bluuebunny/crossref_metadata_2025 huggingface dataset:
Severity of scleroderma lung disease is related to alveolar concentration of nitric oxide
Authors: Tiev K. P. , Cabane J. , Aubourg F. , Kettaneh A. , Ziani M. , Mouthon L. , Duong-Quy S. , Fajac I. , Guillevin L. , Dinh-Xuan A. T.
Published: April 2007

The alveolar concentration of exhaled nitric oxide (CA,NO) is increased in patients with systemic sclerosis (SSc), but whether this increase is related to the severity of interstitial lung disease (ILD) in SSc has not yet been investigated.

In total, 58 SSc patients prospectively underwent pulmonary function tests (PFTs), echocardiogram and fibrosis scoring on pulmonary computed tomography (CT). Patients were divided into two groups according to the presence (or not) of ILD. Measurements of CA,NOwere assessed in all SSc patients and compared with those obtained in 19 healthy volunteers. Relationships were sought between CA,NOPFTs and CT scan fibrosis scores.

Overall, CA,NOwas significantly increased in SSc patients (median (range) 6.2 (3.8–9.9) ppb) as compared with controls (2.0 (1.2–3.0) ppb). Among SSc patients, CA,NOwas significantly higher in patients with ILD compared with patients without ILD (n = 33, 7.5 (5.2–11.9) ppbversusn = 25, 4.9 (3.1–7.0) ppb, respectively). CA,NOwas inversely related to total lung capacity (r =  −0.34) and the diffusing capacity of the lung for carbon monoxide (r =  −0.37) and was directly related to CT scan fibrosis scores (r = 0.36).

An increased alveolar concentration of exhaled nitric oxide could, at least in part, either reflect or contribute to the severity of lung disease and could be used to noninvasively assess the extent of interstitial lung disease in systemic sclerosis.
Reduced mitochondrial density in the vastus lateralis muscle of patients with COPD
Authors: Gosker H. R. , Hesselink M. K. C. , Duimel H. , Ward K. A. , Schols A. M. W. J.
Published: April 2007

Skeletal muscle dysfunction is a well-recognised hallmark of chronic obstructive pulmonary disease (COPD) leading to exercise intolerance. The vastus lateralis of COPD patients is characterised by reduced mitochondrial enzyme activity; however, this is not the case in the tibialis anterior. It is, however, unclear whether the compromised oxidative capacity in the vastus is due to reduced mitochondrial volume density.

Muscle biopsies were obtained from the vastus lateralis of six COPD patients and four healthy age-matched controls, and from the tibialis anterior of another six COPD patients and six controls. Mitochondrial number, fractional area and morphometry, as well as Z-line width (as a surrogate marker of fibre type), were analysed using transmission electron microscopy.

Mitochondrial number (0.34versus0.63 n·µm−2) and fractional area (1.95versus4.25%) were reduced in the vastus of COPD patients compared with controls. Despite a reduced mitochondrial number (0.65versus0.88 n·µm−2), the mitochondrial fractional area was maintained in the tibialis of COPD patients compared with controls.

It can be concluded that the reduced mitochondrial fractional area is likely to contribute to the decreased oxidative capacity in the vastus of chronic obstructive pulmonary disease patients, whereas the maintained mitochondrial fractional area in the tibialis may explain the normal oxidative capacity.
pygopus 2 has a crucial, Wnt pathway-independent function in lens induction
Authors: Song Ni , Schwab Kristopher R. , Patterson Larry T. , Yamaguchi Terry , Lin Xinhua , Potter Steven S. , Lang Richard A.
Published: April 2007

Drosophila Pygopus was originally identified as a core component of the canonical Wnt signaling pathway and a transcriptional coactivator. Here we have investigated the microophthalmia that arises in mice with a germline null mutation of pygopus 2. We show that this phenotype is a consequence of defective lens development at inductive stages. Using a series of regionally limited Cre recombinase transgenes for conditional deletion of Pygo2flox, we show that Pygo2 activity in pre-placodal presumptive lens ectoderm, placodal ectoderm and ocular mesenchyme all contribute to lens development. In each case, Pygo2 is required for normal expression levels of the crucial transcription factor Pax6. Finally, we provide multiple lines of evidence that although Pygo2 can function in the Wnt pathway, its activity in lens development is Wnt pathway-independent.
Akt mediates self-renewal division of mouse spermatogonial stem cells
Authors: Lee Jiyoung , Kanatsu-Shinohara Mito , Inoue Kimiko , Ogonuki Narumi , Miki Hiromi , Toyokuni Shinya , Kimura Tohru , Nakano Toru , Ogura Atsuo , Shinohara Takashi
Published: April 2007

