bluuebunny/crossref_metadata_2025 huggingface dataset:
COMPUTING THE ALL-PAIRS QUARTET DISTANCE ON A SET OF EVOLUTIONARY TREES
Authors: STISSING M. , MAILUND T. , PEDERSEN C. N. S. , BRODAL G. S. , FAGERBERG R.
Published: March 2008

We present two algorithms for calculating the quartet distance between all pairs of trees in a set of binary evolutionary trees on a common set of species. The algorithms exploit common substructure among the trees to speed up the pairwise distance calculations, thus performing significantly better on large sets of trees compared to performing distinct pairwise distance calculations, as we illustrate experimentally, where we see a speedup factor of around 130 in the best case.
DESIGN AND ANALYSIS OF QUANTITATIVE DIFFERENTIAL PROTEOMICS INVESTIGATIONS USING LC-MS TECHNOLOGY
Authors: BUKHMAN YURY V. , DHARSEE MOYEZ , EWING ROB , CHU PETER , TOPALOGLOU THODOROS , LE BIHAN THIERRY , GOH THEO , DUEWEL HENRY , STEWART IAN I. , WISNIEWSKI JACEK R. , NG NANCY F.
Published: March 2008

Liquid chromatography–mass spectrometry (LC-MS)-based proteomics is becoming an increasingly important tool in characterizing the abundance of proteins in biological samples of various types and across conditions. Effects of disease or drug treatments on protein abundance are of particular interest for the characterization of biological processes and the identification of biomarkers. Although state-of-the-art instrumentation is available to make high-quality measurements and commercially available software is available to process the data, the complexity of the technology and data presents challenges for bioinformaticians and statisticians. Here, we describe a pipeline for the analysis of quantitative LC-MS data. Key components of this pipeline include experimental design (sample pooling, blocking, and randomization) as well as deconvolution and alignment of mass chromatograms to generate a matrix of molecular abundance profiles. An important challenge in LC-MS–based quantitation is to be able to accurately identify and assign abundance measurements to members of protein families. To address this issue, we implement a novel statistical method for inferring the relative abundance of related members of protein families from tryptic peptide intensities. This pipeline has been used to analyze quantitative LC-MS data from multiple biomarker discovery projects. We illustrate our pipeline here with examples from two of these studies, and show that the pipeline constitutes a complete workable framework for LC-MS–based differential quantitation. Supplementary material is available at .
ClusFCM: AN ALGORITHM FOR PREDICTING PROTEIN FUNCTIONS USING HOMOLOGIES AND PROTEIN INTERACTIONS
Authors: NGUYEN CAO , MANNINO MICHAEL , GARDINER KATHELEEN , CIOS KRZYSZTOF J.
Published: March 2008

We introduce a new algorithm, called ClusFCM, which combines techniques of clustering and fuzzy cognitive maps (FCM) for prediction of protein functions. ClusFCM takes advantage of protein homologies and protein interaction network topology to improve low recall predictions associated with existing prediction methods. ClusFCM exploits the fact that proteins of known function tend to cluster together and deduce functions not only through their direct interaction with other proteins, but also from other proteins in the network. We use ClusFCM to annotate protein functions for Saccharomyces cerevisiae (yeast), Caenorhabditis elegans (worm), and Drosophila melanogaster (fly) using protein–protein interaction data from the General Repository for Interaction Datasets (GRID) database and functional labels from Gene Ontology (GO) terms. The algorithm's performance is compared with four state-of-the-art methods for function prediction — Majority, χ2 statistics, Markov random field (MRF), and FunctionalFlow — using measures of Matthews correlation coefficient, harmonic mean, and area under the receiver operating characteristic (ROC) curves. The results indicate that ClusFCM predicts protein functions with high recall while not lowering precision. Supplementary information is available at .
FEATURE SELECTION IN VALIDATING MASS SPECTROMETRY DATABASE SEARCH RESULTS
Authors: FANG JIANWEN , DONG YINGHUA , WILLIAMS TODD D. , LUSHINGTON GERALD H.
Published: March 2008

Tandem mass spectrometry (MS/MS) combined with protein database searching has been widely used in protein identification. A validation procedure is generally required to reduce the number of false positives. Advanced tools using statistical and machine learning approaches may provide faster and more accurate validation than manual inspection and empirical filtering criteria. In this study, we use two feature selection algorithms based on random forest and support vector machine to identify peptide properties that can be used to improve validation models. We demonstrate that an improved model based on an optimized set of features reduces the number of false positives by 58% relative to the model which used only search engine scores, at the same sensitivity score of 0.8. In addition, we develop classification models based on the physicochemical properties and protein sequence environment of these peptides without using search engine scores. The performance of the best model based on the support vector machine algorithm is at 0.8 AUC, 0.78 accuracy, and 0.7 specificity, suggesting a reasonably accurate classification. The identified properties important to fragmentation and ionization can be either used in independent validation tools or incorporated into peptide sequencing and database search algorithms to improve existing software programs.
DERIVING TOPOLOGY AND SEQUENCE ALIGNMENT FOR THE HELIX SKELETON IN LOW-RESOLUTION PROTEIN DENSITY MAPS
Authors: LU YONGGANG , HE JING , STRAUSS CHARLIE E. M.
Published: March 2008

