bluuebunny/crossref_metadata_2025_split huggingface dataset:
Calculating the Statistical Significance of Changes in Pathway Activity From Gene Expression Data
Authors: Rahnenführer Jörg , Domingues Francisco S , Maydt Jochen , Lengauer Thomas 
Published: December 2005

We present a statistical approach to scoring changes in activity of metabolic pathways from gene expression data. The method identifies the biologically relevant pathways with corresponding statistical significance. Based on gene expression data alone, only local structures of genetic networks can be recovered. Instead of inferring such a network, we propose a hypothesis-based approach. We use given knowledge about biological networks to improve sensitivity and interpretability of findings from microarray experiments.Recently introduced methods test if members of predefined gene sets are enriched in a list of top-ranked genes in a microarray study. We improve this approach by defining scores that depend on all members of the gene set and that also take pairwise co-regulation of these genes into account. We calculate the significance of co-regulation of gene sets with a nonparametric permutation test. On two data sets the method is validated and its biological relevance is discussed. It turns out that useful measures for co-regulation of genes in a pathway can be identified adaptively.We refine our method in two aspects specific to pathways. First, to overcome the ambiguity of enzyme-to-gene mappings for a fixed pathway, we introduce algorithms for selecting the best fitting gene for a specific enzyme in a specific condition. In selected cases, functional assignment of genes to pathways is feasible. Second, the sensitivity of detecting relevant pathways is improved by integrating information about pathway topology. The distance of two enzymes is measured by the number of reactions needed to connect them, and enzyme pairs with a smaller distance receive a higher weight in the score calculation.
A Nonparametric Dimension Test of the Term Structure
Authors: Gil-Bazo Javier , Rubio Gonzalo 
Published: December 2005

Abstract
In an economy with multiple sources of risk, the short-term interest rate does not capture all the information that determines the conditional distribution of bond yields. This is also true for path-dependent term structure models. In either case, the current short rate level is not a sufficient statistic for the conditional density of future short rates. This paper studies the empirical relevance of both issues from a time-series nonparametric perspective. The analysis is formulated as a test for the dependence of the short rate drift and diffusion on variables other than the short rate, and exploits Ait-Sahalia, Bickel, and Stocker (2001) dimension reduction method. The paper explores the finite sample performance of the method and applies the test to US interest rate data. Results reject a single-factor Markovian model, although conclusions are sensitive to the choice of additional conditioning variables.
The Long Memory of the Efficient Market
Authors: Lillo Fabrizio , Farmer J. Doyne 
Published: December 2005

Abstract
For the London Stock Exchange we demonstrate that the signs of orders obey a long-memory process. The autocorrelation function decays roughly as a power law with an exponent of 0.6, corresponding to a Hurst exponent H = 0.7. This implies that the signs of future orders are quite predictable from the signs of past orders; all else being equal, this would suggest a very strong market inefficiency. We demonstrate, however, that fluctuations in order signs are compensated for by anti-correlated fluctuations in transaction size and liquidity, which are also long-memory processes that act to make the returns whiter. We show that some institutions display long-range memory and others don’t.
Neural Tests for Conditional Heteroskedasticity in ARCH-M Models
Authors: de Peretti Christian , Siani Carole 
Published: December 2005

Abstract
This paper deals with tests for detecting conditional heteroskedasticity in ARCH-M models using three kinds of methods: neural networks techniques, bootstrap methods and both combined.As regards the ARCH models, Péguin-Feissolle (2000) developed tests based on the modelling techniques with neural network. However, as regards the ARCH-M models, a nuisance parameter is not identified and the tests are not applicable. To solve this problem, we propose to adapt these neural tests to Davies procedure (1987) leading to new tests. The performance of these latter tests are compared with those of Bera and Ra test (1995).However, Bera and Ra test has not really satisfactory performance and suffer from serious size distortion. Our neural test will have the same problem. To solve this second problem, without loss of power, we apply parametric and nonparametric bootstrap methods on the underlying test statistics.Lastly, to examine the size and the power properties of the tests in small samples, Monte Carlo simulations are carried out with various standard and non-standard models for conditional heteroskedasticity as to illustrate a variety of situations. In addition, the graphical presentation of Davidson and MacKinnon (1998a) is used to show the "true" power of the tests and not only the (nominal) power, as it is often the case, that can be meaningless.
Evaluation of ligament fibroblast viability in ruptured cranial cruciate ligament of dogs
Authors: Hayashi Kei , Frank Joseph D. , Hao Zhengling , Schamberger Gwenn M. , Markel Mark D. , Manley Paul A. , Muir Peter 
Published: December 2005

