Fibrosis in the kidney: is a problem shared a problem halved?

Fibrotic disorders are commonplace, take many forms and can be life-threatening. No better example of this exists than the progressive fibrosis that accompanies all chronic renal disease. Renal fibrosis is a direct consequence of the kidney's limited capacity to regenerate after injury. Renal scarring results in a progressive loss of renal function, ultimately leading to end-stage renal failure and a requirement for dialysis or kidney transplantation

Calibration of the LIGO displacement actuators via laser frequency modulation

We present a frequency modulation technique for calibration of the displacement actuators of the LIGO 4-km-long interferometric gravitational-wave detectors. With the interferometer locked in a single-arm configuration, we modulate the frequency of the laser light, creating an effective length variation that we calibrate by measuring the amplitude of the frequency modulation. By simultaneously driving the voice coil actuators that control the length of the arm cavity, we calibrate the voice coil actuation coefficient with an estimated 1-sigma uncertainty of less than one percent. This technique enables a force-free, single-step actuator calibration using a displacement fiducial that is fundamentally different from those employed in other calibration methods.Comment: 10 pages, 5 figures, submitted to Classical and Quantum Gravit

A template bank for gravitational waveforms from coalescing binary black holes: non-spinning binaries

Gravitational waveforms from the inspiral and ring-down stages of the binary black hole coalescences can be modelled accurately by approximation/perturbation techniques in general relativity. Recent progress in numerical relativity has enabled us to model also the non-perturbative merger phase of the binary black-hole coalescence problem. This enables us to \emph{coherently} search for all three stages of the coalescence of non-spinning binary black holes using a single template bank. Taking our motivation from these results, we propose a family of template waveforms which can model the inspiral, merger, and ring-down stages of the coalescence of non-spinning binary black holes that follow quasi-circular inspiral. This two-dimensional template family is explicitly parametrized by the physical parameters of the binary. We show that the template family is not only \emph{effectual} in detecting the signals from black hole coalescences, but also \emph{faithful} in estimating the parameters of the binary. We compare the sensitivity of a search (in the context of different ground-based interferometers) using all three stages of the black hole coalescence with other template-based searches which look for individual stages separately. We find that the proposed search is significantly more sensitive than other template-based searches for a substantial mass-range, potentially bringing about remarkable improvement in the event-rate of ground-based interferometers. As part of this work, we also prescribe a general procedure to construct interpolated template banks using non-spinning black hole waveforms produced by numerical relativity.Comment: A typo fixed in Eq.(B11

Bayesian inference on compact binary inspiral gravitational radiation signals in interferometric data

Presented is a description of a Markov chain Monte Carlo (MCMC) parameter estimation routine for use with interferometric gravitational radiational data in searches for binary neutron star inspiral signals. Five parameters associated with the inspiral can be estimated, and summary statistics are produced. Advanced MCMC methods were implemented, including importance resampling and prior distributions based on detection probability, in order to increase the efficiency of the code. An example is presented from an application using realistic, albeit fictitious, data.Comment: submitted to Classical and Quantum Gravity. 14 pages, 5 figure

Different atmospheric moisture divergence responses to extreme and moderate El Niños

On seasonal and inter-annual time scales, vertically integrated moisture divergence provides a useful measure of the tropical atmospheric hydrological cycle. It reflects the combined dynamical and thermodynamical effects, and is not subject to the limitations that afflict observations of evaporation minus precipitation. An empirical orthogonal function (EOF) analysis of the tropical Pacific moisture divergence fields calculated from the ERA-Interim reanalysis reveals the dominant effects of the El Niño-Southern Oscillation (ENSO) on inter-annual time scales. Two EOFs are necessary to capture the ENSO signature, and regression relationships between their Principal Components and indices of equatorial Pacific sea surface temperature (SST) demonstrate that the transition from strong La Niña through to extreme El Niño events is not a linear one. The largest deviation from linearity is for the strongest El Niños, and we interpret that this arises at least partly because the EOF analysis cannot easily separate different patterns of responses that are not orthogonal to each other. To overcome the orthogonality constraints, a self-organizing map (SOM) analysis of the same moisture divergence fields was performed. The SOM analysis captures the range of responses to ENSO, including the distinction between the moderate and strong El Niños identified by the EOF analysis. The work demonstrates the potential for the application of SOM to large scale climatic analysis, by virtue of its easier interpretation, relaxation of orthogonality constraints and its versatility for serving as an alternative classification method. Both the EOF and SOM analyses suggest a classification of “moderate” and “extreme” El Niños by their differences in the magnitudes of the hydrological cycle responses, spatial patterns and evolutionary paths. Classification from the moisture divergence point of view shows consistency with results based on other physical variables such as SST

A structurally distinct TGF-β mimic from an intestinal helminth parasite potently induces regulatory T cells

