Showing papers by "University of Pittsburgh published in 2001"
TL;DR: Severe sepsis is a common, expensive, and frequently fatal condition, with as many deaths annually as those from acute myocardial infarction, and is especially common in the elderly and is likely to increase substantially as the U.S. population ages.
Abstract: ObjectiveTo determine the incidence, cost, and outcome of severe sepsis in the United States.DesignObservational cohort study.SettingAll nonfederal hospitals (n = 847) in seven U.S. states.PatientsAll patients (n = 192,980) meeting criteria for severe sepsis based on the International Classification
7,888 citations
TL;DR: The data support the hypothesis that a human lipoaspirate contains multipotent cells and may represent an alternative stem cell source to bone marrow-derived MSCs.
Abstract: Future cell-based therapies such as tissue engineering will benefit from a source of autologous pluripotent stem cells. For mesodermal tissue engineering, one such source of cells is the bone marrow stroma. The bone marrow compartment contains several cell populations, including mesenchymal stem cells (MSCs) that are capable of differentiating into adipogenic, osteogenic, chondrogenic, and myogenic cells. However, autologous bone marrow procurement has potential limitations. An alternate source of autologous adult stem cells that is obtainable in large quantities, under local anesthesia, with minimal discomfort would be advantageous. In this study, we determined if a population of stem cells could be isolated from human adipose tissue. Human adipose tissue, obtained by suction-assisted lipectomy (i.e., liposuction), was processed to obtain a fibroblast-like population of cells or a processed lipoaspirate (PLA). These PLA cells can be maintained in vitro for extended periods with stable population doubling and low levels of senescence. Immunofluorescence and flow cytometry show that the majority of PLA cells are of mesodermal or mesenchymal origin with low levels of contaminating pericytes, endothelial cells, and smooth muscle cells. Finally, PLA cells differentiate in vitro into adipogenic, chondrogenic, myogenic, and osteogenic cells in the presence of lineage-specific induction factors. In conclusion, the data support the hypothesis that a human lipoaspirate contains multipotent cells and may represent an alternative stem cell source to bone marrow-derived MSCs.
7,402 citations
TL;DR: Two computational modeling studies are reported, serving to articulate the conflict monitoring hypothesis and examine its implications, including a feedback loop connecting conflict monitoring to cognitive control, and a number of important behavioral phenomena.
Abstract: A neglected question regarding cognitive control is how control processes might detect situations calling for their involvement. The authors propose here that the demand for control may be evaluated in part by monitoring for conflicts in information processing. This hypothesis is supported by data concerning the anterior cingulate cortex, a brain area involved in cognitive control, which also appears to respond to the occurrence of conflict. The present article reports two computational modeling studies, serving to articulate the conflict monitoring hypothesis and examine its implications. The first study tests the sufficiency of the hypothesis to account for brain activation data, applying a measure of conflict to existing models of tasks shown to engage the anterior cingulate. The second study implements a feedback loop connecting conflict monitoring to cognitive control, using this to simulate a number of important behavioral phenomena.
6,385 citations
TL;DR: It is shown that a frameshift mutation caused by a cytosine insertion, 3020insC, which is expected to encode a truncated NOD2 protein, is associated with Crohn's disease, and a link between an innate immune response to bacterial components and development of disease is suggested.
Abstract: Crohn's disease is a chronic inflammatory disorder of the gastrointestinal tract, which is thought to result from the effect of environmental factors in a genetically predisposed host. A gene location in the pericentromeric region of chromosome 16, IBD1, that contributes to susceptibility to Crohn's disease has been established through multiple linkage studies, but the specific gene(s) has not been identified. NOD2, a gene that encodes a protein with homology to plant disease resistance gene products is located in the peak region of linkage on chromosome 16 (ref. 7). Here we show, by using the transmission disequilibium test and case-control analysis, that a frameshift mutation caused by a cytosine insertion, 3020insC, which is expected to encode a truncated NOD2 protein, is associated with Crohn's disease. Wild-type NOD2 activates nuclear factor NF-kappaB, making it responsive to bacterial lipopolysaccharides; however, this induction was deficient in mutant NOD2. These results implicate NOD2 in susceptibility to Crohn's disease, and suggest a link between an innate immune response to bacterial components and development of disease.
4,838 citations
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TL;DR: In this article, the authors examine when, how, and for whom specific corporate social responsibility (CSR) initiatives work and find that CSR initiatives can, under certain conditions, decrease consumers' intentions to buy a company's products.