AbstractObjective—To determine fibroblast viability, assess development of apoptosis, and evaluate tissue hypoxia via histochemical, in-situ hybridization, or immunohistochemical staining in ruptured and intact cranial cruciate ligaments (CCLs) of dogs.Animals—32 dogs with ruptured CCLs, and 8 aged and 19 young dogs with intact CCLs.Procedure—Markers of cell viability (lactate dehydrogenase [LDH]), apoptosis (terminal deoxynucleatidyl transferase-mediated deoxyuridine triphosphate-nick end labeling [TUNEL] method), and hypoxia (hypoxiainducible factor-1α [HIF-1α] monoclonal antibody) were applied to CCL specimens; positive cells were assessed objectively (LDH) and subjectively (TUNEL and HIF-1α) in the main axial tissue component (core) and synovial intima and subintima (epiligamentous tissue).Results—Viable fibroblasts were seen in all intact and ruptured CCLs. More nonviable cells were found in the core regions of ruptured CCLs and intact CCLs of young dogs than in the epiligamentous regions. Number of nonviable cells in the core region of ruptured CCLs was greater than that in intact CCLs of young and aged dogs, whereas the number in the epiligamentous region was similar in all specimens. The TUNEL and HIF-1αstaining was only found in the epiligamentous region of ruptured CCLs.Conclusions and Clinical Relevance—Ruptured CCLs contained a high number of nonviable cells but not a great number of apoptotic cells. Repair processes in the epiligamentous region of the CCL include a metabolic response to hypoxia, suggesting that necrosis of ligament fibroblasts and transformation of surviving cells to a spheroid phenotype may be a response to hypoxia cause by microinjury or inadequate blood flow. (Am J Vet Res2003;64:1010–1016)
Seasonal changes in plasma concentrations of cecum-derived amines in clinically normal ponies and ponies predisposed to laminitis
Authors: Bailey Simon R. , Katz Lisa M. , Berhane Yoel , Samuels Tim , Brauvere Nicholas De , Marr Celia M. , Elliott Jonathan 
Published: December 2005

AbstractObjective—To measure concentrations of amines formed in the cecum of clinically normal ponies, determine amine concentrations in plasma samples collected in spring and winter, and compare concentrations of amines and serotonin in plasma samples obtained from clinically normal ponies and ponies predisposed to laminitis.Sample Population—Cecal contents obtained from 10 ponies euthanatized at an abattoir and blood samples obtained from 42 adult ponies.Procedure—Cecal contents were assayed for amines by high-performance liquid chromatography (HPLC). Blood samples were collected at various times of the year from 20 ponies predisposed to acute laminitis and 22 clinically normal ponies. Plasma serotonin concentration was measured by HPLC, and tryptamine (TRP), tyramine (TYR), phenylethylamine (PEA), and isoamylamine (IAA) were measured by liquid chromatography- mass spectrometry.Results—15 amines were identified in cecal contents. Plasma TRP, TYR, PEA, and IAA concentrations ranged from 10pM to 100nM in both groups of ponies. Plasma concentrations of serotonin or other amines did not differ between clinically normal ponies and those predisposed to laminitis; however, significantly higher concentrations of TRP, PEA, and IAA were found in samples obtained in the spring, compared with winter samples.Conclusions and Clinical Relevance—Various amines are found in the cecum of ponies, several of which can be detected in the plasma. Concentrations increase significantly in the spring and may reach concentrations close to the threshold for causing vasoconstriction. Release of amines from the cecum into the systemic circulation may contribute to hemodynamic disturbances in horses and ponies with acute laminitis. (Am J Vet Res2003;64:1132–1138)
Serum concentrations of pepsinogen A in healthy dogs after food deprivation and after feeding
Authors: Suchodolski Jan S. , Steiner Jörg M. , Ruaux Craig G. , Williams David A. 
Published: December 2005

Abstract

Objective—To develop and validate an ELISA for
measurement of serum canine pepsinogen A (cPG A)
as a diagnostic marker of gastric disorders in dogs
and to measure serum cPG A in healthy dogs after
food deprivation and after feeding.

