Signal, noise and resolution in linear and nonlinear structured-illumination microscopy.

Structured-illumination microscopy allows widefield fluorescence imaging with resolution beyond the classical diffraction limit. Its linear form extends resolution by a factor of two, and its nonlinear form by an in-principle infinite factor, the effective resolution in practice being determined by noise. In this paper, we analyse the noise properties and achievable resolution of linear and nonlinear 1D and 2D patterned SIM from a frequency-space perspective. We develop an analytical theory for a general case of linear or nonlinear fluorescent imaging, and verify the analytical calculations with numerical simulation for a special case where nonlinearity is produced by photoswitching of fluorescent labels. We compare the performance of two alternative implementations, using either two-dimensional (2D) illumination patterns or sequentially rotated one-dimensional (ID) patterns. We show that 1D patterns are advantageous in the linear case, and that in the nonlinear case 2D patterns provide a slight signal-to-noise advantage under idealised conditions, but perform worse than 1D patterns in the presence of nonswitchable fluorescent background. LAY DESCRIPTION: Structured-illumination microscopy (SIM) is a high-resolution light microscopy technique that allows imaging of fluorescence at a resolution about twice the classical diffraction limit. There are various ways that the illumination can be structured, but it is not obvious how the choice of illumination pattern affects the final image quality, especially in view of the noise. We present a detailed performance analysis considering two illumination techniques: sequential illumination with line-gratings that are shifted and rotated during image acquisition and two-dimensional (2D) illumination structures requiring only shift operations. Our analysis is based on analytical theory, supported by simulations of images considering noise. We also extend our analysis to a nonlinear variant of SIM, with which enhanced resolution can be achieved, limited only by noise. This includes nonlinear SIM based on the light-induced switching of the fluorescent molecules between a bright and a dark state. We find sequential illumination with line-gratings to be advantageous in ordinary (linear) SIM, whereas 2D patterns provides a slight signal-to-noise advantage under idealised conditions in nonlinear SIM if there is no nonswitching background.

Ultrafast transitions from solid to liquid and plasma states of graphite induced by x-ray free-electron laser pulses.

We used photon pulses from an x-ray free-electron laser to study ultrafast x-ray-induced transitions of graphite from solid to liquid and plasma states. This was accomplished by isochoric heating of graphite samples and simultaneous probing via Bragg and diffuse scattering at high time resolution. We observe that disintegration of the crystal lattice and ion heating of up to 5 eV occur within tens of femtoseconds. The threshold fluence for Bragg-peak degradation is smaller and the ion-heating rate is faster than current x-ray-matter interaction models predict.

Quantifying electron temperature distributions from time-integrated x-ray emission spectra.

K-shell x-ray emission spectroscopy is a standard tool used to diagnose the plasma conditions created in high-energy-density physics experiments. In the simplest approach, the emissivity-weighted average temperature of the plasma can be extracted by fitting an emission spectrum to a single temperature condition. It is known, however, that a range of plasma conditions can contribute to the measured spectra due to a combination of the evolution of the sample and spatial gradients. In this work, we define a parameterized model of the temperature distribution and use Markov Chain Monte Carlo sampling of the input parameters, yielding uncertainties in the fit parameters to assess the uniqueness of the inferred temperature distribution. We present the analysis of time-integrated S and Fe x-ray spectroscopic data from the Orion laser facility and demonstrate that while fitting each spectral region to a single temperature yields two different temperatures, both spectra can be fit simultaneously with a single temperature distribution. We find that fitting both spectral regions together requires a maximum temperature of 1310-70 +90 eV with significant contributions from temperatures down to 200 eV.

Interaction of short x-ray pulses with low-Z x-ray optics materials at the LCLS free-electron laser.

Materials used for hard x-ray-free-electron laser (XFEL) optics must withstand high-intensity x-ray pulses. The advent of the Linac Coherent Light Source has enabled us to expose candidate optical materials, such as bulk B4C and SiC films, to 0.83 keV XFEL pulses with pulse energies between 1 µJ and 2 mJ to determine short-pulse hard x-ray damage thresholds. The fluence required for the onset of damage for single pulses is around the melt fluence and slightly lower for multiple pulses. We observed strong mechanical cracking in the materials, which may be due to the larger penetration depths of the hard x-rays.

