The differential contribution of tumour necrosis factor to thermal and mechanical hyperalgesia during chronic inflammation

Therapies directed against tumour necrosis factor (TNF) are effective for the treatment of rheumatoid arthritis and reduce pain scores in this condition. In this study, we sought to explore mechanisms by which TNF contributes to inflammatory pain in an experimental model of arthritis. The effects of an anti-TNF agent, etanercept, on behavioural pain responses arising from rat monoarthritis induced by complete Freund's adjuvant were assessed and compared with expression of TNF receptors (TNFRs) by dorsal root ganglion (DRG) cells at corresponding time points. Etanercept had no effect on evoked pain responses in normal animals but exerted a differential effect on the thermal and mechanical hyperalgesia associated with rat arthritis induced by complete Freund's adjuvant (CFA). Joint inflammation was associated with increased TNFR1 and TNFR2 expression on DRG cells, which was maintained throughout the time course of the model. TNFR1 expression was increased in neuronal cells of the DRG bilaterally after arthritis induction. In contrast, TNFR2 expression occurred exclusively on nonneuronal cells of the macrophage-monocyte lineage, with cell numbers increasing in a TNF-dependent fashion during CFA-induced arthritis. A strong correlation was observed between numbers of macrophages and the development of mechanical hyperalgesia in CFA-induced arthritis. These results highlight the potential for TNF to play a vital role in inflammatory hyperalgesia, both by a direct action on neurons via TNFR1 and by facilitating the accumulation of macrophages in the DRG via a TNFR2-mediated pathway

Indexing multi-dimensional uncertain data with arbitrary probability density functions

Research Session 26: Spatial and Temporal DatabasesIn an "uncertain database", an object o is associated with a multi-dimensional probability density function (pdf), which describes the likelihood that o appears at each position in the data space. A fundamental operation is the "probabilistic range search" which, given a value p q and a rectangular area r q, retrieves the objects that appear in r q with probabilities at least p q. In this paper, we propose the U-tree, an access method designed to optimize both the I/O and CPU time of range retrieval on multi-dimensional imprecise data. The new structure is fully dynamic (i.e., objects can be incrementally inserted/deleted in any order), and does not place any constraints on the data pdfs. We verify the query and update efficiency of U-trees with extensive experiments.postprintThe 31st International Conference on Very Large Data Bases (VLDB 2005), Trondheim, Norway, 30 August-2 September 2005. In Proceedings of 31st VLDB, 2005, v. 3, p. 922-93

Hysteresis phenomenon in turbulent convection

Coherent large-scale circulations of turbulent thermal convection in air have been studied experimentally in a rectangular box heated from below and cooled from above using Particle Image Velocimetry. The hysteresis phenomenon in turbulent convection was found by varying the temperature difference between the bottom and the top walls of the chamber (the Rayleigh number was changed within the range of $10^7 - 10^8$). The hysteresis loop comprises the one-cell and two-cells flow patterns while the aspect ratio is kept constant ($A=2 - 2.23$). We found that the change of the sign of the degree of the anisotropy of turbulence was accompanied by the change of the flow pattern. The developed theory of coherent structures in turbulent convection (Elperin et al. 2002; 2005) is in agreement with the experimental observations. The observed coherent structures are superimposed on a small-scale turbulent convection. The redistribution of the turbulent heat flux plays a crucial role in the formation of coherent large-scale circulations in turbulent convection.Comment: 10 pages, 9 figures, REVTEX4, Experiments in Fluids, 2006, in pres

Relationship Between Peer Assessment During Medical School, Dean’s Letter Rankings, and Ratings by Internship Directors

BACKGROUND: It is not known to what extent the dean’s letter (medical student performance evaluation [MSPE]) reflects peer-assessed work habits (WH) skills and/or interpersonal attributes (IA) of students. OBJECTIVE: To compare peer ratings of WH and IA of second- and third-year medical students with later MSPE rankings and ratings by internship program directors. DESIGN AND PARTICIPANTS: Participants were 281 medical students from the classes of 2004, 2005, and 2006 at a private medical school in the northeastern United States, who had participated in peer assessment exercises in the second and third years of medical school. For students from the class of 2004, we also compared peer assessment data against later evaluations obtained from internship program directors. RESULTS: Peer-assessed WH were predictive of later MSPE groups in both the second (F = 44.90, P < .001) and third years (F = 29.54, P < .001) of medical school. Interpersonal attributes were not related to MSPE rankings in either year. MSPE rankings for a majority of students were predictable from peer-assessed WH scores. Internship directors’ ratings were significantly related to second- and third-year peer-assessed WH scores (r = .32 [P = .15] and r = .43 [P = .004]), respectively, but not to peer-assessed IA. CONCLUSIONS: Peer assessment of WH, as early as the second year of medical school, can predict later MSPE rankings and internship performance. Although peer-assessed IA can be measured reliably, they are unrelated to either outcome

Effects of tidal-forcing variations on tidal properties along a narrow convergent estuary

A 1D analytical framework is implemented in a narrow convergent estuary that is 78 km in length (the Guadiana, Southern Iberia) to evaluate the tidal dynamics along the channel, including the effects of neap-spring amplitude variations at the mouth. The close match between the observations (damping from the mouth to ∼ 30 km, shoaling upstream) and outputs from semi-closed channel solutions indicates that the M2 tide is reflected at the estuary head. The model is used to determine the contribution of reflection to the dynamics of the propagating wave. This contribution is mainly confined to the upper one third of the estuary. The relatively constant mean wave height along the channel (< 10% variations) partly results from reflection effects that also modify significantly the wave celerity and the phase difference between tidal velocity and elevation (contradicting the definition of an “ideal” estuary). Furthermore, from the mouth to ∼ 50 km, the variable friction experienced by the incident wave at neap and spring tides produces wave shoaling and damping, respectively. As a result, the wave celerity is largest at neap tide along this lower reach, although the mean water level is highest in spring. Overall, the presented analytical framework is useful for describing the main tidal properties along estuaries considering various forcings (amplitude, period) at the estuary mouth and the proposed method could be applicable to other estuaries with small tidal amplitude to depth ratio and negligible river discharge.info:eu-repo/semantics/publishedVersio

