DNA Origami Fiducial for Accurate 3D Atomic Force Microscopy Imaging.

Atomic force microscopy (AFM) is a powerful technique for imaging molecules, macromolecular complexes, and nanoparticles with nanometer resolution. However, AFM images are distorted by the shape of the tip used. These distortions can be corrected if the tip shape can be determined by scanning a sample with features sharper than the tip and higher than the object of interest. Here we present a 3D DNA origami structure as fiducial for tip reconstruction and image correction. Our fiducial is stable under a broad range of conditions and has sharp steps at different heights that enable reliable tip reconstruction from as few as ten fiducials. The DNA origami is readily codeposited with biological and nonbiological samples, achieves higher precision for the tip apex than polycrystalline samples, and dramatically improves the accuracy of the lateral dimensions determined from the images. Our fiducial thus enables accurate and precise AFM imaging for a broad range of applications.

Optical characterization of the on-target OMEGA focal spot at high energy using the full-beam in-tank diagnostic.

The full-beam in-tank (FBIT) diagnostic has been deployed to directly measure the target-plane beam fluence profile, when operated at high energy, of the OMEGA Laser System at the University of Rochester's Laboratory for Laser Energetics. This paper presents the results of early measurements taken with this diagnostic and discusses an improvement that has overcome performance limitations discovered during the initial testing. The diagnostic gives new insight into the ability of the OMEGA Laser System to provide uniform fluence profiles that are consistent across all 60 beams in the laser. The ultimate goal of the FBIT diagnostic is to allow accurate assessment of the fluence uniformity on a spherical target in 60-beam implosion experiments.

Quantification of the Structure of Colloidal Gas-Liquid Interfaces.

We have quantified the structure of the colloidal gas-liquid interface using synchrotron X-ray reflectivity measurements on a model colloid-polymer mixture. The interfacial width shows mean-field scaling with the colloid density difference, and the density profiles appear to be monotonic. Furthermore, our measurements allow us to distinguish between different theoretical polymer descriptions commonly used to model colloid-polymer mixtures. Our results highlight the importance of capturing the correct polymer physics in obtaining a quantitative theoretical description of the colloidal gas-liquid interface.

Tripled yield in direct-drive laser fusion through statistical modelling.

Focusing laser light onto a very small target can produce the conditions for laboratory-scale nuclear fusion of hydrogen isotopes. The lack of accurate predictive models, which are essential for the design of high-performance laser-fusion experiments, is a major obstacle to achieving thermonuclear ignition. Here we report a statistical approach that was used to design and quantitatively predict the results of implosions of solid deuterium-tritium targets carried out with the 30-kilojoule OMEGA laser system, leading to tripling of the fusion yield to its highest value so far for direct-drive laser fusion. When scaled to the laser energies of the National Ignition Facility (1.9 megajoules), these targets are predicted to produce a fusion energy output of about 500 kilojoules-several times larger than the fusion yields currently achieved at that facility. This approach could guide the exploration of the vast parameter space of thermonuclear ignition conditions and enhance our understanding of laser-fusion physics.

Power balancing the multibeam OMEGA laser.

Multibeam lasers often require an output beam balance that specifies the degree of simultaneity of the laser output energy, instantaneous power, or instantaneous irradiance (power per unit area). This work describes the general problem of balancing a multibeam laser. Specific techniques used to balance the output power of the 60-beam pulsed OMEGA Laser System are discussed along with a measured reduction of beam-to-beam imbalance. In particular, the square-pulse distortion induced by a simple saturating amplifier operating with its output at some fraction of its saturation fluence is derived, and a method to exchange gain between saturated amplifiers in a single beam that have different saturation fluences to adjust balance is described.

One-stage combined delayed bladder closure with Kelly radical soft-tissue mobilization in bladder exstrophy: preliminary results.

BACKGROUND: The radical soft-tissue mobilization (RSTM, or Kelly repair) is an anatomical reconstruction of bladder exstrophy generally performed as a second part of a two-step strategy, following successful neonatal bladder closure. OBJECTIVE: The objective of this study is to determine the feasibility of a combined procedure of delayed bladder closure and RSTM in one stage without pelvic osteotomy, in both primary and failed initial closure. DESIGN, SETTING, AND PARTICIPANTS: From 11/2015 to 01/2018, 27 bladder exstrophy patients underwent combined bladder closure with RSTM by the same surgical team at four cooperating tertiary referral centers for bladder exstrophy, including 20 primary repairs (delayed bladder closure, median age 3.0m [0.5-37m]) and seven secondary repairs after failed attempt at neonatal closure, median age 10m [8-33m]. INTERVENTION: RSTM included full mobilization of the bladder plate, urogenital diaphragm, and corpora cavernosa from the medial pelvic walls, followed by anatomical reconstruction with antireflux procedure, bladder closure, urethrocervicoplasty, muscle sphincter approximation, and penile/clitoral reconstruction. OUTCOME MEASUREMENTS: The main criteria were bladder dehiscence or prolapse. Secondary outcomes included bladder neck fistula or urethral fistula, urethral stenosis, and parietal hernia. Continence and voiding have not been addressed at this stage. RESULTS AND LIMITATIONS: All bladder exstrophy cases were successfully closed without osteotomy, with no case of bladder dehiscence after 12 m [3-30] follow-up. COMPLICATIONS: Urethral fistula or stenosis occurred in eight patients: 4/5 fistulae closed spontaneously in less than 3 months; four urethral stenoses were successfully treated with 1-3 sessions of endoscopic high-pressure balloon dilatation or meatoplasty; one patient with persistent bladder neck fistula is currently awaiting repair. Although the follow-up is short, it does allow examination of the main outcome criterion, namely bladder dehiscence, which is usually expected to happen very early after surgery. CONCLUSION: The Kelly RSTM can be safely combined with delayed bladder closure without osteotomy in both primary and redo cases in classic bladder exstrophy.

