A Kerr-microresonator optical clockwork

Kerr microresonators generate interesting and useful fundamental states of electromagnetic radiation through nonlinear interactions of continuous-wave (CW) laser light. Using photonic-integration techniques, functional devices with low noise, small size, low-power consumption, scalable fabrication, and heterogeneous combinations of photonics and electronics can be realized. Kerr solitons, which stably circulate in a Kerr microresonator, have emerged as a source of coherent, ultrafast pulse trains and ultra-broadband optical-frequency combs. Using the f-2f technique, Kerr combs support carrier-envelope-offset phase stabilization for optical synthesis and metrology. In this paper, we introduce a Kerr-microresonator optical clockwork based on optical-frequency division (OFD), which is a powerful technique to transfer the fractional-frequency stability of an optical clock to a lower frequency electronic clock signal. The clockwork presented here is based on a silicon-nitride (Si$_3$N$_4$) microresonator that supports an optical-frequency comb composed of soliton pulses at 1 THz repetition rate. By electro-optic phase modulation of the entire Si$_3$N$_4$ comb, we arbitrarily generate additional CW modes between the Si$_3$N$_4$ comb modes; operationally, this reduces the pulse train repetition frequency and can be used to implement OFD to the microwave domain. Our experiments characterize the residual frequency noise of this Kerr-microresonator clockwork to one part in $10^{17}$, which opens the possibility of using Kerr combs with high performance optical clocks. In addition, the photonic integration and 1 THz resolution of the Si$_3$N$_4$ frequency comb makes it appealing for broadband, low-resolution liquid-phase absorption spectroscopy, which we demonstrate with near infrared measurements of water, lipids, and organic solvents

In vivo manipulation of the extracellular matrix induces vascular regression in a basal chordate.

We investigated the physical role of the extracellular matrix (ECM) in vascular homeostasis in the basal chordate Botryllus schlosseri, which has a large, transparent, extracorporeal vascular network encompassing an area >100 cm2 We found that the collagen cross-linking enzyme lysyl oxidase is expressed in all vascular cells and that in vivo inhibition using β-aminopropionitrile (BAPN) caused a rapid, global regression of the entire network, with some vessels regressing >10 mm within 16 h. BAPN treatment changed the ultrastructure of collagen fibers in the vessel basement membrane, and the kinetics of regression were dose dependent. Pharmacological inhibition of both focal adhesion kinase (FAK) and Raf also induced regression, and levels of phosphorylated FAK in vascular cells decreased during BAPN treatment and FAK inhibition but not Raf inhibition, suggesting that physical changes in the vessel ECM are detected via canonical integrin signaling pathways. Regression is driven by apoptosis and extrusion of cells through the basal lamina, which are then engulfed by blood-borne phagocytes. Extrusion and regression occurred in a coordinated manner that maintained vessel integrity, with no loss of barrier function. This suggests the presence of regulatory mechanisms linking physical changes to a homeostatic, tissue-level response

Developing a Research Mentorship Program: The American Society of Pediatric Nephrology's Experience

Background: Most pediatric nephrologists work in academia. Mentor-mentee relationships provide support and guidance for successful research career. Mentorship program implementation is valuable in medical fields for providing research opportunities to young faculty. Methods: The American Society of Pediatric Nephrology (ASPN) established a research mentorship program to (a) assist with matching of appropriate mentor-mentee dyads and (b) establish metrics for desirable mentor-mentee outcomes with two independent components: (1) the grants review workshop, a short-term program providing mentor feedback on grant proposals, and (2) the longitudinal program, establishing long-term mentor-mentee relationships. Regular surveys of both mentors and mentees were reviewed to evaluate and refine the program. Results: Twelve mentees and 17 mentors participated in the grant review workshop and 19 mentees were matched to mentors in the longitudinal program. A review of NIH RePORTER data indicated that since 2014, 13 NIH grants have been awarded. Mentees in the longitudinal program reported that the program helped most with identifying an outside mentor, improving grant research content, and with general career development. Mentors perceived themselves to be most helpful in assisting with overall career plans. Email communications were preferred over phone or face-to-face communications. Mentees endorsed strong interest in staying in touch with their mentors and 100% of mentors expressed their willingness to serve in the future. Conclusion: This mentorship program was initiated and supported by a relatively small medical society and has shown early success in cultivating mentoring relationships for a future generation of clinician-scientists

