bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of Diet and Housing on Growth, Body Weight, Survival and Tumor Incidences of B6C3F1 Mice in Chronic Studies
Authors: Rao Ghanta N. , Crockett Patrick W.
Published: July 2008

Diet is one of the most important environmental factors influencing growth, body weight, survival, and age-related diseases of rodents in chronic studies. NIH-07 open formula diet was the selected diet for the NTP studies from 1980 to 1994. A new diet designated as NTP-2000 diet is the current diet for mice in the NTP studies beginning in 1994. This report is a summary of results of untreated control groups of B6C3F1 mice fed NTP-2000 or NIH-07 diet from several retrospective 2-year dosed-feed and inhalation studies for differences in growth, body weight, survival, and tumor incidences. The dosed-feed studies were conducted in 3 different facilities located in the United States, and all the inhalation studies were conducted in 1 facility. During dosed-feed studies, male and female mice housed in polycarbonate cages and fed the NTP-2000 diet had lower maximum body weights than those fed NIH-07 diet. However, during inhalation studies, mice housed in wire mesh cages and fed the NTP-2000 diet had higher maximum body weights than the mice fed NIH-07 diet. Survival was higher in groups fed NTP-2000 diet irrespective of sex, housing conditions, or body weight compared to the corresponding groups fed NIH-07 diet. Survival was higher in mice housed in polycarbonate cages irrespective of diet and sex compared to the respective sex and diet groups housed in wire mesh cages. During inhalation studies, survival of male and female mice fed NTP-2000 diet was higher than that of the groups fed NIH-07 diet, although the body weights of NTP-2000 diet groups were higher than those of the groups fed NIH-07 diet. When the NTP-2000 diet was used, male and female mice in dosed-feed studies and male mice in inhalation studies had markedly lower incidences of liver tumors than the corresponding groups fed NIH-07 diet. Significant decreases in the incidences of lung tumors were observed only in the male groups fed NTP-2000 diet during dosed-feed studies. These results suggest that body weight may not be the major contributing factor for mortality and liver tumors and that an interaction between diet and housing conditions appears to affect the growth, survival and tumor incidences of B6C3F1 mice.
Endothelin Antagonist-Induced Coronary and Systemic Arteritis in the Beagle Dog
Authors: Jones Huw B. , Macpherson Allen , Betton Graham R. , Davis A. Stewart , Siddall Robert , Greaves Peter
Published: July 2008

Two endothelin antagonists, ZD1611 (3- {4-[3-(3-methoxy-5-methylpyrazin-2-ylsulfamoyl)-2-pyridyl]phenyl }-2,2-dimethylpropanoic acid) and ZD2574 (2-(4-isobutylphenyl)- N-(3-methoxy-5-methylpyrazin-2-yl)pyridine-3-sulfonamide), selective for the ETA receptor and intended for use in pulmonary hypertension, were tested in Beagle dogs at various doses for periods of up to 4 weeks. These studies included in vivo telemetric hemodynamic assessment, full histopathological and ultrastructural pathological evaluation of coronary arteries. Both drugs produced arteritis in small- and medium-sized coronary arteries after single or multiple doses, some of which were at or below the ED50. The distribution of lesions was predominantly in extramural arteries over the atria and atrioventricular groove of the right side of the heart and consisted of epicardial hemorrhage and arteritis. Systemic arteritis was also present at a lower incidence than the coronary arteritis, was located at different sites and appeared inconsistently. Ultrastructural changes in coronary arteries suggested that damage was the result of mechanical factors. Although these patterns of vascular injury possessed features in common with those induced in dogs by high doses of vasodilating antihypertensive drugs and inotropic agents, they were atypical, as there was no left ventricular myocardial necrosis, papillary muscle damage, or subendocardial hemorrhage suggestive of ischaemia or excessive inotropism. Moreover, physiological monitoring showed no evidence of exaggerated systemic hypotension or reflex tachycardia at doses associated with vascular damage. Consequently, the changes might be the result of a localized pharmacological process such as intense, prolonged vasodilatation in unsupported arteries that are well endowed with endothelin receptors and particularly sensitive to endothelin antagonism.
Case Report of Rat True Hermaphroditism: Colocalization of Oocytes and Granulosa and Sertoli Cells in the Germinal Cord
Authors: Kai Kiyonori , Satoh Norihiro , Watanabe Astushi , Shiraiwa Kazumi , Sasano Hironobu , Furuhama Kazuhisa
Published: July 2008

We describe a case of rat hermaphroditism with bilateral ovotestes. In a 7-week-old apparently male Sprague—Dawley rat, both testes were relatively small, and the right testis with a faint protrusion was somewhat round and small as compared with the left testis. Microscopically, the testes contained ovarian tissues within their tunica albugineas in conjunction with spermatogenesis in the seminiferous tubules. As bilateral changes, oocytes surrounded by granulosa-like cells were present in the seminiferous tubule-like germinal cord. Granulosa-like and Sertoli-like cells were layered together on the basal lamina, and theca interna-like cells were occasionally observed around the basal lamina. As unilateral changes, cystic dilatation of the germinal cords with eosinophilic fluid was seen in the lumen, and the theca interna-like cells appeared to be vacuolated. Immunohistochemically, the granulosa-like and Sertoli-like cells showed positive reactions for 3 β-hydroxysteroid dehydrogenase (3 β-HSD) and vimentin, respectively. Theca interna-like cells reacted positively to both 3 β-HSD and cytochrome P-450 17 α -hydroxylase. Ultrastructurally, the granulosa, Sertoli, and theca interna cells were also identified in the ovarian tissue. From these morphological characteristics, the male rat with bilateral ovotestes was diagnosed as true hermaphroditism.
The Effects of Ad Libitum Overfeeding and Moderate and Marked Dietary Restriction on Age-Related Spontaneous Pituitary Gland Pathology in Sprague—Dawley Rats
Authors: Molon-Noblot Sylvain , Laroque Philippe , Coleman John B. , Hoe Chao-Min , Keenan Kevin P.
Published: July 2008

