Jumping robots: a biomimetic solution to locomotion across rough terrain

This paper introduces jumping robots as a means to traverse rough terrain; such terrain can pose problems for traditional wheeled, tracked and legged designs. The diversity of jumping mechanisms found in nature is explored to support the theory that jumping is a desirable ability for a robot locomotion system to incorporate, and then the size-related constraints are determined from first principles. A series of existing jumping robots are presented and their performance summarized. The authors present two new biologically inspired jumping robots, Jollbot and Glumper, both of which incorporate additional locomotion techniques of rolling and gliding respectively. Jollbot consists of metal hoop springs forming a 300 mm diameter sphere, and when jumping it raises its centre of gravity by 0.22 m and clears a height of 0.18 m. Glumper is of octahedral shape, with four 'legs' that each comprise two 500 mm lengths of CFRP tube articulating around torsion spring 'knees'. It is able to raise its centre of gravity by 1.60 m and clears a height of 1.17 m. The jumping performance of the jumping robot designs presented is discussed and compared against some specialized jumping animals. Specific power output is thought to be the performance-limiting factor for a jumping robot, which requires the maximization of the amount of energy that can be stored together with a minimization of mass. It is demonstrated that this can be achieved through optimization and careful materials selection.     

ADH1 expression inversely correlates with CDR1 and CDR2 in Candida albicans from chronic oral candidosis in APECED (APS-I) patients

Expression of the alcohol dehydrogenase gene ADH1, which converts ethanol into carcinogenic acetaldehyde, significantly inversely correlated with the expression of CDR1 and CDR2, genes linked to azole resistance in Candida albicans isolated from chronic oral candidosis in autoimmune polyendocrinopathy-candidosis-ectodermal dystrophy (APECED, APS-I) patients. This is a novel link between candidal two-carbon metabolism genes and azole resistance.     

Nutritional development of feeding strategies in arctic ruminants: digestive morphometry of reindeer, Rangifer tarandus, and muskoxen, Ovibos moschatus

Reindeer have been classified as intermediate feeders and muskoxen as grazers based on differences in digestive morphology and consumption of fibrous plants. We hypothesized that the digestive morphology of young (<2 months) reindeer and muskoxen anticipates transitions in diet and determines the feeding strategy of each species at adulthood. We compared structural morphology and rates of cell division in the rumen, abomasum, duodenum and liver of reindeer and muskoxen as neonates (1 day old), during the transition from milk to forage (30–60  days old) and in adults (>7 yr). Development in utero provided the neonate with a functioning mucosa of the gastric abomasum and duodenal mucosa with high surface enlargement for digestion and absorption of concentrated milks. Transition to forage was preceded by changes in ruminal papillae structure that increased surface area and likely contributed to active fermentation by 60 days of age. The abomasum also increased in acid-secreting parietal cells during the transition to forage, which may enhance digestion of plant and microbial proteins. Rates of cell division also indicated a sustained differentiation of tissue structure during the transitional period. Young arctic ruminants expressed digestive structures that preceded full function, which indicated the ultimate feeding strategy of each species. For example, the rumen of young muskoxen had thick cornified epithelia and muscle layers that would provide ruminal mucosa with better protection from fibrous abrasion and enhance motility of bulky diets. Conversely, young reindeer had more complex papillary shapes in the rumen and more foliate villi in the duodenum, indicating a greater absorptive capacity of these structures than in muskoxen. Ontogenetic programs, therefore, play the primary role for digestive development of reindeer and muskoxen and determine the nutritional strategies of adults.     

Cantharidin analogues: synthesis and evaluation of growth inhibition in a panel of selected tumour cell lines

Diels-Alder addition of furans (furan, furfuryl alcohol, and 3-bromofuran) to maelic anhydride yields three distinct 5,6-dehydronorcantharidins. Hydrogenation of (4,10-dioxatricyclo[5.2.1.0]decane-3,5-dione) (4a), in dry ethanol affords the monoester (7-oxabicyclo[2.2.1]heptane-2,3-dicarboxylic aid monoethyl ester) (6). Subsequent transesterification affords a series of monoesters (7-oxabicyclo[2.2.1]heptane-2,3-dicarboxylic acid monomethyl ester (7)), 7-oxabicyclo[2.2.1]heptane-2,3-dicarboxylic acid monopropyl ester (8), (7-oxabicyclo[2.2.1]heptane-2,3-dicarboxylic acid monohexyl ester (9)) and differentially substituted diesters (7-oxabicyclo[2.2.1]heptane-2,3-dicarboxylic acid 2-ethyl ester 3-isopropyl ester) (10), and (7-oxabicyclo[2.2.1]heptane-2,3-dicarboxylic acid 2-ethyl ester 3-phenyl ester) (11). Analogues were firstly screened for their ability to inhibit protein phosphatases 1 (PP1) and 2A (PP2A) as the lead compounds cantharidin (1) and norcantharidin (2) are known PP1 and PP2A inhibitors. Only analogues 4a, 6-8 displayed good PP1 and PP2A inhibition (PP1 IC(50)'s=2.0, 2.96, 4.71, and 4.82 microM, respectively; PP2A IC(50)'s=0.2, 0.45, 0.41, and 0.47 microM, respectively). All analogues were also screened for their anti-cancer potential against a panel of tumour cell lines, HL60, L1210, SW480, WiDr, HT29, HCT116, A2780, ADDP, and 143B, producing GI(50) values ranging from 6 microM to >1000 microM. Analogues possessing good PP1 and/or PP2A inhibition also returned moderate to good anti-cancer activity. Analogues with substituents directly attached to the intact bicyclo[2.2.1]heptane skeleton were poor to moderate anti-cancer agents. This correlates well with their lack of PP1 or PP2A activity. Analogues capable of undergoing a facile ring opening of the anhydride or with a single carboxylate were good PP1 and PP2A inhibitors, largely correlating to the observed anti-cancer activity in all cases, except 11. Analogue 11, whist neither a PP1 nor a PP2A inhibitor shows anti-cancer activity comparable to 1 and 2. We believe that intracellular esterases generate the corresponding dicarboxylate, which is a potent PP1 and PP2A inhibitor, and that it is this species which is responsible for the observed anti-cancer activity.     

