Experimental and numerical analysis of the deformed process of cracks/cavities

In this paper, the three-point bending tests of beams with a small single-edge crack are conducted to demonstrate the reliability and accuracy of the laser diffraction technique in detecting its deformation and evolution. As a comparison, the quasi-static analysis of the beam subjected to 3-point bending is further proceeded using the finite element method and the related results have been in good agreement with those from the tests.

Differential effect of inbred mouse strain (C57BL/6, DBA/2, 129T2) on insulin secretory function in response to a high fat diet

The increasing production of genetically-modified mouse models has necessitated studies to determine the inherent physiological characteristics of commonly used mouse strains. In this study we examined insulin secretory function in response to an intravenous bolus of glucose or glucose plus arginine in anesthetized C57BL/6, DBA/2 and 129T2 mice fed either a control or high fat diet for 6 weeks. The results show that 129T2 mice had higher fasting plasma glucose levels and lower fasting plasma insulin levels compared with C57BL/6 and DBA/2 mice regardless of diet. Furthermore, 129T2 mice were glucose intolerant and secreted significantly less insulin in response to glucose and glucose plus arginine irrespective of diet compared with the other two strains of mice. DBA/2 mice hypersecreted insulin in response to glucose and glucose plus arginine compared with C57BL/6 and 129T2 mice. Moreover while first phase insulin secretion was appropriately increased in response to the high fat diet in C57BL/6 and 129T2 mice, this was not the case for DBA/2 mice. Mean islet area was decreased in response to a high fat diet in DBA/2 mice, while there was no dietary effect on the other two strains. This study highlights the inherent genetic differences that exist among seemingly normal strains of mice that are commonly used to make transgenic and knockout mice. Understanding these differences will provide researchers with the information to choose the appropriate genetic background on which to express their particular genetic alteration.

Ground-based survey methods both overestimate and underestimate the abundance of suitable tree-cavities for the endangered Swift Parrot

Most cavity-dependent species select tree-cavities with a narrow range of characteristics so that only a small subset of available cavities may be suitable for any species. Most surveys for tree-cavities are done from the ground using binoculars to reduce effort, but this technique is prone to error. These errors are likely to contribute to the loss of the cavity resource when used to inform conservation efforts for cavity-dependent species. The Swift Parrot (Lathamus discolor) is an endangered migratory bird threatened by ongoing removal of cavity-bearing trees by production forestry. We climbed trees with cavities used for nesting by Swift Parrots and determined that they prefer cavities with small entrances, deep chambers and wide floors. Such cavities are rare and occur in large trees that support higher than average numbers of tree-cavities. Importantly, cavities used by Swift Parrots were also likely to be both overestimated and underestimated using ground-based surveys, and without calibration by climbing, the size and direction of survey error could not be determined. We conclude that the most effective way to gain detailed information about the characteristics and abundance of tree-cavities is to climb a representative sample of trees to calibrate ground-based methods for a specific ecosystem.

A preliminary study on the effect of macro cavities formation on properties of carbon nanotube bucky-paper composites

In this study, we focus on processing and characterizing composite material structures made of carbon nanotubes (CNTs) and reproducibly engineering macro-pores inside their structure. Highly porous bucky-papers were fabricated from pure carbon nanotubes by dispersing and stabilizing large 1 μm polystyrene beads within a carbon nanotube suspension. The polystyrene beads, homogeneously dispersed across the thickness of the bucky-papers, were then either dissolved or carbonized to generate macro cavities of different shape and properties. The impact of adding these macro cavities on the porosity, specific surface area and Young’s modulus was investigated and some benefits of the macro cavities will be demonstrated.

