Enhancing ambient noise correlation processing using vector sensors.

Ambient noise cross-correlations between separated sensors can yield estimates of the Green's function between them. Vector sensors (which record both pressure and acoustic velocity vector components) can leverage their directionality to reject ambient noise sources that do not contribute to the emergence of the Green's function, thus improving performance over standard omnidirectional hydrophones. To quantify this performance gain, a time-domain analytical expression for the correlation between each component of a vector sensor in the presence of an isotropic ambient noise field is derived. Improvement of the velocity channel correlations relative to pressure channel correlations is examined for varying bandwidth, sensor separation distance, and additive channel noise levels. Last, the experimentally measured reduction in variance for the velocity channels correlations vs pressure correlations, using drifting vector sensors deployed in the Long Island Sound, were found to be comparable to the theoretical prediction. Overall, both theoretical and experimental results indicate modest gains are obtained when extracting the Green's function from velocity correlations over using pressure correlations. Thus, vector sensors can be used to reduce the required averaging time for this noise correlation processing, which may be especially useful, for instance, in a fluctuating environment or for drifting sensors.

Passive underwater acoustic tags using layered media.

Autonomous Underwater Vehicle (AUV) navigation requires accurate positioning information from the environment. Existing underwater navigation paradigms employ active acoustic transponders that assist in this task, but these more complex and costly systems require maintenance and power. This paper presents instead a passive underwater marker made of different horizontally stacked acoustically reflective materials that is cost effective and relatively simple to service. A marker's characteristic acoustic signature can be detected by AUVs as acoustic backscattering upon tag insonification, and hence be used for navigation purposes.

A null variant in the apolipoprotein L3 gene is associated with non-diabetic nephropathy.

Background: Inheritance of apolipoprotein L1 gene (APOL1) renal-risk variants in a recessive pattern strongly associates with non-diabetic end-stage kidney disease (ESKD). Further evidence supports risk modifiers in APOL1-associated nephropathy; some studies demonstrate that heterozygotes possess excess risk for ESKD or show earlier age at ESKD, relative to those with zero risk alleles. Nearby loci are also associated with ESKD in non-African Americans. Methods: We assessed the role of the APOL3 null allele rs11089781 on risk of non-diabetic ESKD. Four cohorts containing 2781 ESKD cases and 2474 controls were analyzed. Results: Stratifying by APOL1 risk genotype (recessive) and adjusting for African ancestry identified a significant additive association between rs11089781 and ESKD in each stratum and in a meta-analysis [meta-analysis P = 0.0070; odds ratio (OR) = 1.29]; ORs were consistent across APOL1 risk strata. The biological significance of this association is supported by the finding that the APOL3 gene is co-regulated with APOL1, and that APOL3 protein was able to bind to APOL1 protein. Conclusions: Taken together, the genetic and biological data support the concept that other APOL proteins besides APOL1 may also influence the risk of non-diabetic ESKD.

Passive underwater acoustic markers using Bragg backscattering.

This letter demonstrates the feasibility of a passive underwater acoustic marker technology (or "AcoustiCode") for use in underwater navigation. An AcoustiCode tag is a planar surface with machined periodic patterns capable of producing Bragg backscattering beampatterns with engineered spatial and frequency variations, thus having a unique three-dimensional acoustic signature over a selected frequency band. Hence, these AcoustiCodes enable three-dimensional navigation and information signaling in a totally passive manner for existing high-frequency SONAR systems (potentially mounted on autonomous underwater vehicles), which naturally operate in a narrow frequency band and can also be used over significantly longer ranges compared to optically-based systems.

Cross-coherent vector sensor processing for spatially distributed glider networks.

Autonomous underwater gliders fitted with vector sensors can be used as a spatially distributed sensor array to passively locate underwater sources. However, to date, the positional accuracy required for robust array processing (especially coherent processing) is not achievable using dead-reckoning while the gliders remain submerged. To obtain such accuracy, the gliders can be temporarily surfaced to allow for global positioning system contact, but the acoustically active sea surface introduces locally additional sensor noise. This letter demonstrates that cross-coherent array processing, which inherently mitigates the effects of local noise, outperforms traditional incoherent processing source localization methods for this spatially distributed vector sensor network.

Variation in glucose homeostasis traits associated with P2RX7 polymorphisms in mice and humans.

