Equine sarcoids: Bovine Papillomavirus type 1 transformed fibroblasts are sensitive to cisplatin and UVB induced apoptosis and show aberrant expression of p53

Bovine papillomavirus type 1 infects not only cattle but also equids and is a causative factor in the pathogenesis of commonly occurring equine sarcoid tumours. Whilst treatment of sarcoids is notoriously difficult, cisplatin has been shown to be one of the most effective treatment strategies for sarcoids. In this study we show that in equine fibroblasts, BPV-1 sensitises cells to cisplatin-induced and UVB-induced apoptosis, a known cofactor for papillomavirus associated disease, however BPV-1 transformed fibroblasts show increased clonogenic survival, which may potentially limit the therapeutic effects of repeated cisplatin treatment. Furthermore we show that BPV-1 increases p53 expression in sarcoid cell lines and p53 expression can be either nuclear or cytoplasmic. The mechanism and clinical significance of increase/abnormal p53 expression remains to be established

Mechanisms of vascular smooth muscle contraction and the basis for pharmacologic treatment of smooth muscle disorders

The smooth muscle cell directly drives the contraction of the vascular wall and hence regulates the size of the blood vessel lumen. We review here the current understanding of the molecular mechanisms by which agonists, therapeutics, and diseases regulate contractility of the vascular smooth muscle cell and we place this within the context of whole body function. We also discuss the implications for personalized medicine and highlight specific potential target molecules that may provide opportunities for the future development of new therapeutics to regulate vascular function.Accepted manuscrip

Exploring the use of 25 leading business practices in transitioning market supply chains

Purpose - In the global economy, managers of organizations are constantly innovating with their use of available supply chain management tools. Some tools, like strategic planning and customer segmentation, have gained strong global acceptance while others are less universal. In this study, we focus our contribution on the organizational factors that predict firm usage of supply chain management tools in two Eastern Europe countries, Slovenia and Croatia, while also comparing them to the global use of similar management tools. Design/methodology/approach - This research provides an empirical analysis of supply chain management tool usage from a survey of 155 firms in Slovenia and 185 firms in Croatia while also comparing these findings to results from a global Bain & Company survey. Findings - The 25 most commonly used supply chain management tools in our Eastern European survey were found to be relatively similar to those used across Europe and North America. However, further analysis of five selected tools reveals important differences. Evidence is found to support that particular organizational factors have a significant influence on supply chain management tool usage, of specific importance is the education level of the organization manager. Research limitations/implications - The research study is limited to the research question, selective literature review, and survey sample from Eastern Europe. Practical implications - As firms assess their supply chain management tool usage, the findings presented here might serve as a guide to improve their understanding of why organization managers employ particular tools more consistently than others. Originality/value - The findings are useful for business practice in understanding the influences of organizational factors on supply chain management tool usage. Also, the research is original as previous management literature has not provided a similar approach to researching management tools and their usage

Invariance of the correlation energy at high density and large dimension in two-electron systems

We prove that, in the large-dimension limit, the high-density correlation energy \Ec of two opposite-spin electrons confined in a $D$-dimensional space and interacting {\em via} a Coulomb potential is given by \Ec \sim -1/(8D^2) for any radial confining potential $V(r)$. This result explains the observed similarity of \Ec in a variety of two-electron systems in three-dimensional space.Comment: 4 pages, 1 figure, to appear in Phys. Rev. Let

Morphine Preferentially Activates the Periaqueductal Gray – Rostral Ventromedial Medullary Pathway in the Male Rat: A Potential Mechanism for Sex Differences in Antinociception

The midbrain periaqueductal gray (PAG), and its descending projections to the rostral ventromedial medulla (RVM), provide an essential neural circuit for opioid-produced antinociception. Recent anatomical studies have reported that the projections from the PAG to the RVM are sexually dimorphic and that systemic administration of morphine significantly suppresses pain-induced activation of the PAG in male but not female rats. Given that morphine antinociception is produced in part by disinhibition of PAG output neurons, it is hypothesized that a differential activation of PAG output neurons mediates the sexually dimorphic actions of morphine. The present study examined systemic morphine-induced activation of PAG-RVM neurons in the absence of pain. The retrograde tracer Fluorogold (FG) was injected into the RVM to label PAG-RVM output neurons. Activation of PAG neurons was determined by quantifying the number of Fos-positive neurons 1 h following systemic morphine administration (4.5 mg/kg). Morphine produced comparable activation of the PAG in both male and female rats, with no significant differences in either the quantitative or qualitative distribution of Fos. While microinjection of FG into the RVM labeled significantly more PAG output neurons in female rats than male rats, very few of these neurons (20%) were activated by systemic morphine administration in comparison to males (50%). The absolute number of PAG-RVM neurons activated by morphine was also greater in males. These data demonstrate widespread disinhibition of PAG neurons following morphine administration. The greater morphine-induced activation of PAG output neurons in male compared with female rats is consistent with the greater morphine-induced antinociception observed in males