Sample Population—Sera from 72 healthy dogs.

Procedure—A sandwich ELISA was developed and
validated. The reference range for serum concentrations
of cPG A was determined in 64 healthy dogs.
Postprandial changes in serum concentrations of cPG
A were evaluated in 8 healthy dogs.

Results—Assay sensitivity was 18 µg/L, and the maximum
detectable concentration was 1,080 µg/L. The
observed-to-expected ratio (O:E) for 3 serial dilutions
of 3 serum samples ranged from 69.3 to 104.1%. The
O:E for 3 serum samples spiked with 8 concentrations
of cPG A ranged from 58.8 to 120.4%.
Coefficients of variation for intra- and interassay variability
of 3 serum samples ranged from 7.6 to 11.9%
and from 10.1 to 13.1%, respectively. Mean ± SD
serum concentration of cPG A in healthy dogs was
63.8 ± 31.0 µg/L and the reference range was 18 to
129 µg/L. Significant increases in serum concentrations
of cPG A were observed between 1 and 7 hours
after feeding.

Conclusions and Clinical Relevance—The ELISA for
measuring cPG A was sufficiently sensitive, linear,
accurate, precise, and reproducible for clinical use.
Serum concentrations of cPG A increase substantially
after feeding, which should be taken into account
when conducting clinical studies. (Am J Vet Res 2003;64:1146–1150)
Effect of oral administration of low doses of pentobarbital on the induction of cytochrome P450 isoforms and cytochrome P450-mediated reactions in immature Beagles
Authors: Kawalek Joseph C. , Howard Karyn D. , Farrell Dorothy E. , Derr Janice , Cope Carol V. , Jackson Jean D. , Myers Michael J. 
Published: December 2005

AbstractObjective—To determine the effect of oral administration of low doses of pentobarbital on cytochrome P450 (CYP) isoforms and CYP-mediated reactions in immature Beagles.Animals—42 immature (12-week-old) Beagles.Procedure—Dogs were grouped and treated orally as follows for 8 weeks: low-dose pentobarbital (50 µg/d; 4 males, 4 females), mid-dose pentobarbital (150 µg/d; 4 males, 4 females), high-dose pentobarbital (500 µg/d; 4 males, 4 females), positive-pentobarbital control (10 mg/kg/d; 2 males, 2 females), positivephenobarbital control (10 mg/kg/d; 2 males, 2 females), and negative control (saline [0.9% NaCl] solution; 5 males, 5 females). Serum biochemical and hematologic values were monitored. On necropsy examination, organ weights were determined, and histologic evaluation of tissue sections of liver, kidney, small intestine, testes, epididymis, and ovaries was performed. Hepatic and intestinal drug-metabolizing enzyme activities were measured, and relative amounts of CYP isoforms were determined by western blot analysis.Results—The amount of a hepatic CYP2A-related isoform in dogs from the high-dose pentobarbital treatment group was twice that of dogs from the negative control group. CYP2C was not detectable in small intestinal mucosa of dogs from the negative control group; measurable amounts of CYP2C were found in dogs from the various (low-, mid-, and high-dose) pentobarbital treatment groups and from positive-pentobarbital and positive phenobarbital control groups. Several CYP-mediated reactions increased in a dosedependent manner. The lowest calculated effective dose of pentobarbital ranged from 200 to 450 µg/d.Conclusions and Clinical Relevance—Several CYP isoforms and their associated reactions were induced in dogs by oral administration of low amounts of pentobarbital. (Am J Vet Res2003;64:1167–1175)
Evaluation of survival of Actinobacillus pleuropneumoniae and Haemophilus parasuis in four liquid media and two swab specimen transport systems
Authors: Río Maria L. del , Gutiérrez Beatris , Gutiérrez Cesar B. , Monter Jose L. , Ferri Elias F. Rodríguez 
Published: December 2005

Abstract

Objective—To determine duration and rates of recovery
of Actinobacillus pleuropneumoniae and
Haemophilus parasuis from 4 liquid media and 2 swab
specimen transport systems and compare findings
with those of Escherichia coli.

