Population dynamics of Eldana saccharina Walker (Lepidoptera: Pyralidae): application of a biophysical model to understand phenological variation in an agricultural pest.

Understanding pest population dynamics and seasonal phenology is a critical component of modern integrated pest-management programs. Accurate forecasting allows timely, cost-effective interventions, including maximum efficacy of, for example, biological control and/or sterile insect technique. Due to the variation in life stage-related sensitivity toward climate, insect pest population abundance models are often not easily interpreted or lack direct relevance to management strategies in the field. Here we apply a process-based (biophysical) model that incorporates climate data with life stage-dependent physiology and life history to attempt to predict Eldana saccharina life stage and generation turnover in sugarcane fields. Fitness traits are modelled at two agricultural locations in South Africa that differ in average temperature (hereafter a cold and a warm site). We test whether the life stage population structures in the field entering winter and local climate during winter directly affect development rates, and therefore interact to determine the population dynamics and phenological responses of E. saccharina in subsequent spring and summer seasons. The model predicts that: (1) E. saccharina can cycle through more generations at the warm site where fewer hours of cold and heat stress are endured, and (2) at the cold site, overwintering as pupae (rather than larvae) confer higher relative fitness and fecundity in the subsequent summer adult moths. The model predictions were compared with a large dataset of field observations from scouting records. Model predictions for larval presence (or absence) generally overlapped well with positive (or negative) scout records. These results are important for integrated pest management strategies by providing a useful foundation for future population dynamics models, and are applicable to a variety of agricultural landscapes, but especially the sugarcane industry of South Africa.

Arabidopsis KANADI1 acts as a transcriptional repressor by interacting with a specific cis-element and regulates auxin biosynthesis, transport, and signaling in opposition to HD-ZIPIII factors.

The formation of leaves and other lateral organs in plants depends on the proper specification of adaxial-abaxial (upper-lower) polarity. KANADI1 (KAN1), a member of the GARP family of transcription factors, is a key regulator of abaxial identity, leaf growth, and meristem formation in Arabidopsis thaliana. Here, we demonstrate that the Myb-like domain in KAN1 binds the 6-bp motif GNATA(A/T) and that this motif alone is sufficient to squelch transcription of a linked reporter in vivo. In addition, we report that KAN1 acts as a transcriptional repressor. Among its targets are genes involved in auxin biosynthesis, auxin transport, and auxin response. Furthermore, we find that the adaxializing HD-ZIPIII transcription factor REVOLUTA has opposing effects on multiple components of the auxin pathway. We hypothesize that HD-ZIPIII and KANADI transcription factors pattern auxin accumulation and responsiveness in the embryo. Specifically, we propose the opposing actions of KANADI and HD-ZIPIII factors on cotyledon formation (KANADI represses and HD-ZIPIII promotes cotyledon formation) occur through their opposing actions on genes acting at multiple steps in the auxin pathway.

Establishing a framework for the Ad/abaxial regulatory network of Arabidopsis: ascertaining targets of class III homeodomain leucine zipper and KANADI regulation.

The broadly conserved Class III homeodomain leucine zipper (HD-ZIPIII) and KANADI transcription factors have opposing and transformational effects on polarity and growth in all tissues and stages of the plant's life. To obtain a comprehensive understanding of how these factors work, we have identified transcripts that change in response to induced HD-ZIPIII or KANADI function. Additional criteria used to identify high-confidence targets among this set were presence of an adjacent HD-ZIPIII binding site, expression enriched within a subdomain of the shoot apical meristem, mutant phenotype showing defect in polar leaf and/or meristem development, physical interaction between target gene product and HD-ZIPIII protein, opposite regulation by HD-ZIPIII and KANADI, and evolutionary conservation of the regulator-target relationship. We find that HD-ZIPIII and KANADI regulate tissue-specific transcription factors involved in subsidiary developmental decisions, nearly all major hormone pathways, and new actors (such as indeterminate domain4) in the ad/abaxial regulatory network. Multiple feedback loops regulating HD-ZIPIII and KANADI are identified, as are mechanisms through which HD-ZIPIII and KANADI oppose each other. This work lays the foundation needed to understand the components, structure, and workings of the ad/abaxial regulatory network directing basic plant growth and development.

An upper limit on the stochastic gravitational-wave background of cosmological origin.

