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Time-programmable frequency combs enable new measurement paradigms for dual-comb spectroscopy (DCS) that are free of many of the constraints found in traditional DCS. As opposed to fixing the repetition rate offset between combs, free-form DCS uses full control of the temporal offset between the dual-comb pulse trains, thereby enabling user-selectable sampling patterns that optimize resolution, signal-to-noise ratio, species selectivity or acquisition time. Here we show that free-form DCS enables compressive sensing and demonstrate compression factors of up to 155, with an up to 60-fold reduction in acquisition time, while maintaining identical spectral point spacing and comparable signal-to-noise ratio to traditional DCS. We also demonstrate molecular recurrence sampling (an extreme case of compressive sensing) for methane detection at 22× higher sensitivity than traditional DCS at the cost of requiring a priori knowledge of the probed species. Finally, free-form DCS can enable fast species-selective imaging since its radio frequency signal is narrow band, in contrast to traditional DCS, and therefore compatible with limited camera read out rates. We demonstrate imaging of methane plumes across a 128 × 64-pixel focal plane array at a 250 Hz rate. In the future, this flexible free-form approach can enable applications ranging from rapid open-path spectroscopy to nonlinear multidimensional comb-based spectroscopy.

BackgroundClassic aniridia is a highly penetrant autosomal dominant disorder characterised by congenital absence of the iris, foveal hypoplasia, optic disc anomalies and progressive opacification of the cornea. >90% of cases of classic aniridia are caused by heterozygous, loss-of-function variants affecting the PAX6locus.MethodsShort-read whole genome sequencing was performed on 51 (39 affected) individuals from 37 different families who had screened negative for mutations in the PAX6coding region.ResultsLikely causative mutations were identified in 22 out of 37 (59%) families. In 19 out of 22 families, the causative genomic changes have an interpretable deleterious impact on the PAX6locus. Of these 19 families, 1 has a novel heterozygous PAX6frameshift variant missed on previous screens, 4 have single nucleotide variants (SNVs) (one novel) affecting essential splice sites of PAX65′ non-coding exons and 2 have deep intronic SNV (one novel) resulting in gain of a donor splice site. In 12 out of 19, the causative variants are large-scale structural variants; 5 have partial or whole gene deletions of PAX6, 3 have deletions encompassing critical PAX6 cis-regulatory elements, 2 have balanced inversions with disruptive breakpoints within the PAX6locus and 2 have complex rearrangements disrupting PAX6. The remaining 3 of 22 families have deletions encompassing FOXC1(a known cause of atypical aniridia). Seven of the causative variants occurred de novoand one cosegregated with familial aniridia. We were unable to establish inheritance status in the remaining probands. No plausibly causative SNVs were identified in PAX6 cis-regulatory elements.ConclusionWhole genome sequencing proves to be an effective diagnostic test in most individuals with previously unexplained aniridia.

Increased use of smart technology is seen as a solution to providing equitable and reliable energy access. Consequently, there has been a global push for smart metreing. There is a range of smart metres available with differing features and functionality. This work discusses an approach for rating the degree of smartness of an electric metre to assess whether it can help provide equitable and affordable electricity access to the Global South. Analytic hierarchy process (AHP), the multicriteria decision-making tool, is employed for obtaining a framework for evaluating smartness. India is the country chosen in this paper as a case representing the Global South. Expert opinion is used as input to provide a weightage to various criteria that make up smartness. A survey was conducted to collect data for the AHP in which experts from both industry and academia participated. Based on their inputs, 2 AHP frameworks were created. The data obtained and the AHP results show that there is an agreement between both sets of experts on what constitutes a smart metre for a developing country such as India. Using the expert-agreed AHP framework, a smartness score was then calculated for any given metre. As a case study, few commercially available Indian electricity metres are considered for smartness assessment and affordability, and the results are discussed. It is demonstrated that the new framework allows decision makers to choose economical smart metres that aid in achieving efficient electricity access. Additionally, it is noted that both sets of experts seem to favour similar metres with regard to smartness.