Spermatogonial stem cells have unique properties to self-renew and support spermatogenesis throughout their lifespan. Although glial cell line-derived neurotrophic factor (GDNF) has recently been identified as a self-renewal factor for spermatogonial stem cells, the molecular mechanism of spermatogonial stem cell self-renewal remains unclear. In the present study,we assessed the role of the phosphoinositide-3 kinase (PI3K)-Akt pathway using a germline stem (GS) cell culture system that allows in vitro expansion of spermatogonial stem cells. Akt was rapidly phosphorylated when GDNF was added to the GS cell culture, and the addition of a chemical inhibitor of PI3K prevented GS cell self-renewal. Furthermore, conditional activation of the myristoylated form of Akt-Mer (myr-Akt-Mer) by 4-hydroxy-tamoxifen induced logarithmic proliferation of GS cells in the absence of GDNF for at least 5 months. The myr-Akt-Mer GS cells expressed spermatogonial markers and retained androgenetic imprinting patterns. In addition, they supported spermatogenesis and generated offspring following spermatogonial transplantation into the testes of infertile recipient mice, indicating that they are functionally normal. These results demonstrate that activation of the PI3K-Akt pathway plays a central role in the self-renewal division of spermatogonial stem cells.
Specification ofArabidopsisfloral meristem identity by repression of flowering time genes
Authors: Liu Chang , Zhou Jing , Bracha-Drori Keren , Yalovsky Shaul , Ito Toshiro , Yu Hao
Published: April 2007

Flowering plants produce floral meristems in response to intrinsic and extrinsic flowering inductive signals. In Arabidopsis, the floral meristem identity genes LEAFY (LFY) and APETALA1(AP1) are activated to play a pivotal role in specifying floral meristems during floral transition. We show here that the emerging floral meristems require AP1 to partly specify their floral identities by directly repressing a group of flowering time genes, including SHORT VEGETATIVE PHASE (SVP), AGAMOUS-LIKE 24(AGL24) and SUPPRESSOR OF OVEREXPRESSION OF CO1(SOC1). In wild-type plants, these flowering time genes are normally downregulated in emerging floral meristems. In the absence of AP1,these genes are ectopically expressed, transforming floral meristems into shoot meristems. By post-translational activation of an AP1-GR fusion protein and chromatin immunoprecipitation assays, we further demonstrate the repression of these flowering time genes by induced AP1 activity and in vivo AP1 binding to the cis-regulatory regions of these genes. These findings indicate that once AP1 is activated during the floral transition, it acts partly as a master repressor in floral meristems by directly suppressing the expression of flowering time genes, thus preventing the continuation of the shoot developmental program.
Wiring the nervous system: from form to function
Authors: Matsuzaki Fumio , Sampath Karuna
Published: April 2007

The RIKEN Centre for Developmental Biology recently hosted a joint UK-Asian Pacific Developmental Biology Network meeting called `Development and Emergence of Function in the Nervous System'. The meeting's program, which was organized by James Briscoe and Krishnaswamy VijayRaghavan, covered a spectrum of processes and mechanisms in neurodevelopment, ranging from the patterning of neural tissue to the initiation of a functional nervous system. One idea to have emerged during this meeting is that `form underlies function'. Here we discuss some of the themes that were addressed and provide a broad impression of what was a highly stimulating and successful conference.
Foxp2 and Foxp1 cooperatively regulate lung and esophagus development
Authors: Shu Weiguo , Lu Min Min , Zhang Yuzhen , Tucker Philip W. , Zhou Deying , Morrisey Edward E.
Published: April 2007

The airways of the lung develop through a reiterative process of branching morphogenesis that gives rise to the intricate and extensive surface area required for postnatal respiration. The forkhead transcription factors Foxp2 and Foxp1 are expressed in multiple foregut-derived tissues including the lung and intestine. In this report, we show that loss of Foxp2 in mouse leads to defective postnatal lung alveolarization, contributing to postnatal lethality. Using in vitro and in vivo assays, we show that T1alpha, a lung alveolar epithelial type 1 cell-restricted gene crucial for lung development and function, is a direct target of Foxp2 and Foxp1. Remarkably, loss of a single Foxp1 allele in addition to complete loss of Foxp2 results in increased severity of morphological defects in mutant lungs and leads to perinatal loss of all Foxp2-/-;Foxp1+/- mice. Expression of N-myc and Hop, crucial regulators of lung development, is compromised in Foxp2-/-;Foxp1+/- mutants. In addition to the defects in lung development, esophageal muscle development is disrupted in Foxp2-/-;Foxp1+/- embryos, a tissue where Foxp2 and Foxp1 are co-expressed. These data identify Foxp2 and Foxp1 as crucial regulators of lung and esophageal development, underscoring the necessity of these transcription factors in the development of anterior foregut-derived tissues and demonstrating functional cooperativity between members of the Foxp1/2/4 family in tissues where they are co-expressed.
A new paradigm of mechanical energy dissipation. Part 1: Theoretical aspects and practical solutions
Authors: Eroshenko V A
Published: April 2007

Although fluid viscosity and speed are still most widely used for dissipating mechanical energy, current research and development on conventional dampers is beginning to saturate; creative design initiatives to obtain higher performance with conventional passive dampers are limited. In order to provide new levels of comfort, reliability, and dissipative power of damping, the present author suggests using the repulsive forces acting within interfaces between capillary-porous solids with high specific surface and non-wetting liquids. When placed in working chambers and subjected to periodical compression-expansion processes, such working media demonstrate pronounced hysteresis phenomena in pressure-volume coordinates, which characterize dissipated energy with specific (volumetric) values 10–100 times greater than that of conventional dampers.