Abstract: In the face of marketplace polls that attest to the increasing influence of corporate social responsibility (CSR) on consumers' purchase behavior, this article examines when, how, and for whom specific CSR initiatives work. The findings implicate both company-specific factors, such as the CSR issues a company chooses to focus on and the quality of its products, and individual-specific factors, such as consumers' personal support for the CSR issues and their general beliefs about CSR, as key moderators of consumers' responses to CSR. the results also highlight the mediating role of consumers' perceptions of congruence between their own characters and that of the company in their reactions to its CSR initiatives. More specifically, the authors find that CSR initiatives can, under certain conditions, decrease consumers' intentions to buy a company's products.
3,794 citations
TL;DR: It is argued that moral dilemmas vary systematically in the extent to which they engage emotional processing and that these variations in emotional engagement influence moral judgment.
Abstract: The long-standing rationalist tradition in moral psychology emphasizes the role of reason in moral judgment. A more recent trend places increased emphasis on emotion. Although both reason and emotion are likely to play important roles in moral judgment, relatively little is known about their neural correlates, the nature of their interaction, and the factors that modulate their respective behavioral influences in the context of moral judgment. In two functional magnetic resonance imaging (fMRI) studies using moral dilemmas as probes, we apply the methods of cognitive neuroscience to the study of moral judgment. We argue that moral dilemmas vary systematically in the extent to which they engage emotional processing and that these variations in emotional engagement influence moral judgment. These results may shed light on some puzzling patterns in moral judgment observed by contemporary philosophers.
3,618 citations
TL;DR: In this article, an attitudinal model is developed and empirically tested integrating constructs from technology acceptance research and constructs derived from models of web behavior, and two distinct categories of the interactive shopping environment support the differential importance of immersive, hedonic aspects of the new media as well as the more traditional utilitarian motivations.
2,888 citations
TL;DR: Screening different groups of elderly individuals in a general or specialty practice would be beneficial in detecting dementia and persons with memory impairment who were not demented were characterized in the literature as having mild cognitive impairment.
Abstract: Article abstract—Objective: The goal of this project was to determine whether screening different groups of elderly individuals in a general or specialty practice would be beneficial in detecting dementia. Background: Epidemiologic studies of aging and dementia have demonstrated that the use of research criteria for the classification of dementia has yielded three groups of subjects: those who are demented, those who are not demented, and a third group of individuals who cannot be classified as normal or demented but who are cognitively (usually memory) impaired. Methods: The authors conducted computerized literature searches and generated a set of abstracts based on text and index words selected to reflect the key issues to be addressed. Articles were abstracted to determine whether there were sufficient data to recommend the screening of asymptomatic individuals. Other research studies were evaluated to determine whether there was value in identifying individuals who were memory-impaired beyond what one would expect for age but who were not demented. Finally, screening instruments and evaluation techniques for the identification of cognitive impairment were reviewed. Results: There were insufficient data to make any recommendations regarding cognitive screening of asymptomatic individuals. Persons with memory impairment who were not demented were characterized in the literature as having mild cognitive impairment. These subjects were at increased risk for developing dementia or AD when compared with similarly aged individuals in the general population. Recommendations: There were sufficient data to recommend the evaluation and clinical monitoring of persons with mild cognitive impairment due to their increased risk for developing dementia (Guideline). Screening instruments, e.g., Mini-Mental State Examination, were found to be useful to the clinician for assessing the degree of cognitive impairment (Guideline), as were neuropsychologic batteries (Guideline), brief focused cognitive instruments (Option), and certain structured informant interviews (Option). Increasing attention is being paid to persons with mild cognitive impairment for whom treatment options are being evaluated that may alter the rate of progression to dementia.
2,081 citations
TL;DR: In this paper, the authors present relationships between the durability, the governing material properties and salient morphological features of thermal barrier coatings and show that the failure is ultimately connected to the large residual compression in the thermally grown oxide through its roles in amplifying imperfections near the interface.
2,050 citations
TL;DR: CYP3A5 was more frequently expressed in livers of African Americans than in those of Caucasians, and may be the most important genetic contributor to interindividual and interracial differences in CYP3A-dependent drug clearance and in responses to many medicines.
