Detecting a Stochastic Gravitational-Wave Background: The Overlap Reduction Function

Detection of a gravitational-wave stochastic background via ground or space-based gravitational-wave detectors requires the cross correlation of the response of two or more independent detectors. The cross correlation involves a frequency-dependent factor—the so-called overlap reduction function or Hellings-Downs curve—that depends on the relative geometry of each detector pair, i.e., the detector separations and the relative orientation of their antenna patterns (beams). An incorrect formulation of this geometrical factor has appeared in the literature, leading to incorrect conclusions regarding the sensitivity of proposed detectors to a stochastic gravitational-wave background. To rectify these errors and as a reference for future work we provide here a complete, first-principles derivation of the overlap reduction function and assess the nature of the errors associated with the use of the incorrect expression that has appeared in the literature. We describe the behavior of the overlap reduction function in different limiting regimes, and show how the difference between the correct and incorrect expressions can be understood physically

Interleukin-33 contributes to both M1 and M2 chemokine marker expression in human macrophages

Abstract Background Interleukin-33 is a member of the IL-1 cytokine family whose functions are mediated and modulated by the ST2 receptor. IL-33-ST2 expression and interactions have been explored in mouse macrophages but little is known about the effect of IL-33 on human macrophages. The expression of ST2 transcript and protein levels, and IL-33-mediated effects on M1 (i.e. classical activation) and M2 (i.e. alternative activation) chemokine marker expression in human bone marrow-derived macrophages were examined. Results Human macrophages constitutively expressed the membrane-associated (i.e. ST2L) and the soluble (i.e. sST2) ST2 receptors. M2 (IL-4 + IL-13) skewing stimuli markedly increased the expression of ST2L, but neither polarizing cytokine treatment promoted the release of sST2 from these cells. When added to naïve macrophages alone, IL-33 directly enhanced the expression of CCL3. In combination with LPS, IL-33 blocked the expression of the M2 chemokine marker CCL18, but did not alter CCL3 expression in these naive cells. The addition of IL-33 to M1 macrophages markedly increased the expression of CCL18 above that detected in untreated M1 macrophages. Similarly, alternatively activated human macrophages treated with IL-33 exhibited enhanced expression of CCL18 and the M2 marker mannose receptor above that detected in M2 macrophages alone. Conclusions Together, these data suggest that primary responses to IL-33 in bone marrow derived human macrophages favors M1 chemokine generation while its addition to polarized human macrophages promotes or amplifies M2 chemokine expression.http://deepblue.lib.umich.edu/bitstream/2027.42/78250/1/1471-2172-11-52.xmlhttp://deepblue.lib.umich.edu/bitstream/2027.42/78250/2/1471-2172-11-52.pdfPeer Reviewe

Enhancing Self-Consistency and Performance of Pre-Trained Language Models through Natural Language Inference

While large pre-trained language models are powerful, their predictions often lack logical consistency across test inputs. For example, a state-of-the-art Macaw question-answering (QA) model answers 'Yes' to 'Is a sparrow a bird?' and 'Does a bird have feet?' but answers 'No' to 'Does a sparrow have feet?'. To address this failure mode, we propose a framework, Consistency Correction through Relation Detection, or ConCoRD, for boosting the consistency and accuracy of pre-trained NLP models using pre-trained natural language inference (NLI) models without fine-tuning or re-training. Given a batch of test inputs, ConCoRD samples several candidate outputs for each input and instantiates a factor graph that accounts for both the model's belief about the likelihood of each answer choice in isolation and the NLI model's beliefs about pair-wise answer choice compatibility. We show that a weighted MaxSAT solver can efficiently compute high-quality answer choices under this factor graph, improving over the raw model's predictions. Our experiments demonstrate that ConCoRD consistently boosts accuracy and consistency of off-the-shelf closed-book QA and VQA models using off-the-shelf NLI models, notably increasing accuracy of LXMERT on ConVQA by 5% absolute. See https://ericmitchell.ai/emnlp-2022-concord/ for code and data.Comment: 16 pages. EMNLP 2022 Camera Ready. See https://ericmitchell.ai/emnlp-2022-concord/ for code and dat