Interpreting 16S metagenomic data without clustering to achieve sub-OTU resolution

The standard approach to analyzing 16S tag sequence data, which relies on clustering reads by sequence similarity into Operational Taxonomic Units (OTUs), underexploits the accuracy of modern sequencing technology. We present a clustering-free approach to multi-sample Illumina datasets that can identify independent bacterial subpopulations regardless of the similarity of their 16S tag sequences. Using published data from a longitudinal time-series study of human tongue microbiota, we are able to resolve within standard 97% similarity OTUs up to 20 distinct subpopulations, all ecologically distinct but with 16S tags differing by as little as 1 nucleotide (99.2% similarity). A comparative analysis of oral communities of two cohabiting individuals reveals that most such subpopulations are shared between the two communities at 100% sequence identity, and that dynamical similarity between subpopulations in one host is strongly predictive of dynamical similarity between the same subpopulations in the other host. Our method can also be applied to samples collected in cross-sectional studies and can be used with the 454 sequencing platform. We discuss how the sub-OTU resolution of our approach can provide new insight into factors shaping community assembly.Comment: Updated to match the published version. 12 pages, 5 figures + supplement. Significantly revised for clarity, references added, results not change

Complex nature of SNP genotype effects on gene expression in primary human leucocytes

<p>Abstract</p> <p>Background</p> <p>Genome wide association studies have been hugely successful in identifying disease risk variants, yet most variants do not lead to coding changes and how variants influence biological function is usually unknown.</p> <p>Methods</p> <p>We correlated gene expression and genetic variation in untouched primary leucocytes (n = 110) from individuals with celiac disease – a common condition with multiple risk variants identified. We compared our observations with an EBV-transformed HapMap B cell line dataset (n = 90), and performed a meta-analysis to increase power to detect non-tissue specific effects.</p> <p>Results</p> <p>In celiac peripheral blood, 2,315 SNP variants influenced gene expression at 765 different transcripts (< 250 kb from SNP, at FDR = 0.05, <it>cis </it>expression quantitative trait loci, eQTLs). 135 of the detected SNP-probe effects (reflecting 51 unique probes) were also detected in a HapMap B cell line published dataset, all with effects in the same allelic direction. Overall gene expression differences within the two datasets predominantly explain the limited overlap in observed <it>cis</it>-eQTLs. Celiac associated risk variants from two regions, containing genes <it>IL18RAP </it>and <it>CCR3</it>, showed significant <it>cis </it>genotype-expression correlations in the peripheral blood but not in the B cell line datasets. We identified 14 genes where a SNP affected the expression of different probes within the same gene, but in opposite allelic directions. By incorporating genetic variation in co-expression analyses, functional relationships between genes can be more significantly detected.</p> <p>Conclusion</p> <p>In conclusion, the complex nature of genotypic effects in human populations makes the use of a relevant tissue, large datasets, and analysis of different exons essential to enable the identification of the function for many genetic risk variants in common diseases.</p

Should mechanical dyssynchrony be assessed in patients with implantable cardioverter-defibrillators?

Cardiac Dysfunction and Arrhythmia

Field observations of canopy flows over complex terrain

The investigation of airflow over and within forests in complex terrain has been, until recently, limited to a handful of modelling and laboratory studies. Here, we present an observational dataset of airflow measurements inside and above a forest situated on a ridge on the Isle of Arran, Scotland. The spatial coverage of the observations all the way across the ridge makes this a unique dataset. Two case studies of across-ridge flow under near-neutral conditions are presented and compared with recent idealized two-dimensional modelling studies. Changes in the canopy profiles of both mean wind and turbulent quantities across the ridge are broadly consistent with these idealized studies. Flow separation over the lee slope is seen as a ubiquitous feature of the flow. The three-dimensional nature of the terrain and the heterogeneous forest canopy does however lead to significant variations in the flow separation across the ridge, particularly over the less steep western slope. Furthermore, strong directional shear with height in regions of flow separation has a significant impact on the Reynolds stress terms and other turbulent statistics. Also observed is a decrease in the variability of the wind speed over the summit and lee slope, which has not been seen in previous studies. This dataset should provide a valuable resource for validating models of canopy flow over real, complex terrain

Are Zinc-Finger Domains of Protein Kinase C Dynamic Structures That Unfold by Lipid or Redox Activation?

Protein kinase C (PKC) is activated by lipid second messengers or redox action, raising the question whether these activation modes involve the same or alternate mechanisms. Here we show that both lipid activators and oxidation target the zinc-finger domains of PKC, suggesting a unifying activation mechanism. We found that lipid agonist-binding or redox action leads to zinc release and disassembly of zinc fingers, thus triggering large-scale unfolding that underlies conversion to the active enzyme. These results suggest that PKC zinc fingers, originally considered purely structural devices, are in fact redox-sensitive flexible hinges, whose conformation is controlled both by redox conditions and lipid agonists. Antioxid. Redox Signal. 14, 757-766.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/90473/1/ars-2E2010-2E3773.pd