R. H. Miller

The Stanford linear accelerator polarized electron source

The Stanford 3-km linear accelerator at SLAC has operated exclusively since early 1992 using a polarized electron beam for its high-energy physics programs. The polarized electron source now consists of a diode-type gun with a strained-lattice GaAs photocathode DC biased at high voltage and excited with circularly polarized photons generated by a pulsed, Ti:sapphire laser system. The electron polarization at the source is > 80%. To date the source has met all the beam requirements of the SLC and fixed target programs with < 5% downtime.

Hepatitis B virus DNA forms in nuclear and cytoplasmic fractions of infected human liver

Human liver tissues obtained at autopsy from two patients chronically infected with hepatitis B virus (HBV) were found to contain several distinct species of HBV DNA. Southern blot analysis using a nick-translated HBV [32P]DNA probe identified specific DNA bands migrating at the positions expected for linear double-stranded DNA of 3.6 and 2.0 kb. These DNA bands were shown to represent relaxed circular and closed circular (supercoiled) HBV DNA, respectively. In addition to these distinct bands several minor bands as well as a heterogeneous population of HBV DNA molecules were present. When infected cell nuclei were isolated, and the nuclear and cytoplasmic nucleic acid separately analyzed, the nuclear fraction contained the 2.0-kb DNA species. This species was shown to be supercoiled 3.2-kb HBV DNA by electron microscopy, restriction endonuclease digestion, and thermal denaturation. The cytoplasmic fraction contained DNA forms similar to those found in virions isolated from plasma (i.e., migration in the position of linear double-stranded molecules of 3.6 and 3.2 kb) and no supercoiled DNA was detected. Particles isolated from the cytoplasmic fraction were able to incorporate dNTPs into viral DNA sequences. Southern blot analysis of the nucleic acid isolated from the particles revealed the presence of HBV DNA forms migrating in positions expected for 3.6- and 3.2-kb linear double-stranded molecules as well as a heterogeneous population of HBV molecules. The 3.6- and 3.2-kb species were identified as relaxed circular and double-stranded linear genome-length HBV DNA. Digestion of the viral nucleic acid with pancreatic ribonuclease increased the electrophoretic mobility of a portion of the heterogeneous HBV molecules and resulted in the appearance of a distinct 1.9-kb DNA band suggesting the same viral DNA was complexed with RNA. Experiments to be reported elsewhere showed this DNA species to be genome-length minus-strand HBV DNA which was released from DNA-RNA hybrid molecules by RNase digestion. Thus, supercoiled HBV DNA exists free in the nucleus of infected liver cells and cytoplasmic particles contain relaxed circular and linear HBV DNA as well as a heterogeneous population of HBV DNA and DNA-RNA hybrid molecules, and a DNA polymerase reaction in the particles results in incorporation of dNTP into DNA strands of these molecules.

Research and development toward a 4.5−1.5 Å linac coherent light source (LCLS) at SLAC

Abstract In recent years significant studies have been initiated on the feasibility of utilizing a portion of the 3 km S-band accelerator at SLAC to drive a short wavelength (4.5−1.5 A) Linac Coherent Light Source (LCLS), a Free-Electron Laser (FEL) operating in the Self-Amplified Spontaneous Emission (SASE) regime. Electron beam requirements for single-pass saturation in a minimal time include: 1) a peak current in the 7 kA range, 2) a relative energy spread of e = λ 4π , where λ[m] is the output wavelength. Requirements on the insertion device include field error levels of 0.02% for keeping the electron bunch centered on and in phase with the amplified photons, and a focusing beta of 8 m/rad for inhibiting the dilution of its transverse density. Although much progress has been made in developing individual components and beam-processing techniques necessary for LCLS operation down to ∼20 A, a substantial amount of research and development is still required in a number of theoretical and experimental areas leading to the construction and operation of a 4.5−1.5 A LCLS. In this paper we report on a research and development program underway and in planning at SLAC for addressing critical questions in these areas. These include the construction and operation of a linac test stand for developing laser-driven photocathode rf guns with normalized emittances approaching 1 mm-mrad; development of advanced beam compression, stability, and emittance control techniques at multi-GeV energies; the construction and operation of a FEL Amplifier Test Experiment (FATE) for theoretical and experimental studies of SASE at IR wavelengths; an undulator development program to investigate superconducting, hybrid/permanent magnet (hybrid/PM), and pulsed-Cu technologies; theoretical and computational studies of high-gain FEL physics and LCLS component designs; development of X-ray optics and instrumentation for extracting, modulating, and delivering photons to experimental users; and the study and development of scientific experiments made possible by the source properties of the LCLS.