802.16e System Profile for NASA Extra-Vehicular Activities

This report identifies an 802.16e system profile that is applicable to a lunar surface wireless network, and specifically for meeting extra-vehicular activity (EVA) data flow requirements. EVA suit communication needs are addressed. Design-driving operational scenarios are considered. These scenarios are then used to identify a configuration of the 802.16e system (system profile) that meets EVA requirements, but also aim to make the radio realizable within EVA constraints. Limitations of this system configuration are highlighted. An overview and development status is presented by Toyon Research Corporation concerning the development of an 802.16e compatible modem under NASA s Small Business Innovative Research (SBIR) Program. This modem is based on the recommended system profile developed as part of this report. Last, a path forward is outlined that presents an evolvable solution for the EVA radio system and lunar surface radio networks. This solution is based on a custom link layer, and 802.16e compliant physical layer compliant to the identified system profile, and a later progression to a fully interoperable 802.16e system

Nmnat1 protects neuronal function without altering phospho-tau pathology in a mouse model of tauopathy

OBJECTIVE: The nicotinamide‐nucleotide adenylyltransferase protein Nmnat1 is a potent inhibitor of axonal degeneration in models of acute axonal injury. Hyperphosphorylation and aggregation of the microtubule‐associated protein Tau are associated with neurodegeneration in Alzheimer's Disease and other disorders. Previous studies have demonstrated that other Nmnat isoforms can act both as axonoprotective agents and have protein chaperone function, exerting protective effects in drosophila and mouse models of tauopathy. Nmnat1 targeted to the cytoplasm (cytNmnat1) is neuroprotective in a mouse model of neonatal hypoxia‐ischemia, but the effect of cytNmnat1 on tauopathy remains unknown. METHODS: We examined the impact of overexpression of cytNmnat1 on tau pathology, neurodegeneration, and brain functional connectivity in the P301S mouse model of chronic tauopathy. RESULTS: Overexpression of cytNmnat1 preserved cortical neuron functional connectivity in P301S mice in vivo. However, whereas Nmnat1 overexpression decreased the accumulation of detergent‐insoluble tau aggregates in the cerebral cortex, it exerted no effect on immunohistochemical evidence of pathologic tau phosphorylation and misfolding, hippocampal atrophy, or inflammatory markers in P301S mice. INTERPRETATION: Our results demonstrate that cytNmnat1 partially preserves neuronal function and decreases biochemically insoluble tau in a mouse model of chronic tauopathy without preventing tau phosphorylation, formation of soluble aggregates, or tau‐induced inflammation and atrophy. Nmnat1 might thus represent a therapeutic target for tauopathies

The ESR1 (6q25) locus is associated with calcaneal ultrasound parameters and radial volumetric bone mineral density in European men