Abstract: Variation in the CYP3A enzymes, which act in drug metabolism, influences circulating steroid levels and responses to half of all oxidatively metabolized drugs. CYP3A activity is the sum activity of the family of CYP3A genes, including CYP3A5, which is polymorphically expressed at high levels in a minority of Americans of European descent and Europeans (hereafter collectively referred to as 'Caucasians'). Only people with at least one CYP3A5*1 allele express large amounts of CYP3A5. Our findings show that single-nucleotide polymorphisms (SNPs) in CYP3A5*3 and CYP3A5*6 that cause alternative splicing and protein truncation result in the absence of CYP3A5 from tissues of some people. CYP3A5 was more frequently expressed in livers of African Americans (60%) than in those of Caucasians (33%). Because CYP3A5 represents at least 50% of the total hepatic CYP3A content in people polymorphically expressing CYP3A5, CYP3A5 may be the most important genetic contributor to interindividual and interracial differences in CYP3A-dependent drug clearance and in responses to many medicines.
2,046 citations
Fermilab1, Pennsylvania State University2, University of Cincinnati3, Princeton University4, Johns Hopkins University5, University of Chicago6, Pontifical Catholic University of Chile7, University of Washington8, New Mexico State University9, California Institute of Technology10, University of Toulouse11, University of Pittsburgh12, Eötvös Loránd University13, University of Tokyo14, University of California, Berkeley15, University of Sussex16, Carnegie Mellon University17, United States Department of the Navy18, Rensselaer Polytechnic Institute19, University of Maryland, College Park20
TL;DR: In this article, a variety of composite quasar spectra using a homogeneous data set of over 2200 spectra from the Sloan Digital Sky Survey (SDSS) was created, and the median composite covers a restwavelength range from 800 to 8555 A and reaches a peak signal-to-noise ratio of over 300 per 1 A resolution element in the rest frame.
Abstract: We have created a variety of composite quasar spectra using a homogeneous data set of over 2200 spectra from the Sloan Digital Sky Survey (SDSS). The quasar sample spans a redshift range of 0.044 ≤ z ≤ 4.789 and an absolute r' magnitude range of -18.0 to -26.5. The input spectra cover an observed wavelength range of 3800–9200 A at a resolution of 1800. The median composite covers a rest-wavelength range from 800 to 8555 A and reaches a peak signal-to-noise ratio of over 300 per 1 A resolution element in the rest frame. We have identified over 80 emission-line features in the spectrum. Emission-line shifts relative to nominal laboratory wavelengths are seen for many of the ionic species. Peak shifts of the broad permitted and semiforbidden lines are strongly correlated with ionization energy, as previously suggested, but we find that the narrow forbidden lines are also shifted by amounts that are strongly correlated with ionization energy. The magnitude of the forbidden line shifts is 100 km s-1, compared with shifts of up to 550 km s-1 for some of the permitted and semiforbidden lines. At wavelengths longer than the Lyα emission, the continuum of the geometric mean composite is well fitted by two power laws, with a break at ≈5000 A. The frequency power-law index, αν, is -0.44 from ≈1300 to 5000 A and -2.45 redward of ≈5000 A. The abrupt change in slope can be accounted for partly by host-galaxy contamination at low redshift. Stellar absorption lines, including higher order Balmer lines, seen in the composites suggest that young or intermediate-age stars make a significant contribution to the light of the host galaxies. Most of the spectrum is populated by blended emission lines, especially in the range 1500–3500 A, which can make the estimation of quasar continua highly uncertain unless large ranges in wavelength are observed. An electronic table of the median quasar template is available.
TL;DR: In this paper, a conceptual model for relating satisfaction ratings and repurchase behavior is presented, based on the premise that ratings observed in a typical customer satisfaction survey are error-prone measures of the customer's true satisfaction, and they may vary systematically on the basis of consumer characteristics.
Abstract: Despite the claim that satisfaction ratings are linked to repurchase behavior, few attempts can be found that relate satisfaction ratings to actual repurchase behavior. This article fills this void by presenting a conceptual model for relating satisfaction ratings and repurchase behavior. The model is based on the premise that ratings observed in a typical customer satisfaction survey are error-prone measures of the customer’s true satisfaction, and they may vary systematically on the basis of consumer characteristics. The authors apply the model to a large-scale study of 100,040 automotive customers. Results show that consumers with different characteristics have different thresholds such that, at the same level of rated satisfaction, repurchase rates are systematically different among different customer groups. The authors also find that the nature and extent of response bias in satisfaction ratings varies by customer characteristics. In one group, the response bias is so high that rated satisf...
TL;DR: The International Knee Documentation Committee Subjective Knee Form is a reliable and valid knee-specific measure of symptoms, function, and sports activity that is appropriate for patients with a wide variety of knee problems.
