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The translocator protein (TSPO) is a mitochondrial membrane protein, of as yet uncertain function. Its purported high expression on activated macrophages, has lent utility to TSPO targeted molecular imaging in the form of positron emission tomography (PET), as a means to detect and quantify inflammation in vivo. However, existing literature regarding TSPO expression on human activated macrophages is lacking, mostly deriving from brain tissue studies, including studies of brain malignancy, and inflammatory diseases such as multiple sclerosis. Here, we utilized three human sources of monocyte derived macrophages (MDM), from THP-1 monocytes, healthy peripheral blood monocytes and synovial fluid monocytes from patients with rheumatoid arthritis, to undertake a detailed investigation of TSPO expression in activated macrophages. In this work, we demonstrate a consistent down-regulation of TSPO mRNA and protein in macrophages activated to a pro-inflammatory, or 'M1' phenotype. Conversely, stimulation of macrophages to an M2 phenotype with IL-4, dexamethasone or TGF-β1 did not alter TSPO expression, regardless of MDM source. The reasons for this are uncertain, but our study findings add some supporting evidence for recent investigations concluding that TSPO may be involved in negative regulation of inflammatory responses in macrophages.

PURPOSE:Imaging of the 18-kDa translocator protein (TSPO) is a potential tool for examining microglial activation and neuroinflammation in early Alzheimer's disease (AD). [18F]FEMPA is a novel high-affinity second-generation TSPO radioligand that has displayed suitable pharmacokinetic properties in preclinical studies. The aims of this study were to quantify the binding of [18F]FEMPA to TSPO in AD patients and controls and to investigate whether higher [18F]FEMPA binding in AD patients than in controls could be detected in vivo. METHODS:Ten AD patients (five men, five women; age 66.9 ± 7.3 years; MMSE score 25.5 ± 2.5) and seven controls (three men, four women; age 63.7 ± 7.2 years, MMSE score 29.3 ± 1.0) were studied using [18F]FEMPA at Turku (13 subjects) and at Karolinska Institutet (4 subjects). The in vitro binding affinity for TSPO was assessed using PBR28 in a competition assay with [3H]PK11195 in seven controls and eightAD patients. Cortical and subcortical regions of interest were examined. Quantification was performed using a two-tissue compartment model (2TCM) and Logan graphical analysis (GA). The outcome measure was the total distribution volume (VT). Repeated measures analysis of variance was used to assess the effect of group and TSPO binding status onVT. RESULTS:Five AD patients and four controls were high-affinity binders (HABs). Three AD patients and three controls were mixed-affinity binders.VTestimated with Logan GA was significantly correlated withVTestimated with the 2TCM in both controls (r = 0.97) and AD patients (r = 0.98) and was selected for the final analysis. Significantly higherVTwas found in the medial temporal cortex in AD patients than in controls (p = 0.044) if the TSPO binding status was entered as a covariate. If only HABs were included, significantly higherVTwas found in the medial and lateral temporal cortex, posterior cingulate, caudate, putamen, thalamus and cerebellum in AD patients than in controls (p  CONCLUSION:[18F]FEMPA seems to be a suitable radioligand for detecting increased TSPO binding in AD patients if their binding status is taken into account.

Low affinity α1/α2 containing GABAA receptors are significantly less able to bind [(11) C]/[(3) H]Ro15-4513 following translocation to the endosomal environment. The alterations in [(11) C]Ro15-4513 binding observed in vivo following perturbations in endogenous GABA are likely driven by both alterations in receptor binding parameters following agonist induced internalisation and the GABA Shift.

A variety of stratigraphic analyses (particle grain size, iron concentration, loss on ignition, and macrofossils) from sediments obtained from two marsh sites are used to reconstruct a middle to late Holocene record of stream flow into San Francisco Bay. Browns Island, a freshwater/brackish site, is located at the confluence of the Sacramento and San Joaquin rivers and is dominated by stands ofScirpus americanus.Peyton Hill is a brackish site located near Carquinez Straits and is dominated by stands ofScirpus robustus.Twenty-five AMS14C dates provide chronostratigraphic control. During the Holocene, discharge from the Sacramento and San Joaquin rivers was broadly comparable to modern flows; however, an extended period of higher flow began 3800 cal yr B.P. and continued for almost two millennia. At this time Browns Island supportedPhragmites communis,a freshwater species, and Peyton Hill supportedS. americanus.At least two floods, recognized by discrete increases in sand and silt, occurred at 3600 and 530 cal yr B.P.