PMC42, a novel model for the differentiated human breast

Cultured human breast carcinoma cell lines are important models for investigating the pathogenesis of breast cancer. Their use, however, is limited because of loss of expression of breast-specific markers and the development of a dedifferentiated phenotype after continuous culture. PMC42 is a unique human breast carcinoma line, previously shown to express secretory and myoepithelial markers. We have induced PMC42 cells to form hollow organoids in culture, similar to in vivo breast structures, using a combination of hormones including estrogen, progesterone, dexamethasone, insulin, and prolactin in combination with a permeable extracellular matrix. The organoids comprised polarized cells located around a central lumen. Expression of β-casein was demonstrated in cells within organoids using reverse transcriptase-polymerase chain reaction, Western blot analysis, and confocal immunofluorescence. In this in vitro system, milk-specific gene expression was induced through hormone and matrix interactions which may be similar to those operating in vivo. PMC42 is a novel model for investigations into the molecular mechanisms of carcinogenesis and differentiation in the human breast.

Selection of roost sites by the lesser long-eared bat (Nyctophilus geoffroyi) and Gould`s wattled bat (Chalinolobus gouldii) in south-eastern Australia

Physical characteristics of roost sites used by the lesser long-eared bat Nyctophilus geoffroyi and Gould's wattled bat Chalinolobus gouldii were investigated in a farmland–remnant vegetation mosaic and adjacent forested floodplain in south-eastern Australia. A total of 45 individuals of N. geoffroyi and 27 C. gouldii were fitted with radio-transmitters, resulting in the location of 139 and 89 roosts, respectively. Male N. geoffroyi roosted in trees, fallen and decayed timber and artificial structures. These roosts were low to the ground, mainly under bark and in cracks in timber. Roosts of female N. geoffroyi were located higher above ground, and all within trees. Maternity roosts were predominantly located in large dead trees, approximately twice the diameter of roost trees used by females outside the breeding season. No maternity roosts were found under bark, despite half the roosts used by non-breeding females being located in these situations. Both sexes roosted primarily in dead timber and used cavities where the narrowest dimension of the entrance was 2.5 cm. Most roosts of C. gouldii were in dead spouts on large, live river red gum Eucalyptus camaldulensis trees. Intraspecific differences in roost characteristics were less pronounced for this species. Despite access to the same roosting opportunities, there were marked differences in roost selection between N. geoffroyi and C. gouldii. Both species favoured large diameter trees, but differed significantly for all other measured variables: type of roost structure, condition of roost tree (live or dead), height of roost tree, height of roost, and entrance dimensions. Although these species are among the most widespread bats in Australia and are often considered to be habitat 'generalists', both displayed a high level of discrimination in the roosts used. Clearly, roosting requirements are a complex and important issue in the conservation of even the most common species of bats.

Modeling the tensile behavior of fibers with geometrical and structural irregularities

Virtually all fibers exhibit some dimensional and structural irregularities. These include the conventional textile fibers, the high-performance brittle fibers and even the newly developed nano-fibers. In recent years, we have systematically examined the effect of fiber dimensional irregularities on the mechanical behavior of the irregular fibers. This paper extends our research to include the combined effect of dimensional and structural irregularities, using the finite element method (FEM). The dimensional irregularities are represented by sine waves with a 30 % magnitude of diameter variation while the structural irregularities are represented by longitudinal and horizontal cavities distributed within the fiber structure. The results indicate that fiber geometrical or dimensional variations have a marked influence on the tensile properties of the fiber. It affects not only the values of the breaking load and extension, but also the shape of the load-extension curves. The fiber structural irregularities simulated in this study appear to have little effect on the shape of the load-extension curves.

Identification of a putative egg-laying hormone in neural and ovarian tissues of the black tiger shrimp, Penaeus monodon, using immunocytochemistry

The existence of an egg-laying hormone (ELH) was identified for the first time in the black tiger shrimp, Penaeus monodon, by means of immunoenzyme and immunofluorescence techniques. This was achieved using a polyclonal antibody produced against expressed recombinant ELH of the female Australian blacklip abalone, Haliotis rubra. The shrimp ELH reactive material was found to be localised within female neurosecretory tissues and the secretory tissue of the antennal gland, but was not identified in the X-organ sinus gland within the eyestalk. It was also present in the ovary, where the amount of ELH present was observed to be greatest in the period prior to spawning. These findings implied that the induction of P. monodon spawning might be involved with humoral regulation relating to ELH expression.

