Granulocyte-Colony Stimulating Factor (G-CSF) induces mechanical hyperalgesia via spinal activation of MAP kinases and PI(3)K in mice

Granulocyte-colony stimulating factor (G-CSF) is a current pharmacological approach to increase peripheral neutrophil counts after anti-tumor therapies. Pain is most relevant side effect of G-CSF in healthy volunteers and cancer patients. Therefore, the mechanisms of G-CSF-induced hyperalgesia were investigated focusing on the role of spinal mitogen-activated protein (MAP) kinases ERK (extracellular signal-regulated kinase). JNK (Jun N-terminal Kinase) and p38, and PI(3)K (phosphatidylinositol 3-kinase). G-CSF induced dose (30-300 ng/paw)-dependent mechanical hyperalgesia, which was inhibited by local post-treatment with morphine. This effect of morphine was reversed by naloxone (opioid receptor antagonist). Furthermore, G-CSF-induced hyperalgesia was inhibited in a dose-dependent manner by intrathecal pre-treatment with ERK (PD98059), JNK (SB600125), p38 (SB202190) or PI(3)K (wortmanin) inhibitors. The co-treatment with MAP kinase and PI(3)K inhibitors, at doses that were ineffective as single treatment, significantly inhibited G-CSF-induced hyperalgesia. Concluding, in addition to systemic opioids, peripheral opioids as well as spinal treatment with MAP kinases and PI(3)K inhibitors also reduce G-CSF-induced pain. (C) 2011 Elsevier Inc. All rights reserved.

Periodic orbit quantization of a Hamiltonian map on the sphere

In a previous paper we introduced examples of Hamiltonian mappings with phase space structures resembling circle packings. It was shown that a vast number of periodic orbits can be found using special properties. We now use this information to explore the semiclassical quantization of one of these maps.

MapScript: A map algebra programming language incorporating neighborhood analysis

Map algebra is a data model and simple functional notation to study the distribution and patterns of spatial phenomena. It uses a uniform representation of space as discrete grids, which are organized into layers. This paper discusses extensions to map algebra to handle neighborhood operations with a new data type called a template. Templates provide general windowing operations on grids to enable spatial models for cellular automata, mathematical morphology, and local spatial statistics. A programming language for map algebra that incorporates templates and special processing constructs is described. The programming language is called MapScript. Example program scripts are presented to perform diverse and interesting neighborhood analysis for descriptive, model-based and processed-based analysis.

Human papillomavirus type 6b virus-like particles are able to activate the Ras-MAP kinase pathway and induce cell proliferation

The initial step in viral infection is the attachment of the virus to the host cell via an interaction with its receptor. We have previously shown that a receptor for human papillomavirus is the alpha6 integrin. The alpha6 integrin is involved in the attachment of epithelial cells with the basement membrane, but recent evidence suggests that ligation of many integrins results in intracellular signaling events that influence cell proliferation. sere we present evidence that exposure of A431 human epithelial cells to human papillomavirus type 6b L1 virus-like particles (VLPs) results in a dose-dependent increase in cell proliferation, as measured by bromodeoxyuridine incorporation. This proliferation is Lost if VLPs are first denatured or incubated with a monoclonal antibody against L1 protein. The MEK1 inhibitor PB98059 inhibits the VLP-mediated increase in fell proliferation, suggesting involvement of the Ras-MAP kinase pathway, Indeed, VLP binding results in rapid phosphorylation of the beta4 integrin upon tyrosine residues and subsequent recruitment of the adapter protein She to beta4, Within 30 min, the activation of Ras, Raf, and Erk2 was observed. Finally, the upregulation of c-myc mRNA was observed at 60 min, These data indicate that human papillomavirus type 6b is able to signal cells via the Ras-MAP kinase pathway to induce cell proliferation. We hypothesize that such a mechanism would allow papillomaviruses to infect hosts more successfully by increasing the potential pool of cells they are able to infect via the initiation of proliferation in resting keratinocyte stem and suprabasal cells.

Growth regime map for liquid-bound granules: further development and experimental validation

An attempt was made to quantify the boundaries and validate the granule growth regime map for liquid-bound granules recently proposed by Iveson and Litster (AlChE J. 44 (1998) 1510). This regime map postulates that the type of granule growth behaviour is a function of only two dimensionless groups: the amount of granule deformation during collision (characterised by a Stokes deformation number, St(def)) and the maximum granule pore saturation, s(max). The results of experiments performed with a range of materials (glass ballotini, iron ore fines, copper chalcopyrite powder and a sodium sulphate and cellulose mixture) using both drum and high shear mixer granulators were examined. The drum granulation results gave good agreement with the proposed regime map. The boundary between crumb and steady growth occurs at St(def) of order 0.1 and the boundary between steady and induction growth occurs at St(def) of order 0.001. The nucleation only boundary occurs at pore saturations that increase from 70% to 80% with decreasing St(def). However, the high shear mixer results all had St(def) numbers which were too large. This is most likely to be because the chopper tip-speed is an over-estimate of the average impact velocity granules experience and possibly also due to the dynamic yield strength of the materials being significantly greater than the yield strengths measured at low strain rates. Hence, the map is only a useful tool for comparing the granulation behaviour of different materials in the same device. Until we have a better understanding of the flow patterns and impact velocities in granulators, it cannot be used to compare different types of equipment. Theoretical considerations also revealed that several of the regime boundaries are also functions of additional parameters not explicitly contained on the map, such as binder viscosity. (C) 2001 Elsevier Science B.V. All rights reserved.