Furthermore, it is possible to design a damper where the force may depend insignificantly on the speed of rod displacement (the damping coefficient tending to zero) within a wide range of speed values. In this way, there is a new solution to the ‘comfort-road holding’ trade-off; reliable wheel-road adhesion is possible even for zero damping coefficient (perfect comfort).

This new paradigm of mechanical energy dissipation substantially improves damper performance qualitatively and quantitatively and extends its scope of application. The search for such a concept, its thermodynamic substantiation, and practical construction are the main objectives of this paper.
Fuzzy control of spark advance by ion current sensing
Authors: Shamekhi A H , Ghaffari A
Published: April 2007

The desired performance of a spark ignition (SI) engine is highly related to the position of the spark advance, and consequently to the beginning of stable combustion inside the cylinder. The magnitude of the generated ion current signal, measured by a sensor inside cylinder, is closely correlated to the cylinder pressure magnitude. Their maximum values almost coincide at the same crank angle position. In this paper, a feedback control system is designed to fix the position of the maximum pressure at a given desired value of the crank angle. Noting that SI engines are highly non-linear systems, a fuzzy logic controller is developed. The simulation results present a quite satisfactory performance of the closed-loop system.
The prediction of low- and mid-frequency internal road vehicle noise: A literature survey
Authors: Lalor N , Priebsch H-H
Published: April 2007

Over the past 40 years the low- and mid-frequency internal noise of road vehiles has been of increasing interest to both manufacturers and customers, and there have been many papers written on the subject. It is particularly important that manufacturers are able to predict the noise at an early stage of a new design so that expensive mistakes can be avoided. This paper reviews the relevant literature published over this 40 year period and concludes that the finite element method (FEM), and/or the boundary element method (BEM) are currently the most accurate ways of predicting this noise. However, although the emphasis of this review is on the low- and mid-frequency structure-borne aspect of the noise, other prediction methods (which are normally considered to be only applicable at high frequencies) are also considered. In particular, the statistical energy analysis (SEA) is shown to be an increasingly useful tool for predicting structure-borne noise, as is the newly developed FEM/SEA hybrid method. Other essentially high-frequency techniques are also considered in this review because recent research indicates that it might be possible to apply these methods over a broader frequency range than was initially envisaged.
Modelling three-way catalytic converters: An effort to predict the effect of precious metal loading
Authors: Konstantas G , Stamatelos A M
Published: April 2007

The need to deliver ultra-low emitting vehicles at a reasonable cost is driving the automotive industry to invest significant manpower in computer aided design and optimization of exhaust treatment systems. The significant fluctuations in the stock exchange market values of the precious metals employed in the manufacture of automotive catalytic converters has increased interest in the possibility of assisting precious metal loading optimization by means of mathematical modelling. Currently employed models of real world performance of catalytic converters cannot predict this effect. Recent improvements in the core chemical reaction modelling of the CATRAN code, reported in this paper, allow a good correlation to be made of precious metal loading with apparent kinetics, at least in the case of Pt-Rh catalysts. This may open new frontiers to the use of mathematical modelling in automotive exhaust after-treatment system optimization.
Time history-based excitation in the dynamic characterization of automotive elastomers
Authors: Holt J G , Rao M D , Blough J R , Gruenberg S B
Published: April 2007

Different input excitation approaches to measure the dynamic stiffness and damping properties of two automotive elastomer mounts were investigated in this research. The traditional methods of dynamic characterization of elastomers are based largely on sinusoidal input excitation where discrete frequency sine wave signals at specified amplitudes are used to excite an elastomer sample in a step-sine sweep fashion. This method is straight-forward in its signal processing and can easily be performed with a wide variety of available test equipment. However, many questions remain unanswered with respect to the behaviour of an elastomer during broadband frequency excitation. This paper examines how various other types of excitation affect the dynamic characterization results. These excitation inputs include continuous sine sweep (chirp), shaped random, and acquired road profile data. Use of the broadband data types is expected to provide a more accurate representation of conditions seen in the field, while helping to eliminate much of the interpolation that is inherent with the classic discrete step-sine technique. This paper elaborates on the use of time histories to facilitate broadband excitation, as well as to provide a description of accurate digital signal post-processing methods recommended for the various types of input.
Structural analysis and optimization of a low-speed vehicle body
Authors: Shin Moon-Kyun , Shin Jung-Kyu , Hwang Sang-Jin , Park Gyung-Jin
Published: April 2007

