Expression of C5a receptor in mouse brain: Role in signal transduction and neurodegeneration

In this study we explored the potential role of the complement derived anaphylatoxin C5a and the expression of its receptor in mouse brain. Using in situ hybridization, we found that C5a receptor messenger RNA is expressed in mouse brain. In response to intraventricular kainic acid injection, there was marked increase in the C5a receptor messenger RNA expression, particularly in hippocampal formation and cerebral cortex. C5a ligand-binding autoradiography confirmed the functional expression and elevation of the C5a receptor post-lesioning. The expression of Cia receptor messenger RNA in brain was confirmed by northern blot hybridization of total RNA from neuronal and glial cells in vitiro. Based on these findings we explored the role of C5a in mechanisms of signal transduction in brain cells. Treatment of primary cultures of mouse astrocytes with human recombinant C5a resulted in the activation of mitogen-activated extracellular signal-regulated protein kinase. This response appeared to be mediated by the C5a receptor since astrocyte cultures derived from C5a receptor knockout mice were not responsive to the treatment. Understanding the regulation of C5a receptor in brain and mechanisms by which pro-inflammatory C5a modulates specific signal transduction pathways in brain cells is crucial to studies of inflammatory mechanisms in neurodegeneration. (C) 1998 IBRO. Published by Elsevier Science Ltd.

Activation of extracellular signal-regulated kinase in proliferative glomerulonephritis in rats

Multiple extracellular mitogens are involved in the pathogenesis of proliferative forms of glomerulonephritis (GN), In vitro studies demonstrate the pivotal role of extracellular signal-regulated kinase (ERK) in the regulation of cellular proliferation in response to extracellular mitogens. In this study, we examined whether this kinase, as a convergence point of mitogenic stimuli, is activated in proliferative GN in vivo, Two different proliferative forms of anti-glomerular basal membrane (GEM) GN in rats were induced and whole cortical tissue as well as isolated glomeruli examined using kinase activity assays and Western blot analysis, Administration of rabbit anti-rat GEM serum to rats, preimmunized with rabbit IgG, induced an accelerated crescentic anti-GEM GN. A significant increase in cortical, and more dramatically glomerular ERK activity was detected at 1, 3, and 7 d after induction of GN, Immunization of Wistar-Kyoto rats with bovine GEM also induced a crescentic anti-GBM GN with an increase of renal cortical ERK activity after 4, 6, and 8 wk, ERK is phosphorylated and activated by the MAP kinase/ERK kinase (MEK), We detected a significant increase in the expression of glomerular MEK in the accelerated form of anti-GEM CN, providing a possible mechanism of long-term activation of ERK in this disease model, In contrast to ERK, activation of stress-activated protein kinase was only detectable at early stages of proliferative GN, indicating these related kinases to serve distinct roles in the pathogenesis of GN, Our observations point to ERK as a putative mediator of the proliferative response to immune injury in GN and suggest that upregulation of MEK is involved in the long-term regulation of ERK in vivo.

Amnesties in Transition: Punishment, Restoration, and the Governance of Mercy

Despite the much vaunted triumph of human rights, amnesties continue to be a frequently used technique of post-conflict transitional justice. For many critics, they are synonymous with unaccountability and injustice. This article argues that despite the rhetoric, there is no universal duty to prosecute under international law and that issues of selectivity and proportionality present serious challenges to the retributive rationale for punishment in international justice. It contends that many of the assumptions concerning the deterrent effect in the field are also oversold and poorly theorized. It also suggests that appropriately designed restorative amnesties can be both lawful and effective as routes to truth recovery, reconciliation, and a range of other peacemaking goals. Rather than mere instruments of impunity, amnesties should instead be seen as important institutions in the governance of mercy, the reassertion of state sovereignty and, if properly constituted, the return of law to a previously lawless domain.

Signal and variability within a Holocene peat bog - Chronological uncertainties of pollen, macrofossil and fungal proxies

A single raised bog from the eastern Netherlands has been repeatedly analysed and ¹⁴C dated over the past few decades. Here we assess the within-site variability of fossil proxy data through comparing the regional
pollen, macrofossils and non-pollen palynomorphs of four of these profiles. High-resolution chronologies were obtained using ¹⁴C dating and Bayesian age-depth modelling. Where chronologies of profiles overlap, proxy curves are compared between the profiles using greyscale graphs that visualise chronological uncertainties. Even at this small spatial scale, there is considerable variability of the fossil proxy curves. Implications regarding signal (climate) and noise (internal dynamics) of the different types of fossil proxies are discussed. Single cores are of limited value for reconstructing centennial-scale climate change, and only by combining multiple cores and proxies can we obtain a reliable understanding of past environmental change and possible forcing factors (e.g., solar variability).