Cryoelectron microscopy (cryoEM) is an experimental technique to determine the three-dimensional (3D) structure of large protein complexes. Currently, this technique is able to generate protein density maps at 6–9 Å resolution, at which the skeleton of the structure (which is composed of α-helices and β-sheets) can be visualized. As a step towards predicting the entire backbone of the protein from the protein density map, we developed a method to predict the topology and sequence alignment for the skeleton helices. Our method combines the geometrical information of the skeleton helices with the Rosetta ab initio structure prediction method to derive a consensus topology and sequence alignment for the skeleton helices. We tested the method with 60 proteins. For 45 proteins, the majority of the skeleton helices were assigned a correct topology from one of our top ten predictions. The offsets of the alignment for most of the assigned helices were within ±2 amino acids in the sequence. We also analyzed the use of the skeleton helices as a clustering tool for the decoy structures generated by Rosetta. Our comparison suggests that the topology clustering is a better method than a general overlap clustering method to enrich the ranking of decoys, particularly when the decoy pool is small.
A SURVEY ON HAPLOTYPING ALGORITHMS FOR TIGHTLY LINKED MARKERS
Authors: LI JING , JIANG TAO
Published: March 2008

Two grand challenges in the postgenomic era are to develop a detailed understanding of heritable variation in the human genome, and to develop robust strategies for identifying the genetic contribution to diseases and drug responses. Haplotypes of single nucleotide polymorphisms (SNPs) have been suggested as an effective representation of human variation, and various haplotype-based association mapping methods for complex traits have been proposed in the literature. However, humans are diploid and, in practice, genotype data instead of haplotype data are collected directly. Therefore, efficient and accurate computational methods for haplotype reconstruction are needed and have recently been investigated intensively, especially for tightly linked markers such as SNPs. This paper reviews statistical and combinatorial haplotyping algorithms using pedigree data, unrelated individuals, or pooled samples.
TALI: LOCAL ALIGNMENT OF PROTEIN STRUCTURES USING BACKBONE TORSION ANGLES
Authors: MIAO XIJIANG , WADDELL PETER J. , VALAFAR HOMAYOUN
Published: March 2008

Torsion angle alignment (TALI) is a novel approach to local structural motif alignment, based on backbone torsion angles (ϕ, ψ) rather than the more traditional atomic distance matrices. Representation of a protein structure in the form of a sequence of torsion angles enables easy integration of sequence and structural information, and adopts mature techniques in sequence alignment to improve performance and alignment quality. We show that TALI is able to match local structural motifs as well as identify global structural similarity. TALI is also compared to other structure alignment methods such as DALI, CE, and SSM, as well as sequence alignment based on PSI-BLAST; TALI is shown to be equally successful as, or more successful than, these other methods when applied to challenging structural alignments. The inference of the evolutionary tree of class II aminoacyl-tRNA synthetase shows the potential for TALI in estimating protein structural evolution and in identifying structural divergence among homologous structures. Availability: .
Calmodulin in adult mammalian skeletal muscle: localization and effect on sarcoplasmic reticulum Ca2+ release
Authors: Rodney George G.
Published: March 2008

Calmodulin is a ubiquitous Ca2+ binding protein that binds to ryanodine rectors (RyR) and is thought to modulate its activity. Here we evaluated the effects of recombinant calmodulin on the rate of occurrence and spatial properties of Ca2+ sparks as an assay of activation in saponin-permeabilized mouse myofibers. Control myofibers exhibited a time-dependent increase and subsequent decrease in spark frequency. Recombinant wild-type calmodulin prevented the time-dependent appearance of Ca2+ sparks and decreased the derived Ca2+ flux from the sarcoplasmic reticulum during a spark by ∼37%. A recombinant Ca2+-insensitive form of calmodulin resulted in an instantaneous increase in spark frequency as well as an increase in the derived Ca2+ flux by ∼24%. Endogenous calmodulin was found to primarily localize to the Z-line. Surprisingly, removal of endogenous calmodulin did not alter the time dependence of Ca2+ spark appearance. These results indicate that calmodulin may not be essential for RyR1-dependent Ca2+ release in adult mammalian skeletal muscle.
Molecular mechanisms of epithelial cell-specific expression and regulation of the human anion exchanger (pendrin) gene
Authors: Adler Lior , Efrati Edna , Zelikovic Israel
Published: March 2008

Pendrin, a Cl−/anion exchanger encoded by the gene PDS, is highly expressed in the kidney, thyroid, and inner ear epithelia and is essential for bicarbonate secretion, iodide accumulation, and endolymph ion balance, respectively. This study aimed to define promoter regulatory elements essential for renal, thyroid, and inner ear epithelial cell-specific expression of human PDS (hPDS) and to explore the effect of ambient pH and aldosterone on hPDS promoter activity. Endogenous pendrin mRNA and protein were detected in renal HEK293, thyroid LA2, and inner ear VOT36 epithelial cell lines, but not in the fibroblast cell line, NIH3T3. A 4.2-kb hPDS 5′-flanking DNA sequence and consecutive 5′-deletion products were cloned into luciferase reporter vectors and transiently transfected into the above cell lines. Distinct differences in expression/activity of deduced positive/negative regulatory elements within the hPDS promoter between HEK293, LA2, and VOT36 cells were demonstrated, with only basal activity in NIH3T3 cells. Acidic pH (7.0–7.1) decreased and alkaline pH (7.6–7.7) increased hPDS promoter activity in transfected HEK293 and VOT36, but not in LA2 cells. Aldosterone (10−8 M) reduced hPDS promoter activity in HEK293 but had no effect in LA2 and VOT36 cells. These pH and aldosterone-induced effects on the hPDS promoter occurred within 96-bp and 89-bp regions, respectively, which likely contain distinct response elements to these modulators. Acidic pH and aldosterone decreased, and alkaline pH increased, endogenous pendrin mRNA level in HEK293 cells. In conclusion, pendrin-mediated HCO3− secretion in the renal tubule and anion transport in the endolymph may be regulated transcriptionally by systemic pH and aldosterone.
Redox regulation of diaphragm proteolysis during mechanical ventilation
Authors: McClung J. M. , Whidden M. A. , Kavazis A. N. , Falk D. J. , DeRuisseau K. C. , Powers S. K.
Published: March 2008