The Sydney Cyprus Survey Project (SCSP) began work in the north central Troodos Mountains of Cyprus in 1992. The aim of the project is to examine the relationships among the exploitation of natural resources (especially copper mining and agriculture), the development of complex social systems, and the changes taking place in the physical landscape. This interim report puts our fieldwork and interpretation into the context of contemporary regional survey practice, and describes our approaches to methodological problems such as sampling strategies, analytical units, and field walking techniques. We present an integrated discussion of two specific areas of interest and an overview of the main results and conclusions of the project to date.

Computerized literature searches have become a standard way of collecting articles when reviewing various topical areas in science. In particular, researchers involved with the DSM-IV used computerized literature searches as a basis of the initial reviews when forming this classification. This article examined the performance of MEDLINE and PsycLIT when searching the 1985 personality disorder literature in nine psychiatric and psychological journals. MEDLINE identified the largest number of articles but tended to be overinclusive in its selection of articles. PsycLIT identified fewer articles and errored in the direction of being underinclusive. Of the 114 articles of possible relevance to the personality disorders, a citation analysis from the Journal of Personality Disorders showed that only 15 articles had substantial impact on the field. All 15 articles were identified by both search systems.

This paper presents a general framework for modeling distributed computing environments for performance analysis by means of Timed Hierarchical Coloured Petri Nets. The proposed framework was used to build and analyze a Coloured Petri Net model of a HTTP web server. Analysis of the performance of the web server model reveals how the web server will respond to changes in the arrival rate of requests, and alternative configurations of the web server model are examined. These are the results of a research project conducted in cooperation between the CPN Centre and Hewlett-Packard Corporation on capacity planning and performance analysis of distributed computing environments.

Physical and cultural landscapes evolve in response to a combination of natural and anthropogenic factors. Therefore any attempt to understand landscape evolution requires the integration of anthropology and the physical sciences. As such, both landscape archaeology and geomorphology are interdependent and interdisciplinary endeavors. Unfortunately, we are hampered in our re-creation of past landscapes by the set of assumptions and the scientific language we bring to this endeavor. This chapter attempts to present a geomorphological approach to re-creating physical and cultural landscapes and in this process elucidates the strengths and weaknesses of this approach.

We present a model of estuarine mixing, removal, and input for dissolved constituents, and apply the model to 39 nutrient (P, N, Si) profiles collected over a 14-month period in a pristine river/ estuary: Ochlockonee Bay, Florida. Each profile is deconvolved into three component functions: linear mixing (conservative) first-order removal (biological productivity), and parabolic input (regeneration). After correction for temporal variations in the fluvial end-members, the model provides quantitative estimates of total estuarine primary production, net regeneration, and subsequent fluxes to the ocean over a year-long period. The modeled data set is internally self-consistent: virtually perfect mass balances are obtained for P and Si. All biological P-uptake is regenerated within the estuary so that virtually 100% of the fluvial reactive-P enters the ocean. One-third of the fluvial reactive-P enters the estuary as particles whose phosphate is released after deposition in estuarine sediments. About 20% of the dissolved fluvial silica flux is removed biologically; all of this biogenic silica dissolves in the estuary and enters the ocean. N cannot be mass balanced, probably because it enters and escapes the bay in unmeasured forms (as NH4 or via denitrification to N2 and N2O). In the Ochlockonee, biological productivity removes nutrients in the ratios N:P ≅ 9:1 and Si:P ≅ 20:1.

Eleven monthly estuarine profiles of dissolved inorganic germanium (Gei) and silica (Si) in a natural, pristine river/bay system demonstrate that Ge-removal and -input parallel the seasonal silica cycle, reflecting Ge-uptake by and -dissolution from diatoms. The Ge/Si atom ratio of the river is 0.6 ± 0.15 × 10−6, which is near the average value for continental granites and for uncontaminated, remote, natural rivers (0.7 ± 0.3 × 10−6). The Ge Si ratio escaping this estuary to the ocean is 0.8 × 10−6, reflecting some estuarine enhancement of the fluvial Ge-flux, probably due to release of Gei from fluvial particulates. Nevertheless, the post-estuarine Ge Si ratio is not significantly different from the continental crustal ratio but is very different from the ratio in sea-floor hot springs and mid-ocean ridge hydrothermal plumes (4 ± 2 × 10−6) and in oceanic basalts (2.6 × 10−6). Thus natural estuarine processes do not obscure the contrasting Ge Si signatures entering the ocean from dissolution of continental and sea-floor silicates.