Grasping is the process of picking up an object by applying forces and torques at a set of contacts. Recent advances in deep learning methods have allowed rapid progress in robotic object grasping. In this systematic review, we surveyed the publications over the last decade, with a particular interest in grasping an object using all six degrees of freedom of the end-effector pose. Our review found four common methodologies for robotic grasping: sampling-based approaches, direct regression, reinforcement learning, and exemplar approaches In addition, we found two “supporting methods” around grasping that use deep learning to support the grasping process, shape approximation, and affordances. We have distilled the publications found in this systematic review (85 papers) into ten key takeaways we consider crucial for future robotic grasping and manipulation research.

The seawater inlet pipe is critical to the operation of any water treatment plant and any reduction in diameter can reduce plant efficiency and increase pumping costs. The objective of pipeline pigging is to keep the pipeline running to full capacity and avoid the build-up of mussels and other sea water/marine growth, which can cause significant and fast growing biofouling throughout water intake pipes. In order to control this potential reduction to pipeline efficiency the most environmentally friendly option is to periodically mechanically clean or scrape off, termed pigging, the organic growth and ensure a clean pipeline. The bespoke cleaning tools can be also be used to monitor and predict the potential build up and so develop an economical periodic cleaning schedule. Another option to consider may be chemical dosing, however sometimes environmental considerations prohibit chemical options. However, the organisms inhabiting the pipeline may be able to overcome such methods so perhaps a combination approach should be considered. Established in 1984 and with almost four decades of experience in pipeline cleaning and isolation, iNPIPE PRODUCTS™ have developed an integrated and systematic approach to mechanical cleaning of large diameter pipes. This includes bespoke designs and cost-effective methods to introducing the cleaning tools into the pipeline, specific designs of cleaning tools in order to systematically remove problematic organisms and deposits. Inlet spools to integrate pigging into the seawater inlet pipeline system together with outlet options for the safe and environmentally friendly removal of the debris and the cleaning tool into the sea.

APPAREL: Companies today are challenged to offer ever-greater innovation, customization, speed and value to their customers. And PLM systems have matured in recent years to help with these demands. What [...]

Many of our GA airplanes now have two altimeters: an electronic PFD like Aspen, Avidyne, or Garmin indicators, and the requisite standby, be it the original round dials or another [...]

The combination of optical time transfer and optical clocks opens up the possibility of large-scale free-space networks that connect both ground-based optical clocks and future space-based optical clocks. Such networks promise better tests of general relativity1–3, dark-matter searches4and gravitational-wave detection5. The ability to connect optical clocks to a distant satellite could enable space-based very long baseline interferometry6,7, advanced satellite navigation8, clock-based geodesy2,9,10and thousandfold improvements in intercontinental time dissemination11,12. Thus far, only optical clocks have pushed towards quantum-limited performance13. By contrast, optical time transfer has not operated at the analogous quantum limit set by the number of received photons. Here we demonstrate time transfer with near quantum-limited acquisition and timing at 10,000 times lower received power than previous approaches14–24. Over 300 km between mountaintops in Hawaii with launched powers as low as 40 µW, distant sites are synchronized to 320 attoseconds. This nearly quantum-limited operation is critical for long-distance free-space links in which photons are few and amplification costly: at 4.0 mW transmit power, this approach can support 102 dB link loss, more than sufficient for future time transfer to geosynchronous orbits.

The article reviews the exhibition "Clarissa Tossin: Falling from Earth" at the Museum of Contemporary Art, Denver, Colorado, from June 3 to August 28, 2022.