This study compared the effects of ad libitum (AL) overfeeding and moderate or marked dietary restriction (DR) on the pathogenesis of aged-related pituitary gland changes in Sprague—Dawley (SD) rats. SD rats were fed Purina Certified Rodent Diet AL (group 1), DR at 72—79% of AL (group 2), DR at 68—72% of AL (group 3) or DR at 47—48% of AL (group 4) for 106 weeks. Interim necropsies were performed at 13, 26, and 53 weeks, after a 7-day 5-bromo-2-deoxyuridine (BrdU)-filled minipump implantation. Body weights, organ weights and insulin-like growth factor 1 (IGF-1) serum levels were measured at interim and final necropsies. Serum levels of prolactin (PRL), progesterone, estradiol, luteinizing hormone (LH) and follicle stimulating hormone (FSH) were measured at 53 and/or 106 weeks. In addition to the routine histopathologic examination, determination of 7 stereologic parameters after pituitary immunohistochemistry of PRL, growth hormone (GH) and BrdU was done in both sexes at 13, 26, and 53 weeks. Body and pituitary weights were proportional to the food intake. In AL-fed rats, hyperplastic and neoplastic changes developed early and progressed with age, affecting almost all animals by 106 weeks. These changes were associated with high PRL serum levels. Pituitary adenomas were the most common cause of death in both sexes. In DR rats, a delayed onset and a decreased incidence of pituitary tumors were observed in association with decreased serum IGF-1, PRL, estradiol, and LH levels. The results of the stereological analysis demonstrated that, compared to AL-fed rats, pituitary glands from DR rats contained lower PRL and GH secreting cell volumes, and a lower epithelial cell BrdU labeling index, which correlated with a lower incidence of pituitary tumors at study termination. Moderate and marked degrees of DR delayed the onset of pituitary tumors in a temporal-and dose-related manner. In contrast to marked DR, which dramatically reduced the incidence of hyperplastic and neoplastic pituitary gland changes, moderate DR delayed the onset but did not prevent the development of pituitary tumors.
Toxic Rhinitis-Induced Changes of Human Nasal Mucosa Innervation
Authors: Groneberg David A. , Heppt Werner , Cryer Annette , Wussow Anke , Peiser Christian , Zweng Martina , Thai Dinh Q. , Witt Christian , Fischer Axel
Published: July 2008

Irritative toxic rhinitis is a nasal disorder induced by chemical compounds like ozone, formaldehyde, nickel, chrome, solvents and tobacco smoke. These noxious stimuli may have effects on the nasal innervation leading to a cascade of neuro-immune interactions and an augmentation of the symptoms. Here we examined changes in the neuropeptide content of mucosal parasympathetic, sympathetic and sensory nerves of patients with toxic rhinitis caused by chronic cigarette smoke exposure. Semiquantitative immunohistochemistry using antibodies against calcitonin gene-related peptide (CGRP), substance P (SP), neuropeptide tyrosine (NPY), and vasoactive intestinal peptide (VIP) was carried out on cryostat sections of human nasal mucosa obtained from normal subjects and patients with toxic rhinitis and revealed significant differences between both groups. Toxic rhinitis patients had significantly elevated expression scores for VIP (2.83 ± 0.31 vs 1.27 ± 0.47 control group) and NPY (3.17 ± 0.31 vs 0.91 ± 0.37 control group) revealing an increase of mediators in distinct subpopulations of airway nerves. In summary, the present studies indicate a differential participation of subclasses of mucosal nerves in the pathophysiology of toxic rhinitis. Airway innervation may have a major role in the pathophysiology of toxic rhinitis associated with chronic cigarette smoke exposure.
Three-Dimensional Mapping of the Lesions Induced by β-β'-Iminodiproprionitrile, Methyl Iodide and Methyl Methacrylate in the Rat Nasal Cavity
Authors: Robinson Darren A. , Foster John R. , Nash John A. , Reed Celia J.
Published: July 2008

The nasal cavity is an important target organ for toxicity, and many chemicals induce site-specific lesions in this region. The factors responsible for this site-selectivity have not been unequivocally identified, but probably include regional dosimetry and bioactivation. The purpose of this study was to map, in 3 dimensions, the lesions induced by β- β'-iminodipropionitrile (IDPN), methyl iodide (MeI) and methyl methacrylate (MMA) in the rat nasal cavity. Animals were administered IDPN (150 mg/kg, IP) or exposed via inhalation to MeI (100 ppm, 2 hours) or MMA (400 ppm, 4 hours) and sacrificed after 24 hours. Heads were decalcified, step-sections (1 every 400 μm) cut and stained, and the severity of the epithelial lesion graded as mild (vacuolation and pyknosis), moderate (undulation and mild stripping), or marked (complete stripping). These grades were mapped onto a 3D-model of a rat nasal cavity using the KS400 imaging system (Imaging Associates, Thame, UK). Despite the different routes of exposure the lesions induced by the 3 compounds had very similar distributions, predominantly affecting the dorsal-medial aspects of the ethmoturbinates and, in the case of MMA, the organ of Rodolfo Masera. These results suggest that, with these chemicals, local bioactivation plays a more important role than dosimetry in determining lesion distribution.
Thresholds in Chemical Carcinogenesis: What Are Animal Experiments Telling Us?
Authors: Waddell William J.
Published: July 2008