Prevention of oxidative stress via antioxidants attenuates diaphragm myofiber atrophy associated with mechanical ventilation (MV). However, the specific redox-sensitive mechanisms responsible for this remain unknown. We tested the hypothesis that regulation of skeletal muscle proteolytic activity is a critical site of redox action during MV. Sprague-Dawley rats were assigned to five experimental groups: 1) control, 2) 6 h of MV, 3) 6 h of MV with infusion of the antioxidant Trolox, 4) 18 h of MV, and 5) 18 h of MV with Trolox. Trolox did not attenuate MV-induced increases in diaphragmatic levels of ubiquitin-protein conjugation, polyubiquitin mRNA, and gene expression of proteasomal subunits (20S proteasome α-subunit 7, 14-kDa E2, and proteasome-activating complex PA28). However, Trolox reduced both chymotrypsin-like and peptidylglutamyl peptide hydrolyzing (PGPH)-like 20S proteasome activities in the diaphragm after 18 h of MV. In addition, Trolox rescued diaphragm myofilament protein concentration (μg/mg muscle) and the percentage of easily releasable myofilament protein independent of alterations in ribosomal capacity for protein synthesis. In summary, these data are consistent with the notion that the protective effect of antioxidants on the diaphragm during MV is due, at least in part, to decreasing myofilament protein substrate availability to the proteasome.
Cyclic GMP alters the firing rate and thermosensitivity of hypothalamic neurons
Authors: Wright Chadwick L. , Burgoon Penny W. , Bishop Georgia A. , Boulant Jack A.
Published: March 2008

The rostral hypothalamus, especially the preoptic-anterior hypothalamus (POAH), contains temperature-sensitive and -insensitive neurons that form synaptic networks to control thermoregulatory responses. Previous studies suggest that the cyclic nucleotide cGMP is an important mediator in this neuronal network, since hypothalamic microinjections of cGMP analogs produce hypothermia in several species. In the present study, immunohistochemisty showed that rostral hypothalamic neurons contain cGMP, guanylate cyclase (necessary for cGMP synthesis), and CNG A2 (an important cyclic nucleotide-gated channel). Extracellular electrophysiological activity was recorded from different types of neurons in rat hypothalamic tissue slices. Each recorded neuron was classified according to its thermosensitivity as well as its firing rate response to 2–100 μM 8-bromo-cGMP (a membrane-permeable cGMP analog). cGMP has specific effects on different neurons in the rostral hypothalamus. In the POAH, the cGMP analog decreased the spontaneous firing rate in 45% of temperature-sensitive and -insensitive neurons, an effect that is likely due to cGMP-enhanced hyperpolarizing K+ currents. This decreased POAH activity could attenuate thermoregulatory responses and produce hypothermia during exposures to cool or neutral ambient temperatures. Although 8-bromo-cGMP did not affect the thermosensitivity of most POAH neurons, it did increase the warm sensitivity of neurons in other hypothalamic regions located dorsal, lateral, and posterior to the POAH. This increased thermosensitivity may be due to pacemaker currents that are facilitated by cyclic nucleotides. If some of these non-POAH thermosensitive neurons promote heat loss or inhibit heat production, then their increased thermosensitivity could contribute to cGMP-induced decreases in body temperature.
Gene expression profiling in human skeletal muscle during recovery from eccentric exercise
Authors: Mahoney D. J. , Safdar A. , Parise G. , Melov S. , Fu Minghua , MacNeil L. , Kaczor J. , Payne E. T. , Tarnopolsky M. A.
Published: March 2008

We used cDNA microarrays to screen for differentially expressed genes during recovery from exercise-induced muscle damage in humans. Male subjects ( n = 4) performed 300 maximal eccentric contractions, and skeletal muscle biopsy samples were analyzed at 3 h and 48 h after exercise. In total, 113 genes increased 3 h postexercise, and 34 decreased. At 48 h postexercise, 59 genes increased and 29 decreased. On the basis of these data, we chose 19 gene changes and conducted secondary analyses using real-time RT-PCR from muscle biopsy samples taken from 11 additional subjects who performed an identical bout of exercise. Real-time RT-PCR analyses confirmed that exercise-induced muscle damage led to a rapid (3 h) increase in sterol response element binding protein 2 ( SREBP-2), followed by a delayed (48 h) increase in the SREBP-2 gene targets Acyl CoA:cholesterol acyltransferase ( ACAT)-2 and insulin-induced gene 1 ( insig-1). The expression of the IL-1 receptor, a known regulator of SREBP-2, was also elevated after exercise. Taken together, these expression changes suggest a transcriptional program for increasing cholesterol and lipid synthesis and/or modification. Additionally, damaging exercise induced the expression of protein kinase H11, capping protein Z alpha ( capZα), and modulatory calcineurin-interacting protein 1 ( MCIP1), as well as cardiac ankryin repeat protein 1 ( CARP1), DNAJB2, c-myc, and junD, each of which are likely involved in skeletal muscle growth, remodeling, and stress management. In summary, using DNA microarrays and RT-PCR, we have identified novel genes that respond to skeletal muscle damage, which, given the known biological functions, are likely involved in recovery from and/or adaptation to damaging exercise.
Effect of exercise and calorie restriction on biomarkers of aging in mice
Authors: Huffman Derek M. , Moellering Douglas R. , Grizzle William E. , Stockard Cecil R. , Johnson Maria S. , Nagy Tim R.
Published: March 2008