Abstract: A committee of international knee experts created the International Knee Documentation Committee Subjective Knee Form, which is a knee-specific, rather than a disease-specific, measure of symptoms, function, and sports activity. The purpose of this study was to evaluate the reliability and validity of the new International Knee Documentation Committee Subjective Knee Form. To provide evidence for reliability and validity, we administered the final version of the form, along with the Short Form-36, to 533 patients with a variety of knee problems. Analyses were performed to determine reliability, validity, and differential item function related to age, sex, and diagnosis. Factor analysis revealed a single dominant component, making it reasonable to combine all questions into a single score. Internal consistency and test-retest reliability were 0.92 and 0.95, respectively. Based on test-retest reliability, the value for a true change in the score was 9.0 points. The International Knee Documentation Committee Subjective Knee Form score was related to concurrent measures of physical function (r = 0.47 to 0.66) but not to emotional function (r = 0.16 to 0.26). Analysis of differential item function indicated that the questions functioned similarly for men versus women, young versus old, and for those with different diagnoses. In conclusion, the International Knee Documentation Committee Subjective Knee Form is a reliable and valid knee-specific measure of symptoms, function, and sports activity that is appropriate for patients with a wide variety of knee problems. Use of this instrument will permit comparisons of outcome across groups with different knee problems.
Baylor College of Medicine1, University of Arkansas for Medical Sciences2, University of Kansas3, Oregon Health & Science University4, Duke University5, Veterans Health Administration6, University of California, San Diego7, Case Western Reserve University8, University of Pittsburgh9, University of California, Los Angeles10
TL;DR: Dementia criteria for dementia have improved since the 1994 practice parameter, and further research is needed to improve clinical definitions of dementia and its subtypes, as well as to determine the utility of various instruments of neuroimaging, biomarkers, and genetic testing in increasing diagnostic accuracy.
Abstract: Article abstract—Objective: To update the 1994 practice parameter for the diagnosis of dementia in the elderly. Background: The AAN previously published a practice parameter on dementia in 1994. New research and clinical developments warrant an update of some aspects of diagnosis. Methods: Studies published in English from 1985 through 1999 were identified that addressed four questions: 1) Are the current criteria for the diagnosis of dementia reliable? 2) Are the current diagnostic criteria able to establish a diagnosis for the prevalent dementias in the elderly? 3) Do laboratory tests improve the accuracy of the clinical diagnosis of dementing illness? 4) What comorbidities should be evaluated in elderly patients undergoing an initial assessment for dementia? Recommendations: Based on evidence in the literature, the following recommendations are made. 1) The DSM-III-R definition of dementia is reliable and should be used (Guideline). 2) The National Institute of Neurologic, Communicative Disorders and Stroke‐AD and Related Disorders Association (NINCDS-ADRDA) or the Diagnostic and Statistical Manual, 3rd edition, revised (DSM-IIIR) diagnostic criteria for AD and clinical criteria for Creutzfeldt‐Jakob disease (CJD) have sufficient reliability and validity and should be used (Guideline). Diagnostic criteria for vascular dementia, dementia with Lewy bodies, and frontotemporal dementia may be of use in clinical practice (Option) but have imperfect reliability and validity. 3) Structural neuroimaging with either a noncontrast CT or MR scan in the initial evaluation of patients with dementia is appropriate. Because of insufficient data on validity, no other imaging procedure is recommended (Guideline). There are currently no genetic markers recommended for routine diagnostic purposes (Guideline). The CSF 14-3-3 protein is useful for confirming or rejecting the diagnosis of CJD (Guideline). 4) Screening for depression, B12 deficiency, and hypothyroidism should be performed (Guideline). Screening for syphilis in patients with dementia is not justified unless clinical suspicion for neurosyphilis is present (Guideline). Conclusions: Diagnostic criteria for dementia have improved since the 1994 practice parameter. Further research is needed to improve clinical definitions of dementia and its subtypes, as well as to determine the utility of various instruments of neuroimaging, biomarkers, and genetic testing in increasing diagnostic accuracy.
TL;DR: Spike timing-dependent modifications, together with selective spread of synaptic changes, provide a set of cellular mechanisms that are likely to be important for the development and functioning of neural networks.