Sample Population—One strain each of A pleuropneumoniae(
biovar 1, serotype 1), H parasuis (serovar
5), and E coli (serotype O149:K91:H19).

Procedure—Strains were incubated in brain heart
infusion broth supplemented with horse serum and
other nutrients or in horse serum alone, with and
without nicotinamide-adenine dinucleotide in both
instances, for 150 days at 4°C or room temperature
(21°C). Similarly, strains were tested in Stuart and
Amies transport systems after storage at room temperature
for 8 days.

Results—Colony counts greater than those of the initial
inoculum were observed after incubation in horse
serum for A pleuropneumoniae but not for H parasuis.
Overall, incubation at 4°C in the 4 liquid media
resulted in longer recovery duration and higher rates
than at room temperature. Culture of H parasuis
resulted in lower recovery rates and shorter durations
of recovery than culture of A pleuropneumoniae,
except for culture in horse serum. Haemophilus parasuis
survived longer than A pleuropneumoniae in the
transport systems, and all organisms survived longer
in the Amies system.

Conclusions and Clinical Relevance—Survival of A
pleuropneumoniae and H parasuis indicated that horse
serum prolongs survivability, which may result in exposure
of more animals during a prolonged period. The
Amies system might be a good choice for collection of
clinical samples from animals, especially for recovery
of H parasuis. (Am J Vet Res 2003;64:1176–1180)
Determination of calcium fractionation in dogs with chronic renal failure
Authors: Schenck Patricia A. , Chew Dennis J. 
Published: December 2005

AbstractObjective—To determine concentrations of calcium (total [tCa], ionized [iCa], protein-bound [pCa], and complexed [cCa]) in dogs with chronic renal failure (CRF).Animals—23 dogs with CRF.Procedure—Serum calcium was fractionated by use of a micropartition system. Total calcium and iCa concentrations and pH were measured in unfractionated serum, and tCa concentration was measured in the ultrafiltrate. The pCa fraction was calculated by subtracting tCa of the ultrafiltrate from tCa concentration of unfractionated serum. The iCa concentration in unfractionated serum was subtracted from tCa concentration in the ultrafiltrate to determine the concentration of cCa.Results—Concentrations of tCa, iCa, pCa, and cCa had wide ranges among dogs with CRF. Dogs with significantly low tCa concentration (7.70 ± 1.73 mg/dL) had cCa concentration (0.76 ± 0.38 mg/dL) within reference range, whereas dogs with reference range to high tCa concentration (10.85 ± 1.13 mg/dL) had significantly high cCa concentration (2.62 ± 1.04 mg/dL). There was no significant difference in iCa or pCa concentrations between groups.Conclusions and Clinical Relevance—Concentrations of tCa, iCa, cCa, and pCa varied widely in dogs with CRF. Overall, cCa concentration was high, although subpopulations differed in cCa and tCa concentrations. Differences in tCa concentration were primarily attributable to differences in cCa fraction. (Am J Vet Res2003;64:1181–1184)
Effect of induced unilateral synovitis of distal intertarsal and tarsometatarsal joints on sagittal plane kinematics and kinetics of trotting horses
Authors: Khumsap Siriporn , Lanovaz Joel L. , Rosenstein Diana S. , Byron Christopher , Clayton Hilary M. 
Published: December 2005

AbstractObjective—To study the effect of unilateral synovitis in the distal intertarsal and tarsometatarsal joints on locomotion, including the compensating effects within and between limbs.Animals—4 clinically normal horses.Procedure—Gait analyses including kinematics, force plate, and inverse dynamic analysis were performed at the trot before lameness, after which synovitis was induced by injecting endotoxin into the right distal intertarsal and tarsometatarsal joints. Gait analyses were repeated 24 to 30 hours later during lameness. Differences between the stride variables during the 2 conditions (lame and sound) were identified.Results—Tarsal joint range of motion, peak vertical force, and vertical impulse were decreased during lameness. Mechanical deficits included a decrease in negative work performed by the tarsal extensors during the early stance phase and a decrease in positive work by the tarsal extensors during push off. No compensatory changes in work were performed by other joints within the lame hind limb during the stance phase. Vertical impulse in the diagonal forelimb decreased, but there were no significant changes in forces or impulses in the ipsilateral forelimb or contralateral hind limb.Conclusions and Clinical Relevance—Results indicate that horses are able to manage mild, unilateral hind limb lameness by reducing the airborne phase of the stride rather than by increased loading of the compensating limbs. (Am J Vet Res2003;64:1491–1495)
In vitro effects of Actinobacillus pleuropneumoniae on inducible nitric oxide synthase and cyclooxygenase-2 in porcine alveolar macrophages
Authors: Cho Wan-Seob , Chae Chanhee 
Published: December 2005