A stochastic background of gravitational waves is expected to arise from a superposition of a large number of unresolved gravitational-wave sources of astrophysical and cosmological origin. It should carry unique signatures from the earliest epochs in the evolution of the Universe, inaccessible to standard astrophysical observations. Direct measurements of the amplitude of this background are therefore of fundamental importance for understanding the evolution of the Universe when it was younger than one minute. Here we report limits on the amplitude of the stochastic gravitational-wave background using the data from a two-year science run of the Laser Interferometer Gravitational-wave Observatory (LIGO). Our result constrains the energy density of the stochastic gravitational-wave background normalized by the critical energy density of the Universe, in the frequency band around 100 Hz, to be <6.9 x 10(-6) at 95% confidence. The data rule out models of early Universe evolution with relatively large equation-of-state parameter, as well as cosmic (super)string models with relatively small string tension that are favoured in some string theory models. This search for the stochastic background improves on the indirect limits from Big Bang nucleosynthesis and cosmic microwave background at 100 Hz.

Brassinosteroids regulate organ boundary formation in the shoot apical meristem of Arabidopsis.

Spatiotemporal control of the formation of organ primordia and organ boundaries from the stem cell niche in the shoot apical meristem (SAM) determines the patterning and architecture of plants, but the underlying signaling mechanisms remain poorly understood. Here we show that brassinosteroids (BRs) play a key role in organ boundary formation by repressing organ boundary identity genes. BR-hypersensitive mutants display organ-fusion phenotypes, whereas BR-insensitive mutants show enhanced organ boundaries. The BR-activated transcription factor BZR1 directly represses the cup-shaped cotyledon (CUC) family of organ boundary identity genes. In WT plants, BZR1 accumulates at high levels in the nuclei of central meristem and organ primordia but at a low level in organ boundary cells to allow CUC gene expression. Activation of BR signaling represses CUC gene expression and causes organ fusion phenotypes. This study uncovers a role for BR in the spatiotemporal control of organ boundary formation and morphogenesis in the SAM.

Local leadership and the Affordable Care Act.

Local health departments are in key positions to lead in the education and implementation efforts to advance the Patient Protection and Affordable Care Act. The first enrollment period is over, but the efforts to enroll the uninsured and advocate for expansion of Medicaid in the states that have not yet taken on this expansion will continue for years to come. Political climates may be unsupportive, but some actions may still be possible.

A per-ARNT-sim-like sensor domain uniquely regulates the activity of the homeodomain leucine zipper transcription factor REVOLUTA in Arabidopsis.

Class III homeodomain leucine zipper (HD-ZIP III) transcription factors regulate critical developmental programs in plants; these include leaf polarity, polarity along the shoot-root axis, and stem cell specification and proliferation. One of the defining features of HD-ZIP III proteins is the presence of a Per-ARNT-Sim-like (PAS-like) MEKHLA domain at the C terminus. PAS-like domains are known to respond to a variety of chemical and physical stimuli. Here, we provide evidence that the MEKHLA domain acts as a negative regulator of Arabidopsis thaliana HD-ZIP III REVOLUTA activity. Based on experiments in yeast and plants, we propose a model in which the MEKHLA domain inhibits dimerization through a sequence-independent steric masking mechanism. This inhibition is relieved in response to a cellular signal that requires the C terminus of the MEKHLA domain for its perception. Overexpression experiments suggest that this signal is unequally distributed and/or sensed in the plant. Our data show that the function of the REVOLUTA MEKHLA domain differs among other HD-ZIP III family members; this difference may explain the genetic differences that have been observed among family members. This finding, combined with our phylogenetic analysis, suggests that REVOLUTA is the latest type of HD-ZIP III protein to have evolved in land plants.

Constraints on cosmic strings from the LIGO-Virgo gravitational-wave detectors.

Cosmic strings can give rise to a large variety of interesting astrophysical phenomena. Among them, powerful bursts of gravitational waves (GWs) produced by cusps are a promising observational signature. In this Letter we present a search for GWs from cosmic string cusps in data collected by the LIGO and Virgo gravitational wave detectors between 2005 and 2010, with over 625 days of live time. We find no evidence of GW signals from cosmic strings. From this result, we derive new constraints on cosmic string parameters, which complement and improve existing limits from previous searches for a stochastic background of GWs from cosmic microwave background measurements and pulsar timing data. In particular, if the size of loops is given by the gravitational backreaction scale, we place upper limits on the string tension Gµ below 10(-8) in some regions of the cosmic string parameter space.