It appears that the controversy over whether animal experiments demonstrate a threshold for carcinogenicity from chemicals was due to an error in plotting dose response. A linear (arithmetic) scale for the dose of chemicals obscures effects at doses below those used in the experiment and distorts the effect seen over the range of doses used. Gaddum ( Nature 156: 463, 1946) pointed out that, empirically, dose should be on a logarithmic scale to effect a linear quantal response. It now is proposed that this logarithmic relationship of dose to effect has a sound basis in chemical thermodynamics (Waddell, Toxicol Sci 68: 275—279, 2002). When the results of major studies (e.g., ED01, etc.) done in the past were reanalyzed with this in mind using the Rozman et al scale ( Drug Metab Rev 28: 29—52, 1996), which has a logarithmic scale down to one molecule (100), unequivocal thresholds were demonstrated. Many animal studies now have been reanalyzed by this procedure (e.g., Waddell, Toxicol Sci 72: 158—163, 2003; Waddell, Food Chem Toxicol, in press; Waddell, Hum Exp Toxicol, in press); these studies show thresholds for carcinogenicity at doses ranging from 1017 .1 to 1021 .92 molecules/kg/day. These results require a complete reevaluation of human risk assessment for carcinogenesis from chemicals and a redirection of basic research to discover the system, or systems, that are overwhelmed at these thresholds.
Histopathological Study on the PTHrP-Induced Incisor Lesions in Rats
Authors: Kato Atsuhiko , Suzuki Masami , Karasawa Yayoi , Sugimoto Tetsuro , Doi Kunio
Published: July 2008

Parathyroid hormone related peptide (PTHrP) was discovered as a causative factor of humoral hypercalcemia of malignancy (HHM). The present study elucidates the histopathological characters of incisor lesions in the HHM rat model. Nude rats were implanted with PTHrP-expressing tumor (LC-6) cells, maintained for 12 weeks, after which the mandibular incisors were collected. Incisor fractures were observed grossly. Microscopically, hypercalcified dentin, dentin niche with osteodentin, and thinning of dentin were observed. Hypercalcified dentin was observed as a basophilic line of calcified dentin without associated odontoblastic changes, whereas dentin niche and thinning of dentin occurred with osteodentin and loss of cell height, respectively. In contrast with hypercalcified dentin, which was distributed throughout the dentin, dentin niche and thinning of dentin were localized to the labial area of the apical and middle region, and to the labial and lingual areas of the middle and incisal region, respectively. These results suggest that hypercalcemia affected the entire calcification process resulting in hypercalcified dentin, and that high PTHrP concentrations affected selective populations of odontoblasts resulting in formation of dentin niche and thinning of dentin. The localization of dentin niche and thinning of dentin also suggest that PTHrP may also be involved odontoblastic development in the rat.
Malignant Myoepithelioma with a Squamous Epithelial Component in the Mammary Gland of a Cynomolgus Monkey
Authors: Xiuying Yang  , Hori Takao , Fukuda Ayako , Kamimura Yasuhiro , Hirakawa Kimiaki , Maeda Hiroshi , Miyajima Hiroaki
Published: July 2008

A solid mass arising from the mammary gland was found in a 7-year-old female cynomolgus monkey. Histologically, the mass consisted of 2 components: spindle-shaped or ovoid sarcomatous cells and squamous epithelial cells. Metastatic nodules noted in the lung, liver and the gallbladder had the same histological features as the mammary mass. Immunohistochemistry revealed that the sarcomatous cells were positive for alpha-smooth muscle actin ( α-SMA), vimentin, calponin, S-100 protein, epithelial membranous antigen (EMA), cytokeratin (large spectrum) and cytokeratin 14 (CK 14) in the cytoplasm, and p53, erbB-2 and progesterone receptor in the nuclei, but negative for desmin and estrogen receptor. The squamous epithelial cells were positive for EMA, cytokeratin (large spectrum) and CK 14, but negative for the rest. Both sarcomatous and squamous epithelial components were negative for glial fibrillary acidic protein (GFAP). Based on histological and immunohistochemical features, the present case was diagnosed as a malignant myoepithelioma with a squamous epithelial component in the mammary gland with distant metastases.
The new age of the molecular family An anthropological view on the medicalisation of kinship
Authors: Sachs Lisbeth
Published: July 2008

Now that genetic inheritance is featuring more and more as an explanation of disease and human behaviour in general, a question that needs to be asked is how such explanations affect people's perceptions of family and kinship and to what extent genetic explanations conflict with broader social developments. Ideas about the genetic inheritance of disease place the family and kin group in the spotlight, requiring all its members to be scrutinised. Research on inheritable diseases entails a medicalisation of kinship that reflects and promotes a view of family relationships at odds with the ongoing changes in the structure of families. At a time when family structures are more fluid and less determined by ``blood'' relationships than ever before we have an increasing emphasis on genetic inheritance as the transmitter of both human behaviour and kinship. Embedded in concepts of genetic inheritance is thus the notion that family and kin are the medium through which inheritance flows. Two cases from an anthropological study will illustrate how genetic mapping leads to the medicalisation of kinship.
Extensive meiotic asynapsis in mice antagonises meiotic silencing of unsynapsed chromatin and consequently disrupts meiotic sex chromosome inactivation
Authors: Mahadevaiah Shantha K. , Bourc'his Déborah , de Rooij Dirk G. , Bestor Timothy H. , Turner James M.A. , Burgoyne Paul S.
Published: July 2008