The low-speed vehicle (LSV) is being employed for various usages. The body of the LSV is usually made of the aluminium space frame (ASF) type rather than the monocoque or unitary construction type. The reason is that it is easier to reduce mass efficiently while the required stiffness and strength are maintained. A design flow for the LSV is proposed. Design specifications for structural performances of the LSV do not yet exist. Therefore, they are defined through a comparative study with general passenger automobiles. An optimization problem is formulated by the defined specifications. First, the A-pillar which has an important role in structural performance is selected, and the candidates of reinforcement in the pillar are determined from topology optimization to maximize the stiffness. Based on this, the thicknesses of the cross-sections are determined to minimize the mass of the body while design specifications are satisfied. The optimum solution is compared with an existing design. The optimization process has been performed using a commercial optimization software system, GENESIS 7.0.
Effect of a fastener hole design of inlet flanges on the durability of the exhaust manifold for a turbo-diesel engine
Authors: Kim Beomkeun , Lee Seong Beom , Lee Eunhyun
Published: April 2007

A clever design of fastener hole, which allows sliding behaviour, is investigated so as to understand the effect on the durability of the exhaust manifold for a turbo-diesel engine. Finite element analysis and experiments are performed to investigate the thermal deformation of the exhaust manifold with the fastener hole design. Temperature-dependent material properties of the exhaust manifold and sliding behaviour between the manifold and cylinder head are considered for the finite element model. A considerable amount of sliding between the manifold and cylinder head owing to the permanent deformation of the exhaust manifold are expected from the analysis. Experiments followed to verify results of the analysis. The plastic strain range, which is often used as the criterion for crack initiation, was estimated and compared with that of the exhaust manifold with a conventional fastener hole design, which does not allow sliding between the manifold and the cylinder head. Results revealed that a fastener hole design that allows sliding of the exhaust manifold, increases the durability of the exhaust manifold for the turbo-diesel engine.
An experimental study to assess the potential of homogeneous charge compression ignition diesel combustion with various fuels for light-duty engines
Authors: Wagner U , Wiemer S , Velji A , Spicher U
Published: April 2007

Single-cylinder engine tests were carried out to assess the potential of homogeneous charge compression ignition (HCCI) diesel combustion compared to the conventional heterogeneous operation mode. For the experiments a single-cylinder engine with a cylinder volume of 0.421 litre was used. Besides the comparison of conventional operation and HCCI operation of the same engine special emphasis was put on the utilization of synthetic fuels such as gas-to-liquid (GtL) or biomass-to-liquid (BtL) fuels. Therefore, in addition to a standard winter diesel, a fuel with mid-sized n-alkanes and mixtures of n-alkanes and aromatic hydrocarbons was used to investigate the influence of different ignitabilities and boiling curves on the combustion. A great advantage of synthetic fuels is the possibility to design them according to the combustion process requirements. In addition, these GtL or BtL fuels will lead to a higher independence from fossil fuels.

To assess the potential of HCCI combustion compared to conventional diesel combustion the engine must have the capability to run in both modes. While using the different fuels several engine operation parameters like injection timing and splitting were varied in order to obtain information about their effect on combustion as well as on engine out-emissions. Furthermore, full-load curves for the different fuels were identified to find out where HCCI operation can be applied in an engine map.
Combustion control and operating range expansion in an homogeneous charge compression ignition engine with suppression of low-temperature oxidation by methanol: Influence of compression ratio and octane number of main fuel
Authors: Ogawa H , Azuma K , Miyamoto N
Published: April 2007

Characteristics of combustion control with direct methanol injection in homogeneous charge compression ignition (HCCI) combustion were investigated over a wide operating range under several conditions including different compression ratios and three main fuels with different octane numbers. The operating range of HCCI combustion is limited by knocking at one extreme and misfire at the other. On the knocking side, moderate methanol injection is shown to be effective at preventing knock. In addition, a lower compression ratio can delay the onset of both low- and high-temperature oxidations and suppress rapid combustion due to the lower in-cylinder gas temperature while not directly affecting the quantity of heat released during low-temperature oxidation. To extend the misfire limit, a lower octane number fuel yields a greater low-temperature heat release, increasing the temperature in the interval between the low- and high-temperature oxidation, which prevents misfiring. Therefore, a combination of lower compression ratio and lower octane number fuel assisted by a direct methanol injection can expand the operating load range envelope as the low-temperature oxidation can be controlled flexibly by varying the quantity of methanol injection with the operating condition. It was concluded that the ignition suppression effect of methanol in HCCI combustion is much stronger than those of other fuels with a similar octane number.
Dual injection homogeneous charge compression ignition engine simulation using a stochastic reactor model
Authors: Mosbach S , Su H , Kraft M , Bhave A , Mauss F , Wang Z , Wang J-X
Published: April 2007