Publisher's Note: Demonstration of Fuel Hot-Spot Pressure in Excess of 50 Gbar for Direct-Drive, Layered Deuterium-Tritium Implosions on OMEGA [Phys. Rev. Lett. 117, 025001 (2016)].

This corrects the article DOI: 10.1103/PhysRevLett.117.025001.

Demonstration of Fuel Hot-Spot Pressure in Excess of 50 Gbar for Direct-Drive, Layered Deuterium-Tritium Implosions on OMEGA.

A record fuel hot-spot pressure P_{hs}=56±7 Gbar was inferred from x-ray and nuclear diagnostics for direct-drive inertial confinement fusion cryogenic, layered deuterium-tritium implosions on the 60-beam, 30-kJ, 351-nm OMEGA Laser System. When hydrodynamically scaled to the energy of the National Ignition Facility, these implosions achieved a Lawson parameter ∼60% of the value required for ignition [A. Bose et al., Phys. Rev. E 93, 011201(R) (2016)], similar to indirect-drive implosions [R. Betti et al., Phys. Rev. Lett. 114, 255003 (2015)], and nearly half of the direct-drive ignition-threshold pressure. Relative to symmetric, one-dimensional simulations, the inferred hot-spot pressure is approximately 40% lower. Three-dimensional simulations suggest that low-mode distortion of the hot spot seeded by laser-drive nonuniformity and target-positioning error reduces target performance.

A picosecond beam-timing system for the OMEGA laser.

A timing system is demonstrated for the OMEGA Laser System that guarantees all 60 beams will arrive on target simultaneously with a root mean square variability of 4 ps. The system relies on placing a scattering sphere at the target position to couple the ultraviolet light from each beam into a single photodetector.

Scaling hot-electron generation to high-power, kilojoule-class laser-solid interactions.

Thin-foil targets were irradiated with high-power (1 ≤ P(L) ≤ 210 TW), 10-ps pulses focused to intensities of I>10(18) W/cm(2) and studied with K-photon spectroscopy. Comparing the energy emitted in K photons to target-heating calculations shows a laser-energy-coupling efficiency to hot electrons of η(L-e) = 20 ± 10%. Time-resolved x-ray emission measurements suggest that laser energy is coupled to hot electrons over the entire duration of the incident laser drive. Comparison of the K-photon emission data to previous data at similar laser intensities shows that η(L-e) is independent of laser-pulse duration from 1 ≤ τ(p) ≤ 10 ps.

Demonstration of large-aperture tiled-grating compressors for high-energy, petawatt-class, chirped-pulse amplification systems.

Two large-aperture tiled-grating (1.5 m) compressors, each consisting of four sets of tiled-grating assemblies, have been built for the OMEGA EP high-energy petawatt-class laser system. The techniques used for tiling individual tiled-grating assemblies and for optimizing the overall performance of a tiled-grating compressor are described. Both compressors achieved subpicosecond pulse duration without tiling-induced temporal degradation. A ray-tracing model predicted that the static wavefront of the grating tiles dominated focal-spot degradations when submicroradian tiling accuracy is achieved. The tiled-grating compressors delivered a tighter focal spot compared with subaperture grating compressors with single central tiles.

High-contrast plasma-electrode Pockels cell.

A plasma-electrode Pockels cell (PEPC) has been developed for use on the OMEGA extended performance (EP) laser system that can be used in a high-contrast optical switch, as required for isolation of the system from retroreflected pulses. Contrast ratios reliably exceeded 500:1 locally everywhere in the clear aperture. The key to achieving this improvement was the use of circular windows simply supported on compliant O rings, which is shown to produce very low stress-induced birefringence despite vacuum loading. Reliable operation was achieved operating at a relatively high operating pressure, low operating pressures being found to be strongly correlated to occurrences of local loss of plasma density.

Large-aperture grating tiling by interferometry for petawatt chirped-pulse-amplification systems.

A tiled-grating assembly with three large-scale gratings is developed with real-time interferometric tiling control for the OMEGA EP Laser Facility. An automatic tiling method is achieved and used to tile a three-tile grating assembly with the overall wavefront reconstructed. Tiling-parameters sensitivity and focal-spot degradation from all combined tiling errors are analyzed for a pulse compressor composed of four such assemblies.