Improved upper limits on the stochastic gravitational-wave background from 2009-2010 LIGO and Virgo data.

Gravitational waves from a variety of sources are predicted to superpose to create a stochastic background. This background is expected to contain unique information from throughout the history of the Universe that is unavailable through standard electromagnetic observations, making its study of fundamental importance to understanding the evolution of the Universe. We carry out a search for the stochastic background with the latest data from the LIGO and Virgo detectors. Consistent with predictions from most stochastic gravitational-wave background models, the data display no evidence of a stochastic gravitational-wave signal. Assuming a gravitational-wave spectrum of Ω_{GW}(f)=Ω_{α}(f/f_{ref})^{α}, we place 95% confidence level upper limits on the energy density of the background in each of four frequency bands spanning 41.5-1726 Hz. In the frequency band of 41.5-169.25 Hz for a spectral index of α=0, we constrain the energy density of the stochastic background to be Ω_{GW}(f)<5.6×10^{-6}. For the 600-1000 Hz band, Ω_{GW}(f)<0.14(f/900 Hz)^{3}, a factor of 2.5 lower than the best previously reported upper limits. We find Ω_{GW}(f)<1.8×10^{-4} using a spectral index of zero for 170-600 Hz and Ω_{GW}(f)<1.0(f/1300 Hz)^{3} for 1000-1726 Hz, bands in which no previous direct limits have been placed. The limits in these four bands are the lowest direct measurements to date on the stochastic background. We discuss the implications of these results in light of the recent claim by the BICEP2 experiment of the possible evidence for inflationary gravitational waves.

Search for gravitational waves associated with γ-ray bursts detected by the interplanetary network.

We present the results of a search for gravitational waves associated with 223 γ-ray bursts (GRBs) detected by the InterPlanetary Network (IPN) in 2005-2010 during LIGO's fifth and sixth science runs and Virgo's first, second, and third science runs. The IPN satellites provide accurate times of the bursts and sky localizations that vary significantly from degree scale to hundreds of square degrees. We search for both a well-modeled binary coalescence signal, the favored progenitor model for short GRBs, and for generic, unmodeled gravitational wave bursts. Both searches use the event time and sky localization to improve the gravitational wave search sensitivity as compared to corresponding all-time, all-sky searches. We find no evidence of a gravitational wave signal associated with any of the IPN GRBs in the sample, nor do we find evidence for a population of weak gravitational wave signals associated with the GRBs. For all IPN-detected GRBs, for which a sufficient duration of quality gravitational wave data are available, we place lower bounds on the distance to the source in accordance with an optimistic assumption of gravitational wave emission energy of 10(-2)M⊙c(2) at 150 Hz, and find a median of 13 Mpc. For the 27 short-hard GRBs we place 90% confidence exclusion distances to two source models: a binary neutron star coalescence, with a median distance of 12 Mpc, or the coalescence of a neutron star and black hole, with a median distance of 22 Mpc. Finally, we combine this search with previously published results to provide a population statement for GRB searches in first-generation LIGO and Virgo gravitational wave detectors and a resulting examination of prospects for the advanced gravitational wave detectors.

Assessing a Suitable Radiotherapy Utilisation Benchmark for Older Patients With Head and Neck Cancer.

AIMS: To (i) determine the actual radiotherapy utilization (RTU) stratified by age, (ii) develop an age- and co-morbidity adjusted optimal RTU model and (iii) examine the tolerance and toxicity of treatment of older patients with head and neck cancer. MATERIALS AND METHODS: A retrospective cohort study based on New South Wales Cancer Registry records (2010-2014) linked to radiotherapy data (2010-2015) and admitted patient data (2008-2015) for patients diagnosed with head and neck cancer. We calculated the actual RTU, defined as the proportion of patients who received at least one course of radiotherapy within a year of diagnosis, by age group, including patients aged 80+ years. We also calculated the age and comorbidity-adjusted optimal RTU. For treatment tolerance, the radiotherapy dose for each age group and the completion rate for a seven week 70 Gray (Gy) course of curative intent radiotherapy were computed. The number of emergency department (ED) presentations were used as a surrogate measure of acute treatment toxicity for patients receiving 70 Gy. RESULTS: Of the 5966 patients diagnosed with head and neck cancer, 814 (13.6%) were aged 80+ years. For all age groups, the actual RTU was less than the optimal RTU. The age- and comorbidity-adjusted optimal RTU for patients aged 80+ was 52% (95% CI: 51%-53%), and the actual RTU was 40% (95% CI: 37%-44%). Only 4.4% of patients aged 80+ received 70 Gy, and the completion rate for a 70 Gy course of radiotherapy for these patients was 92%. The ED presentation rate was similar for all age groups. CONCLUSION: The actual RTU was less in the 80+ years patients and across all age groups. Fewer patients in the 80+ group received curative intent schedules compared to the actual RTU rate for younger age groups, despite similar rates of completion of curative intent radiotherapy and acute toxicity.