Chromosome synapsis during zygotene is a prerequisite for the timely homologous recombinational repair of meiotic DNA double-strand breaks (DSBs). Unrepaired DSBs are thought to trigger apoptosis during midpachytene of male meiosis if synapsis fails. An early pachytene response to asynapsis is meiotic silencing of unsynapsed chromatin (MSUC), which, in normal males, silences the X and Y chromosomes (meiotic sex chromosome inactivation [MSCI]). In this study, we show that MSUC occurs in Spo11-null mouse spermatocytes with extensive asynapsis but lacking meiotic DSBs. In contrast, three mutants (Dnmt3l, Msh5, and Dmc1) with high levels of asynapsis and numerous persistent unrepaired DSBs have a severely impaired MSUC response. We suggest that MSUC-related proteins, including the MSUC initiator BRCA1, are sequestered at unrepaired DSBs. All four mutants fail to silence the X and Y chromosomes (MSCI failure), which is sufficient to explain the midpachytene apoptosis. Apoptosis does not occur in mice with a single additional asynapsed chromosome with unrepaired meiotic DSBs and no disturbance of MSCI.
Building a spindle of the correct length in human cells requires the interaction between TPX2 and Aurora A
Authors: Bird Alexander W. , Hyman Anthony A.
Published: July 2008

To assemble mitotic spindles, cells nucleate microtubules from a variety of sources including chromosomes and centrosomes. We know little about how the regulation of microtubule nucleation contributes to spindle bipolarity and spindle size. The Aurora A kinase activator TPX2 is required for microtubule nucleation from chromosomes as well as for spindle bipolarity. We use bacterial artificial chromosome–based recombineering to introduce point mutants that block the interaction between TPX2 and Aurora A into human cells. TPX2 mutants have very short spindles but, surprisingly, are still bipolar and segregate chromosomes. Examination of microtubule nucleation during spindle assembly shows that microtubules fail to nucleate from chromosomes. Thus, chromosome nucleation is not essential for bipolarity during human cell mitosis when centrosomes are present. Rather, chromosome nucleation is involved in spindle pole separation and setting spindle length. A second Aurora A–independent function of TPX2 is required to bipolarize spindles.
The first “Slit” is the deepest: the secret to a hollow heart
Authors: Helenius Iiro Taneli , Beitel Greg J.
Published: July 2008

Tubular organs are essential for life, but lumen formation in nonepithelial tissues such as the vascular system or heart is poorly understood. Two studies in this issue (Medioni, C., M. Astier, M. Zmojdzian, K. Jagla, and M. Sémériva. 2008. J. Cell Biol. 182:249–261; Santiago-Martínez, E., N.H. Soplop, R. Patel, and S.G. Kramer. 2008. J. Cell Biol. 182:241–248) reveal unexpected roles for the Slit–Robo signaling system during Drosophila melanogaster heart morphogenesis. In cardioblasts, Slit and Robo modulate the cell shape changes and domains of E-cadherin–based adhesion that drive lumen formation. Furthermore, in contrast to the well-known paracrine role of Slit and Robo in guiding cell migrations, here Slit and Robo may act by autocrine signaling. In addition, the two groups demonstrate that heart lumen formation is even more distinct from typical epithelial tubulogenesis mechanisms because the heart lumen is bounded by membrane surfaces that have basal rather than apical attributes. As the D. melanogaster cardioblasts are thought to have significant evolutionary similarity to vertebrate endothelial and cardiac lineages, these findings are likely to provide insights into mechanisms of vertebrate heart and vascular morphogenesis.
Ni2+ Block of CaV3.1 (α1G) T-type Calcium Channels
Authors: Obejero-Paz Carlos A. , Gray I. Patrick , Jones Stephen W.
Published: July 2008

Ni2+ inhibits current through calcium channels, in part by blocking the pore, but Ni2+ may also allosterically affect channel activity via sites outside the permeation pathway. As a test for pore blockade, we examined whether the effect of Ni2+ on CaV3.1 is affected by permeant ions. We find two components to block by Ni2+, a rapid block with little voltage dependence, and a slow block most visible as accelerated tail currents. Rapid block is weaker for outward vs. inward currents (apparent Kd = 3 vs. 1 mM Ni2+, with 2 mM Ca2+ or Ba2+) and is reduced at high permeant ion concentration (110 vs. 2 mM Ca2+ or Ba2+). Slow block depends both on the concentration and on the identity of the permeant ion (Ca2+ vs. Ba2+ vs. Na+). Slow block is 2–3× faster in Ba2+ than in Ca2+ (2 or 110 mM), and is ∼10× faster with 2 vs. 110 mM Ca2+ or Ba2+. Slow block is orders of magnitude slower than the diffusion limit, except in the nominal absence of divalent cations (∼3 μM Ca2+). We conclude that both fast and slow block of CaV3.1 by Ni2+ are most consistent with occlusion of the pore. The exit rate of Ni2+ for slow block is reduced at high Ni2+ concentrations, suggesting that the site responsible for fast block can “lock in” slow block by Ni2+, at a site located deeper within the pore. In contrast to the complex pore block observed for CaV3.1, inhibition of CaV3.2 by Ni2+ was essentially independent of voltage, and was similar in 2 mM Ca2+ vs. Ba2+, consistent with inhibition by a different mechanism, at a site outside the pore.
α-Scorpion Toxin Impairs a Conformational Change that Leads to Fast Inactivation of Muscle Sodium Channels
Authors: Campos Fabiana V. , Chanda Baron , Beirão Paulo S.L. , Bezanilla Francisco
Published: July 2008