IMPLEMENTATION OF SIGNAL PROCESSING FUNCTIONS USING 1-BIT SYSTOLIC ARRAYS.

The use of systolic arrays of 1-bit cells to implement a range of important signal processing functions is demonstrated. Two examples, a pipelined multiplier and a pipelined bit-slice transform circuit, are given. This approach has many important implications for silicon technology, and these are outlined.

DESIGNING VLSI SIGNAL PROCESSING CHIPS USING DATA DEPENDENCE GRAPHS.

The highly structured nature of many digital signal processing operations allows these to be directly implemented as regular VLSI circuits. This feature has been successfully exploited in the design of a number of commercial chips, some examples of which are described. While many of the architectures on which such chips are based were originally derived on heuristic basis, there is an increasing interest in the development of systematic design techniques for the direct mapping of computations onto regular VLSI arrays. The purpose of this paper is to show how the the technique proposed by Kung can be readily extended to the design of VLSI signal processing chips where the organisation of computations at the level of individual data bits is of paramount importance. The technique in question allows architectures to be derived using the projection and retiming of data dependence graphs.

BIT-LEVEL SYSTOLIC ARRAYS FOR SIGNAL AND IMAGE PROCESSING.

This paper describes the design and the architecture of a bit-level systolic array processor. The bit-level systolic array described is directly applicable to a wide range of image processing operations where high performance and throughput are essential. The architecture is illustrated by describing the operation of the correlator and convolver chips which are being developed. The advantage of the system is also discussed.

Amplitude-modulation characteristics of power-combining Class-E amplifier with finite choke

Power back-off performances of a new variant power-combining Class-E amplifier under different amplitude-modulation schemes such as continuous wave (CW), envelope elimination and restoration (EER), envelope tracking (ET) and outphasing are for the first time investigated in this study. Finite DC-feed inductances rather than massive RF chokes as used in the classic single-ended Class-E power amplifier (PA) resulted from the approximate yet effective frequency-domain circuit analysis provide the wherewithal to increase modulation bandwidth up to 80% higher than the classic single-ended Class-E PA. This increased modulation bandwidth is required for the linearity improvement in the EER/ET transmitters. The modified output load network of the power-combining Class-E amplifier adopting three-harmonic terminations technique relaxes the design specifications for the additional filtering block typically required at the output stage of the transmitter chain. Qualitative agreements between simulation and measurement results for all four schemes were achieved where the ET technique was proven superior to the other schemes. When the PA is used within the ET scheme, an increase of average drain efficiency of as high as 40% with respect to the CW excitation was obtained for a multi-carrier input signal with 12 dB peak-to-average power ratio. © 2011 The Institution of Engineering and Technology.

Identifying optimal sites for natural recovery and restoration of impacted biogenic habitats in a special area of conservation using hydrodynamic and habitat suitability modelling

Selection of sites for successful restoration of impacted shellfish populations depends on understanding the dispersion capability and habitat requirements of the species involved. In Strangford Lough, Northern Ireland, the horse mussel (Modiolus modiolus) biogenic reefs cover only a fraction of their historical range with the remaining reefs badly damaged and requiring restoration. Previous experimental trials suggest that translocation of horse mussels accelerates reef recovery and has therefore been proposed as a suitable restoration technique. We used a series of coupled hydrodynamic and particle dispersal models to assess larval dispersion from remnant and translocated populations to identify suitable areas for adult live M. modiolus translocation in Strangford Lough, Northern Ireland. A maximum entropy model (MAXENT) was used to identify if dispersing larvae could reach habitat suitable for adult M. modiolus. From these we predicted if translocated mussels will reseed themselves or be able to act as larval sources for nearby reefs. The dispersal models showed that the remnant M. modiolus populations are largely self-recruiting with little connectivity between them. The majority of larvae settled near the sources and movement was largely dependent on the tides and not influenced by wind or waves. Higher reef elevation resulted in larvae being able to disperse further away from the release point. However, larval numbers away from the source population are likely to be too low for successful recruitment. There was also little connectivity between the Irish Sea and Strangford Lough as any larvae entering the Lough remained predominantly in the Strangford Narrows. The areas covered by these self-seeding populations are suitable for M. modiolus translocation according to the MAXENT model. As a result of this work and in conjunction with other field work we propose a combination of total protection of all remaining larval sources and small scale translocations onto suitable substrata in each of the identified self-recruiting areas.