Hepatitis B viral DNA-RNA hybrid molecules in particles from infected liver are converted to viral DNA molecules during an endogenous dna polymerase reaction

Particles purified from the liver of hepatitis B virus-infected patients were previously shown by us to incorporate 32P-deoxynucleotides into viral DNA and DNA-RNA hybrid molecules when incubated in a DNA polymerase reaction mixture. In this investigation, similar particles from duck and ground squirrel livers infected with viruses closely related to HBV were also shown to incorporate 32P-deoxynucleotides into viral-specific DNA and DNA-RNA hybrid molecules when incubated in vitro in a DNA polymerase reaction mixture. The particles from duck hepatitis B virus-infected liver contained a heterogeneous population of hybrid molecules, while those from ground squirrel hepatitis virus-infected liver contained hybrid molecules with densities similar to those found in HBV particles including a distinct population of molecules with an average density of 1.57 g/cm3. Brief endogenous DNA polymerase reactions with particles from all three livers, resulted in incorporation of 32P-deoxynucleotides into viral DNA of DNA-RNA hybrid as well as viral DNA molecules. When the reaction was continued in the presence of a 1000-fold molar excess of unlabeled deoxynucleotides, a decrease in [32P]DNA in the DNA-RNA hybrid region of the Cs2SO4 density gradient and a proportional increase in [32P]DNA in the DNA region of the gradient was observed. This effect was seen most dramatically with particles isolated from freshly obtained ground squirrel hepatitis virus-infected livers in which 90% of the pulse labeled DNA in the hybrid species at the buoyant density of 1.57 g/cm3 appeared to be converted to a form with the buoyant density of pure DNA (1.42 g/cm3). Storage of virus particles at 4 degrees, or prior freezing of infected ground squirrel liver almost completely abolished the ability of the endogenous DNA polymerase activity to incorporate 32P-deoxynucleotides into hybrid molecules, while incorporation into DNA molecules was apparently unaffected. These results suggest that different enzymatic activities catalyze synthesis of the viral DNA in DNA-RNA hybrids and in molecules with buoyant density of pure DNA. Thus particles from infected liver synthesize DNA of DNA-RNA hybrid molecules which can be converted in the particles into molecules with the buoyant density of pure DNA. This indicates that DNA-RNA hybrids may be intermediates in viral DNA replication and that the mechanism of hepatitis B virus (and closely related viruses of ground squirrels and ducks) DNA replication differs from that known for other DNA viruses.

A High Current, Short Pulse, RF Synchronized Electron Gun for the Stanford Linear Accelerator

For the generation of intense single and multiple bunches of electrons (>8 nc per bunch) for accelerator studies at SLAC, a high peak current photoemission electron gun has been developed. A gallium arsenide photocathode is illuminated by the optical beam from a frequency doubled, actively mode-locked and Q-switched Nd:YAG laser. The mode-locked optical pulses are of variable, sub-nanosecond width and occur with a spacing of 8.4 nsec, synchronized with the 2856 MHz accelerator rf. The gun is designed to be space charge limited at 15 A and 200 kV, although emission of 60 A was obtained with a 57 kV test structure, corresponding to a current density of 180 A/cm2. With the proper choice of laser wavelength, the electron beam may be 40% longitudinally polarized.

A multi-moded rf delay line distribution system for the next linear collider

The Delay Line Distribution System (DLDS) is an alternative to conventional pulse compression, which enhances the peak power of rf sources while matching the long pulse of those sources to the shorter filling time of accelerator structures. We present an implementation of this scheme that combines pairs of parallel delay lines of the system into single lines. The power of several sources is combined into a single waveguide delay line using a multi-mode launcher. The output mode of the launcher is determined by the phase coding of the input signals. The combined power is extracted from the delay line using mode-selective extractors, each of which extracts a single mode. Hence, the phase coding of the sources controls the output port of the combined power. The power is then fed to the local accelerator structures. We present a detailed design of such a system, including several implementation methods for the launchers, extractors, and ancillary high power rf components. The system is designed so that it can handle the 600 MW peak power required by the NLC design while maintaining high efficiency.