Multiple direct injection (MDI) is a promising strategy to enable fast-response ignition control as well as expansion of the homogeneous charge compression ignition (HCCI) engine operating window, thus realizing substantial reductions of soot and NOx emissions. The present paper extends a zero-dimensional-probability-density-function-based stochastic reactor model (SRM) for HCCI engines in order to incorporate MDI and an improved turbulent mixing model. For this, a simplistic spray model featuring injection, penetration, and evaporation sub-models is formulated, and mixing is described by the Euclidean minimal spanning tree (EMST) sub-model accounting for localness in composition space. The model is applied to simulate a gasoline HCCI engine, and the in-cylinder pressure predictions for single and dual injection cases show a satisfactory agreement with measurements. From the parametric studies carried out it is demonstrated that, as compared with single injection, the additional second injection contributes to prolonged heat release and consequently helps to prevent knock, thereby extending the operating range on the high load side. Tracking the phase space trajectories of individual stochastic particles provides significant insight into the influence of local charge stratification owing to direct injection on HCCI combustion.
Effect of gasoline homogeneous charge compression ignition on engine acoustics and vibration
Authors: Stoffels H , Collings N
Published: April 2007

The homogeneous charge compression ignition (HCCI) gasoline engine promises low fuel consumption without expensive NOx aftertreatment. Owing to the self-ignition, HCCI has a faster combustion and therefore a higher level of vibration and acoustic excitation than DI-spark ignition (SI) engines. To effect a gasoline engine running in HCCI mode, residual gases must be trapped in the combustion chamber in HCCI mode. One solution to trap residual gases is to establish a negative valve timing overlap. This was done on a gasoline I4 engine, which is able to run in SI or HCCI mode by using independently controlled overhead camshafts. Noise and vibration analysis has been carried out on such an HCCI engine to quantify the impact of HCCI on the combustion and intake orifice noise. The noise and vibration analysis was done using either directly measured noise and vibrations from the development dynamometer or a noise prediction method based on recorded cylinder pressures and known transfer functions. The investigations were carried out at different speed and load points while changing control parameters such as intake cam timing, throttle, spark and injection timing and strategy. Using different data evaluation methods it was found that the HCCI mode with base settings can deliver higher NVH excitation than the SI mode at the same speed and load. However, by applying different combinations of control parameters, the NVH of the HCCI operation mode can be controlled in order to reduce its level of excitation and noise characteristics.
Ultrastructural characteristics of the external surfaces of Pasteurella pneumotropica from mice and Pasteurella multocida from rabbits
Authors: Kawamoto E , Okiyama E , Sasaki H , Sawada T , Mikazuki K , Ueshiba H
Published: April 2007

The surface structures of the cells of Pasteurella pneumotropica from mice and Pasteurella multocida from rabbits were examined by transmission electron microscopy after ruthenium red staining and polycationic ferritin labelling. P. pneumotropica strains ATCC 35149 and K 79114 had slight extracellular fibrous materials associated with cell walls with ruthenium red staining. Ferritin labelling method revealed thick strands or sparsely ferritin-labelled materials on the cell surface of the strains. P. multocida strains Pm-78 and P-2440 had ferritin-labelled capsules surrounded with the cell wall. Strain Pm-78, which was serotyped as A:12, had a thick capsule, whereas serotype -:3 strain P-2440 had a thin and irregular capsule.
Acclimatization of rats after ground transportation to a new animal facility
Authors: Capdevila S , Giral M , Ruiz de la Torre J L , Russell R J , Kramer K
Published: April 2007

This study aimed to assess the time needed by rats, which had not been previously transported, to acclimatize to a new environment after 5 h of van transport, using physiological parameters as measures of acclimatization. Animal shipping boxes and transport van conditions were standardized to minimize stress factors that could be associated with transport. Heart rate (HR), body temperature and activity levels were measured in the rats before and after transport using previously implanted radio-telemetry transmitters. Body weight was also recorded. All parameters were changed significantly except for body temperature. Results suggest that rats take three days to acclimatize to a new environment, as measured by the physiological parameters of body weight, HR and activity.
Identification of a genetic contamination in a commercial mouse strain using two panels of polymorphic markers
Authors: Nitzki F , Kruger A , Reifenberg K , Wojnowski L , Hahn H
Published: April 2007

Rapid detection of genetic contamination is critical in mouse studies involving inbred strains. During a Quantitative Trait Locus (QTL) study using simple sequence length polymorphism (SSLP) markers, we noticed heterozygosity at some loci of a commercially available inbred C57BL/6N mouse strain, suggesting a contamination by another mouse strain. A panel of 100 single-nucleotide polymorphism (SNP) markers was used to confirm and specify the genetic contamination suspected. Retrospective analyses demonstrated that the contamination took place as early as autumn 2003 and has persisted ever since at a fairly constant level. Contaminating alleles most probably originated from a DBA strain. Our data demonstrate the suitability of SNP markers for rapid detection and identification of the source of genetic contamination. Further, our results show the importance of a state-of-theart genetic monitoring of the authenticity of murine inbred strains.
Comparative analysis and physiological impact of different tissue biopsy methodologies used for the genotyping of laboratory mice
Authors: Cinelli Paolo , Rettich Andreas , Seifert Burkhardt , Bürki Kurt , Arras Margarete
Published: April 2007