ABSTRACTBackgroundRecent studies have highlighted a role for trace elements and toxic metals across neurodevelopmental disorders, including developmental stuttering, Autistic Spectrum Disorders (ASD), and Attention Deficit/Hyperactivity Disorder (ADHD). However, these environmental influences have yet to be explored in relation to Developmental Language Disorder (DLD).MethodsElemental hair composition of seven elements; zinc (64Zn), magnesium (26Mg), iron (57Fe), potassium (39K), aluminum (27Al), lead (208Pb), and barium (138Ba) were analyzed in hair samples from 35 children affected by DLD and 35 controls with typical language development (TLD) using both inductive coupled plasma optical emission spectroscopy (ICP–OES) and inductive coupled plasma mass spectroscopy (ICP–MS).ResultsThe concentration of 64Zn was significantly lower in the hair of DLD group compared to the TLD control group. All other elements showed similar levels between cases and controls. This pilot study demonstrates the utility of trace elements and toxic metals screening in relation to language disorders and the use of hair samples in such investigations.ConclusionThe finding that zinc levels differed between cases and controls could represent a clinically relevant result and should be replicated in larger sample size across time. A wider battery of related elements will help to better understand the role of trace elements and toxic metals in DLD.

Company executives and employees are not the only ones feeling the pay ramifications of the economic crisis. Decisions on pay for nonexecutive directors have clearly been influenced by the crisis [...]

An analysis of filler metals for 36Ni alloy cryogenic pipeline construction reveals the susceptibility of this alloy class to weld-cracking phenomena. Impact, tensile, and bend tests were used to support this conclusion

We are what we eat. Now, many who have joined the Real Food Revival to find fresh, quality foods for themselves are beginning to apply that Same standard to their […]

People across the country are finding new and reliable ways to out fresher, healthier food on the dinner table. They are buying locally--milk, eggs and meat from the farm down [...]

The article focuses on the importance of safeguarding livestock during adverse events, emphasizing the need for emergency preparedness and proactive planning. Topics include the development of farm emergency preparedness handbooks, the significance of caring for animals during emergencies, and practical advice for farmers and lifestyle block owners on preparing for, evacuating, and assessing animals after adverse events.

Mutations at the SALL4 locus on chromosome 20 result in a range of clinically overlapping phenotypes, including Okihiro syndrome, Holt-Oram syndrome, acro-renal-ocular syndrome, and patients previously reported to represent thalidomide [...]

ABSTRACTLanguage-rich experiences in early childhood play a critical role in a child’s language development, academic success and well-being. This study aimed to understand New Zealand parents/caregivers’ knowledge and beliefs about language rich experiences and child language development. A survey was developed and distributed online using Qualtrics. Items sought information about participants’ demographics, perceived influences and sources of information about child language development. Participants were asked to indicate ‘agree’ or ‘disagree’ with 30 statements on child language development using a five point Likert-type scale. Five hundred responses were analyzed. The participant sample was skewed towards those with higher levels of education. Participants showed strong general knowledge of the importance of interpersonal interaction in developing language. The importance of early vocabulary development on children’s learning trajectories was not well understood. Levels of parent/caregiver education were correlated with higher accuracy on child language development items. Approximately half the participants had sought information on child speech/language development, with health professionals and the internet being the most commonly used sources. Education opportunities for parent/caregivers on how to maximize child language development in the preschool years may be indicated.

The article offers a review of the Land Art: Expanding the Atlas, an exhibition on global political ecology, held at Nevada Museum of Art (NMA) in Reno, Nevada in 2020.

The thrombocytopenia-absent radius (TAR) syndrome is a congenital malformation syndrome characterised by bilateral absence of the radii and a thrombocytopenia. The lower limbs, gastrointestinal, cardiovascular, and other systems may also [...]

Research undertaken in the Adelaide Western Division of General Practice in Adelaide, Australia, into the outcomes of a health assessment of people aged 75 years and over is presented. This randomized controlled trial did not show improvement in primary outcome measures in the intervention group a year after a health assessment compared with the control group.

