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Perhaps the most exciting area of astronomical research today is the study of exoplanets and exoplanetary systems, engaging the imagination not just of the astronomical community, but of the general population. Astronomical instrumentation has matured to the level where it is possible to detect terrestrial planets orbiting distant stars via radial velocity (RV) measurements, with the most stable visible light spectrographs reporting RV results the order of 1 m/s. This, however, is an order of magnitude away from the precision needed to detect an Earth analog orbiting a star such as our sun, the Holy Grail of these efforts. By performing these observations in near infrared (NIR) there is the potential to simplify the search for distant terrestrial planets by studying cooler, less massive, much more numerous class M stars, with a tighter habitable zone and correspondingly larger RV signal. This NIR advantage is undone by the lack of a suitable high precision, high stability wavelength standard, limiting NIR RV measurements to tens or hundreds of m/s [1, 2]. With the improved spectroscopic precision provided by a laser frequency comb based wavelength reference producing a set of bright, densely and uniformly spaced lines, it will be possible to achieve up to two orders of magnitude improvement in RV precision, limited only by the precision and sensitivity of existing spectrographs, enabling the observation of Earth analogs through RV measurements. We discuss the laser frequency comb as an astronomical wavelength reference, and describe progress towards a near infrared laser frequency comb at the National Institute of Standards and Technology and at the University of Colorado where we are operating a laser frequency comb suitable for use with a high resolution H band astronomical spectrograph.

Author(s): F. Lecocq [sup.1] [sup.2] , F. Quinlan [sup.1] , K. Cicak [sup.1] , J. Aumentado [sup.1] , S. A. Diddams [sup.1] [sup.2] , J. D. Teufel [sup.1] Author Affiliations: [...], Delivering on the revolutionary promise of a universal quantum computer will require processors with millions of quantum bits (qubits).sup.1-3. In superconducting quantum processors.sup.4, each qubit is individually addressed with microwave signal lines that connect room-temperature electronics to the cryogenic environment of the quantum circuit. The complexity and heat load associated with the multiple coaxial lines per qubit limits the maximum possible size of a processor to a few thousand qubits.sup.5. Here we introduce a photonic link using an optical fibre to guide modulated laser light from room temperature to a cryogenic photodetector.sup.6, capable of delivering shot-noise-limited microwave signals directly at millikelvin temperatures. By demonstrating high-fidelity control and readout of a superconducting qubit, we show that this photonic link can meet the stringent requirements of superconducting quantum information processing.sup.7. Leveraging the low thermal conductivity and large intrinsic bandwidth of optical fibre enables the efficient and massively multiplexed delivery of coherent microwave control pulses, providing a path towards a million-qubit universal quantum computer. High-fidelity control and readout of a superconducting qubit is performed with a low-noise optical fibre link that delivers microwave signals directly to the millikelvin quantum computing environment.

Abstract Background Over the last decade the drop in short-read sequencing costs has allowed experimental techniques utilizing sequencing to address specific biological questions to proliferate, oftentimes outpacing standardized or effective analysis approaches for the data generated. There are growing amounts of bacterial 3′-end sequencing data, yet there is currently no commonly accepted analysis methodology for this datatype. Most data analysis approaches are somewhat ad hoc and, despite the presence of substantial signal within annotated genes, focus on genomic regions outside the annotated genes (e.g. 3′ or 5′ UTRs). Furthermore, the lack of consistent systematic analysis approaches, as well as the absence of genome-wide ground truth data, make it impossible to compare conclusions generated by different labs, using different organisms. Results We present PIPETS, (Poisson Identification of PEaks from Term-Seq data), an R package available on Bioconductor that provides a novel analysis method for 3'-end sequencing data. PIPETS is a statistically informed, gene-annotation agnostic methodology. Across two different datasets from two different organisms, PIPETS identified significant 3'-end termination signal across a wider range of annotated genomic contexts than existing analysis approaches, suggesting that existing approaches may miss biologically relevant signal. Furthermore, assessment of the previously called 3′-end positions not captured by PIPETS showed that they were uniformly very low coverage. Conclusions PIPETS provides a broadly applicable platform to explore and analyze 3′-end sequencing data sets from across different organisms. It requires only the 3′-end sequencing data, and is broadly accessible to non-expert users.