Precision spectral sculpting for narrow-band amplification of broadband frequency-modulated pulses.

Amplification of broadband frequency-modulated (FM) pulses in high-efficiency materials such as ytterbium-doped strontium fluorapatite results in significant gain narrowing, leading to reduced on-target bandwidths for beam smoothing and to conversion from frequency modulation to amplitude modulation (AM). To compensate for these effects, we have applied precision spectral sculpting, requiring both amplitude and phase shaping, to the amplification of broadband FM pulses in narrow-band gain media. We have demonstrated sculpting for centerline small-signal gains of 10(4), producing amplified pulses that have both sufficient bandwidths for on-target beam smoothing and temporal profiles that have no potentially damaging AM.

A fluorescent cell-based assay for cytochrome P-450 isozyme 1A2 induction and inhibition.

High throughput lead optimization requires simple, homogeneous cell-based assays capable of defining the druglike properties of first-round screening hits. Induction and inhibition of the Phase I drug-metabolizing enzymes are central to this process. We report here an assay for induction and inhibition of cytochrome P-450 (CYP) isozyme 1A2 that meets these requirements. It utilizes HepG2/C3A, a human liver cell line, and ethoxyresorufin. Using methylcholanthrene, CYP1A2 can be induced dramatically, and it is inhibited by furafylline, a mechanism-based inhibitor of this enzyme.

Management of upper esophageal sphincter disorders: indications and complications of myotomy.

Since 1951, when it was first used as a treatment for post-poliomyelitis dysphagia, cricopharyngeal myotomy (CPM) has been used in the treatment of various neurogenic, myogenic, structural, and idiopathic disorders. Yet, the efficacy of CPM in treating patients with upper esophageal sphincter (UES) disorders remains controversial. Despite favorable reports regarding its success, too few studies about indications, complications, and outcomes of CPM have been conducted to quell the controversy. Swallowing is accomplished when three primary conditions exist: (1) the cricopharyngeus muscle (CP) relaxes--that is, it is not tonically contracted, (2) the laryngo-hyoid complex elevates in an anterior-superior direction to open the sphincter, and (3) pharyngeal pressure is sufficient to propel a bolus through the open sphincter. CPM is indicated when the second and third conditions are "adequate" but the first is inadequate, thus resulting in pharyngeal dysphagia associated with a defective opening of the UES. UES dysfunction is determined most often through patient history, physical examination, and testing. Patients with Zenker's (pharyngoesophageal) diverticulum, oculopharyngeal dystrophy, or inclusion body myositis are among those reported to have the most positive responses to CPM. Modified barium swallow is the most common measurement of UES dysfunction; manometry also is used, but to a lesser degree because of catheter motion during swallowing. There are four approaches to CPM, including: (1) the external technique, which is indicated when a muscle biopsy or neck exploration is needed; (2) the endoscopic approach, which is reported to work best with patients with Zenker's diverticulum and offers the choice of electrocautery, laser, or the surgical stapler--the last option being the best choice for high-risk patients; (3) balloon dilatation of the UES, a low-risk option that reportedly works best in patients with fibrosis of the CP; and (4) botulinum toxin injection of the CP transcervically or endoscopically, which offers low risk and minimal or no anesthesia. This approach best serves cases of failed relaxation of the CP. Each approach has potential complications, but reports of such are few and rarely severe. In all cases, massive reflux should be controlled before CPM and the patient should be medically stable. Patient selection for CPM remains inadequate. To assess the efficacy of CPM, more multi-institutional outcome studies need to be conducted. In the meanwhile, clinical judgment and selective testing via modified barium swallow are the best methods for identifying patients who may derive the most benefit from CPM.

Balanitis xerotica obliterans with urethral stricture after hypospadias repair.

Three cases of urethral stricture due to balanitis xerotica obliterans (BXO) after hypospadias repair are reported. The first patient showed white, dense scarring on the prepuce before the hypospadias repair and developed a stricture of the urethra after the operation. The second and the third were uneventful for 6 and 2 years, respectively, after the hypospadias repair, and then developed urethral strictures. Pathologic diagnosis of the stenotic lesion is essential. Complete excision of the affected urethra with topical steroid ointment or sublesional triamcinolone injection is recommended for this condition. Although the complication of BXO after hypospadias repair is rare (3 out of 796 cases with hypospadias in our series), surgeons need to be aware of this condition as a cause for late onset of urethral problems.

Current evaluation and treatment of patients with swallowing disorders.

To determine the varied causes of oropharyngeal dysphagia and their respective pathophysiology, a working understanding of the normal anatomy and function of the highly integrated mechanism of swallowing is outlined. This information is presented as the basis for a reasoned and detailed approach to the history, physical examination, and endoscopic evaluation of normal and altered oropharyngeal swallowing. The management of swallowing disorders depends on the nature and magnitude of the responsible clinical condition. Conservative and surgical approaches are discussed. These modalities and their indications are described in detail.