Non-thermal desorption/ablation of molecular solids induced by ultra-short soft x-ray pulses.

We report the first observation of single-shot soft x-ray laser induced desorption occurring below the ablation threshold in a thin layer of poly (methyl methacrylate)--PMMA. Irradiated by the focused beam from the Free-electron LASer in Hamburg (FLASH) at 21.7 nm, the samples have been investigated by atomic-force microscope (AFM) enabling the visualization of mild surface modifications caused by the desorption. A model describing non-thermal desorption and ablation has been developed and used to analyze single-shot imprints in PMMA. An intermediate regime of materials removal has been found, confirming model predictions. We also report below-threshold multiple-shot desorption of PMMA induced by high-order harmonics (HOH) at 32 nm. Short-time exposure imprints provide sufficient information about transverse beam profile in HOH's tight focus whereas long-time exposed PMMA exhibits radiation-initiated surface ardening making the beam profile measurement infeasible.

Measurement of Laser-Plasma Electron Density with a Soft X-ray Laser Deflectometer.

A soft x-ray laser (wavelength lambda = 15.5 nanometers) was used to create a moiré deflectogram of a high-density, laser-produced plasma. The use of deflectometry at this short wavelength permits measurement of the density spatial profile in a long-scalelength (3 millimeters), high-density plasma. A peak density of 3.2 x 10(21) per cubic centimeter was recorded.

Molecular dynamics simulations of temperature equilibration in dense hydrogen.

The temperature equilibration rate between electrons and protons in dense hydrogen has been calculated with molecular dynamics simulations for temperatures between 10 and 600eV and densities between 10;{20}cm;{-3}to10;{24}cm;{-3} . Careful attention has been devoted to convergence of the simulations, including the role of semiclassical potentials. We find that for Coulomb logarithms L greater, similar1 , a model by Gericke-Murillo-Schlanges (GMS) [D. O. Gericke, Phys. Rev. E 65, 036418 (2002)] based on a T -matrix method and the approach by Brown-Preston-Singleton [L. S. Brown, Phys. Rep. 410, 237 (2005)] agrees with the simulation data to within the error bars of the simulation. For smaller Coulomb logarithms, the GMS model is consistent with the simulation results. Landau-Spitzer models are consistent with the simulation data for L>4 .

Characteristics of focused soft X-ray free-electron laser beam determined by ablation of organic molecular solids.

A linear accelerator based source of coherent radiation, FLASH (Free-electron LASer in Hamburg) provides ultra-intense femtosecond radiation pulses at wavelengths from the extreme ultraviolet (XUV; lambda<100nm) to the soft X-ray (SXR; lambda<30nm) spectral regions. 25-fs pulses of 32-nm FLASH radiation were used to determine the ablation parameters of PMMA - poly (methyl methacrylate). Under these irradiation conditions the attenuation length and ablation threshold were found to be (56.9+/-7.5) nm and approximately 2 mJ*cm(-2), respectively. For a second wavelength of 21.7 nm, the PMMA ablation was utilized to image the transverse intensity distribution within the focused beam at mum resolution by a method developed here.

Beyond the gain exponent: Effect of damping, scale length, and speckle length on stimulated scatter.

Three-dimensional wave propagation simulations and experiments show that the gain exponent, an often used metric to assess the likelihood of stimulated Brillouin scatter, is insufficient and must be augmented with another parameter, Nr, the ratio of the resonance length, Lres, to the laser speckle length. The damping rate of ion acoustic waves, ν, and thus Lres, which is proportional to ν, are easily varied with plasma species composition, e.g., by varying the ratio of hydrogen and carbon ions. As Nr decreases, stimulated Brillouin scattering increases despite the same gain exponent.

Immersion anesthesia for extracorporeal shock wave lithotripsy. Review of two hundred twenty treatments.