α-Scorpion toxins bind in a voltage-dependent way to site 3 of the sodium channels, which is partially formed by the loop connecting S3 and S4 segments of domain IV, slowing down fast inactivation. We have used Ts3, an α-scorpion toxin from the Brazilian scorpion Tityus serrulatus, to analyze the effects of this family of toxins on the muscle sodium channels expressed in Xenopus oocytes. In the presence of Ts3 the total gating charge was reduced by 30% compared with control conditions. Ts3 accelerated the gating current kinetics, decreasing the contribution of the slow component to the ON gating current decay, indicating that S4-DIV was specifically inhibited by the toxin. In addition, Ts3 accelerated and decreased the fraction of charge in the slow component of the OFF gating current decay, which reflects an acceleration in the recovery from the fast inactivation. Site-specific fluorescence measurements indicate that Ts3 binding to the voltage-gated sodium channel eliminates one of the components of the fluorescent signal from S4-DIV. We also measured the fluorescent signals produced by the movement of the first three voltage sensors to test whether the bound Ts3 affects the movement of the other voltage sensors. While the fluorescence–voltage (F-V) relationship of domain II was only slightly affected and the F-V of domain III remained unaffected in the presence of Ts3, the toxin significantly shifted the F-V of domain I to more positive potentials, which agrees with previous studies showing a strong coupling between domains I and IV. These results are consistent with the proposed model, in which Ts3 specifically impairs the fraction of the movement of the S4-DIV that allows fast inactivation to occur at normal rates.
Viscoelastic Characterization of Transversely Isotropic Composite Laminae
Authors: Melo José Daniel D. , Radford D. W.
Published: July 2008

Understanding and designing for damping in composite laminates has become a topic of great interest; unfortunately, only limited viscoelastic property data is presently available. Direct experimental measurement of the three-dimensional viscoelastic properties is not simple to implement and, thus, an approach leading to the complete 3-D viscoelastic characterization using a reduced number of measured parameters is desirable. To address the difficulties related to direct measurement of properties, this work proposes a reduced number of material coefficients, which allow the specification of the viscoelastic constitutive relationships for a transversely isotropic material, based on only five independent dynamic stiffness parameters and three independent damping loss factors. Further, using this model, a method is developed, based on energy equations, which allows the viscoelastic properties to be evaluated from experimental data, collected from three bend-beam oscillatory tests and two measured Poisson’s ratios. The approach is validated through the use of both published data and an experimental investigation conducted using a Dynamic Mechanical Analyzer.
Homogenization Modeling and Effective Mechanical Constants for EM Composite Conductor with Cooling Channel
Authors: Sun W. , Tzeng J. T.
Published: July 2008

A homogenization modeling to predict the effective mechanical properties of electric machinery composite conductor consisting of metallic core with cooling channel, and multi-layer of insulating materials was presented. A two-level homogenization scheme to model complex composite with multi-phase materials and the validation of using finite element method was developed. Composite cylinder assembly model was adopted in the Level 1homogenization for the metallic core and the cooling channel was analyzed as a fiber void with null material properties. The effective mechanical properties of the composite insulation layers were homogenized by smearing the properties of the multiple insulation layers of bonding, insulation and insulation–fiber-reinforced composite. Level 2 homogenization derived nine effective mechanical constants for conductor through a combined homogenization sequences. The good comparisons between the analytical predictions and the results obtained from the finite element analyses demonstrated the applicability of the model.
Synthesis and Application of AN-g-EPDM and AA-g-EPDM as Compatibilizers for CR/EPDM and NBR/EPDM Rubber Blends
Authors: Botros S. H. , Moustafa A. F.
Published: July 2008

The graft polymerization of acrylonitrile (AN) or acrylic acid (AA) onto ethylene-propylene-diene terpolymer rubber (EPDM) was carried out in toluene, using dibenzoyl peroxide (BPO) as an initiator. The synthesized AN-g-EPDM and AA-g-EPDM were characterized by FT-IR spectroscopy and thermal gravimetric analysis (TGA). AN-g-EPDM and AA-g-EPDM were incorporated into chloroprene rubber (CR)/EPDM and butadiene acrylonitrile rubber (NBR)/EPDM blends. The compatibility of EPDM/CR and EPDM/NBR blends was examined with scanning electron microscope (SEM) and differential scanning calorimetry (DSC). The physico-mechanical properties of the vulcanizates were investigated after and before thermal aging. AN-g-EPDM and AA-g-EPDM improved the morphology of CR/EPDM and NBR/EPDM rubber blends. The mechanical properties illustrate that the compatibilized blends possessed good thermal stability.
Dynamic Mechanical Relaxation Behavior of Block Copolymers: Styrene-Butadiene-Styrene Rubber, SBS
Authors: Mansour Ashraf A. , Mohammady Sayed Z.
Published: July 2008