Unlike calorie restriction, exercise fails to extend maximum life span, but the mechanisms that explain this disparate effect are unknown. We used a 24-wk protocol of treadmill running, weight matching, and pair feeding to compare the effects of exercise and calorie restriction on biomarkers related to aging. This study consisted of young controls, an ad libitum-fed sedentary group, two groups that were weight matched by exercise or 9% calorie restriction, and two groups that were weight matched by 9% calorie restriction + exercise or 18% calorie restriction. After 24 wk, ad libitum-fed sedentary mice were the heaviest and fattest. When weight-matched groups were compared, mice that exercised were leaner than calorie-restricted mice. Ad libitum-fed exercise mice tended to have lower serum IGF-1 than fully-fed controls, but no difference in fasting insulin. Mice that underwent 9% calorie restriction or 9% calorie restriction + exercise, had lower insulin levels; the lowest concentrations of serum insulin and IGF-1 were observed in 18% calorie-restricted mice. Exercise resulted in elevated levels of tissue heat shock proteins, but did not accelerate the accumulation of oxidative damage. Thus, failure of exercise to slow aging in previous studies is not likely the result of increased accrual of oxidative damage and may instead be due to an inability to fully mimic the hormonal and/or metabolic response to calorie restriction.
Mechanisms underlying the long-term regulation of NHE3 by parathyroid hormone
Authors: Bezerra Camila Nogueira Alves , Girardi Adriana Castello Costa , Carraro-Lacroix Luciene Regina , Rebouças Nancy Amaral
Published: March 2008

The activity of the Na+/H+ exchanger NHE3 is regulated by a number of factors including parathyroid hormone (PTH). In the current study, we used a renal epithelial cell line, the opossum kidney (OKP) cell, to elucidate the mechanisms underlying the long-term effects of PTH on NHE3 transport activity and expression. We observed that NHE3 activity was reduced 6 h after addition of PTH, and this reduction persisted almost unaltered after 24 h. The decrease in activity was associated with diminished NHE3 cell surface expression at 6, 16, and 24 h after PTH addition, total cellular NHE3 protein at 16 and 24 h, and NHE3 mRNA abundance at 24 h. The lower levels of NHE3 mRNA were associated to a small, but significant, decrease in mRNA stability. Additionally, by analyzing the rat NHE3 gene promoter activity in OKP cells, we verified that the regulatory region spanning the segment −152 to +55 was mildly reduced under the influence of PTH. This effect was completely abolished by the presence of the PKA inhibitor KT 5720. In conclusion, long-term exposure to PTH results in reduction of NHE3 mRNA levels due to a PKA-dependent inhibitory effect on the NHE3 promoter and a small reduction of mRNA half-life, and decrease in the total amount of protein which is preceded by endocytosis of the apical surface NHE3. The decreased NHE3 expression is likely to be responsible for the reduction of sodium, bicarbonate, and fluid reabsorption in the proximal tubule consistently perceived in experimental models of PTH disorders.
Mesenchymal transition in kidney collecting duct epithelial cells
Authors: Ivanova Larissa , Butt Michael J. , Matsell Douglas G.
Published: March 2008

Progressive organ damage due to tissue scarring and fibrosis is a paradigm shared by numerous human diseases including chronic kidney disease. The purpose of this study was to confirm the hypothesis that collecting duct (CD) epithelial cells can undergo mesenchymal transition (EMT) in vitro. The mechanism by which CDs undergo EMT is complex and involves both early and late cellular events. Early events include rapid insulin-like growth factor (IGF)-induced Akt and GSK-3β phosphorylation, associated with early disruption of E-cadherin-β-catenin membrane colocalization, with translocation of E-cadherin to endosomes, with translocation of β-catenin to the nucleus, and with an increase in Snail expression. Transforming growth factor-β1, on the other hand, induced early activation of Smad3 and its translocation to the nucleus, Erk1/2 phosphorylation, and early disruption of membrane E-cadherin localization. The late consequences of these events included a phenotypic transformation of the cells to a mesenchymal morphology with associated increase in vimentin and α-smooth muscle actin protein expression and a decrease in total cellular E-cadherin expression, detectable as early as 24 h after stimulation.
Sensitization of pelvic afferent nerves in the in vitro rat urinary bladder-pelvic nerve preparation by purinergic agonists and cyclophosphamide pretreatment
Authors: Yu Yongbei , de Groat William C.
Published: March 2008