Fbw7 is a tumor suppressor that regulates the degradation of oncogenic substrates such as c-Jun, c-Myc, Notch1 intracellular domain (ICD), and cyclin E by functioning as the substrate recognition protein in the Skp1-Cullin-F-box (SCF) ubiquitin ligase complex. Consequently, low expression or loss of FBXW7 in breast cancer has been hypothesized to result in the accumulation of oncogenic transcription factors that are master regulators of proliferation, apoptosis, and ultimately transformation. Despite this, the direct effect of Fbw7 loss on mammary gland morphology and tumorigenesis has not been examined. Here, we demonstrate that conditional deletion of Fbxw7 in murine mammary tissue initiates breast tumor development and also results in lactation and involution defects. Further, while Fbxw7 loss results in the overexpression of Notch1-ICD, c-Jun, cyclin E, and c-Myc, the downstream transcription factor pathways associated with c-Myc and cyclin E are the most dysregulated, including at the single-cell level. These pathways are dysregulated early after Fbxw7 loss, and their sustained loss results in tumorigenesis and reinforced c-Myc and cyclin E-E2F pathway disruption. We also find that loss of Fbxw7 is linked to the acquisition of Trp53 mutations, similar to the mutational spectrum observed in patients. Our results demonstrate that the loss of Fbxw7 promotes the acquisition of Trp53 mutations and that the two cooperate in breast tumor development. Targeting c-Myc, E2F, or p53 may therefore be a beneficial treatment strategy for FBXW7-altered breast cancer patients.

Fundamental science, as well as all communications and navigation systems, are heavily reliant on the phase, timing, and synchronization provided by low-noise and agile frequency sources. Although research into varied photonic and electronic schemes have strived to improve upon the spectral purity of microwave and millimeter-wave signals, the reliance on conventional electronic synthesis for tuning has resulted in limited progress in broadband sources. Using a digital-photonic synthesizer architecture that derives its time-base from a high-stability optical reference cavity, we generate frequency-agile and wideband microwave signals with exceptional dynamic range and with a fractional frequency instability of 1 × 10−15 at 1 s. The presented architecture demonstrates digitally controlled, user defined and broadband frequency tuning from RF to 100 GHz with orders-of-magnitude improvement in noise performance over room-temperature electronic wide-bandwidth synthesis schemes. [ABSTRACT FROM AUTHOR]

Abstract Background Acute lymphoblastic leukemia (ALL) is the most common hematologic malignancy in children, representing 25% of all new cancer diagnoses. Advances in genomic sequencing have demonstrated that inherited genetic risk factors play a larger role in leukemia development than previously appreciated. Aim We identified a father–daughter dyad with childhood B‐cell ALL and aimed to investigate whether the pair shared a gene associated with leukemia predisposition. Methods We performed whole exome sequencing on their leukemia and germline samples and RNA‐seq on their leukemia samples. Results We discovered a novel germline chromosomal structural variant in chromosome 1q32.2 within the TRAF3IP3 gene. TRAF3IP3 regulates B‐cell lymphopoiesis, and this mutation likely resulted in a predisposition to leukemia by causing expansion of immature B‐cell precursors which are highly vulnerable to secondary somatic mutations. Based on the lack of concordance in the somatic mutational profiles between this dyad's leukemia samples, we suspect that the acquired somatic mutations rather than this germline mutation are what dictated their leukemia phenotypes, which we confirmed through RNA‐seq by comparing to sporadic cases of B‐cell ALL. Conclusion This research may have identified a novel gene involved in leukemogenesis which may also be involved in de novo cases of ALL. Additional studies are needed to further characterize this TRAF3IP3 structural variant, the co‐occurring somatic mutations within these leukemia samples and their combined role in leukemogenesis.