Genotyping of genetically modified mice and control of authenticity of the genetic background of congenic or coisogenic strains by polymerase chain reaction (PCR) is a routine procedure that can be performed with different tissue biopsies causing variable grades of trauma. In this study, some invasive and non-invasive sampling methods were compared, with the main focus on the impact on animal physiology. We compared ear punch, tail biopsy, hair plugging, mouth and rectum swabs and the simple restraint of the animals, scoring for the impact on heart rate (HR), core body temperature (BT) and motor activity by telemetry, during biopsy and for the following 6 h. Furthermore, in order to correlate the physiological impact with the practicability and reliability of the genotyping results, we performed a PCR analysis of the biopsy samples obtained by using the same collection procedures analysed by telemetry. All sampling methods and restraint induced significant increase in HR and BT and a slight increase in motor activity for 1 h, independent of the invasiveness of the method used. Genotyping of all biopsies allowed the proper identification of transgenic animals, tail biopsies, ear punches and hair follicles giving clear signals, the last method being fast, but also susceptible to cross contaminations during sampling by large numbers of animals. Restraint and all biopsy methods provoked similar physiological changes, indicating that the handling of the animals is of major importance and that the sampling procedure does not strongly influence the physiological parameters.
The antinociceptive efficacy of buprenorphine administered through the drinking water of rats
Authors: Jessen L , Christensen S , Bjerrum O J
Published: April 2007

Postoperative pain management in laboratory animals is important for animal welfare and required under law in many countries. Frequent injection of analgesics to rodents after surgery is stressful for the animals and labour-intensive for animal care personnel. An alternative dosing scheme such as administration of analgesics in the drinking water would be desirable. However, the efficacy of a chronic oral analgesic treatment via this route has not yet been documented. This study investigated the antinociceptive efficacy of buprenorphine administered ad libitum via the drinking water of laboratory rats. The antinociceptive efficacy of buprenorphine in drinking water was compared with repeated subcutaneous injections. A comparison was also made between buprenorphine in drinking water and the combination of one single subcutaneous injection of buprenorphine followed by buprenorphine in drinking water. Antinociception was assessed by use of an analgesiometric model measuring the rats' latency time to withdrawal from a noxious heat stimulus applied to the plantar surface of the paw. Results revealed that buprenorphine in drinking water (0.056 mg/mL) induced significant increases in paw withdrawal latency times during a three-day period of administration with a maximal effect at 39 h after the start of buprenorphine administration. One single injection of buprenorphine (0.1 mg/kg s.c.) followed by buprenorphine in the drinking water (0.056 mg/mL) induced an earlier onset of antinociception than buprenorphine in drinking water alone. In contrast, buprenorphine (0.1 mg/kg s.c.) injected every 8 h over a period of three days did not result in significant increases in paw withdrawal latency times. In conclusion, our results suggest that one single subcutaneous injection of buprenorphine followed by buprenorphine in drinking water may be a viable treatment option for the relief of pain in laboratory rats, but at the doses used in this study in pain-free rats it was associated with a decrease in water intake and some behavioural changes.
Nociception after intraperitoneal injection of a sodium pentobarbitone formulation with and without lidocaine in rats quantified by expression of neuronal c-fos in the spinal cord – a preliminary study
Authors: Svendsen Ove , Kok Lisbet , Lauritzenã Brian
Published: April 2007

After a search on Medline, it appears that intraperitoneal injection of sodium pentobarbitone is often used for anaesthesia and euthanasia of rodents. In the present pilot study in rats, spinal nociception after intraperitoneal injection of sodium pentobarbitone, with and without lidocaine, was examined by estimation of the number of c-fos-expressing neurones in the spinal dorsal horn. One group of rats received an intraperitoneal injection of 0.4 mL/kg sodium pentobarbitone (100 mg/mL; n = 4). Another group of rats received a similar intraperitoneal injection of sodium pentobarbitone formulated with lidocaine 10 mg/mL ( n = 4); a control group received a similar intraperitoneal injection of 0.9% saline ( n = 4). After 3 h, the animals were re-anaesthetized and perfused with 4% formaldehyde, and the spinal cord was collected and processed by immunohistochemistry for stereological quantification of the number of neurones with c-fos-like immunoreactivity (FLI). Intraperitoneal injection of the sodium pentobarbitone formulation caused a significantly increased number of neurones with FLI in the spinal cord (3930 ± 247; mean ± SEM; P < 0.001) compared with the saline control group (765 ± 131). The lidocaine added to the sodium pentobarbitone formulation significantly reduced the number to 2716 ± 393 ( P < 0.05). In conclusion, intraperitoneal injection of sodium pentobarbitone caused a significant increase in nociception which was lowered by adding lidocaine to the formulation, although it was still significantly higher than the control level. Further studies are needed with the aim of optimizing the lidocaine concentration and also to examine the effect of the combination of lidocaine with a long-acting local anaesthetic agent, e.g. bupivacaine.
The Saanen goat as an animal model for post-laryngectomy research: practical implications
Authors: ten Hallers E J Olivier , Marres Henri A M , Rakhorst Gerhard , Jansen John A , Sommers Mathieu G , Van der Houwen Eduard B , Schutte Harm K , Van Kooten Theo G , Van Loon Jan-Paul , Verkerke Gijsbertus J
Published: April 2007