Purification and membrane reconstitution of catalytically active Menkes copper-transporting P-type ATPase (MNK; ATP7A)

The MNK (Menkes disease protein; ATP7A) is a major copper- transporting P-type ATPase involved in the delivery of copper to cuproenzymes in the secretory pathway and the efflux of excess copper from extrahepatic tissues. Mutations in the MNK (ATP7A) gene result in Menkes disease, a fatal neurodegenerative copper deficiency disorder. Currently, detailed biochemical and biophysical analyses of MNK to better understand its mechanisms of copper transport are not possible due to the lack of purified MNK in an active form. To address this issue, we expressed human MNK with an N-terminal Glu-Glu tag in Sf9 [Spodoptera frugiperda (fall armyworm) 9] insect cells and purified it by antibody affinity chromatography followed by size-exclusion chromatography in the presence of the non-ionic detergent DDM (n-dodecyl b-D-maltopyranoside). Formation of the classical vanadate-sensitive phosphoenzyme by purified MNK was activated by Cu(I) [EC50=0.7 µM; h (Hill coefficient) was 4.6]. Furthermore, we report the first measurement of Cu(I)-dependent ATPase activity of MNK (K0.5=0.6 µM; h=5.0). The purified MNK demonstrated active ATP-dependent vectorial 64Cu transport when reconstituted into soya-bean asolectin liposomes. Together, these data demonstrated that Cu(I) interacts with MNK in a co-operative manner and with high affinity in the sub-micromolar range. The present study provides the first biochemical characterization of a purified full-length mammalian copper-transporting P-type ATPase associated with a human disease.

Fur seal adaptations to lactation: insights into mammary gland function

The fur seal (Arctocephalus spp. and Callorhinus spp., members of the pinniped family) is a mammal with the unusual capability to modulate its lactation cycle by turning milk production on and off without the typical mammalian regression and involution of the mammary gland. Lactation has evolved from constraints arising from the spatial and temporal separation of infant nursing and maternal foraging as the mother gives birth and feeds the pup on land while acquisition of nutrients for milk production occurs at sea. The lactation cycle begins with the female fur seal undergoing a perinatal fast of approximately 1 wk, after which time she departs the breeding colony to forage at sea. For the remainder of the long lactation period (116–540 days), the mother alternates between short periods ashore suckling the young with longer periods of up to 4 wk of foraging at sea. Milk production continues while foraging at sea, but at less than 20% the rate of production on land. Fur seals produce one of the richest milk reported, with a very high lipid content contributing up to 85% of total energy. This feature serves as an adaptation to the young's need to produce an insulating blubber layer against heat loss and to serve as an energy store when the mother is away foraging at sea. This atypical pattern of lactation means mothers have long periods with no suckling stimulus and can transfer high-energy milk rapidly while on land to minimize time away from foraging grounds. The absence of suckling stimulus and milk removal during foraging does not result in the onset of involution with associated apoptosis of mammary secretory cells and a subsequent progressive breakdown of the cellular structure of the mammary gland. The mechanisms controlling lactation in the fur seal mammary gland have been investigated using molecular and cellular techniques. These findings have shed light on the processes by which the unique features of lactation in the fur seal are regulated.