Genome-wide binding-site analysis of REVOLUTA reveals a link between leaf patterning and light-mediated growth responses.

Unlike the situation in animals, the final morphology of the plant body is highly modulated by the environment. During Arabidopsis development, intrinsic factors provide the framework for basic patterning processes. CLASS III HOMEODOMAIN LEUCINE ZIPPER (HD-ZIPIII) transcription factors are involved in embryo, shoot and root patterning. During vegetative growth HD-ZIPIII proteins control several polarity set-up processes such as in leaves and the vascular system. We have identified several direct target genes of the HD-ZIPIII transcription factor REVOLUTA (REV) using a chromatin immunoprecipitation/DNA sequencing (ChIP-Seq) approach. This analysis revealed that REV acts upstream of auxin biosynthesis and affects directly the expression of several class II HD-ZIP transcription factors that have been shown to act in the shade-avoidance response pathway. We show that, as well as involvement in basic patterning, HD-ZIPIII transcription factors have a critical role in the control of the elongation growth that is induced when plants experience shade. Leaf polarity is established by the opposed actions of HD-ZIPIII and KANADI transcription factors. Finally, our study reveals that the module that consists of HD-ZIPIII/KANADI transcription factors controls shade growth antagonistically and that this antagonism is manifested in the opposed regulation of shared target genes.

Automated detection, delineation and quantification of whole-body bone metastasis using FDG-PET/CT images.

Non-small cell lung cancer (NSCLC) patients with the metastatic spread of disease to the bone have high morbidity and mortality. Stereotactic ablative body radiotherapy increases the progression free survival and overall survival of these patients with oligometastases. FDG-PET/CT, a functional imaging technique combining positron emission tomography (PET) with 18 F-fluorodeoxyglucose (FDG) and computer tomography (CT) provides improved staging and identification of treatment response. It is also associated with reduction in size of the radiotherapy tumour volume delineation compared with CT based contouring in radiotherapy, thus allowing for dose escalation to the target volume with lower doses to the surrounding organs at risk. FDG-PET/CT is increasingly being used for the clinical management of NSCLC patients undergoing radiotherapy and has shown high sensitivity and specificity for the detection of bone metastases in these patients. Here, we present a software tool for detection, delineation and quantification of bone metastases using FDG-PET/CT images. The tool extracts standardised uptake values (SUV) from FDG-PET images for auto-segmentation of bone lesions and calculates volume of each lesion and associated mean and maximum SUV. The tool also allows automatic statistical validation of the auto-segmented bone lesions against the manual contours of a radiation oncologist. A retrospective review of FDG-PET/CT scans of more than 30 candidate NSCLC patients was performed and nine patients with one or more metastatic bone lesions were selected for the present study. The SUV threshold prediction model was designed by splitting the cohort of patients into a subset of 'development' and 'validation' cohorts. The development cohort yielded an optimum SUV threshold of 3.0 for automatic detection of bone metastases using FDG-PET/CT images. The validity of the derived optimum SUV threshold on the validation cohort demonstrated that auto-segmented and manually contoured bone lesions showed strong concordance for volume of bone lesion (r = 0.993) and number of detected lesions (r = 0.996). The tool has various applications in radiotherapy, including but not limited to studies determining optimum SUV threshold for accurate and standardised delineation of bone lesions and in scientific studies utilising large patient populations for instance for investigation of the number of metastatic lesions that can be treated safety with an ablative dose of radiotherapy without exceeding the normal tissue toxicity.