Oncolog, Volume 37, Issue 03, July-September 1992

Retinoic acid/interferon combination shows promising response rates Cross-matching test helps find donors for patients in dire need of platelets Silicone gel-filled implants: Women should have the option to choosehttps://openworks.mdanderson.org/oncolog/1039/thumbnail.jp

A Large, Uniform Sample of X-Ray-emitting Active Galactic Nuclei from the ROSAT All Sky and Sloan Digital Sky Surveys: The Data Release 5 Sample

We describe further results of a program aimed at yielding ~104 fully characterized optical identifications of ROSAT X-ray sources. Our program employs X-ray data from the ROSAT All Sky Survey (RASS) and both optical imaging and spectroscopic data from the Sloan Digital Sky Survey (SDSS). RASS/SDSS data from 5740 deg² of sky spectroscopically covered in SDSS Data Release 5 provide an expanded catalog of 7000 confirmed quasars and other active galactic nuclei (AGNs) that are probable RASS identifications. Again, in our expanded catalog the identifications as X-ray sources are statistically secure, with only a few percent of the SDSS AGNs likely to be randomly superposed on unrelated RASS X-ray sources. Most identifications continue to be quasars and Seyfert 1 galaxies with 15 < m < 21 and 0.01 < z < 4, but the total sample size has grown to include very substantial numbers of even quite rare AGNs, e.g., it now includes several hundreds of candidate X-ray-emitting BL Lac objects and narrow-line Seyfert 1 galaxies. In addition to exploring rare subpopulations, such a large total sample may be useful when considering correlations between the X-ray and the optical and may also serve as a resource list from which to select the "best" object (e.g., X-ray-brightest AGN of a certain subclass at a preferred redshift or luminosity) for follow-up X-ray spectral or alternate detailed studies

Heterodyne-based hybrid controller for wide dynamic range optoelectronic frequency synthesis

Chip scale optical frequency combs using microresonators can enable a wide variety of applications from metrology to telecommunications. While tremendous progress has been made in miniaturizing the optical components, sources of variability and drift due to ambient conditions often limit their performance. We describe the design and implementation of a mixed-signal controller for optoelectronic frequency synthesis with notable frequency stability by locking it to an RF reference. A C-band tunable laser is phase-locked using commercial off the shelf components and custom board-level designs. Utilizing several laser inputs, our hybrid control loop enables a 50 nm tuning range with less than 10-12&nbsp;frequency instability for 1 second averaging. A heterodyne receiver overcomes poor SNR of the photonics, and also features a scan-and-lock algorithm to facilitate an extended acquisition range. We report &gt; 500 GHz frequency steps in 4.4 ms. All of the frequency settings and loop stability dynamics are programmable in real-time via a custom Graphical User Interface.</p

ALS-linked FUS exerts a gain of toxic function involving aberrant p38 MAPK activation

© The Author(s), 2017. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Scientific Reports 7 (2017): 115, doi:10.1038/s41598-017-00091-1.Mutations in Fused in Sarcoma/Translocated in Liposarcoma (FUS) cause familial forms of amyotrophic lateral sclerosis (ALS), a neurodegenerative disease characterized by progressive axonal degeneration mainly affecting motor neurons. Evidence from transgenic mouse models suggests mutant forms of FUS exert an unknown gain-of-toxic function in motor neurons, but mechanisms underlying this effect remain unknown. Towards this end, we studied the effect of wild type FUS (FUS WT) and three ALS-linked variants (G230C, R521G and R495X) on fast axonal transport (FAT), a cellular process critical for appropriate maintenance of axonal connectivity. All ALS-FUS variants impaired anterograde and retrograde FAT in squid axoplasm, whereas FUS WT had no effect. Misfolding of mutant FUS is implicated in this process, as the molecular chaperone Hsp110 mitigated these toxic effects. Interestingly, mutant FUS-induced impairment of FAT in squid axoplasm and of axonal outgrowth in mammalian primary motor neurons involved aberrant activation of the p38 MAPK pathway, as also reported for ALS-linked forms of Cu, Zn superoxide dismutase (SOD1). Accordingly, increased levels of active p38 MAPK were detected in post-mortem human ALS-FUS brain tissues. These data provide evidence for a novel gain-of-toxic function for ALS-linked FUS involving p38 MAPK activation.We are grateful for funding from NIH/NINDS (R01 NS078145, R01 NS090352, and R21 NS091860 to D.A.B., R01 NS066942A and R21 NS096642 to G.M., R01NS023868 and R01NS041170 to S.T.B.), the ALS Therapy Alliance/CVS Pharmacy (to D.A.B. and G.M.) and the ALS Association (to C.F. and J.M.)