A modern way of voice rehabilitation after total laryngectomy includes the use of shunt valves and tracheostoma valves. Problems of fixation to the surrounding tissue are a major drawback in the use of the shunt valve, heat and moisture exchange (HME) filters and, especially, the tracheostoma valve. To solve these problems different tissue connectors were developed. The main objective was to test the feasibility of these prototypes in a new animal model. Here we discuss the results, problems and complications of the selected Saanen goat model. In this prospective laboratory study, 19 healthy adult female Saanen goats ( Capra hircus) were used and observed post-surgically for 12 weeks. Selection criteria such as comparable anatomy to humans and easy handling were used for animal model development. Also a literature search using the Medline and the ISI Web of Science databases was performed. The anatomy of the Saanen goat was investigated in a separate postmortem study. Surgery consisted of a laryngotracheal separation and implantation of a tracheo-oesophageal and tracheostoma tissue connector with fibrin tissue glue. Postoperative care consisted of frequent stoma care, monitoring appetite, weight, vital signs and administration of antibiotics, analgesics and mucolytic agents. All animals survived the surgical procedure. However, postoperative care was extensive, labour intensive and was accompanied by several complications. Eleven animals died spontaneously before the end of the experiment. The tracheostoma tissue connector caused signs of local infection in all cases. There was no evidence of infection around the tracheo-oesophageal tissue connector in 18 cases. It was concluded that the use of goats in this tracheostoma model was associated with major complications and should, therefore, only be used for short-term experiments with intensive care. Additional research is needed to see if clinical application of the tissue connectors is possible in the future.
Influence of environmental enrichment and handling on the acute stress response in individually housed mice
Authors: Meijer M K , Sommer R , Spruijt B M , van Zutphen L F M , Baumans V
Published: April 2007

In this study we investigated the effect of environmental enrichment and handling on the acute physiological stress response caused by short periods of restraint in individually housed female mice. Heart rate (HR) and body temperature (BT) were measured by radiotelemetry and compared with plasma corticosterone (pCORT) levels. Also, postmortem thymus weight and tyrosine hydroxylase (TH) activity were assessed. The acute stress response was seen in both HR and BT. Enrichment and handling were found to increase rather than decrease this stress response, but pCORT values, measured 90 min after restraint, suggested a lower stress response in the enriched groups. No effect was found with thymus weight or TH as parameters.
Intraperitoneal versus subcutaneous telemetry devices in young Mongolian gerbils (Meriones unguiculatus)
Authors: Moons Christel P H , Hermans Katleen , Remie René , Duchateau Luc , Ödberg Frank O
Published: April 2007

Radiotelemetry has become a very popular biotelemetric tool for measuring physiological parameters such as heart rate, blood pressure, body temperature and muscle activity, as well as general behavioural activity in undisturbed, freely moving animals. In most studies using this technique, adult subjects are used. However, sometimes an ontogenetic approach is required to clarify whether changes in one parameter are preceeded or followed by changes in another parameter. Tracking physiological changes in young, developing individuals could explain given states of these animals as adults. Implanting telemetry devices can be done subcutaneously and intraperitoneally, the former method posing less of a challenge on the animal and its recovery from surgery. Because telemetry will be used in weanling gerbils during subsequent studies, we needed to investigate whether subcutaneous implantation of telemetric devices is preferable to intraperitoneal surgery with respect to animal welfare. This is a technical paper describing anaesthetic and surgical techniques in detail during a pre-trial involving subcutaneous ( n = 10, aged 21–29 days) and intraperitoneal ( n = 10, aged 19–34 days) implantation of dummy telemetry transmitters (1.9 cm3, 3.6 g after shortening of leads) in weanling gerbils, Meriones unguiculatus. Body weight was measured and analysed over four-day intervals. Optimizing anaesthetic dosages was a first step in this pilot trial. This occurred during the first few subcutaneous implantations. Three animals died while anaesthetized during the subcutaneous procedure but none post-surgery. All animals survived anaesthesia during the intraperitoneal implantation, but two died in the first three days post-surgery. In the former method, the tension on the dermal sutures caused by the presence of the transmitters was too great, resulting in the animals opening the sutures by chewing them. The animals died during the latter procedure probably due to strangulation of the intestine by the excess lead that was coiled in the abdomen. Furthermore, placement of the exposed negative lead of the transmitter on the underlying muscle had to be done on the m. pectoralis transversus in order for it to stay in place as the animal developed. This paper showed that the implantation of a telemetric device in weanling gerbils is feasible and is best executed through the intraperitoneal technique.
Serological survey of virus infection among wild house mice (Mus domesticus) in the UK
Authors: Becker S D , Bennett M , Stewart J P , Hurst J L
Published: April 2007