Effects of purinergic agonists (α,β-meATP and ATP) and cyclophosphamide-induced cystitis on bladder afferent nerve (BAN) activity were studied in an in vitro bladder-pelvic nerve preparation. Distension of the bladder induced spontaneous bladder contractions that were accompanied by multiunit afferent firing. Intravesical administration of 40 and 130 μM α,β-meATP increased afferent firing from 27 ± 3 to 53 ± 6 and 61 ± 2 spikes/s, respectively, but did not change the maximum amplitude of spontaneous bladder contractions. Electrical stimulation on the surface of the bladder elicited action potentials (AP) in BAN. α,β-meATP decreased the voltage threshold from 9.0 ± 1.2 to 3.5 ± 0.5 V (0.15-ms pulse duration) and increased the area of the APs (82% at 80-V stimulus intensity). These effects were blocked by TNP-ATP (30 μM). ATP (2 mM) applied in the bath produced similar changes in BAN activity. These effects were blocked by bath application of PPADS (30 μM). Neither TNP-ATP nor PPADS affected BAN activity induced by distension of the bladder. Cystitis induced by pretreatment of the rats with cyclophosphamide (100 mg/kg ip) increased afferent firing in response to isotonic bladder distension (10–40 cmH2O), decreased the threshold, and increased the area of evoked APs. The increase in afferent firing at 10 cmH2O intravesical pressure was reduced 52% by PPADS. These results indicate that purinergic agonists acting on P2X receptors and cystitis induced by cyclophosphamide can increase excitability of the BANs.
Changes in Granule Cell Firing Rates Precede Locally Recorded Spontaneous Seizures by Minutes in an Animal Model of Temporal Lobe Epilepsy
Authors: Bower Mark R. , Buckmaster Paul S.
Published: March 2008

Although much is known about persistent molecular, cellular, and circuit changes associated with temporal lobe epilepsy, mechanisms of seizure onset remain unclear. The dentate gyrus displays many persistent epilepsy-related abnormalities and is in the mesial temporal lobe where seizures initiate in patients. However, little is known about seizure-related activity of individual neurons in the dentate gyrus. We used tetrodes to record action potentials of multiple, single granule cells before and during spontaneous seizures in epileptic pilocarpine-treated rats. Subsets of granule cells displayed four distinct activity patterns: increased firing before seizure onset, decreased firing before seizure onset, increased firing only after seizure onset, and unchanged firing rates despite electrographic seizure activity in the immediate vicinity. No cells decreased firing rate immediately after seizure onset. During baseline periods between seizures, action potential waveforms and firing rates were similar among the four subsets of granule cells in epileptic rats and in granule cells of control rats. The mean normalized firing rate of granule cells whose firing rates increased before seizure onset deviated from baseline earliest, beginning 4 min before dentate gyrus electrographic seizure onset, and increased progressively, more than doubling by seizure onset. It is generally assumed that neuronal firing rates increase abruptly and synchronously only when electrographic seizures begin. However, these findings show heterogeneous and gradually building changes in activity of individual granule cells minutes before spontaneous seizures.
Noah Webster and the Invention of Immigration
Authors: Shumsky Neil Larry
Published: March 2008

Like all lexicographers, Noah Webster built his dictionaries on the works of others. But in the case of the verb to immigrate and its derivatives, he coined a new definition, one that has had a profound impact on how Americans conceive of the phenomenon of immigration.
The Myth of Imperiled Whiteness and Ethan Frome
Authors: Ammons Elizabeth
Published: March 2008

Blanketed in whiteness—bleak, frozen, snowed in—the widely read and taught Ethan Frome has a little-recognized racist subtext. Expressing early-twentieth-century nativist anxieties about immigrants of color, Wharton warns that old, white, Yankee New England is disappearing, its farms withering, as swarthy foreigners increasingly dominate the newly industrialized landscape.
Shopping for the Nation: Women's China Collecting in Late-Nineteenth-Century New England
Authors: Lockwood J. Samaine
Published: March 2008

Hunting for china in rural New England was more than a shopping expedition; it was a patriotic act, a tribute to America's commerce, and a form of historic preservation. Against the backdrops of nativism, the Arts and Crafts movement, and the Colonial Revival, late-nineteenth-century women sought to return the nation to its Anglo-American roots.
Captain John Smith and the Campaign for New England: A Study in Early Modern Identity and Promotion
Authors: Woodward Walter W.
Published: March 2008

In print, on maps, and in person, Captain John Smith tirelessly promoted English-controlled northeast North America as a “new” England. His creative, multi-pronged campaign reveals the difficulties of raising venture capital for English Atlantic world colonization and offers an important example of early modern place branding and regional identity creation.
Effects of Finescale Debris on Near-Surface Tornado Dynamics
Authors: Lewellen D. C. , Gong Baiyun , Lewellen W. S.
Published: March 2008

