical raced-gendered epistemologies recognize students of color as holders and creators of knowledge. In doing so, she discusses how CRT and LatCrit provide an appropriate lens for qualitative research in the field of education. She then compares and contrasts the experiences of Chicana/Chicano students through a Eurocentric and a critical raced-gendered epistemological perspective and demonstrates that each perspective holds vastly different views of what counts as knowledge, specifically regarding language, culture, and commitment to communities. She then offers implications of critical raced-gendered epistemologies for both research and practice and concludes by discussing some of the critiques of the use of the...

Journal ArticleDOI
TL;DR: This work shows that 11 tumors from 3 affected siblings contain 18 somatic inactivating mutations of APC and that 15 of these mutations are G:C→T:A transversions, which implicate defective base excision repair in predisposition to tumors in humans.
Abstract: Inherited defects of base excision repair have not been associated with any human genetic disorder, although mutations of the genes mutM and mutY, which function in Escherichia coli base excision repair, lead to increased transversions of G:C to T:A1, 2, 3, 4. We have studied family N, which is affected with multiple colorectal adenomas and carcinoma but lacks an inherited mutation of the adenomatous polyposis coli gene (APC) that is associated with familial adenomatous polyposis5. Here we show that 11 tumors from 3 affected siblings contain 18 somatic inactivating mutations of APC and that 15 of these mutations are G:CT:A transversions—a significantly greater proportion than is found in sporadic tumors or in tumors associated with familial adenomatous polyposis. Analysis of the human homolog of mutY, MYH6, showed that the siblings were compound heterozygotes for the nonconservative missense variants Tyr165Cys and Gly382Asp. These mutations affect residues that are conserved in mutY of E. coli (Tyr82 and Gly253). Tyrosine 82 is located in the pseudo-helix-hairpin-helix (HhH) motif and is predicted to function in mismatch specificity7. Assays of adenine glycosylase activity of the Tyr82Cys and Gly253Asp mutant proteins with 8-oxoG:A and G:A substrates show that their activity is reduced significantly. Our findings link the inherited variants in MYH to the pattern of somatic APC mutation in family N and implicate defective base excision repair in predisposition to tumors in humans.

Journal Article
TL;DR: This correlative study in a large series of patients revealed that EGFR expression, which varied considerably among HNSCCs, was a strong independent prognostic indicator for OS and DFS and a robust predictor for LR relapse but not for distant metastasis.
Abstract: A correlative study was performed to address the impact of epidermal growth factor receptor (EGFR) overexpression on survival and pattern of failure in patients with advanced head and neck squamous cell carcinomas (HNSCCs) enrolled in a Phase III trial and randomized to receive conventional radiotherapy. The study population comprised 155 of 268 (58%) randomized patients with sufficient pretreatment biopsy specimens for immunohistochemical assay. The specimens were dewaxed and incubated after standard preparation with mouse monoclonal antibodies recognizing the extracellular domain of the EGFR molecule. The catalyzed product was visualized with 3,3'-diaminobenzidine Chromogen Kit and lightly counterstained with Mayer's hematoxylin. Quantitative EGFR immunohistochemistry (IHC) was done with SAMBA 4000 Cell Image Analysis System, without knowledge of the clinical outcome, to yield mean absorbance (MOD), staining index (SI), and quick score (QS). These EGFR IHC parameters were correlated with the T stage, N stage, combined stage grouping, and recursive partitioning analysis classes. Subsequently, the EGFR parameters were correlated with the outcome end points, i.e., overall survival (OS), disease-free survival (DFS), local-regional (LR) relapse, and distant metastasis rates. We found that HNSCCs exhibited a wide variation in EGFR expression (MOD, 0.2-66.0; SI, 0.3-97.0; QS, 0.01-69.9) with a relatively strong but nonlinear correlation between MOD and SI (r = 0.79). There was no correlation between EGFR expression and T stage, N stage, stage grouping, and recursive partitioning analysis classes (r = -0.07 to 0.17). The OS and DFS rates of patients with high EGFR-expressing HNSCCs (>median MOD) were highly significantly lower (P = 0.0006 and P = 0.0016, respectively) and the LR relapse rate was highly significantly higher (P = 0.0031) compared with those of patients with low EGFR-expressing HNSCCs. However, there was no difference in the distant metastasis rate between the two groups (P = 0.96). Significant correlations, although somewhat less robust than MOD, were also observed between SI and QS and the OS, DFS, and LR relapse rates. Multivariate analysis showed that EGFR expression was an independent determinant of survival and a robust independent predictor of LR relapse. In summary, this correlative study in a large series of patients revealed that EGFR expression, which varied considerably among HNSCCs, was a strong independent prognostic indicator for OS and DFS and a robust predictor for LR relapse but not for distant metastasis. The data suggest that EGFR IHC should be considered for selecting patients for more aggressive combined therapies or enrollment into trials targeting EGFR signaling pathways.