Abstract: ■ Abstract Correlated spiking of pre- and postsynaptic neurons can result in strengthening or weakening of synapses, depending on the temporal order of spiking. Recent findings indicate that there are narrow and cell type‐specific temporal windows for such synaptic modification and that the generally accepted input- (or synapse-) specific rule for modification appears not to be strictly adhered to. Spike timing‐ dependent modifications, together with selective spread of synaptic changes, provide a set of cellular mechanisms that are likely to be important for the development and functioning of neural networks. When an axon of cell A is near enough to excite cell B or repeatedly or consistently takes part in firing it, some growth or metabolic change takes place in one or both cells such that A’s efficiency, as one of the cells firing B, is increased. Donald Hebb (1949)
TL;DR: Further vector refinement and/or development is required before gene therapy will become standard care for any individual disorder, and some clinical successes are over the horizon.
Abstract: Considered by some to be among the simpler forms of life, viruses represent highly evolved natural vectors for the transfer of foreign genetic information into cells. This attribute has led to extensive attempts to engineer recombinant viral vectors for the delivery of therapeutic genes into diseased tissues. While substantial progress has been made, and some clinical successes are over the horizon, further vector refinement and/or development is required before gene therapy will become standard care for any individual disorder.
TL;DR: Treatment with hypothermia, with the body temperature reaching 33 degrees C within eight hours after injury, is not effective in improving outcomes in patients with severe brain injury.
Abstract: Background Induction of hypothermia in patients with brain injury was shown to improve outcomes in small clinical studies, but the results were not definitive. To study this issue, we conducted a multicenter trial comparing the effects of hypothermia with those of normothermia in patients with acute brain injury. Methods The study subjects were 392 patients 16 to 65 years of age with coma after sustaining closed head injuries who were randomly assigned to be treated with hypothermia (body temperature, 33°C), which was initiated within 6 hours after injury and maintained for 48 hours by means of surface cooling, or normothermia. All patients otherwise received standard treatment. The primary outcome measure was functional status six months after the injury. Results The mean age of the patients and the type and severity of injury in the two treatment groups were similar. The mean (±SD) time from injury to randomization was 4.3±1.1 hours in the hypothermia group and 4.1±1.2 hours in the normothermia group, a...
National Institute of Advanced Industrial Science and Technology1, University of Bari2, Air Products & Chemicals3, University of Delaware4, University of Pittsburgh5, University of California, Berkeley6, California Institute of Technology7, Brookhaven National Laboratory8, Karlsruhe Institute of Technology9, Environmental Molecular Sciences Laboratory10, Tokyo Institute of Technology11, National Renewable Energy Laboratory12, Los Alamos National Laboratory13, University of Louisville14, Texas A&M University15, Sandia National Laboratories16, Northwestern University17, DuPont18, Emory University19, University of Oklahoma20, University of Southern California21, University of Minnesota22, Pennsylvania State University23, Idaho National Laboratory24
TL;DR: The goal of the "Opportunities for Catalysis Research in Carbon Management" workshop was to review within the context of greenhouse gas/carbon issues the current state of knowledge, barriers to further scientific and technological progress, and basic scientific research needs in the areas of H2 generation and utilization.
Abstract: There is increased recognition by the world’s scientific, industrial, and political communities that the concentrations of greenhouse gases in the earth’s
atmosphere, particularly CO_2, are increasing. For
example, recent studies of Antarctic ice cores to
depths of over 3600 m, spanning over 420 000 years,
indicate an 80 ppm increase in atmospheric CO_2 in
the past 200 years (with most of this increase
occurring in the past 50 years) compared to the
previous 80 ppm increase that required 10 000 years.2
The 160 nation Framework Convention for Climate
Change (FCCC) in Kyoto focused world attention on
possible links between CO2 and future climate change
and active discussion of these issues continues.3 In
the United States, the PCAST report4 “Federal
Energy Research and Development for the Challenges
of the Twenty First Century” focused attention
on the growing worldwide demand for energy and the
need to move away from current fossil fuel utilization.
According to the U.S. DOE Energy Information
Administration,5 carbon emission from the transportation
(air, ground, sea), industrial (heavy manufacturing,
agriculture, construction, mining, chemicals,
petroleum), buildings (internal heating, cooling, lighting),
and electrical (power generation) sectors of the
World economy amounted to ca. 1823 million metric
tons (MMT) in 1990, with an estimated increase to
2466 MMT in 2008-2012 (Table 1).
TL;DR: The pre-supplementary motor area and the rostral portion of the dorsal premotor cortex, the 'pre-PMd', are, in many respects, more like prefrontal areas than motor areas.