Reducing control noise in gravitational wave detectors with interferometric local damping of suspended optics.

Control noise is a limiting factor in the low-frequency performance of the Advanced Laser Interferometer Gravitational-Wave Observatory (LIGO). In this paper, we model the effects of using new sensors called Homodyne Quadrature Interferometers (HoQIs) to control the suspension resonances. We show that if we were to use HoQIs, instead of the standard shadow sensors, we could suppress resonance peaks up to tenfold more while simultaneously reducing the noise injected by the damping system. Through a cascade of effects, this will reduce the resonant cross-coupling of the suspensions, allow for improved stability for feed-forward control, and result in improved sensitivity of the detectors in the 10-20 Hz band. This analysis shows that improved local sensors, such as HoQIs, should be used in current and future detectors to improve low-frequency performance.

The ins and outs of Arabidopsis embryogenesis.

In this issue of Developmental Cell, Nodine and colleagues show that two related leucine-rich repeat receptor kinases, RECEPTOR-LIKE PROTEIN KINASE1 and TOADSTOOL2, are critical in establishing radial pattern in the Arabidopsis embryo (Nodine et al., 2007). Embryos lacking these kinases show replacement of outer cell fates with inner cell fates.

Antimicrobial susceptibilities and resistance genes in Campylobacter strains isolated from poultry and pigs in Australia.

AIMS: To evaluate the phenotypic and genotypic profiles of Campylobacter spp. from poultry faecal samples from free range or intensively raised meat chickens and free range egg layers. In addition, a case-comparison study of antibiotic resistance genes from different groups of poultry and some pig strains previously collected was carried out. METHODS: Resistance to different antibiotics was assessed using the agar dilution method. In addition, all the strains were tested for ampicillin (bla(OXA-61) ), erythromycin (aph-3-1), tetracycline tet(O), streptomycin (aadE), and the energy-dependent multi-drug efflux pump (cmeB) resistance genes using multiplex polymerase chain reaction. RESULTS: The evaluation of phenotypic resistance revealed all of the strains from poultry were sensitive to ciprofloxacin, gentamicin, erythromycin or tylosin. But, widespread resistance to lincomycin (51-100%), extensive resistance to ampicillin (33·3-60·2%) and less resistance to tetracycline (5·6-40·7%) were observed in the different groups of chickens. Antibiotic resistance genes bla(OXA-61,) cmeB and tet(O) were found in 82·6-92·7%, 80·3-89% and 22·3-30·9% Camp. coli isolates from pigs, whilst 59-65·4% and 19·2-40·7% Camp. jejuni from chickens were found to encode bla(OXA-61) and tet(O), respectively. CONCLUSION: No significant difference between isolates from free range egg layers and meat chickens (P < 0·05) was found. However, there were significant differences between the pig strains and all the groups of poultry strains (P < 0·05) with regard to carriage of resistance genes. In addition, pulsed field gel electrophoresis of selected resistant isolates from the poultry and pig revealed closely related clonal groups. SIGNIFICANCE AND IMPACT OF THE STUDY: Our results suggest the resistant strains are persisting environmental isolates that have been acquired by the different livestock species. Furthermore, the different treatment practices in poultry and pigs have resulted in differences in resistance profiles in Campylobacter isolates.

Antibacterial spectrum and cytotoxic activities of serrulatane compounds from the Australian medicinal plant Eremophila neglecta.

AIMS: To determine the antibacterial spectrum and cytotoxic activities of serrulatane compounds from the Australian plant Eremophila neglecta. METHODS AND RESULTS: Antimicrobial activities of serrulatane compounds 8,19-dihydroxyserrulat-14-ene (1) and 8-hydroxyserrulat-14-en-19-oic acid (2) were tested against Gram-negative and Gram-positive bacteria including human and veterinary pathogens and some multidrug-resistant isolates. Minimum inhibitory concentrations (MICs) and minimum bactericidal concentrations (MBCs) of the compounds were determined by broth microdilution assay. Both compounds exhibited antibacterial activity against all Gram-positive test strains. They showed antimycobacterial activity against isolates of Mycobacterium fortuitum and Mycobacterium chelonae. Of the five Gram-negative bacteria tested, only Moraxella catarrhalis showed susceptibility to the compounds. Cytotoxic activities were tested in the Vero cell line. Compound 1 showed more activity than 2 in both antibacterial and cytotoxicity assays with cytotoxicity at concentrations similar to the MBC. CONCLUSIONS: Serrulatane compounds showed significant activity against medically important bacteria, with 1 exhibiting stronger antibacterial activity. However, they also displayed toxicity to mammalian cells. SIGNIFICANCE AND IMPACT OF THE STUDY: Serrulatanes are of interest as novel antibacterial compounds for use in biomedical applications; this study reports data obtained with a range of bacterial strains and mammalian cells, essential for assessing the capabilities and limitations of potential applicability of these compounds.