Journal ArticleDOI
TL;DR: This review summarizes ongoing investigations of the enzyme family and their substrates, focusing on biological function as well as biochemical mechanism.
Abstract: ▪ Abstract ADARs are RNA editing enzymes that target double-stranded regions of nuclear-encoded RNA and viral RNA. These enzymes are particularly abundant in the nervous system, where they diversify the information encoded in the genome, for example, by altering codons in mRNAs. The functions of ADARs in known substrates suggest that the enzymes serve to fine-tune and optimize many biological pathways, in ways that we are only starting to imagine. ADARs are also interesting in regard to the remarkable double-stranded structures of their substrates and how enzyme specificity is achieved with little regard to sequence. This review summarizes ongoing investigations of the enzyme family and their substrates, focusing on biological function as well as biochemical mechanism.

Journal ArticleDOI
24 Apr 2002-JAMA
TL;DR: Dietary patterns characterized by increased dairy consumption have a strong inverse association with IRS among overweight adults and may reduce risk of type 2 diabetes and cardiovascular disease.
Abstract: ContextComponents of the insulin resistance syndrome (IRS), including obesity, glucose intolerance, hypertension, and dyslipidemia, are major risk factors for type 2 diabetes and heart disease. Although diet has been postulated to influence IRS, the independent effects of dairy consumption on development of this syndrome have not been investigated.ObjectiveTo examine associations between dairy intake and incidence of IRS, adjusting for confounding lifestyle and dietary factors.DesignThe Coronary Artery Risk Development in Young Adults (CARDIA) study, a population-based prospective study.Setting and ParticipantsGeneral community sample from 4 US metropolitan areas of 3157 black and white adults aged 18 to 30 years who were followed up from 1985-1986 to 1995-1996.Main Outcome MeasureTen-year cumulative incidence of IRS and its association with dairy consumption, measured by diet history interview.ResultsDairy consumption was inversely associated with the incidence of all IRS components among individuals who were overweight (body mass index ≥25 kg/m2) at baseline but not among leaner individuals (body mass index <25 kg/m2). The adjusted odds of developing IRS (2 or more components) were 72% lower (odds ratio, 0.28; 95% confidence interval, 0.14-0.58) among overweight individuals in the highest (≥35 times per week, 24/102 individuals) compared with the lowest (<10 times per week, 85/190 individuals) category of dairy consumption. Each daily occasion of dairy consumption was associated with a 21% lower odds of IRS (odds ratio, 0.79; 95% confidence interval, 0.70-0.88). These associations were similar for blacks and whites and for men and women. Other dietary factors, including macronutrients and micronutrients, did not explain the association between dairy intake and IRS.ConclusionsDietary patterns characterized by increased dairy consumption have a strong inverse association with IRS among overweight adults and may reduce risk of type 2 diabetes and cardiovascular disease.

Journal ArticleDOI
TL;DR: Findings suggest that TAM may be more appropriate than TPB for examining technology acceptance by individual professionals and that the integrated model, although more fully depicting physicians’ technology acceptance, may not provide significant additional explanatory power.


Journal ArticleDOI
TL;DR: Voriconazole is a suitable alternative to amphotericin B preparations for empirical antifungal therapy in patients with neutropenia and persistent fever in a randomized, international, multicenter trial.
Abstract: Background Patients with neutropenia and persistent fever are often treated empirically with amphotericin B or liposomal amphotericin B to prevent invasive fungal infections. Antifungal triazoles offer a potentially safer and effective alternative. Methods In a randomized, international, multicenter trial, we compared voriconazole, a new second-generation triazole, with liposomal amphotericin B for empirical antifungal therapy. Results A total of 837 patients (415 assigned to voriconazole and 422 to liposomal amphotericin B) were evaluated for success of treatment. The overall success rates were 26.0 percent with voriconazole and 30.6 percent with liposomal amphotericin B (95 percent confidence interval for the difference, –10.6 to 1.6 percentage points); these rates were independent of the administration of antifungal prophylaxis or the use of colony-stimulating factors. There were fewer documented breakthrough fungal infections in patients treated with voriconazole than in those treated with liposomal a...