The real and imaginary parts of the complex shear compliance (J0 and J00) of styrene-butadiene-styrene block copolymer, SBS, have been measured isothermally over the frequency range; 0.03-30 Hz, at different temperatures ranging from -70 to 130°C. SBS is taken as representative example of thermoplastic rubbers, which are not susceptible for direct construction of master curves by the usual time-temperature-superposition, tTs, technique. A method has been developed to construct master curves, which we call “step mastering technique”. The step mastering was carried out by constructing different master curves at different temperatures covering both glass transitions which were then superpositioned as whole to maintain the individual shift factors of different processes unchanged. The relaxation frequency of the low temperature glass process can be obtained at any given reference temperature by fitting and extrapolating the activation curve in order to superposition its low temperature master curve (as whole) on the high temperature master one at the correct position of frequency that corresponds the new reference temperature. Accordingly, it was possible for the first time to construct a complete master curve for J0 and J00 for SBS at 30°.

The validity of the master curves obtained by the step mastering technique were confirmed by real frequency measurements in the MHz region using the Quartz method. The analysis showed that the relaxation spectrum consists of four relaxation processes. Using a molecular (meander) model, it was possible from the plateau compliance to determine the size of the structural units of the two phases, which was estimated to be 6.5 and 19.5 nm for PB- and PS-phases, respectively. A possible geometrical packing of the different domains is suggested and compared with the literature data.
Studies on Acrylonitrile Butadiene Rubber/Reclaimed Rubber Blends
Authors: Sreeja T. D. , Kutty S. K. N.
Published: July 2008

Cure characteristics and mechanical properties of acrylonitrile butadiene rubber/reclaimed rubber blends were studied. Minimum torque, (maximum -minimum) torque, scorch time, cure time and cure rate decreased in presence of reclaimed rubber. Tensile strength, elongation at break and compression set increased with increase in reclaim content. Resilience and abrasion resistance decreased with reclaim loading. Heat build up was higher for the blends. The ageing resistance of the blends was inferior to that of the gum compound.
Computer Simulation as a Tool to Investigate the Shearing Deformation of Nonhomogeneous Elastomers
Authors: Bilgili Ecevit
Published: July 2008

The large deformation of elastomeric (rubber-like) materials has been commonly analyzed within the context of hyper elasticity. Although there is ample experimental evidence suggesting the nonhomogeneity of these materials, the majority of the hyperelastic models assume the material homogeneity. In the present study, a Gent material model is generalized in light of recent experimental studies to be able to simulate the shearing deformation of a non-homogeneous isotropic incompressible elastomeric slab. The numerical solution of the static equilibrium equations shows that the shearing response of non-homogeneous slabs is substantially different from that of homogeneous slabs. The finite chain extensibility, which is a characteristic of most rubber-like materials, is shown to have a self-homogenizing effect on the strain field in addition to its well-known stiffening effect on the stress field.
Delaminated Woven Fabric Composite Plates under Transverse Quasi-Static Loading: Experimental Studies
Authors: Naik N. K. , Reddy K. Satyanarayana
Published: July 2008

Laminated composite plates are very sensitive to transverse loading because of weak interfaces between layers. During transverse loading, delamination can initiate and propagate at the interfaces. Also, in-plane failure of layers can initiate and grow further because of the in-plane stresses. Such damages can cause severe structural disintegration leading to a reduction in stiffness and strength. The delamination may be caused by manufacturing defects also. Such delamination can grow during service condition. Experimental studies have been carried out on the damage evolution in a typical plain weave fabric composite plate under transverse quasi-static loading. Studies have been carried out on composite plates with central artificial delamination of 5 mm, 10 mm and 15 mm diameter sizes, and also on undelaminated composite plates. Load-displacement behavior, damage evolution and damage sizes and damage shapes have been studied.
Targeting of Polyelectrolyte RNA Complexes to Cell Surface Integrins as an Efficient Cytoplasmic Transfection Mechanism
Authors: Parker Alan L. , Seymour Leonard W.
Published: July 2008

This is the first demonstration of receptor-mediated delivery of mRNA and establishes a new approach to gene therapy. Messenger RNA (mRNA) provides a promising alternative to plasmid DNA as a genetic material for delivery in non-viral gene therapy strategies. Since it does not require access to the nucleus and is less dependent on the cell cycle for expression, mRNA delivered using cationic lipids or short cationic polymers can be effectively translated within target cells. In this study, mRNA formed discrete nanoparticles following self assembly with a range of cationic polymers. Based on transfection activities, the low molecular weight polycations were more efficient than high molecular weight, while protamine and polyethylenimine were far more efficient than poly(L-lysine). Receptor-mediated delivery of mRNA was demonstrated using the synthetic polyamino acid (K)16GACDCRGDCFCA designed to promote cell entry following interaction with cell surface αυ integrins. RGD-bearing mRNA complexes showed very high levels of expression, reaching over 60% transduction of B16F10 cells.
Suggestions for Skillful Proposal Writing
Authors: Anderson Gary L. , Garg Devendra P.
Published: July 2008

This brief paper is written to provide instructions and suggestions for preparing research proposals for possible funding. Whereas the emphasis of the present document is on the funding process used by the Army Research Office (ARO), the suggestions could be utilized as a proposal preparation guide for submitting applications to many other funding agencies as well. In this paper, first the various programs at ARO such as the core programs and the special initiatives that are available for funding in the Engineering Sciences Directorate are pointed out. Next, the process of receiving and evaluating proposals in the Structures and Dynamics Program of the Mechanical and Environmental Sciences Division is described. This is followed by a discussion of specific issues such as the need for the Army relevance, cost sharing, and technology transfer. Finally, additional information, including a list of recent publications that could serve as supplementary resource material, and contact information is given.
Development of ER Brake and its Application to Passive Force Display
Authors: Furusho Junji , Sakaguchi Masamichi , Takesue Naoyuki , Koyanagi Ken’ichi
Published: July 2008