Hepatitis B virus particles of plasma and liver contain viral DNA-RNA hybrid molecules

Hepatitis B virions in plasma (Dane particles) are known to contain small circular DNA molecules. The experiments described here indicate that virions in plasma, as well as particles from hepatitis B virus-infected human liver, also contain viral DNA-RNA hybrid molecules, and deoxynucleotides can be incorporated into the DNA of these hybrids by DNA polymerase activities in the virions. Thus, two viral DNA synthetic reactions appear to take place in virions: repair of the single-stranded region of circular DNA molecules and synthesis or elongation of the DNA strand of DNA-RNA hybrid molecules. Centrifugation of virion nucleic acid to equilibrium in Cs2SO4 density gradients revealed the presence of viral DNA-RNA hybrid molecules over a density range of 1.45 to 1.60 g/cm3. Distinct species of hybrid molecules were found with an average density of 1.57 g/cm3 in Dane particles and 1.52 and 1.57 g/cm3 in particles from liver. Fractionation of nucleic acid from Cs2SO4 density gradients by gel electrophoresis demonstrated that the majority of hybrid molecules migrated faster than molecules with the density of pure DNA (1.42 g/cm3). One notable exception was the finding of DNA-RNA hybrid molecules migrating slower than open circular viral DNA. Characterization of viral DNA-RNA hybrids by heat denaturation Cs2SO4 density gradient fractionation, and recombinant M13-HBV single-stranded probe hybridization revealed that the hybrid molecules consisted of viral plus-strand RNA hydrogen bonded to viral minus-strand DNA sequences. Data obtained by pancreatic ribonuclease digestion revealed that the hybrid molecules at density 1.45 to 1.52 g/cm3 contained HBV RNA strands base paired over only part of their length in contrast to the hybrid species at density 1.57 g/cm3 which contained RNA strands apparently base paired over most of their length. Further characterization showed that the hybrid at 1.57 g/cm3 contained genome-length minus-strand viral DNA. The experiments rule out the possibility that the hybrid molecules are transcriptional complexes. Data presented in a companion manuscript indicate that the hybrid molecules may represent intermediates in the synthesis of viral DNA in the endogenous DNA polymerase reaction.

Microwave measurements of the BNL/SLAC/UCLA 1.6 cell photocathode RF gun

The longitudinal accelerating field E/sub z/ has been measured as a function of azimuthal angle in the full cell of the cold test model for the 1.6 cell BNL/SLAC/UCLA 3 S-band RF gun using a needle rotation/frequency perturbation technique. These measurements were conducted before and after symmetrizing the full cell with a vacuum pump out port and an adjustable short. Two different waveguide to full cell coupling schemes were studied. The dipole mode of the full cell is an order of magnitude less severe before symmetrization for the /spl theta/-coupling scheme. The multi-pole contribution to the longitudinal field asymmetry are calculated using standard Fourier series techniques. The Panofsky-Wenzel theorem is used in estimating the transverse emittance due to the multipole components of E/sub z/.

The Slac Injector

The injector for the Stanford Two-Mile Linear Accelerator has been designed to achieve optimum bunching, optimum beam optics and flexible operational control of beam parameters. A test injector has achieved 5-degree bunching and 10-2 mc-cm area in the X-PX plane.

Portable, X-Band, Linear Accelerator Systems

Three light-weight, x-band, electron accelerators have been developed to provide a series of highly portable sources of x-rays and neutrons for nondestructive testing. The 1.5 MeV x-ray unit has a 200 kW magnetron for an RF source and an air-cooled, traveling wave accelerating structure to minimize Its weight. The 4 and 6 MeV units share the same drive system which contains a 1.2 MW magnetron. The 4 MeV unit uses a traveling-wave guide to produce x-rays and the 6MeV unit uses a standing-wave guide to produce x-rays or neutrons. The choice of 9.3 GHz was dictated by the availability of a high power coaxial magnetron and by the obvious dimensional and weight advantages of a higher frequency over the more common S-band frequencies around 3 GHz.