Journal ArticleDOI
TL;DR: It is found that, as postulated, PLL diffuses throughout the film down into the substrate after each new PLL injection and out of the film after each PLL rinsing and further after each HA injection, which explains the exponential growth regime.
Abstract: The structure of poly(l-lysine) (PLL)/hyaluronan (HA) polyelectrolyte multilayers formed by electrostatic self-assembly is studied by using confocal laser scanning microscopy, quartz crystal microbalance, and optical waveguide lightmode spectroscopy. These films exhibit an exponential growth regime where the thickness increases exponentially with the number of deposited layers, leading to micrometer thick films. Previously such a growth regime was suggested to result from an “in” and “out” diffusion of the PLL chains through the film during buildup, but direct evidence was lacking. The use of dye-conjugated polyelectrolytes now allows a direct three-dimensional visualization of the film construction by introducing fluorescent polyelectrolytes at different steps during the film buildup. We find that, as postulated, PLL diffuses throughout the film down into the substrate after each new PLL injection and out of the film after each PLL rinsing and further after each HA injection. As PLL reaches the outer layer of the film it interacts with the incoming HA, forming the new HA/PLL layer. The thickness of this new layer is thus proportional to the amount of PLL that diffuses out of the film during the buildup step, which explains the exponential growth regime. HA layers are also visualized but no diffusion is observed, leading to a stratified film structure. We believe that such a diffusion-based buildup mechanism explains most of the exponential-like growth processes of polyelectrolyte multilayers reported in the literature.

Journal ArticleDOI
TL;DR: How the peroxisome proliferator-activated receptors, a subset of the nuclear-hormone-receptor superfamily, have important regulatory roles in innate and adaptive immunity is described.
Abstract: Lipids and lipid metabolism have well-documented regulatory effects on inflammatory processes. Recent work has highlighted the role of the peroxisome proliferator-activated receptors (PPARs)--a subset of the nuclear-hormone-receptor superfamily that are activated by various lipid species--in regulating inflammatory responses. Here, we describe how the PPARs, through their interactions with transcription factors and other cell-signalling systems, have important regulatory roles in innate and adaptive immunity.

Journal ArticleDOI
TL;DR: The authors examined the relationship between book-to-market equity, distress risk, and stock returns among firms with the highest distress risk as proxied by Ohlson's ~1980! O-score, finding that the difference in returns between high and low book-tomarket securities is more than twice as large as that in other firms.
Abstract: This paper examines the relationship between book-to-market equity, distress risk, and stock returns Among firms with the highest distress risk as proxied by Ohlson’s ~1980! O-score, the difference in returns between high and low book-tomarket securities is more than twice as large as that in other firms This large return differential cannot be explained by the three-factor model or by differences in economic fundamentals Consistent with mispricing arguments, firms with high distress risk exhibit the largest return reversals around earnings announcements, and the book-to-market effect is largest in small firms with low analyst coverage ONE PROMINENT EXPLANATION OF THE book-to-market equity premium in returns is that high book-to-market equity firms are assigned a higher risk premium because of the greater risk of distress 1 Consistent with this view, Fama and French ~1995! and Chen and Zhang ~1998! show that firms with high bookto-market equity ~BE0ME! have persistently low earnings, higher financial leverage, more earnings uncertainty, and are more likely to cut dividends compared to their low BE0ME counterparts In contrast, Dichev ~1998! uses measures of bankruptcy risk proposed by Ohlson ~1980! and Altman ~1968! to identify firms with a high likelihood of financial distress and finds that these firms tend to have low average stock returns Dichev’s results appear to be inconsistent with the view that firms with high BE0ME earn high returns as a premium for distress risk 2

Journal ArticleDOI
01 Jul 2002-Genetics
TL;DR: Designing a pair of ZFNs that recognize a unique site in the yellow (y) gene of Drosophila led to somatic mutations specifically in the y gene, exactly the types of alterations expected from nonhomologous end joining (NHEJ) following double-strand cleavage of the target.
Abstract: Zinc-finger nucleases (ZFNs) are hybrids between a nonspecific DNA-cleavage domain and a DNA-binding domain composed of Cys(2)His(2) zinc fingers. Because zinc fingers can be manipulated to recognize a broad range of sequences, these enzymes have the potential to direct cleavage to arbitrarily chosen targets. We have tested this idea by designing a pair of ZFNs that recognize a unique site in the yellow (y) gene of Drosophila. When these nucleases were expressed in developing larvae, they led to somatic mutations specifically in the y gene. These somatic mosaics were observed in approximately one-half of the males expressing both nucleases. Germline y mutations were recovered from 5.7% of males, but from none of the females, tested. DNA sequences were determined and showed that all of the mutations were small deletions and/or insertions located precisely at the designed target. These are exactly the types of alterations expected from nonhomologous end joining (NHEJ) following double-strand cleavage of the target. This approach promises to permit generation of directed mutations in many types of cells and organisms.