TL;DR: Skeletal muscle of trained endurance athletes is markedly insulin sensitive and has a high oxidative capacity, despite having an elevated lipid content, according to quantitative image analysis of Oil Red O staining.
Abstract: We examined the hypothesis that an excess accumulation of intramuscular lipid (IMCL) is associated with insulin resistance and that this may be mediated by the oxidative capacity of muscle. Nine sedentary lean (L) and 11 obese (O) subjects, 8 obese subjects with type 2 diabetes mellitus (D), and 9 lean, exercise-trained (T) subjects volunteered for this study. Insulin sensitivity (M) determined during a hyperinsulinemic (40 mU x m(-2)min(-1)) euglycemic clamp was greater (P < 0.01) in L and T, compared with O and D (9.45 +/- 0.59 and 10.26 +/- 0.78 vs. 5.51 +/- 0.61 and 1.15 +/- 0.83 mg x min(-1)kg fat free mass(-1), respectively). IMCL in percutaneous vastus lateralis biopsy specimens by quantitative image analysis of Oil Red O staining was approximately 2-fold higher in D than in L (3.04 +/- 0.39 vs. 1.40 +/- 0.28% area as lipid; P < 0.01). IMCL was also higher in T (2.36 +/- 0.37), compared with L (P < 0.01). The oxidative capacity of muscle determined with succinate dehydrogenase staining of muscle fibers was higher in T, compared with L, O, and D (50.0 +/- 4.4, 36.1 +/- 4.4, 29.7 +/- 3.8, and 33.4 +/- 4.7 optical density units, respectively; P < 0.01). IMCL was negatively associated with M (r = -0.57, P < 0.05) when endurance-trained subjects were excluded from the analysis, and this association was independent of body mass index. However, the relationship between IMCL and M was not significant when trained individuals were included. There was a positive association between the oxidative capacity and M among nondiabetics (r = 0.37, P < 0.05). In summary, skeletal muscle of trained endurance athletes is markedly insulin sensitive and has a high oxidative capacity, despite having an elevated lipid content. In conclusion, the capacity for lipid oxidation may be an important mediator of the association between excess muscle lipid accumulation and insulin resistance.
TL;DR: It is concluded that with little implementation effort a simple regular expression algorithm for determining whether a finding or disease mentioned within narrative medical reports is present or absent can identify a large portion of the pertinent negatives from discharge summaries.
TL;DR: The use of opinion was made explicit by employing a structured questionnaire, appropriateness scores, and consensus scores with a Delphi technique to be relevant to physicians who make management decisions for the care of patients with pneumothorax.
University of Arizona1, University of Chicago2, Fermilab3, Princeton University4, Johns Hopkins University5, University of Pittsburgh6, Carnegie Mellon University7, University of Chile8, Yale University9, University of Tokyo10, New York University11, Space Telescope Science Institute12, California Institute of Technology13, Rochester Institute of Technology14, Pennsylvania State University15, Drexel University16, Ohio State University17
TL;DR: In this paper, the authors describe the target selection and resulting properties of a spectroscopic sample of luminous red galaxies (LRGs) from the imaging data of the Sloan Digital Sky Survey (SDSS).
Abstract: We describe the target selection and resulting properties of a spectroscopic sample of luminous red galaxies (LRGs) from the imaging data of the Sloan Digital Sky Survey (SDSS). These galaxies are selected on the basis of color and magnitude to yield a sample of luminous intrinsically red galaxies that extends fainter and farther than the main flux-limited portion of the SDSS galaxy spectroscopic sample. The sample is designed to impose a passively evolving luminosity and rest-frame color cut to a redshift of 0.38. Additional, yet more luminous red galaxies are included to a redshift of ~0.5. Approximately 12 of these galaxies per square degree are targeted for spectroscopy, so the sample will number over 100,000 with the full survey. SDSS commissioning data indicate that the algorithm efficiently selects luminous (M^+_g ≈ -21.4) red galaxies, that the spectroscopic success rate is very high, and that the resulting set of galaxies is approximately volume limited out to z = 0.38. When the SDSS is complete, the LRG spectroscopic sample will fill over 1 h^(-3) Gpc^3 with an approximately homogeneous population of galaxies and will therefore be well suited to studies of large-scale structure and clusters out to z = 0.5.
TL;DR: It is shown that XIAP associates with the active caspase-9–Apaf-1 holoenzyme complex through binding to the amino terminus of the linker peptide on the small subunit of caspite-9, which becomes exposed after proteolytic processing of procaspases-9 at Asp 315.