Using visual spatial search interface for WWW applications

Most Internet search engines are keyword-based. They are not efficient for the queries where geographical location is important, such as finding hotels within an area or close to a place of interest. A natural interface for spatial searching is a map, which can be used not only to display locations of search results but also to assist forming search conditions. A map-based search engine requires a well-designed visual interface that is intuitive to use yet flexible and expressive enough to support various types of spatial queries as well as aspatial queries. Similar to hyperlinks for text and images in an HTML page, spatial objects in a map should support hyperlinks. Such an interface needs to be scalable with the size of the geographical regions and the number of websites it covers. In spite of handling typically a very large amount of spatial data, a map-based search interface should meet the expectation of fast response time for interactive applications. In this paper we discuss general requirements and the design for a new map-based web search interface, focusing on integration with the WWW and visual spatial query interface. A number of current and future research issues are discussed, and a prototype for the University of Queensland is presented. (C) 2001 Published by Elsevier Science Ltd.

Development of a mungbean (Vigna radiata) RFLP linkage map and its comparison with lablab (Lablab purpureus) revelas a high level of colinearity between the two genomes

A genetic linkage map of mungbean (Vigna radiata, 2n = 2x = 22) consisting of 255 RFLP loci was developed using a recombinant inbred population of 80 individuals. The population was derived from an intersubspecific cross between the cultivated mungbean variety 'Berken' and a wild mungbean genotype 'ACC 41' (V radiata subsp. sublobata). The total length of the map, which comprised 13 linkage groups, spanned 737.9 cM with an average distance between markers of 3.0 cM and a maximum distance between linked markers of 15.4 cM. The mungbean map was compared to a previously published map of lablab (Lablab purpureus, 2n = 2x = 24) using a common set of 65 RFLP probes. In contrast to some other comparative mapping studies among members of the Fabaceae, where a high level of chromosomal rearrangement has been observed, marker order between mungbean and lablab was found to be highly conserved. However, the two genomes have apparently accumulated a large number of duplications/deletions after they diverged.

Interactive expectations

In modeling expectation formation, economic agents are usually viewed as forming expectations adaptively or in accordance with some rationality postulate. We offer an alternative nonlinear model where agents exchange their opinions and information with each other. Such a model yields multiple equilibria, or attracting distributions, that are persistent but subject to sudden large jumps. Using German Federal Statistical Office economic indicators and German IFO Poll expectational data, we show that this kind of model performs well in simulation experiments. Focusing upon producers' expectations in the consumption goods sector, we also discover evidence that structural change in the interactive process occurred over the period of investigation (1970-1998). Specifically, interactions in expectation formation seem to have become less important over time.

Multiple axon guidance cues establish the olfactory topographic map: how do these cues interact?

Each primary olfactory neuron stochastically expresses one of similar to1000 odorant receptors. The total population of these neurons therefore consists of similar to1,000 distinct subpopulations, each of which are mosaically dispersed throughout one of four semi-annular zones in the nasal cavity. The axons of these different subpopulations are initially intermingled within the olfactory nerve. However, upon reaching the olfactory bulb, they sort out and converge so that axons expressing the same odorant receptor typically target one or two glomeruli. The spatial location of each of these 1800 glomeruli are topographically-fixed in the olfactory bulb and are invariant from animal to animal. Thus, while odorant receptors are expressed mosaically by neurons throughout the olfactory neuroepithelium their axons sort out, converge and target the same glomerulus within the olfactory bulb. How is such precise and reproducible topographic targeting generated? While some of the mechanisms governing the growth cone guidance of olfactory sensory neurons are understood, the cues responsible for homing axons to their target site remain elusive.

Making developmental biology relevant to undergraduates in an era of economic rationalism in Australia

This report describes the road map we followed at our university to accommodate three main factors: financial pressure within the university system; desire to enhance the learning experience of undergraduates; and motivation to increase the prominence of the discipline of developmental biology in our university. We engineered a novel, multi-year undergraduate developmental biology program which was student-oriented, ensuring that students were continually exposed to the underlying principles and philosophy of this discipline throughout their undergraduate career. Among its key features are introductory lectures in core courses in the first year, which emphasize the relevance of developmental biology to tissue engineering, reproductive medicine, therapeutic approaches in medicine, agriculture and aquaculture. State-of-the-art animated computer graphics and images of high visual impact are also used. In addition, students are streamed into the developmental biology track in the second year, using courses like human embryology and courses shared with cell biology, which include practicals based on modern experimental approaches. Finally, fully dedicated third-year courses in developmental biology are undertaken in conjunction with stand-alone practical courses where students experience first-hand work in a research laboratory. Our philosophy is a cradle-to-grave approach to the education of undergraduates so as to prepare highly motivated, enthusiastic and well-educated developmental biologists for entry into graduate programs and ultimately post-doctoral research.