Journal ArticleDOI
TL;DR: In this article, the authors investigated the relation between cross listing in the U.S., with its resulting commitment to increased disclosure, and the information environment of non-U.S. firms.
Abstract: This paper investigates the relation between cross listing in the U.S., with its resulting commitment to increased disclosure, and the information environment of non-U.S. firms. We find that firms that cross-list on U.S. exchanges have greater analyst coverage and increased forecast accuracy relative to firms that are not cross listed. A time-series analysis shows that the change in analyst coverage and forecast accuracy occurs around cross listing. We also document that firms that have more analyst coverage and higher forecast accuracy have a higher valuation. Further, the change in firm value around cross listing is correlated with changes in the firm's information environment. Our findings support the hypothesis that cross-listed firms have better information environments, which are associated with higher market valuations.

Journal ArticleDOI
TL;DR: It is determined that Borrelia burgdorferi strain B31 MI carries 21 extrachromosomal DNA elements, the largest number known for any bacterium, and the nucleotide sequence of three linear and seven circular plasmids in this infectious isolate is reported.
Abstract: We have determined that Borrelia burgdorferi strain B31 MI carries 21 extrachromosomal DNA elements, the largest number known for any bacterium. Among these are 12 linear and nine circular plasmids, whose sequences total 610 694 bp. We report here the nucleotide sequence of three linear and seven circular plasmids (comprising 290 546 bp) in this infectious isolate. This completes the genome sequencing project for this organism; its genome size is 1 521 419 bp (plus about 2000 bp of undetermined telomeric sequences). Analysis of the sequence implies that there has been extensive and sometimes rather recent DNA rearrangement among a number of the linear plasmids. Many of these events appear to have been mediated by recombinational processes that formed duplications. These many regions of similarity are reflected in the fact that most plasmid genes are members of one of the genome's 161 paralogous gene families; 107 of these gene families, which vary in size from two to 41 members, contain at least one plasmid gene. These rearrangements appear to have contributed to a surprisingly large number of apparently non-functional pseudogenes, a very unusual feature for a prokaryotic genome. The presence of these damaged genes suggests that some of the plasmids may be in a period of rapid evolution. The sequence predicts 535 plasmid genes ≥300 bp in length that may be intact and 167 apparently mutationally damaged and/or unexpressed genes (pseudogenes). The large majority, over 90%, of genes on these plasmids have no convincing similarity to genes outside Borrelia, suggesting that they perform specialized functions.

Journal ArticleDOI
TL;DR: It is found that monosynaptic horizontal connections within area V1 are of an appropriate spatial scale to mediate interactions within the SF of V1 neurons and to underlie contrast-dependent changes in SF size, which could represent an anatomical substrate for contextual modulation and global-to-local integration of visual signals.
Abstract: Contrast-dependent changes in spatial summation and contextual modulation of primary visual cortex (V1) neuron responses to stimulation of their receptive field reveal long-distance integration of visual signals within V1, well beyond the classical receptive field (cRF) of single neurons. To identify the cortical circuits mediating these long-distance computations, we have used a combination of anatomical and physiological recording methods to determine the spatial scale and retinotopic logic of intra-areal V1 horizontal connections and inter-areal feedback connections to V1. We have then compared the spatial scales of these connectional systems to the spatial dimensions of the cRF, spatial summation field (SF), and modulatory surround field of macaque V1 neurons. We find that monosynaptic horizontal connections within area V1 are of an appropriate spatial scale to mediate interactions within the SF of V1 neurons and to underlie contrast-dependent changes in SF size. Contrary to common beliefs, these connections cannot fully account for the dimensions of the surround field. The spatial scale of feedback circuits from extrastriate cortex to V1 is, instead, commensurate with the full spatial range of center-surround interactions. Thus these connections could represent an anatomical substrate for contextual modulation and global-to-local integration of visual signals. Feedback projections connect corresponding and equal-sized regions of the visual field in striate and extrastriate cortices and cover anisotropic parts of visual space, unlike V1 horizontal connections that are isotropic in the macaque. V1 isotropic connectivity demonstrates that anisotropic horizontal connections are not necessary to generate orientation selectivity. Anisotropic feedback connections may play a role in contour completion.

Journal ArticleDOI
TL;DR: This review will introduce the most important cationic polymers used as non-viral vectors for gene and oligonucleotide delivery and will summarize strategies for the targeting of these agents to cancer tissues.