Force display systems are important in virtual reality and other applications. While conventional force displays are active systems with actuators and as such may become inherently dangerous, passive force displays are effective methods for assuring safety. In this paper, we developed a brake using electrorheological (ER) fluid, and showed a passive force display system using ER brakes with two degrees of freedom. We also discuss basic control experiments of the system.
Computational Characterization of Micro- to Macroscopic Mechanical Behavior and Damage of Polymers Containing Second-Phase Particles
Authors: Tomita Yoshihiro , Lu Wei
Published: July 2008

To clarify the mechanical characteristics and damage of polymers containingsecond-phase particles, i.e., blended polymers, a homogenization method has been developed which can handle the large deformation problems, including onset and propagation of instability, and completely reproduce the periodic feature of the distribution of second-phase particles under any macroscopically homogeneous loading condition. The parametric study has clarified the characteristic features of polymers containingperiodically distributed soft cylindrical particles of different volume fractions and sizes subjected to macroscopically homogeneous stress in different directions. The results indicate that, dependingon the tensional direction with respect to the unit cell, different types of shear bands are observed, and that the shear band connectingthe particles that appeared in the early stages of deformation is responsible for the reduction of the macroscopic yield stress. Increasingthe volume fraction of particles causes a decrease of the macroscopic yield stress and of the directional dependence of the macroscopic stress–strain relation. The size difference of particles causes very complicated and different types of shear bands, however, due to the high stress concentration caused by the presence of small particles, the onset and propagation of shear bands are promoted, and the macroscopic deformation behaviors become essentially isotropic. The maximum mean stress appears in the small particle, which suggests that the blending of particles of different sizes promotes the onset of cavitation, which suppresses the maximum mean stress in the matrix and results in additional shear deformation and in preventing onset of damage in matrix caused by crazing. The location of maximum normal stress on the boundary surface between particles and matrix moves with the propagation of the shear band. The magnitude of maximum normal stress increases with the increase of the size difference between the particles and with the decrease of the volume fraction within the present simulation.
Experimental Study of Biaxial Creep Damage for Type 304 Stainless Steel
Authors: Sakane Masao , Tokura Hiroto
Published: July 2008

This paper studies the biaxial creep damage of type 304 stainless steel at 923 K. Biaxial tension creep tests were carried out using cruciform specimens and the effect of stress biaxiality on rupture lifetime and creep voiding was discussed. Mises equivalent stress and the equivalent stress based on crack opening displacement were a suitable parameter to assess the biaxial creep damage. The equivalent stress proposed by Huddleston overestimated the biaxial creep damage by more than a factor of two. Stress biaxiality had almost no influence on the orientation of voided grain boundaries and the critical value ofparameter A. Tests of alternative loading direction significantly dispersed the biaxial creep damage resulting in larger creep lifetime.
Damage Characterization and its Incorporation into the Constitutive Model for Several Solders in Electronic Packaging
Authors: Wen Shengmin , Keer Leon M.
Published: July 2008

A materials science based damage metric is presented for solders in electronic packaging. The damage metric characterizes the damage state when solders are subjected to cyclic thermal strain due to mismatch of the coefficient of thermal expansion (CTE). The damage metric is derived through a micromechanics approach, and its relationship to the damage parameters is assumed to follow power law. A unified creep and plasticity constitutive model with damage incorporation showed reasonable agreement with the experimental results for two solders under a one-dimensional strain controlled fatigue test.
The Use of High Performance Textiles in Construction Projects
Authors: Isley Fred
Published: July 2008

A niche in the textile industry provides high strength, high modulus textile fabrics to the construction industry as a potential replacement for more traditional building materials such as wood, concrete, masonry, and steel. The mechanical properties of fabrics made of aramid, carbon and glass fibers lend themselves to the needs of the design engineer by providing high strength to weight, high stiffness to weight and extreme flexibility in use and design. Combined with cross-linking resins systems to form a composite, the fabrics are being widely accepted by the civil engineers serving the construction trades Thousands of structures around the world have been repaired, retrofitted or built of such fabrics in the past 10 years.
Biocidal Copolymers of N-Haloacryloxymnethylhydantoin
Authors: Li Yanjun , Worley S. D.
Published: July 2008

A series of new biocidal copolymers containing N-chloro-and N-bromo-acrYloxymethylhydantoin moieties have been prepared in granular form, as surface coatings and as grafts to fibers. The copolymers have been tested for bactericidal effects against Staphylococcus aureus and have been evaluated for stability in terms of retention of their biocidal halogen contents. They have been demonstrated to have potential application for polymeric materials for which a biocidal functionality might be benefical.
Multi-Duct ER Dampers
Authors: Gavin Henri P.
Published: July 2008