Dynamic Contrast-enhanced Magnetic Resonance Imaging Evaluation of Whole Tumour Perfusion Heterogeneity Predicts Distant Disease-free Survival in Locally Advanced Rectal Cancer.

AIMS: To evaluate diffusion-weighted imaging and dynamic contrast-enhanced magnetic resonance imaging for the prediction of disease-free survival (DFS) in patients with locally advanced rectal cancer. MATERIALS AND METHODS: Patients with stage II or III rectal adenocarcinoma undergoing neoadjuvant chemoradiotherapy (CRT) and surgery were eligible. Patients underwent multi-parametric magnetic resonance imaging (diffusion-weighted imaging and dynamic contrast-enhanced) before CRT, during CRT (week 3) and after CRT (1 week prior to surgery). Whole tumour apparent diffusion coefficient (ADC) and Ktrans histogram quantiles (10th, 25th, 50th, 75th, 90th) were extracted for analysis. The associations between ADC and Ktrans at three timepoints with time to relapse were analysed as a continuous variable using a Cox proportional hazard model. RESULTS: Thirty-three patients were included in this analysis. The median follow-up was 4.4 years. No patient had locoregional relapse. Nine patients developed distant metastases. The hazard ratios for after CRT Ktrans 10th (P = 0.035), 25th (P = 0.048), 50th (P = 0.046) and 75th (P = 0.045) quantiles were statistically significant for DFS. The best Ktrans cut-off point after CRT for predicting relapse was 28 × 10-3 mL/g/min (10th quantile), with a higher Ktrans value predicting distant relapse. The 4-year DFS probability was 0.93 for patients with after CRT Ktrans value ≤28 × 10-3 mL/g/min versus 0.45 for patients with after CRT Ktrans value >28 × 10-3 mL/g/min. ADC was not able to predict DFS. CONCLUSIONS: Patients with higher Ktrans values after CRT (before surgery) in a histogram analysis of whole tumour heterogeneity had a significantly lower 4-year distant DFS and could be considered for more intense systemic therapy.

Twenty years on: the inner workings of the shoot apical meristem, a developmental dynamo.

The shoot apical meristem of angiosperm plants generates leaf, stem and floral structures throughout the plant's lifetime. To do this, the plant must maintain a population of stem cells within the meristem while at the same time carefully controlling the placement and establishment of new leaf primordia. As there is little cell rearrangement in plants, underlying patterning mechanisms must exert careful control of cell division rates and orientations to achieve the correct final form. It has been twenty years since the first genes controlling meristem development were molecularly cloned. In the intervening decades, our understanding of the inner workings directing meristem development has increased enormously. This review summarizes our current knowledge of how the meristem functions as a persistent organ generating center. The story that emerges is one in which transcription factor activity combines with the action of the classic plant growth regulators auxin and cytokinin and with the action of more recently discovered small peptides to control proliferation and cell fate in the shoot apical meristem.

Directional limits on persistent gravitational waves using LIGO S5 science data.

The gravitational-wave (GW) sky may include nearby pointlike sources as well as stochastic backgrounds. We perform two directional searches for persistent GWs using data from the LIGO S5 science run: one optimized for pointlike sources and one for arbitrary extended sources. Finding no evidence to support the detection of GWs, we present 90% confidence level (C.L.) upper-limit maps of GW strain power with typical values between 2-20×10(-50) strain(2) Hz(-1) and 5-35×10(-49) strain(2) Hz(-1) sr(-1) for pointlike and extended sources, respectively. The latter result is the first of its kind. We also set 90% C.L. limits on the narrow-band root-mean-square GW strain from interesting targets including Sco X-1, SN 1987A and the Galactic center as low as ≈7×10(-25) in the most sensitive frequency range near 160 Hz.