Debris clouds provide an important visual signature of tornadoes and can potentially significantly affect the wind structure, damage potential, and Doppler radar measurements of tornado wind speeds. To study such issues, the dynamics of finescale debris have been added to an existing high-resolution large-eddy simulation model of tornado dynamics. A so-called “two-fluid” or “Eulerian–Eulerian” approach is employed, together with a surface layer model for lofting and depositing debris. In this paper the debris implementation is described, three critical dimensionless parameters governing tornado debris effects are identified, and sample results from a large set of simulations of tornadoes with idealized debris are presented. The results demonstrate that the accumulation of small-scale debris within the surface layer and corner flow can significantly alter the wind speeds and flow structure of the tornado vortex within a few hundred meters of the surface. They suggest that the total mass of the debris cloud can reach tens of thousands of tons. Near the surface, the debris mass loading can be well above 1, the peak mean velocities can be reduced by as much as half, and the total momentum (air plus debris) can either significantly increase or decrease. Local air and debris velocities can differ significantly and in a nontrivial fashion, thereby complicating the interpretation of Doppler radar measurements of tornado structure. Debris fluctuations, centrifuging, negative buoyancy, and angular momentum transport are all significant mechanisms for the debris effects. A negative physical feedback reduces the sensitivity of the results to changes in the parameterization of the surface debris fluxes. The realistic simulation of tornado debris clouds and surface damage tracks should prove useful in identifying the dynamics governing their observed counterparts.
Regional Analysis of Trend and Step Changes Observed in Hydroclimatic Variables around the Colorado River Basin
Authors: Miller W. Paul , Piechota Thomas C.
Published: March 2008

Recent research has suggested that changes in temperature and precipitation events due to climate change have had a significant impact on the availability and timing of streamflow. In this study, monthly temperature and precipitation data collected over 29 climate divisions covering the entire Colorado River basin and monthly natural flow data from 29 U.S. Geological Survey (USGS) gauge locations along the Colorado River are investigated for trend or step changes using parametric and nonparametric statistical tests. Temperature increases are persistent (at least 10 climate divisions over 6 months in trend analysis) throughout the year over the Colorado River basin, whereas precipitation only notably increased over 17 climate divisions (during trend analysis) during February and remained relatively unchanged otherwise. These results correspond with changes in naturalized streamflow throughout the year. Streamflow increases are recorded between November and February but exhibit a decreasing trend over the traditional peak runoff season (April through July). Under trend analysis, 18 flow stations exhibited increasing trends in January and 19 flow stations exhibited decreasing trends in June. It is likely that increasing temperature trends have affected the character of precipitation in the Colorado River basin, causing a change in the timing of runoff events.
The Optimal Bulk Wind Differential Depth and the Utility of the Upper-Tropospheric Storm-Relative Flow for Forecasting Supercells
Authors: Houston Adam L. , Thompson Richard L. , Edwards Roger
Published: March 2008

An analysis of 4 yr of Rapid Update Cycle-2 (RUC-2) derived soundings in proximity to radar-observed supercells and nonsupercells is conducted in an effort to answer two questions: 1) over what depth is the fixed-layer bulk wind differential (BWD; the vector difference between the wind velocity at a given level and the wind velocity at the surface) the best discriminator between supercell and nonsupercell environments and 2) does the upper-tropospheric storm-relative flow (UTSRF) discriminate between the environments of supercells and nonsupercells? Previous climatologies of sounding-based supercell forecast parameters have documented the ability of the 0–6-km BWD in delineating supercell from nonsupercell environments. However, a systematic examination of a wide range of layers has never been documented. The UTSRF has previously been tested as a parameter for discriminating between supercell and nonsupercell environments and there is some evidence that supercells may be sensitive to the UTSRF. However, this sensitivity may be a consequence of the correlation between UTSRF and the surface to midtropospheric BWD. Accurately assessing the ability of the UTSRF to distinguish between supercell and nonsupercell environments requires controlling for the surface to midtropospheric BWD.

It is shown that the bulk wind differential within the 0–5-km layer delineates best between supercell and nonsupercell environments. Analysis of the UTSRF demonstrates that even when not controlling for the BWD, the UTSRF has limited reliability in forecasting supercells. The lack of merit in using the UTSRF to forecast supercells is particularly evident when it is isolated from the BWD. Because the UTSRF and BWD are not independent, controlling for the BWD when examining the UTSRF reveals that the UTSRF is not a fundamental parameter that can be used to distinguish supercell from nonsupercell environments. Therefore, this work demonstrates that the UTSRF is an unreliable metric for forecasting supercell events.
Performing Gender in the Workplace
Authors: Lester Jaime
Published: March 2008

Organizational cultures shape and reinforce socially appropriate roles for men and women. Drawing on a performativity framework, which assumes that gender is socially constructed through gendered “performances,” this study employs interviews with and observations of six women faculty members to examine how dominant discourses define and maintain the formation of gender roles within a community college context. The experiences of one of these faculty members, a welding instructor, are highlighted. Results indicate that the women faculty members performed a variety of stereotypical feminine gender roles based on (a) socialization experiences external to the college, (b) socialization within the college's organizational culture, and (c) the individual's construction and negotiation of gender identity.
Editor's Choice Essay
Authors: Katsinas Stephen G.
Published: March 2008

Raymond J. Young (1923—2007) played a key role in the post—World War II development of community colleges in Illinois, Michigan, Ohio, and elsewhere. This article describes his scholarly and professional contributions in developing “bottom-up,” grassroots citizen's participatory studies that led to the establishment 60 community colleges in 33 states between 1955 and 1976.
A Preliminary Examination of Trauma History, Locus of Control, and PTSD Symptom Severity in African American Women
Authors: Hood Sarah K. , Carter Michele M.
Published: March 2008