This paper describes the design, construction, testing and modeling of controllable damping devices utilizing electro-rheological (ER) materials. The rheological properties of ER materials (yield stress and viscoelasticity) are extremely sensitive to electric fields. Modulations of the electric field in an electrorheological damper results in a corresponding change in device forces. The key feature of the ER devices described in this paper is a set of multiple concentric annular ducts through which the ER material flows. The annular ducts are formed by a set of concentric metallic tubes, which may be electrically charged with a high voltage potential, or electrically grounded. Three designs targeting different force levels (2-6 kN), are designed, tested and modeled. The device analyses used in the design incorporate a simplified closed form relation for the flow behavior of ER materials. Evolutionary and algebraic device models are fit to the measured force response of the devices over a range of harmonic frequencies and at zero and high electric field magnitudes. The evolutionary model is motivated by observations and simulations of ER materials in simple shear, and the algebraic model is convenient for control and feedback linearization applications. The algebraic model is evaluated with data collected with random excitation and with switching electric fields. The three devices display different levels of pre-yield viscoelasticity. Friction, due to seals in the device, was not accounted for in the initial design, and affected the behavior of the device as tested.
Feasibility Study of Microfabrication by Coextrusion (MFCX) Hollow Fibers for Active Composites
Authors: Cannon Bryan J. , Brei Diann
Published: July 2008

Active composites based on a hollow fiber topology have advantages over solid piezoelectric fiber composites in that they require lower voltages for activation and are not limited to electrically non-conductive matrix materials. One critical issue for hollow fiber composites is the fiber aspect ratio (ratio of wall thickness to fiber radius). In this paper analytical and finite element models, which include electric field variations, were developed to determine the “effective d31”of an individual piezoelectric hollow fiber. The effective fiber properties were used to derive a single-row lamina strain/electric field model from classical composite theory. The models were validated with a series of deflection/voltage experiments conducted with hollow piezoelectric fibers fabricated utilizing microfabrication by coextrusion (MFCX) techniques. To determine the feasibility of MFCX hollow fiber composites, the models and experimental results were employed to study the effect of the fiber aspect ratio on a variety of fiber/composite design issues: fiber/lamina performance, fiber strength, matrix material, and electric field effects (incomplete poling and field concentrations).
Medical Applications of Magnetorheological Fluids a Possible New Cancer Therapy
Authors: Flores G. A. , Sheng R. , Liu J.
Published: July 2008

This work demonstrates the principle of a novel cancer therapeutic method using magnetic fluids to block the blood supply to a tumor in order to starve it. Plastic tubes are used to simulate the simplest blood network. The sealing effect to the fluid flow is easily achieved at low particle concentrations with strong pressure resistance and reasonable sealing times at low flow rate (Q = 0.078 ml/min). At high flow rate (Q > 0.62 ml/min), oscillations in pressure and step increases in weight of the fluid are found.
Actuators Making Use of Electro-Rheological Fluids: Movable Electrode Type ER Actuators
Authors: Kondoh Yutaka , Yokota Shinichi
Published: July 2008

By employing ER fluids as working fluids in fluid power systems, direct interface can be realized between electric signals and fluid power without the need for mechanical moving parts like spools in control valves. In this paper, first, novel hydraulic actuators with ER fluids and with movable electrodes (METERA: Movable Electrode-Type ER Actuator) are proposed, which are classified into a linear type (L-METERA) and a rotary-type (R-METERA). Secondly, a design method of L-METERA is described and a small sized L-METERA is fabricated, whose size is 40 mm x 18 mm x 16 mm. Thirdly, a design method of R-METERA is described and a small sized R-METERA is fabricated, whose size is 067 mm x 53 mm. Principles of METERA are confirmed with the fabricated METERA.
In vitroallergen challenge of peripheral blood induces differential gene expression in mononuclear cells of asthmatic patients: inhibition of cytosolic phospholipase A2αovercomes the asthma‐associated response
Authors: Whalen K. A. , Legault H. , Hang C. , Hill A. , Kasaian M. , Donaldson D. , Bensch G. W. , Bensch G. , Baker J. , Reddy P. S. , Wood N. , Ramarao M. K. , Ellis D. K. , Csimma C. , McKee C. , Clark J. D. , Ryan J. , Dorner A. J. , O'Toole M.
Published: July 2008

BackgroundExisting treatments for asthma are not effective in all patients and disease exacerbations are common, highlighting the need for increased understanding of disease mechanisms and novel treatment strategies. The leukotriene pathway including the enzyme responsible for arachidonic acid release from cellular phospholipids, cPLA2α, is a major contributor to asthmatic responses and an attractive target in asthma therapies.

ObjectiveThe study reported here investigates (a) the differential effects ofin vitroexposure of peripheral blood mononuclear cells (PBMCs) to allergen between asthma and healthy subjects, and (b) the contribution of cPLA2α to these differences in gene expression.

MethodsIn vitroresponses of asthma (N=26) and healthy (N=11) subject PBMC samples to allergen stimulation in the presence and absence of cPLA2α inhibition or 5‐lipoxygenase inhibition were compared at the gene expression level using oligonucleotide arrays and at the protein level using ELISA.

ResultsSubject samples within both asthma and healthy groups showed allergen‐dependent cytokine production and allergen‐dependent gene expression changes, although transcriptional profiling identified 153 genes that were modulated significantly differently by allergen between asthma and healthy subjects. Among these were genes previously associated with asthma, but the majority (about 80%) have not previously been associated with asthma.

ConclusionsTranscriptional profiling elucidated novel gene expression differences between the asthmatic and healthy subject samples. Although 5‐lipoxygenase inhibition did not significantly affect allergen‐modulated gene expression, the inhibition of cPLA2α activity affected many of the allergen‐dependent, asthma‐associated gene expression changes.