<p><b>Purpose:</b> Genome-wide association studies (GWAS) have identified 6q25, which incorporates the oestrogen receptor alpha gene (ESR1), as a quantitative trait locus for areal bone mineral density (BMD(a)) of the hip and lumbar spine. The aim of this study was to determine the influence of this locus on other bone health outcomes; calcaneal ultrasound (QUS) parameters, radial peripheral quantitative computed tomography (pQCT) parameters and markers of bone turnover in a population sample of European men.</p> <p><b>Methods:</b> Eight single nucleotide polymorphisms (SNP) in the 6q25 locus were genotyped in men aged 40-79 years from 7 European countries, participating in the European Male Ageing Study (EMAS). The associations between SNPs and measured bone parameters were tested under an additive genetic model adjusting for centre using linear regression.</p> <p><b>Results:</b> 2468 men, mean (SD) aged 59.9 (11.1) years had QUS measurements performed and bone turnover marker levels measured. A subset of 628 men had DXA and pQCT measurements. Multiple independent SNPs showed significant associations with BMD using all three measurement techniques. Most notably, rs1999805 was associated with a 0.10 SD (95%CI 0.05, 0.16; p = 0.0001) lower estimated BMD at the calcaneus, a 0.14 SD (95%CI 0.05, 0.24; p = 0.004) lower total hip BMD(a), a 0.12 SD (95%CI 0.02, 0.23; p = 0.026) lower lumbar spine BMD(a) and a 0.18 SD (95%CI 0.06, 0.29; p = 0.003) lower trabecular BMD at the distal radius for each copy of the minor allele. There was no association with serum levels of bone turnover markers and a single SNP which was associated with cortical density was also associated with cortical BMC and thickness.</p> <p><b>Conclusions:</b> Our data replicate previous associations found between SNPs in the 6q25 locus and BMD(a) at the hip and extend these data to include associations with calcaneal ultrasound parameters and radial volumetric BMD.</p&gt

Active vitamin D (1,25-dihydroxyvitamin D) and bone health in middle-aged and elderly men: the European male aging study (EMAS)

<p>Context: There is little information on the potential impact of serum 1,25-dihydroxyvitamin D [1,25(OH)2D] on bone health including turnover.</p> <p>Objective: The objective of the study was to determine the influence of 1,25(OH)2D and 25-hydroxyvitamin D [25(OH)D] on bone health in middle-aged and older European men.</p> <p>Design, Setting, and Participants: Men aged 40–79 years were recruited from population registers in 8 European centers. Subjects completed questionnaires that included questions concerning lifestyle and were invited to attend for quantitative ultrasound (QUS) of the heel, assessment of height and weight, and a fasting blood sample from which 1,25(OH)2D, 25(OH)D, and PTH were measured. 1,25(OH)2D was measured using liquid chromatography tandem mass spectrometry. Bone markers serum N-terminal propeptide of type 1 procollagen (P1NP) and crosslinks (β-cTX) were also measured. Dual-energy x-ray absorptiometry (DXA) of the hip and lumbar spine was performed in 2 centers.</p> <p>Main Outcome Measure(s): QUS of the heel, bone markers P1NP and β-cTX, and DXA of the hip and lumbar spine were measured.</p> <p>Results: A total of 2783 men, mean age 60.0 years (SD 11.0) were included in the analysis. After adjustment for age and center, 1,25(OH)2D was positively associated with 25(OH)D but not with PTH. 25(OH)D was negatively associated with PTH. After adjustment for age, center, height, weight, lifestyle factors, and season, 1,25(OH)2D was associated negatively with QUS and DXA parameters and associated positively with β-cTX. 1,25(OH)2D was not correlated with P1NP. 25(OH)D was positively associated with the QUS and DXA parameters but not related to either bone turnover marker. Subjects with both high 1,25(OH)2D (upper tertile) and low 25(OH)D (lower tertile) had the lowest QUS and DXA parameters and the highest β-cTX levels.</p> <p>Conclusions: Serum 1,25(OH)2D is associated with higher bone turnover and poorer bone health despite being positively related to 25(OH)D. A combination of high 1,25(OH)2D and low 25(OH)D is associated with the poorest bone health.</p&gt

Active vitamin D (1,25-dihydroxyvitamin D) and bone health in middle-aged and elderly men: the European male aging study (EMAS)