Two hundred twenty extracorporeal shockwave lithotripsy (ESWL) treatments at the New York Hospital-Cornell Medical Center between September, 1984, and April, 1985, were reviewed with respect to anesthetic management. One hundred seventy-four treatments (79%) were performed under a regional anesthetic technique (RA), either with an indwelling epidural catheter (155 treatments), or with a single spinal injection (19 treatments). Forty-six treatments (21%) were performed under general anesthesia (GA). Ninety per cent of the patients were classified as ASA I or II. Hypotension during treatment, defined as blood pressure falls greater than 20 per cent of baseline mean arterial pressure, was recorded with 19.5 per cent of the regional anesthetic treatments (18.7% of the epidurals and 26.3% of the spinals) and 13.0 per cent of the general anesthetic treatments. Blood pressure falls were larger in the regional group than in the general group. The average recovery room stay was longer for the bupivacaine (0.25-0.5%) epidurals and the tetracaine (0.4%) spinals (252 min and 212.1 min, respectively) than for the lidocaine (1.5-2.0%) epidurals and the general anesthetics (101.7 min and 102.1 min, respectively). General anesthesia, with controlled ventilation, was advantageous in minimizing renal excursion and stone movement during treatment. Yet, in appropriately selected and sedated patients, regional anesthesia with continuous lidocaine epidural techniques was found to provide acceptable anesthesia for patients undergoing ESWL.

Experimental and computational laser tissue welding using a protein patch.

An in vitro study of laser tissue welding mediated with a dye-enhanced protein patch was conducted. Fresh sections of porcine aorta were used for the experiments. Arteriotomies were treated using an indocyanine green dye-enhanced collagen patch activated by an 805-nm continuous-wave fiber-delivered diode laser. Temperature histories of the surface of the weld site were obtained using a hollow glass optical fiber-based two-color infrared thermometer. The experimental effort was complemented by simulations with the LATIS (LAser-TISsue) computer code, which uses coupled Monte Carlo, thermal transport, and mass transport models. Comparison of simulated and experimental thermal data indicated that evaporative cooling clamped the surface temperature of the weld site below 100 °C. For fluences of approximately 200 J/cm2, peak surface temperatures averaged 74°C and acute burst strengths consistently exceeded 0.14×106 dyn/cm (hoop tension). The combination of experimental and simulation results showed that the inclusion of water transport and evaporative losses in the computer code has a significant impact on the thermal distributions and hydration levels throughout the tissue volume. The solid-matrix protein patch provided a means of controllable energy delivery and yielded consistently strong welds. © 1998 Society of Photo-Optical Instrumentation Engineers.

State abortion rates. The impact of policies, providers, politics, demographics, and economic environment.

This paper uses data on abortion rates by state from 1974-1988 to estimate two-stage least squares models with fixed state and year effects. Restrictions on Medicaid funding for abortion are correlated with lower abortion rates in-state and higher rates among nearby states. A maximal estimate suggests that 19-25% of the abortions among low-income women that are publicly funded do not take place after funding is eliminated. Parental notification laws for teen abortions do not significantly affect aggregate abortion rates. A larger number of abortion providers in a state increases the abortion rate, primarily through inducing cross-state travel.

Temperature distribution for combined laser hyperthermia-photodynamic therapy in the esophagus.

In recent years photodynamic laser therapy (PDT) has been tested in animal and clinical studies for treatment of esophageal cancer. In several animal experiments a synergistic effect was found by simultaneously applying PDT and hyperthermia (HT). In this paper an optical fibre system is described which can be used in the esophagus for combined PDT with a 1 W dye laser and HT with a 15 W Nd:YAG laser. A phantom was built simulating the geometry of the esophagus using cow muscle. The spatial temperature field during HT was measured versus irradiation time. The results were compared with calculations using a coupled Monte Carlo laser transport/finite difference heat transport model using the LATIS computer program. Measurements and calculations yield a realistic description of the temperature distribution during HT under various experimental conditions. The LATIS program allows the prediction of the effects of blood perfusion for in vivo situations. The results show that perfusion has considerable influence on the temperature field, reducing the effective depth in tissue for HT.

X-ray bang-time and fusion reaction history at picosecond resolution using RadOptic detection.

We report recent progress in the development of RadOptic detectors, radiation to optical converters, that rely upon x-ray absorption induced modulation of the optical refractive index of a semiconductor sensor medium to amplitude modulate an optical probe beam. The sensor temporal response is determined by the dynamics of the electron-hole pair creation and subsequent relaxation in the sensor medium. Response times of a few ps have been demonstrated in a series of experiments conducted at the LLNL Jupiter Laser Facility (JLF). This technology will enable x-ray bang-time and fusion burn-history measurements with ∼ ps resolution.