Novel agents that potentially inhibit irinotecan-induced diarrhea

Irinotecan (CPT-11, 7-ethyl-10-[4-(1-piperidino)-1-piperidino] carbonyloxycamptothecin) has exhibited clinical activities against a broad spectrum of carcinomas by inhibiting DNA topoisomerase I (Topo I). However, severe and unpredictable dosing-limiting toxicities (mainly myelosuppression and severe diarrhea) hinder its clinical use. The latter consists of early and late-onset diarrhea, occurring within 24 hr or ≥ 24 hr after CPT-11 administration, respectively. This review highlights novel agents potentially inhibiting CPT-11-induced diarrhea, which are designed and tested under guidance of disposition pathways and potential toxicity mechanisms. Early-onset diarrhea is observed immediately after CPT-11 infusion and probably due to the inhibition of acetylcholinesterase activity, which can be eliminated by administration of atropine. Lateonset diarrhea appears to be associated with intestinal exposure to SN-38 (7-ethyl-10-hydroxycamptothecin), the major active metabolite of CPT-11, which may bind to Topo I and induce apoptosis of intestinal epithelia, leading to the disturbance in the absorptive and secretory functions of mucosa. CPT-11 and SN-38 may also stimulate the production of pro-inflammatory cytokines and prostaglandins (PGs), thus inducing the secretion of Na⁺ and Cl^-. Early treatment of severe late-onset diarrhea with oral high-dose loperamide has decreased patient morbidity. Extensive studies have been conducted to identify other potential agents to ameliorate diarrhea in preclinical and clinical models. These include intestinal alkalizing agents, oral antibiotics, enzyme inducers, P-glycoprotein (PgP) inhibitors, cyclooxygenase-2 (COX-2) inhibitors, tumor necrosis factor-agr (TNF-α) inhibitors, or blockers of biliary excretion of SN-38. Further studies are needed to identify the molecular targets associated with CPT-11 toxicity and safe and effective agents for alleviating CPT-11-induced diarrhea.

Extracellular matrix induces formation of organoids and changes in cell surface morphology in cultured human breast carcinoma cells PMC42-LA

In the lactating breast, the development of secretory alveoli consisting of differentiated cells arranged around a central lumen is dependent on signals from the extracellular environment of the cells. There are few cell lines that model this process. We previously showed that the human breast carcinoma line PMC42-LA can be induced to form organoids, reminiscent of secretory alveoli found in the lactating human breast. In this report, we used high-resolution scanning electron microscopy to show that the formation of organoids is accompanied by development of cell surface microvilli. Extracellular matrix-induced formation of microvilli occurred on the internal and external surfaces of cells in the organoids and not on surfaces in contact with the extracellular matrix. Organoid formation of PMC42-LA cells induced a rearrangement of the extracellular matrix, seen in the form of radiating fibers from the organoids. In summary, there is an interaction between PMC42-LA cells and the underlying extracellular matrix, which leads to the formation of polarized cells with well-developed microvilli. This is accompanied by organization of the extracellular matrix. PMC42-LA is a relevant model of the human breast for investigations into cell-cell and cell-matrix interactions.

Adamts5, the gene encoding a proteoglycan-degrading metalloprotease, is expressed by specific cell lineages during mouse embryonic development and in adult tissues.

The secreted metalloprotease ADAMTS5 is implicated in destruction of the cartilage proteoglycan aggrecan in arthritis, but its physiological functions are unknown. Its expression profile during embryogenesis and in adult tissues is therefore of considerable interest. β-Galactosidase (β-gal) histochemistry, enabled by a LacZ cassette inserted in the Adamts5 locus, and validated by in situ hybridization with an Adamts5 cRNA probe and ADAMTS5 immunohistochemistry, was used to profile Adamts5 expression during mouse embryogenesis and in adult mouse tissues. Embryonic expression was scarce prior to 11.5 days of gestation (E11.5) and noted only in the floor plate of the developing brain at E9.5. After E11.5 there was continued expression in brain, especially in the choroid plexus, peripheral nerves, dorsal root ganglia, cranial nerve ganglia, spinal and cranial nerves, and neural plexuses of the gut. In addition to nerves, developing limbs have Adamts5 expression in skeletal muscle (from E13.5), tendons (from E16.5), and inter-digital mesenchyme of the developing autopod (E13.5–15.5). In adult tissues, there is constitutive Adamts5 expression in arterial smooth muscle cells, mesothelium lining the peritoneal, pericardial and pleural cavities, smooth muscle cells in bronchi and pancreatic ducts, glomerular mesangial cells in the kidney, dorsal root ganglia, and in Schwann cells of the peripheral and autonomic nervous system. Expression of Adamts5 during neuromuscular development and in smooth muscle cells coincides with the broadly distributed proteoglycan versican, an ADAMTS5 substrate. These observations suggest the major contexts in which developmental and physiological roles could be sought for this protease.