Most B-Raf proto-oncogene (BRAF)–mutant melanoma tumors respond initially to BRAF inhibitor (BRAFi)/mitogen-activated protein kinase kinase 1 inhibitor (MEKi) therapy, although few patients have durable long-term responses to these agents. The goal of this study was to use an unbiased computational approach to identify inhibitors that reverse an experimentally derived BRAFi resistance gene expression signature. Using this approach, we found that ibrutinib effectively reverses this signature, and we demonstrate experimentally that ibrutinib resensitizes a subset of BRAFi-resistant melanoma cells to vemurafenib. Ibrutinib is used clinically as an inhibitor of the Src family kinase Bruton tyrosine kinase (BTK); however, neither BTK deletion nor treatment with acalabrutinib, another BTK inhibitor with reduced off-target activity, resensitized cells to vemurafenib. These data suggest that ibrutinib acts through a BTK-independent mechanism in vemurafenib resensitization. To better understand this mechanism, we analyzed the transcriptional profile of ibrutinib-treated BRAFi-resistant melanoma cells and found that the transcriptional profile of ibrutinib was highly similar to that of multiple Src proto-oncogene kinase inhibitors. Since ibrutinib, but not acalabrutinib, has appreciable off-target activity against multiple Src family kinases, it suggests that ibrutinib may be acting through this mechanism. Furthermore, genes that are differentially expressed in ibrutinib-treated cells are enriched in Yes1-associated transcriptional regulator (YAP1) target genes, and we showed that ibrutinib, but not acalabrutinib, reduces YAP1 activity in BRAFi-resistant melanoma cells. Taken together, these data suggest that ibrutinib, or other Src family kinase inhibitors, may be useful for treating some BRAFi/MEKi-refractory melanoma tumors.SIGNIFICANCE STATEMENTMAPK-targeted therapies provide dramatic initial responses, but resistance develops rapidly; a subset of these tumors may be rendered sensitive again by treatment with an approved Src family kinase inhibitor—ibrutinub—potentially providing improved clinical outcomes.

Two decades after its invention, the classic self-referenced frequency comb laser is an unrivalled ruler for frequency, time and distance metrology owing to the rigid spacing of its optical output1,2. As a consequence, it is now used in numerous sensing applications that require a combination of high bandwidth and high precision3–5. Many of these applications, however, are limited by the trade-offs inherent in the rigidity of the comb output and operate far from quantum-limited sensitivity. Here we demonstrate an agile programmable frequency comb where the pulse time and phase are digitally controlled with ±2-attosecond accuracy. This agility enables quantum-limited sensitivity in sensing applications as the programmable comb can be configured to coherently track weak returning pulse trains at the shot-noise limit. To highlight its capabilities, we use this programmable comb in a ranging system, reducing the required power to reach a given precision by about 5,000-fold compared with a conventional dual-comb system. This enables ranging at a mean photon per pulse number of 1/77 while retaining the full accuracy and precision of a rigid frequency comb. Beyond ranging and imaging6–12, applications in time and frequency metrology1,2,5,13–23, comb-based spectroscopy24–32, pump–probe experiments33and compressive sensing34,35should benefit from coherent control of the comb-pulse time and phase.

ABSTRACTWith the increasing availability of head-mounted displays for virtual reality and augmented reality, we can create immersive maps in which the user is closer to the data. Embodiment is a key concept, allowing the user to act upon virtual objects in an immersive environment. Our work explores the use of embodied interaction for immersive maps. We propose four design considerations for embodied maps and embodied gesture interaction with immersive maps: object presence, consistent physics, human body skills, and direct manipulation. We present an example of an immersive flow map with a series of novel embodied gesture interactions, which adhere to the proposed design considerations. The embodied interactions allow users to directly manipulate immersive flow maps and explore origin-destination flow data in novel ways. Authors of immersive maps can use the four proposed design considerations for creating embodied gesture interactions. The discussed example interactions apply to diverse types of immersive maps and will hopefully incite others to invent more embodied interactions for immersive maps.