Karyotypic analysis of adult pluripotent stem cells

Three categories of precursor cells have been identified in postnatal mammals: tissue-committed progenitor cells, germ layer lineage-committed stem cells and lineage-uncommitted pluripotent stem cells. Progenitor cells are the immediate precursors of differentiated tissues. Germ layer lineage stem cells can be induced to form multiple cell types belonging to their respective ectodermal, mesodermal, and endodermal embryological lineages. Pluripotent stem cells will form somatic cell types from all three primary germ layer lineages. Progenitor cells demonstrate a finite life span before replicative senescence and cell death occur. Both germ layer lineage stem cells and pluripotent stem cells are telomerase positive and display extensive capabilities for self-renewal. Stem cells which undergo such extensive replication have the potential for undergoing mutations that may subsequently alter cellular functions. Gross mutations in the genome may be visualized as chromosomal aneuploidy and/or chromosomes that appear aberrant. This study was designed to determine whether any gross genomic mutations occurred within the adult pluripotent stem cells. Karyotypic analysis was performed using pluripotent stem cells purified from adult male rats using established procedures. Giemsa Banding was used in conjunction with light microscopy to visualize metaphase chromosome spreads. To date over 800 metaphase spreads have been analyzed. We found that the metaphase spreads averaged 42 chromosomes and concluded that these pluripotent stem cells isolated from adult rats have a normal karyotype.     

Multiple-testing strategy for analyzing cDNA array data on gene expression

An objective of many functional genomics studies is to estimate treatment-induced changes in gene expression. cDNA arrays interrogate each tissue sample for the levels of mRNA for hundreds to tens of thousands of genes, and the use of this technology leads to a multitude of treatment contrasts. By-gene hypotheses tests evaluate the evidence supporting no effect, but selecting a significance level requires dealing with the multitude of comparisons. The p-values from these tests order the genes such that a p-value cutoff divides the genes into two sets. Ideally one set would contain the affected genes and the other would contain the unaffected genes. However, the set of genes selected as affected will have false positives, i.e., genes that are not affected by treatment. Likewise, the other set of genes, selected as unaffected, will contain false negatives, i.e., genes that are affected. A plot of the observed p-values (1 - p) versus their expectation under a uniform [0, 1] distribution allows one to estimate the number of true null hypotheses. With this estimate, the false positive rates and false negative rates associated with any p-value cutoff can be estimated. When computed for a range of cutoffs, these rates summarize the ability of the study to resolve effects. In our work, we are more interested in selecting most of the affected genes rather than protecting against a few false positives. An optimum cutoff, i.e., the best set given the data, depends upon the relative cost of falsely classifying a gene as affected versus the cost of falsely classifying a gene as unaffected. We select the cutoff by a decision-theoretic method analogous to methods developed for receiver operating characteristic curves. In addition, we estimate the false discovery rate and the false nondiscovery rate associated with any cutoff value. Two functional genomics studies that were designed to assess a treatment effect are used to illustrate how the methods allowed the investigators to determine a cutoff to suit their research goals.     

NAD-sensitive hydrogel for the release of macromolecules

A hydrogel membrane containing immobilized ligands and receptors was synthesized and investigated for the controlled diffusion of test proteins (cytochrome C and hemoglobin). Both Cibacron blue (ligand) and lysozyme (receptor) were covalently linked to dextran molecules that were subsequently crosslinked to form a gel. The resulting stable hydrogels contained both covalent and affinity crosslinks such that their intrinsic porosities were sensitive to competitive displacers of the affinity interaction between lysozyme and Cibacron blue. Transport experiments in a twin chamber diffusion cell showed that as NAD was added to the donor side, the dissociation of the binding sites between the Cibacron blue and the lysozyme led to an increase in protein diffusion through the hydrogel. The results showed that addition of NAD caused a saturable concentration-dependent increase in the transport of both cytochrome C and hemoglobin. This effect was shown to be both specific and reversible.     

Anhydride modified cantharidin analogues: synthesis, inhibition of protein phosphatases 1 and 2A and anticancer activity

Two series of anhydride modified cantharidin analogues were synthesised and screened for their phosphatase inhibition (PP1 and PP2A) and cytotoxicity in various cancer cell lines (Ovarian A2780, ADDP; Osteosarcoma 143B; and Colon HCT116 and HT29). One series was synthesised by a novel, high yielding one-pot hydrogenation-ring-opening-esterification procedure, the other by acid catalysed acetal formation. Analogues 5-7 and 9 displayed moderate PP2A selectivity (ca. 5- to 20-fold) and inhibition typically in the low microM range (comparable, in some cases to cantharidin). The anticancer activity of these analogues varied with the cell line under study; however, many of them showed selective cytotoxicity for the colon tumour cell lines.