<p>Context: There is little information on the potential impact of serum 1,25-dihydroxyvitamin D [1,25(OH)2D] on bone health including turnover.</p> <p>Objective: The objective of the study was to determine the influence of 1,25(OH)2D and 25-hydroxyvitamin D [25(OH)D] on bone health in middle-aged and older European men.</p> <p>Design, Setting, and Participants: Men aged 40–79 years were recruited from population registers in 8 European centers. Subjects completed questionnaires that included questions concerning lifestyle and were invited to attend for quantitative ultrasound (QUS) of the heel, assessment of height and weight, and a fasting blood sample from which 1,25(OH)2D, 25(OH)D, and PTH were measured. 1,25(OH)2D was measured using liquid chromatography tandem mass spectrometry. Bone markers serum N-terminal propeptide of type 1 procollagen (P1NP) and crosslinks (β-cTX) were also measured. Dual-energy x-ray absorptiometry (DXA) of the hip and lumbar spine was performed in 2 centers.</p> <p>Main Outcome Measure(s): QUS of the heel, bone markers P1NP and β-cTX, and DXA of the hip and lumbar spine were measured.</p> <p>Results: A total of 2783 men, mean age 60.0 years (SD 11.0) were included in the analysis. After adjustment for age and center, 1,25(OH)2D was positively associated with 25(OH)D but not with PTH. 25(OH)D was negatively associated with PTH. After adjustment for age, center, height, weight, lifestyle factors, and season, 1,25(OH)2D was associated negatively with QUS and DXA parameters and associated positively with β-cTX. 1,25(OH)2D was not correlated with P1NP. 25(OH)D was positively associated with the QUS and DXA parameters but not related to either bone turnover marker. Subjects with both high 1,25(OH)2D (upper tertile) and low 25(OH)D (lower tertile) had the lowest QUS and DXA parameters and the highest β-cTX levels.</p> <p>Conclusions: Serum 1,25(OH)2D is associated with higher bone turnover and poorer bone health despite being positively related to 25(OH)D. A combination of high 1,25(OH)2D and low 25(OH)D is associated with the poorest bone health.</p&gt

A validation of the first genome-wide association study of calcaneus ultrasound parameters in the European Male Ageing Study

RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are.Abstract Background A number of single nucleotide polymorphisms (SNPs) have been associated with broadband ultrasound attenuation (BUA) and speed of sound (SOS) as measured by quantitative ultrasound (QUS) at the calcaneus in the Framingham 100K genome-wide association study (GWAS) but have not been validated in independent studies. The aim of this analysis was to determine if these SNPs are associated with QUS measurements assessed in a large independent population of European middle-aged and elderly men. The association between these SNPs and bone mineral density (BMD) measured using dual-energy X-ray absorptiometry (DXA) was also tested. Methods Men aged 40-79 years (N = 2960) were recruited from population registers in seven European centres for participation in an observational study of male ageing, the European Male Ageing Study (EMAS). QUS at the calcaneus was measured in all subjects and blood was taken for genetic analysis. Lumbar spine (LS), femoral neck (FN) and total hip (TH) BMD were measured by DXA in a subsample of 620 men in two centres. SNPs associated with BUA or SOS in the Framingham study with p < 10-4 were selected and genotyped using SEQUENOM technology. Linear regression was used to test for the association between SNPs and standardised (SD) bone outcomes under an additive genetic model adjusting for centre. The same direction of effect and p < 0.05 indicated replication. Results Thirty-four of 38 selected SNPs were successfully genotyped in 2377 men. Suggestive evidence of replication was observed for a single SNP, rs3754032, which was associated with a higher SOS (β(SD) = 0.07, p = 0.032) but not BUA (β(SD) = 0.02, p = 0.505) and is located in the 3'UTR of WDR77 (WD repeat domain 77) also known as androgen receptor cofactor p44. A single SNP, rs238358, was associated with BMD at the LS (β(SD) = -0.22, p = 0.014), FN (β(SD) = -0.31,p = 0.001) and TH (β(SD) = -0.36, p = 0.002) in a locus previously associated with LS BMD in large-scale GWAS, incorporating AKAP11 and RANKL. Conclusions We found suggestive evidence of association between a single SNP located in the 3'UTR of WDR77 with calcaneal ultrasound parameters. The majority of SNPs, associated with QUS parameters in the Framingham Study, were not replicated in an independent population sample of European men.Published versio