Abstract: X-linked inhibitor-of-apoptosis protein (XIAP) interacts with caspase-9 and inhibits its activity, whereas Smac (also known as DIABLO) relieves this inhibition through interaction with XIAP. Here we show that XIAP associates with the active caspase-9-Apaf-1 holoenzyme complex through binding to the amino terminus of the linker peptide on the small subunit of caspase-9, which becomes exposed after proteolytic processing of procaspase-9 at Asp315. Supporting this observation, point mutations that abrogate the proteolytic processing but not the catalytic activity of caspase-9, or deletion of the linker peptide, prevented caspase-9 association with XIAP and its concomitant inhibition. We note that the N-terminal four residues of caspase-9 linker peptide share significant homology with the N-terminal tetra-peptide in mature Smac and in the Drosophila proteins Hid/Grim/Reaper, defining a conserved class of IAP-binding motifs. Consistent with this finding, binding of the caspase-9 linker peptide and Smac to the BIR3 domain of XIAP is mutually exclusive, suggesting that Smac potentiates caspase-9 activity by disrupting the interaction of the linker peptide of caspase-9 with BIR3. Our studies reveal a mechanism in which binding to the BIR3 domain by two conserved peptides, one from Smac and the other one from caspase-9, has opposing effects on caspase activity and apoptosis.
TL;DR: Table of contents Preamble Scope of the document: Classification, epidemiology and prognosis and diagnosis strategy of evaluation, method, and findings.
Abstract: Table of contents Preamble Scope of the document 1256 Method 1257 Part 1. Classification, epidemiology and prognosis Definition 1258 Brief overview of pathophysiology of syncope 1258 Classification 1259 Epidemiological considerations 1259 Prognostic stratification: identification of factors predictive of adverse outcome 1260 Part 2. Diagnosis Strategy of evaluation (flow chart) 1262 Initial evaluation (history, physical examination, baseline electrocardiogram) 1264 Echocardiogram 1266 Carotid sinus massage 1266 Tilt testing 1268 Electrocardiographic monitoring (non-invasive and invasive) 1271 Electrophysiological testing 1273 ATP test 1277 Ventricular signal-averaged electrocardiogram 1278 Exercise testing 1278 Cardiac catheterization and angiography 1279 Neurological and psychiatric evaluation 1279 Diagnostic yield and prevalence of causes of syncope 1282
TL;DR: It is demonstrated that the attenuation values of muscle on computed tomography in older persons can account for differences in muscle strength not attributed to muscle quantity.
Abstract: Although loss of muscle mass is considered a cause of diminished muscle strength with aging, little is known regarding whether composition of aging muscle affects strength. The skeletal muscle atte...
TL;DR: In this article, a case study of one California elementary school is used to examine the processes by which teachers construct and reconstruct multiple policy messages about reading instruction in the context of their professional communities.
Abstract: Recent research on the relationship between instructional policy and classroom practice suggests that teachers interpret, adapt, and even transform policies as they put them into place. This paper extends this line of research, using an in-depth case study of one California elementary school to examine the processes by which teachers construct and reconstruct multiple policy messages about reading instruction in the context of their professional communities. Drawing primarily on institutional and sensemaking theory, this paper puts forth a model of collective sensemaking that focuses on the ways teachers co-construct understandings of policy messages, make decisions about which messages to pursue in their classrooms, and negotiate the technical and practical details of implementation in conversations with their colleagues. It also argues that the nature and structure of formal networks and informal alliances among teachers shape the process, with implications for ways in which messages from the policy env...
TL;DR: The observations indicate that the cerebellum influences several areas of prefrontal cortex via the thalamus, and separate output channels exist in the dentate to influence motor and cognitive operations.
Abstract: The cerebellum is known to project via the thalamus to multiple motor areas of the cerebral cortex. In this study, we examined the extent and anatomical organization of cerebellar input to multiple regions of prefrontal cortex. We first used conventional retrograde tracers to map the origin of thalamic projections to five prefrontal regions: medial area 9 (9m), lateral area 9 (9l), dorsal area 46 (46d), ventral area 46, and lateral area 12. Only areas 46d, 9m, and 9l received substantial input from thalamic regions included within the zone of termination of cerebellar efferents. This suggested that these cortical areas were the target of cerebellar output. We tested this possibility using retrograde transneuronal transport of the McIntyre-B strain of herpes simplex virus type 1 from areas of prefrontal cortex. Neurons labeled by retrograde transneuronal transport of virus were found in the dentate nucleus only after injections into areas 46d, 9m, and 9l. The precise location of labeled neurons in the dentate varied with the prefrontal area injected. In addition, the dentate neurons labeled after virus injections into prefrontal areas were located in regions spatially separate from those labeled after virus injections into motor areas of the cerebral cortex. Our observations indicate that the cerebellum influences several areas of prefrontal cortex via the thalamus. Furthermore, separate output channels exist in the dentate to influence motor and cognitive operations. These results provide an anatomical substrate for the cerebellum to be involved in cognitive functions such as planning, working memory, and rule-based learning.