Soft x-ray images of the laser entrance hole of ignition hohlraums.

Hohlraums are employed at the national ignition facility to convert laser energy into a thermal x-radiation drive, which implodes a fusion capsule, thus compressing the fuel. The x-radiation drive is measured with a low spectral resolution, time-resolved x-ray spectrometer, which views the region around the hohlraum's laser entrance hole. This measurement has no spatial resolution. To convert this to the drive inside the hohlraum, the size of the hohlraum's opening ("clear aperture") and fraction of the measured x-radiation, which comes from this opening, must be known. The size of the clear aperture is measured with the time integrated static x-ray imager (SXI). A soft x-ray imaging channel has been added to the SXI to measure the fraction of x-radiation emitted from inside the clear aperture. A multilayer mirror plus filter selects an x-ray band centered at 870 eV, near the peak of the x-ray spectrum of a 300 eV blackbody. Results from this channel and corrections to the x-radiation drive are discussed.

Amplification of light in a plasma by stimulated ion acoustic waves driven by multiple crossing pump beams.

Experiments demonstrate the amplification of 351 nm laser light in a hot dense plasma similar to those in inertial confinement fusion ignition experiments. A seed beam interacts with one or two counter-propagating pump beams, each with an intensity of 1.2×10(15) W/cm2 at 351 nm, crossing the seed at 24.8° at the position where the flow is Mach 1, allowing resonant stimulation of ion acoustic waves. Results show that the energy and power transferred to the seed are increased with two pumps beyond the level that occurs with a single pump, demonstrating that, under conditions similar to ignition experiments where each beam has a low gain exponent, the total scatter produced by the multiple beams can be significantly larger than that of the individual beams. It is further demonstrated that the amplification is greatly reduced when the pump polarization is orthogonal to the seed, as expected from models of stimulated scatter.

Design and measurement of a Cu L-edge x-ray filter for free electron laser pumped x-ray laser experiments.

An inner-shell photoionized x-ray laser pumped by the Linac Coherent Light Source (LCLS) free electron laser has been proposed recently. The measurement of the on-axis 849 eV Ne Kα laser and protection of the x-ray spectrometer from damage require attenuation of the 1 keV LCLS beam. An Al/Cu foil combination is well suited, serving as a low energy bandpass filter below the Cu L-edge at 933 eV. A high resolution grating spectrometer is used to measure the transmission of a candidate filter with an intense laser-produced x-ray backlighter developed at the Lawrence Livermore National Laboratory Jupiter Laser Facility Janus. The methodology and discussion of the observed fine structure above the Cu L-edge will be presented.

Observation of the density threshold behavior for the onset of stimulated Raman scattering in high-temperature hohlraum plasmas.

We show that the measured stimulated Raman scattering (SRS) in a large-scale high-temperature plasma scales strongly with the plasma density, increasing by an order of magnitude when the electron density is increased by 20%. This is consistent with linear theory, including pump depletion, in a uniform plasma and, as the density is typically constrained by other processes, this effect will set a limit on drive laser beam intensity for forthcoming ignition experiments at the National Ignition Facility. Control of SRS at laser intensities consistent with 285 eV ignition hohlraums is achieved by using polarization smoothing which increases the intensity threshold for the onset of SRS by 1.6 +/- 0.2. These results were quantitatively predicted by full beam three-dimensional numerical laser-plasma interaction simulations.

Direct measurements of an increased threshold for stimulated brillouin scattering with polarization smoothing in ignition hohlraum plasmas.

We demonstrate a significant reduction of stimulated Brillouin scattering by polarization smoothing in large-scale high-temperature hohlraum plasma conditions where filamentation is measured to be negligible. The stimulated Brillouin scattering experimental threshold (defined as the intensity at which 5% of the incident light is backscattered) is measured to increase by a factor of 1.7+/-0.2 when polarization smoothing is applied. An analytical model relevant to inertial confinement fusion plasma conditions shows that the measured reduction in backscatter with polarization smoothing results from the random spatial variation in polarization of the laser beam, not from the reduction in beam contrast.