AbstractObjective—To determine the amount of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) activity in alveolar macrophages in response toActinobacillus pleuropneumoniae(APP) by determining nitric oxide (NO) and prostaglandin E2(PGE2) concentrations.Sample Population—Freshly isolated porcine alveolar macrophages.Procedure—Alveolar macrophages were incubated for 48 hours with APP (1 × 104colony-forming units/mL), interleukin-1β (IL-1β; 5 U/mL), tumor necrosis factor-α (TNF-α; 500 U/mL), interferon-γ (IFN-γ; 100 U/mL), or lipopolysaccharide (LPS; 10 µg/mL). In a second experiment, alveolar macrophages were incubated with fresh medium (negative control), APP alone, or APP with 1 of the following: IL-1β, TNF-α, or IFN-γ. In a third experiment, alveolar macrophages were incubated with fresh medium (negative control), LPS (positive control), APP alone, or APP with 1 of the following: an iNOS inhibitor (3.3µM), a COX-2 inhibitor (10µM); or both the iNOS and COX-2 inhibitors. Supernatant was obtained at 0, 3, 6, 9, 12, 24, and 48 hours after treatment for determination of NO and PGE2production.Results—The addition of APP to alveolar macrophages resulted in significant increases in NO and PGE2production. The addition of APP and IFN-γ synergistically induced NO production. Inhibition of iNOS and COX-2 decreased NO and PGE2production, respectively.Conclusions and Clinical Relevance—In vitro activation of alveolar macrophages by APP results in increased production of NO and PGE2. Nitric oxide and PGE2production appears to be largely dependent on iNOS and COX-2 activity. Pharmacologic modulation of iNOS and COX-2 activity may represent a therapeutic target for pigs with pleuropneumonia. (Am J Vet Res2003;64:1514–1518)
Effects of hydrochloric, valeric, and other volatile fatty acids on pathogenesis of ulcers in the nonglandular portion of the stomach of horses
Authors: Nadeau Jenifer A. , Andrews Frank M. , Patton Clark S. , Argenzio Robert A. , Mathew Alan G. , Saxton Arnold M. 
Published: December 2005

AbstractObjective—To identify in vitro effects of hydrochloric acid, valeric acid, and other volatile fatty acids (VFAs) on the pathogenesis of ulcers in the nonglandular portion of the equine stomach.Sample Population—Gastric tissues from 13 adult horses.Procedure—Nonglandular gastric mucosa was studied by use of Ussing chambers. Short-circuit current (Isc) and potential difference were measured and electrical resistance and conductance calculated after tissues were bathed in normal Ringer's solution (NRS) or NRS and hydrochloric, valeric, acetic, propionic, and butyric acids. Treated tissues were examined histologically.Results—Incubation in 60mM valeric acid at pH ≤ 7.0 abruptly and irreversibly abolished Isc, which was followed by a slower decrease in resistance and an increase in conductance. Incubation in 60mM acetic, propionic, and butyric acids and, to a lesser extent, hydrochloric acid at pH ≤ 7.0 significantly decreased Isc, which was followed by an increase in resistance and a decrease in conductance.Conclusions and Clinical Relevance—Incubation in valeric acid at pH ≤ 7.0 caused a dramatic decrease in mucosal barrier function in the nonglandular portion of the stomach. Changes in barrier function attributable to exposure to valeric acid were associated with histopathologic evidence of cellular swelling in all layers of the nonglandular mucosa. Because of its high lipid solubility, valeric acid penetrates the nonglandular gastric mucosa, resulting in inhibition of sodium transport and cellular swelling. Valeric acid and other VFAs in gastric contents may contribute to the pathogenesis of ulcers in the nonglandular portion of the stomach of horses. (Am J Vet Res2003;64:413–417)