Helminth parasites defy immune exclusion through sophisticated evasion mechanisms, including activation of host immunosuppressive regulatory T (Treg) cells. The mouse parasite Heligmosomoides polygyrus can expand the host Treg population by secreting products that activate TGF-β signalling, but the identity of the active molecule is unknown. Here we identify an H. polygyrus TGF-β mimic (Hp-TGM) that replicates the biological and functional properties of TGF-β, including binding to mammalian TGF-β receptors and inducing mouse and human Foxp3+ Treg cells. Hp-TGM has no homology with mammalian TGF-β or other members of the TGF-β family, but is a member of the complement control protein superfamily. Thus, our data indicate that through convergent evolution, the parasite has acquired a protein with cytokine-like function that is able to exploit an endogenous pathway of immunoregulation in the host

Phenomenological template family for black-hole coalescence waveforms

Recent progress in numerical relativity has enabled us to model the non-perturbative merger phase of the binary black-hole coalescence problem. Based on these results, we propose a phenomenological family of waveforms which can model the inspiral, merger, and ring-down stages of black hole coalescence. We also construct a template bank using this family of waveforms and discuss its implementation in the search for signatures of gravitational waves produced by black-hole coalescences in the data of ground-based interferometers. This template bank might enable us to extend the present inspiral searches to higher-mass binary black-hole systems, i.e., systems with total mass greater than about 80 solar masses, thereby increasing the reach of the current generation of ground-based detectors.Comment: Minor changes, Submitted to Class. Quantum Grav. (Proc. GWDAW11

A comparison of methods for gravitational wave burst searches from LIGO and Virgo

The search procedure for burst gravitational waves has been studied using 24 hours of simulated data in a network of three interferometers (Hanford 4-km, Livingston 4-km and Virgo 3-km are the example interferometers). Several methods to detect burst events developed in the LIGO Scientific Collaboration (LSC) and Virgo collaboration have been studied and compared. We have performed coincidence analysis of the triggers obtained in the different interferometers with and without simulated signals added to the data. The benefits of having multiple interferometers of similar sensitivity are demonstrated by comparing the detection performance of the joint coincidence analysis with LSC and Virgo only burst searches. Adding Virgo to the LIGO detector network can increase by 50% the detection efficiency for this search. Another advantage of a joint LIGO-Virgo network is the ability to reconstruct the source sky position. The reconstruction accuracy depends on the timing measurement accuracy of the events in each interferometer, and is displayed in this paper with a fixed source position example.Comment: LIGO-Virgo working group submitted to PR

Anakinra reduces blood pressure and renal fibrosis in one kidney/DOCA/salt-induced hypertension

OBJECTIVE: To determine whether a clinically-utilised IL-1 receptor antagonist, anakinra, reduces renal inflammation, structural damage and blood pressure (BP) in mice with established hypertension. METHODS: Hypertension was induced in male mice by uninephrectomy, deoxycorticosterone acetate (2.4mg/d,s.c.) and replacement of drinking water with saline (1K/DOCA/salt). Control mice received uninephrectomy, a placebo pellet and normal drinking water. 10days post-surgery, mice commenced treatment with anakinra (75mg/kg/d, i.p.) or vehicle (0.9% saline, i.p.) for 11 days. Systolic BP was measured by tail cuff while qPCR, immunohistochemistry and flow cytometry were used to measure inflammatory markers, collagen and immune cell infiltration in the kidneys. RESULTS: By 10 days post-surgery, 1K/DOCA/salt-treated mice displayed elevated systolic BP (148.3+/-2.4mmHg) compared to control mice (121.7+/-2.7mmHg; n=18, P\u3c0.0001). The intervention with anakinra reduced BP in 1K/DOCA/salt-treated mice by approximately 20mmHg (n=16, P\u3c0.05), but had no effect in controls. In 1K/DOCA/salt-treated mice, anakinra modestly reduced ( approximately 30%) renal expression of some (CCL5, CCL2; n=7-8; P\u3c0.05) but not all (ICAM-1, IL-6) inflammatory markers, and had no effect on immune cell infiltration (n=7-8, P \u3e 0.05). Anakinra reduced renal collagen content (n=6, P\u3c0.01) but paradoxically appeared to exacerbate the renal and glomerular hypertrophy (n=8-9, P\u3c0.001) that accompanied 1K/DOCA/salt-induced hypertension. CONCLUSION: Despite its anti-hypertensive and renal anti-fibrotic actions, anakinra had minimal effects on inflammation and leukocyte infiltration in mice with 1K/DOCA/salt-induced hypertension. Future studies will assess whether the anti-hypertensive actions of anakinra are mediated by protective actions in other BP-regulating or salt-handling organs such as the arteries, skin and brain