Sexually Dimorphic Activation of the Periaqueductal Gray – Rostral Ventromedial Medullary Circuit during the Development of Morphine Tolerance in the Rat

Previous studies have shown that tolerance develops to a greater degree in male compared to female rats. The midbrain periaqueductal gray (PAG), and its descending projections to the rostral ventromedial medulla (RVM), provides an essential neural circuit for the antinociceptive effects of opiates and has been implicated in the development of tolerance to morphine. We have previously reported that systemic morphine administration activates a greater proportion of PAG-RVM neurons in male versus female rats; our hypothesis is that if the PAG-RVM pathway is essential for the development of morphine tolerance, then (1) morphine activation of the PAG-RVM pathway should decline as tolerance develops, and (2) sex differences should be reflected as a greater decline in males. These hypotheses were tested using behavioral and neuroanatomical techniques to map the activation of the PAG-RVM pathway during the development of tolerance to repeated morphine administration (4.5 mg/kg; s.c.). We found that as male rats develop tolerance (D50 increased from 3.0 to 6.3 mg/kg), there was no significant decline in the overall activation of the PAG, however, there was a steady decline in the percentage of PAG-RVM output neurons activated by morphine. This reduction occurred in males only; there was no significant decline in the activity of PAG-RVM output neurons in females. These data demonstrate that the greater development of tolerance to morphine administration in male rats corresponds with a significant reduction in the activation of the PAG-RVM circuit. Our results provide additional data demonstrating a central role for the PAG in morphine tolerance

One-loop corrections to the D3 brane action

We calculate one-loop corrections to the effective Lagrangian for the D3 brane. We perform the gauge-fixing of the kappa-symmetric Born-Infeld D3 brane action in the flat background using Killing gauge. The linearized supersymmetry of the gauge-fixed action coincides with that of the N=4 Yang-Mills theory. We use the helicity amplitude and unitarity technique to calculate the one-loop amplitudes at order alpha^4. The counterterms and the finite 1-loop corrections are of the form (dF)^4 and their supersymmetric generalization. This is to be contrasted with the Born-Infeld action which contains (F)^4 and other terms which do not depend on derivatives of the vector field strength.Comment: 21 pages, LaTex with Axodraw figures. In the revised version new references have been adde

Supersymmetry Relations Between Contributions To One-Loop Gauge Boson Amplitudes

We apply ideas motivated by string theory to improve the calculational efficiency of one-loop weak interaction processes with massive external gauge bosons. In certain cases ``supersymmetry'' relations between diagrams with a fermion loop and with a gauge boson loop hold. This is explicitly illustrated for a particular one-loop standard model process with four-external gauge bosons. The supersymmetry relations can be used to provide further significant improvements in calculational efficiency.Comment: 21 pages of plain TeX + 5 PostScript figures (compressed and uuencoded), UCLA/93/TEP/36 and DTP/93/8

Simplifying Algebra in Feynman Graphs, Part III: Massive Vectors

A T-dualized selfdual inspired formulation of massive vector fields coupled to arbitrary matter is generated; subsequently its perturbative series modeling a spontaneously broken gauge theory is analyzed. The new Feynman rules and external line factors are chirally minimized in the sense that only one type of spin index occurs in the rules. Several processes are examined in detail and the cross-sections formulated in this approach. A double line formulation of the Lorentz algebra for Feynman diagrams is produced in this formalism, similar to color ordering, which follows from a spin ordering of the Feynman rules. The new double line formalism leads to further minimization of gauge invariant scattering in perturbation theory. The dualized electroweak model is also generated.Comment: 39 pages, LaTeX, 8 figure