CONTEXT: Extracellular nucleotide receptors are expressed in pancreatic B-cells. Purinergic signaling via these receptors may regulate pancreatic B-cell function. OBJECTIVE: We hypothesized that purinergic signaling might influence glucose regulation and sought evidence in human studies of glycemic variation and a mouse model of purinergic signaling dysfunction. DESIGN: In humans, we mined genome-wide meta-analysis data sets to examine purinergic signaling genes for association with glycemic traits and type 2 diabetes. We performed additional testing in two genomic regions (P2RX4/P2RX7 and P2RY1) in a cohort from the Prevalence, Prediction, and Prevention of Diabetes in Botnia (n = 3504), which includes more refined measures of glucose homeostasis. In mice, we generated a congenic model of purinergic signaling dysfunction by crossing the naturally hypomorphic C57BL6 P2rx7 allele onto the 129SvJ background. RESULTS: Variants in five genes were associated with glycemic traits and in three genes with diabetes risk. In the Prevalence, Prediction, and Prevention of Diabetes in Botnia study, the minor allele in the missense functional variant rs1718119 (A348T) in P2RX7 was associated with increased insulin sensitivity and secretion, consistent with its known effect on increased pore function. Both male and female P2x7-C57 mice demonstrated impaired glucose tolerance compared with matched P2x7-129 mice. Insulin tolerance testing showed that P2x7-C57 mice were also less responsive to insulin than P2x7-129 mice. CONCLUSIONS: We show association of the purinergic signaling pathway in general and hypofunctioning P2X7 variants in particular with impaired glucose homeostasis in both mice and humans.

Innate immunity pathways regulate the nephropathy gene Apolipoprotein L1.

Apolipoprotein L1 (APOL1) risk variants greatly elevate the risk of kidney disease in African Americans. Here we report a cohort of patients who developed collapsing focal segmental glomerulosclerosis while receiving therapeutic interferon, all of whom carried the APOL1 high-risk genotype. This finding raised the possibility that interferons and the molecular pattern recognition receptors that stimulate interferon production may contribute to APOL1-associated kidney disease. In cell culture, interferons and Toll-like receptor (TLR) agonists increased APOL1 expression by up to 200-fold, in some cases with the appearance of transcripts not detected under basal conditions. PolyI:C, a double-stranded RNA TLR3 agonist, increased APOL1 expression by upregulating interferons directly or through an interferon-independent, IFN-regulatory factor 3 (IRF3)-dependent pathway. Using pharmacological inhibitors, small hairpin RNA knockdown, and chromatin immunoprecipitation, we found that the interferon-independent TLR3 pathway relied on signaling through TBK1, NF-κB, and Jak kinases, and on binding of IRF1, IRF2, and STAT2 at the APOL1 transcription start site. We also demonstrate that overexpression of the APOL1 risk variants is more injurious to cells than overexpression of the wild-type APOL1 protein. Our study illustrates that antiviral pathways may be important inducers of kidney disease in individuals with the APOL1 high-risk genotype and identifies potential targets for prevention or treatment.

Control-relevant erythropoiesis modeling in end-stage renal disease.

Anemia is prevalent in end-stage renal disease (ESRD). The discovery of recombinant human erythropoietin (rHuEPO) over 30 years ago has shifted the treatment of anemia for patients on dialysis from blood transfusions to rHuEPO therapy. Many anemia management protocols (AMPs) used by clinicians comprise a set of experience-based rules for weekly-to-monthly titration of rHuEPO doses based on hemoglobin (Hb) measurements. In order to facilitate the design of an AMP using model-based feedback control theory, we present a physiologically relevant erythropoiesis model and demonstrate its applicability using clinical data.

Impact of activated vitamin D on insulin resistance in nondiabetic chronic kidney disease patients.

UNLABELLED: Although vitamin D deficiency has been associated with increased insulin resistance, a causal link has not been established. Interpreting the relationship has been confounded by a close correlation between vitamin D deficiency and obesity. The current clinical approach of assessing endogenous 25-hydroxyvitamin D (25(OH)D) concentrations in patients with chronic kidney disease (CKD), and independently administering activated vitamin D (AD), allows a unique opportunity to clarify cause and effect in the relationship of vitamin D, obesity and insulin resistance. METHODS: We assessed how 25(OH)D and body mass index (BMI) related to fasting insulin concentrations in 120 nondiabetic patients with CKD. In addition, we described how treatment with AD modified these relationships. RESULTS: In the full cohort, fasting insulin concentrations varied inversely with both 25(OH)D (r = -0·22, P = 0·02) and BMI (r = -0·36, P < 0·0001). The administration of AD altered these relationships. In individuals treated with AD, there was no association between 25(OH)D and fasting insulin, and the mean fasting insulin concentrations were significantly lower than in those not receiving AD (40·5 ± 22·0 vs 54·1 ± 30·9 pm, P = 0·01). In a multivariate analysis, both AD treatment and BMI were independent predictors of fasting insulin. Furthermore, obese patients treated with AD had insulin concentrations similar to nonobese patients (46·1 ± 24·9 vs 40·2 ± 21·5 pm), whereas untreated obese patients had markedly higher fasting insulin concentrations (74·4 ± 33·4 pm, P = 0·003). CONCLUSION: 25(OH)D deficiency is associated with insulin resistance in CKD. Replacement with pharmacologic doses of AD is associated with lower fasting insulin concentrations, especially in obese patients.