Prior research has established a relationship between external locus of control and posttraumatic stress disorder (PTSD) symptom severity among Caucasians. There is also evidence that African Americans tend to exhibit an elevated external locus of control. However, the relationship between external control and PTSD symptom severity has not been examined among African American women. Using a sample of African American adult female volunteers who self-reported a history of child abuse and/or sexual or physical assault in adulthood, the present study sought to examine the relationships between trauma history, locus of control, and PTSD symptom severity. Participants in the child/adult trauma group reported fewer PTSD symptoms than those with a history of adult trauma only. Contrary to expectations, however, trauma history was not related to locus of control in this sample of African American women. It is possible that factors associated with African American socialization may serve as a buffer to the development or maintenance of PTSD.
Respiratory Toxicologic Pathology of Inhaled Diacetyl in Sprague-Dawley Rats
Authors: Hubbs Ann F. , Goldsmith William T. , Kashon Michael L. , Frazer David , Mercer Robert R. , Battelli Lori A. , Kullman Gregory J. , Schwegler-Berry Diane , Friend Sherri , Castranova Vincent
Published: March 2008

Inhalation of butter flavoring vapors by food manufacturing workers causes an emerging lung disease clinically resembling bronchiolitis obliterans. Diacetyl, an α-diketone, is a major component of these vapors. In rats, we investigated the toxicity of inhaled diacetyl at concentrations of up to 365 ppm (time weighted average), either as six-hour continuous exposures or as four brief, intense exposures over six hours. A separate group inhaled a single pulse of ~1800 ppm diacetyl (92.9 ppm six-hour average). Rats were necropsied 18 to 20 hours after exposure. Diacetyl inhalation caused epithelial necrosis and suppurative to fibrinosuppurative inflammation in the nose, larynx, trachea, and bronchi. Bronchi were affected at diacetyl concentrations of 294.6 ppm or greater; the trachea and larynx were affected at diacetyl concentrations of 224 ppm or greater. Both pulsed and continuous exposure patterns caused epithelial injury. The nose had the greatest sensitivity to diacetyl. Ultrastructural changes in the tracheal epithelium included whorling and dilation of the rough endoplasmic reticulum, chromatin clumping beneath the nuclear membrane, vacuolation, increased inter-cellular space and foci of denuded basement membrane. Edema and hemorrhage extended into the lamina propria. These findings are consistent with the conclusion that inhaled diacetyl is a respiratory hazard.
From Autonomy to Reciprocity, or Vice Versa? French Personalism's Contribution to a New Perspective on Self-Directed Learning
Authors: Eneau Jerome
Published: March 2008

After many years of research focused on the individual and psychological aspects of self-directed learning, the field has taken into consideration the context and situation surrounding the education of an adult, placing the development of individual autonomy into a constructivist perspective. But it is only recently, in France at least, that researchers have begun to look more closely at the interpersonal dimensions of learning and that new theoretical approaches have introduced the ideas of reciprocity and exchange, allowing the consideration of the construction of this autonomy in new ways. Referring particularly to French personalist philosophy, following Mounier's and Ricœur's line of thought, Labelle's theory of educational reciprocity reverses the perspective, seeing the process of an adult's autonomization as the result of the reciprocal relationship between him or her and another person.
Process-Based Forgiveness Interventions: A Meta-Analytic Review
Authors: Lundahl Brad W. , Taylor Mary Jane , Stevenson Ryan , Roberts K. Daniel
Published: March 2008

Objective: To investigate the impact of forgiveness interventions designed to help individuals who have suffered because of betrayals, offenses, or victimization. Forgiveness is believed to be a mechanism through which individuals can experience increases in hope and positive emotions and relief from negative emotions, cognitions, and behaviors. Method: Fourteen published reports of process-based forgiveness interventions that included a comparison group are meta-analyzed. Results/Conclusions: Samples that received forgiveness interventions forgave more (effect size [ES] = .82) and enjoyed increased positive affect (ES = .81) and self-esteem (ES = .60) and less negative affect (ES = .54). Such gains were largely maintained at follow-up periods. Individually delivered programs are superior to group delivery, and some forgiveness programs are superior to others. Further moderators are discussed.
On the Meaning and Measurement of Engagement in Youth Residential Treatment Centers
Authors: Cunningham Wm. Scott , Duffee David E. , Yufan Huang  , Steinke Camela M. , Naccarato Toni
Published: March 2008

Objective: This study describes the development of an engagement scale for use with youth in residential treatment centers. Engagement includes attitude about treatment, bond with providers, and participation in treatment activities. Method: Interview data were collected at the midpoint in residence of 130 youth in two centers. Items were selected to capture practitioners' description of three related concepts in a logic model. The authors conducted confirmatory factor analysis and examined interitem reliability. Results: Results indicate a single underlying factor, which the authors label engagement, an acceptable level of reliability, and strong content validity. Conclusion: The scale integrates several concepts in the treatment process literature and might serve to assess youth engagement in residential settings. Additional study should examine construct and construct validity.
Mycobacterium aviumcomplex disease: prognostic implication of high-resolution computed tomography findings
Authors: Kuroishi S. , Nakamura Y. , Hayakawa H. , Shirai M. , Nakano Y. , Yasuda K. , Suda T. , Nakamura H. , Chida K.
Published: March 2008

To evaluate the prognostic implications of computed tomography (CT) findings in assessing responses to treatment inMycobacterium aviumcomplex (MAC) pulmonary disease without underlying lung disease, high-resolution (HR)CT findings were correlated based on the results of sputum conversion after anti-MAC therapy.