Princeton University1, Lawrence Livermore National Laboratory2, University of California, Davis3, Space Telescope Science Institute4, Max Planck Society5, University of Hawaii at Manoa6, Pennsylvania State University7, University of Washington8, New Mexico State University9, University of Pittsburgh10, Eötvös Loránd University11, Johns Hopkins University12, University of Tokyo13, University of Chicago14, United States Department of the Navy15, Carnegie Mellon University16, Spanish National Research Council17
TL;DR: In this article, the authors present the results from a survey of i-dropout objects selected from ~1550 deg2 of multicolor imaging data from the Sloan Digital Sky Survey to search for luminous quasars at z 5.8.
Abstract: We present the results from a survey of i-dropout objects selected from ~1550 deg2 of multicolor imaging data from the Sloan Digital Sky Survey to search for luminous quasars at z 5.8. Objects with i*-z* > 2.2 and z* 0.90. The ARC 3.5 m spectrum of SDSSp J103027.10+052455.0 shows that over a range of ~300 A immediately blueward of the Lyα emission, the average transmitted flux is only 0.003 ± 0.020 times that of the continuum level, consistent with zero flux over a ~300 A range of the Lyα forest region and suggesting a tentative detection of the complete Gunn-Peterson trough. The existence of strong metal lines in the quasar spectra suggests early metal enrichment in the quasar environment. The three new objects, together with the previously published z = 5.8 quasar SDSSp J104433.04-012502.2, form a complete color-selected flux-limited sample at z 5.8. We estimate the selection function of this sample, taking into account the estimated variations in the quasar spectral energy distribution, as well as observational photometric errors. We find that at z = 6, the comoving density of luminous quasars at M1450 < -26.8 (H0 = 50 km s-1 Mpc-1, Ω = 1) is 1.1 × 10-9 Mpc-3. This is a factor of ~2 lower than that at z ~ 5 and is consistent with an extrapolation of the observed quasar evolution at z < 5. Using the current sample, we discuss the constraint on the shape of the quasar luminosity function and the implications for the contribution of quasars to the ionizing background at z ~ 6. The luminous quasars discussed in the paper have central black hole masses of several times 109 M⊙ by the Eddington argument, with likely dark halo masses on the order of 1013 M⊙. Their observed space density provides a sensitive test of models of quasar and galaxy formation at high redshift.
TL;DR: The validity of a global rating of change as a reflection of meaningful change in patient status was supported by the stability of the Physical Impairment Index across the study period in patients defined as stable by the global rating and by the decrease in physical impairment across thestudy period.
Abstract: Background and Purpose. The quality of a disability scale should dictate when it is used. The purposes of this study were to examine the validity of a global rating of change as a reflection of meaningful change in patient status and to compare the measurement properties of a modified Oswestry Low Back Pain Disability Questionnaire (OSW) and the Quebec Back Pain Disability Scale (QUE). Subjects. Sixty-seven patients with acute, work-related low back pain referred for physical therapy participated in the study. Methods. The 2 scales were administered initially and after 4 weeks of physical therapy. The Physical Impairment Index, a measure of physical impairment due to low back pain, was measured initially and after 2 and 4 weeks. A global rating of change survey instrument was completed by each subject after 4 weeks. Results. An interaction existed between patients defined as improved or stable based on the global rating using a 2-way analysis of variance for repeated measures on the impairment index. The modified OSW showed higher levels of test-retest reliability and responsiveness compared with the QUE. The minimum clinically important difference, defined as the amount of change that best distinguishes between patients who have improved and those remaining stable, was approximately 6 points for the modified OSW and approximately 15 points for the QUE. Conclusion and Discussion. The construct validity of the global rating of change was supported by the stability of the Physical Impairment Index across the study period in patients defined as stable by the global rating and by the decrease in physical impairment across the study period in patients defined as improved by the global rating. The modified OSW demonstrated superior measurement properties compared with the QUE.