The serological prevalence of 13 murine viruses was surveyed among 103 wild-caught and 51 captive-bred house mice ( Mus domesticus), originating from several trapping locations in northwest England, using blood samples obtained during routine health screening of an established wild mouse colony. A high proportion of recently caught wild mice were seropositive for mouse hepatitis virus (86%), mouse cytomegalovirus (79%), mouse thymic virus (78%), mouse adenovirus (68%), mouse parvovirus (59%) and minute virus of mice (41%). Seroprevalences of lymphocytic choriomeningitis virus (LCMV), orthopoxvirus, reovirus-3 and murid herpesvirus 4 (MuHV-4, also called murine γ-herpesvirus [MHV-68]) were low (3–13%), and no animals were seropositive to Sendai virus, pneumonia virus or polyomavirus. Seroprevalence in wild-caught animals that had been in captivity for over six months was generally consistent with the range found in recently caught wild animals, while seroprevalence was generally much lower in captive-bred mice despite no attempt to prevent viral spread. A notable exception to this was LCMV, which appeared to have spread efficiently through the captive population (both captive-bred and wild-caught animals). Given the known viral life cycles in laboratory mice, it appears that viral persistence in the host was an important contributing factor in the spread of infection in captivity.
Research Note—The Effects of Costs and Competition on Slotting Allowances
Authors: Kuksov Dmitri , Pazgal Amit
Published: April 2007

We consider the optimal two-part tariff contract between a manufacturer and a retailer. We show that retail competition (in the presence of either fixed costs or bargaining power) may lead to slotting allowances in an optimal contract, even with a monopoly manufacturer and no information asymmetry. On the other hand, slotting allowances do not arise with a monopoly retailer and no information asymmetry, whether the manufacturer is a monopoly or not. We also show that more intense retail competition, higher retail bargaining power, larger retailer fixed costs, lower marginal costs of retailing, as well as larger relative retailer size (whether coming from a location or operating advantage), have a positive impact on the incidence and the magnitude of slotting allowances. The opposing effects of the fixed and marginal operating costs on slotting allowances, as well as the impact of competition and bargaining power on profits, underscore the importance of careful definitions of these variables in empirical research.
Wearout Effects of Different Advertising Themes: A Dynamic Bayesian Model of the Advertising-Sales Relationship
Authors: Bass Frank M. , Bruce Norris , Majumdar Sumit , Murthi B. P. S.
Published: April 2007

Models of advertising response implicitly assume that the entire advertising budget is spent on disseminating one message. In practice, managers use different themes of advertising (for example, price advertisements versus product advertisements) and within each theme they employ different versions of an advertisement. In this study, we evaluate the dynamic effects of different themes of advertising that have been employed in a campaign. We develop a model that jointly considers the effects of wearout as well as that of forgetting in the context of an advertising campaign that employs five different advertising themes. We quantify the differential wearout effects across the different themes of advertising and examine the interaction effects between the different themes using a Bayesian dynamic linear model (DLM). Such a response model can help managers decide on the optimal allocation of resources across the portfolio of ads as well as better manage their scheduling. We develop a model to show how our response model parameters can be used to improve the effectiveness of advertising budget allocation across different themes. We find that a reallocation of resources across different themes according to our model results in a significant improvement in demand.
Bayesian Estimation of Bid Sequences in Internet Auctions Using a Generalized Record-Breaking Model
Authors: Bradlow Eric T. , Park Young-Hoon
Published: April 2007

A sequence of bids in Internet auctions can be viewed as record-breaking events in which only those data points that break the current record are observed. We investigate stochastic versions of the classical record-breaking problem for which we apply Bayesian estimation to predict observed bids and bid times in Internet auctions. Our approach to addressing this type of data is through data augmentation in which we assume that participants (bidders) have dynamically changing valuations for the auctioned item, but the latent number of bidders “competing” in those events is unseen.

We use data from notebook auctions provided by one of the largest Internet auction sites in Korea. We find significant variation in the number of latent bidders across auctions. Our other primary findings are as follows: (1) the latent bidders are significant in number relative to observed bidders, (2) the latent number of remaining bidders is considerably smaller than that of new entrants to the auction after a given bid, and (3) larger bid and time increments significantly influence the bidding participation behavior of the remaining bidders. As part of our substantive contribution, we highlight the model’s ability to understand brand equity in an Internet auction context through a brand’s ability to simultaneously bring in bidders, higher bid amounts, and faster bidding.
Strategic Manufacturer Response to a Dominant Retailer
Authors: Geylani Tansev , Dukes Anthony J. , Srinivasan Kannan
Published: April 2007

The growing dominance of large retailers has altered traditional channel incentives for manufacturers. In this paper, we present a theoretical model to illustrate a strategic manufacturer response to a dominant retailer. In our model, a dominant and a weak retailer compete for the sale of a single product supplied by a single manufacturer. The dominant retailer has the power to dictate the wholesale price, but the manufacturer sets the wholesale price for the weak retailer. The manufacturer also has partial ability to transfer demand between retailers. In the strategic manufacturer response, the manufacturer begins by raising the wholesale price for the weak retailer over that for the dominant retailer. This makes the weak retailer the high-margin channel. The manufacturer then transfers demand to the weak retailer by engaging in joint promotions and advertising. We then use this strategic response model to derive a testable hypothesis that may guide future research in determining the source of dominant retailers’ low prices.