A total of 59 patients underwent HRCT before treatment and the therapeutic efficacy was evaluated by the results of sputum conversion.

Atelectasis, cavities and pleural thickening on HRCT were significantly more frequent and extensive among patients in the sputum nonconverted group than among those in the converted group. Furthermore, bronchiectasis was also significantly more extensive among patients in the nonconverted group, even though there was no significant difference in frequency between these two groups.

These results suggest that high-resolution computed tomography findings are good predictors of response to treatment inMycobacterium aviumcomplex pulmonary disease.
C-reactive protein, obesity, atopy and asthma symptoms in middle-aged adults
Authors: Butland B. K. , Strachan D. P. , Rudnicka A. R.
Published: March 2008

Recent research has suggested an association between circulating C-reactive protein (CRP) and adult asthma, confined to those without evidence of allergic predisposition. The current authors investigated the role of smoking and obesity as possible explanations for this relationship.

At 44–45 yrs of age, members of the British 1958 birth cohort participated in a biomedical survey involving the measurement of the following: CRP; the specific immunoglobulin E to grass, cat and dust mite; standing height; and weight. Information on asthma and related symptoms was collected by computer-aided interview when the subjects were 42 yrs of age. Complete data were available for a total of 6,490 subjects.

CRP levels were positively correlated with the body mass index (BMI) and were found to be higher among females when compared with males, and higher among heavy smokers (≥20 cigarettes·day−1) when compared with never-smokers. After adjustment for sex and region, the odds ratios, comparing asthma prevalence in subjects above the fourth CRP quartile with subjects below the first quartile, were 1.85 (95% confidence interval 1.15–2.99) for nonatopics and 0.94 (0.62–1.41) for atopics, changing to 1.36 (0.80–2.32) and 1.07 (0.67–1.69), respectively, when additionally adjusted for smoking and BMI.

Any association between C-reactive protein and asthma prevalence confined to nonatopics may be due to confounding factors. Alternatively, it may reflect a more general association of C-reactive protein with smoking-related obstructive airways disease.
Modulation of bleomycin-induced lung fibrosis by serotonin receptor antagonists in mice
Authors: Fabre A. , Marchal-Sommé J. , Marchand-Adam S. , Quesnel C. , Borie R. , Dehoux M. , Ruffié C. , Callebert J. , Launay J-M. , Hénin D. , Soler P. , Crestani B.
Published: March 2008

Serotonin (5-hydroxytryptamine; 5-HT) is known to increase proliferation and collagen synthesis by fibroblasts. Two receptor subtypes, 5-HT2A and 5-HT2B, have been shown to play the most important roles in the lung.

In the present study, the role of serotonin in lung fibrosis was investigated using the bleomycin mouse model.

Serotonin concentrations in lung homogenates increased significantly over the time course of bleomycin-induced fibrosis, with a maximum at day seven. The expression of serotonin receptors 5-HT2A and 5-HT2B increased in the lung after bleomycin treatment, as assessed by PCR, specific binding and immunohistochemistry. Blockage of 5-HT2A receptors by ketanserin and 5-HT2B receptors by SB215505 reduced bleomycin-induced lung fibrosis, as demonstrated by reduced lung collagen content and reduced procollagen 1 and procollagen 3 mRNA expression. Serotonin antagonists promoted an antifibrotic environment by decreasing the lung mRNA levels of transforming growth factor-β1, connective growth factor and plasminogen activator inhibitor-1 mRNA, but had minimal effects on lung inflammation as assessed by bronchoalveolar lavage cytology analysis. Interestingly, the 5-HT2B receptor was strongly expressed by fibroblasts in the fibroblastic foci in human idiopathic pulmonary fibrosis samples.

In conclusion, the present study showed involvement of serotonin in the pathophysiology of bleomycin-induced lung fibrosis in mice and identified it as a potential therapeutic target in lung fibrotic disorders.
Effects of inhaled human insulin on airway lining fluid composition in adults with diabetes
Authors: Liu M. C. , Riese R. J. , Van Gundy K. , Norwood P. , Sullivan B. E. , Schwartz P. F. , Teeter J. G.
Published: March 2008

Inhaled human insulin (Exubera® (human insulin of rDNA origin) Inhalation Powder) causes small, early and reversible changes in pulmonary function in subjects with diabetes mellitus. The present study assessed whether changes occur in cellular and soluble constituents of airway lining fluid consistent with inflammation as a possible cause for Exubera®-associated lung function alterations.

Two 31-week, open-label, sequential design phase 2 studies were conducted, one with 20 subjects with type 1 and one with 24 subjects with type 2 diabetes. After run-in, all subjects received subcutaneous insulin for 12 weeks, followed after 1 week by 12 weeks of Exubera®. Bronchoalveolar lavage fluid cell counts and protein constituents were determined at baseline, after 12 weeks of subcutaneous insulin and after 12 weeks of Exubera®.

Baseline cellular and soluble constituents of lavage fluid were similar to those reported for nondiabetic adults. Exubera® produced no consistent clinically or statistically significant changes in total or differential lavage fluid cell counts or protein concentrations, even though Exubera®-associated changes in pulmonary function are known to be fully manifest within 12 weeks.

Therefore, 12 weeks of Exubera® treatment is not associated with evidence of pulmonary inflammation. The treatment effects on lung function observed in Exubera® trials are not caused by lung inflammation.