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The compact linear accelerator for research and applications (CLARA) is an ultrabright electron beam test facility being developed at STFC Daresbury Laboratory. The ultimate aim of CLARA is to test advanced free electron laser (FEL) schemes that can later be implemented on existing and future short-wavelength FELs. In addition, CLARA is a unique facility to provide a high-quality electron beam to test novel concepts and ideas in a wide range of disciplines and to function as a technology demonstrator for a future United Kingdom x-ray FEL facility. CLARA is being built in three phases; the first phase, or front end (FE), comprises an S-band rf photoinjector, a linac, and an S-bend merging with the existing versatile electron linear accelerator beam line; the second phase will complete the acceleration to full beam energy of 250 MeV and also incorporate a separate beam line for use of electrons at 250 MeV; and the third phase will include the FEL section. The CLARA FE was commissioned during 2018, and the facility was later made available for user experiments. Significant advancements have been made in developing high-level software and a simulation framework for start-to-end simulations. The high-level software has been successfully used for unmanned rf conditioning and for characterization of the electron beam. This paper describes the design of the CLARA FE, performance of technical systems, high-level software developments, preliminary results of measured beam parameters, and plans for improvements and upgrades. © 2020 authors. Published by the American Physical Society.

A design concept for a soft X-ray monochromator that can preserve the length of a FEL pulse at the femtosecond level is presented. The design is based around a plane diffraction grating in a classical mount operating in collimated light. Designing the beamline requires a thorough knowledge of the source behaviour, which is achieved by wavefront propagation of the simulations of the FEL output. The effect on the spectral filtering on the pulse profile has been explored and is found to improve the contrast ratio without significantly reducing the peak power.

A high resolution online grating spectrometer has been set up at the free electron laser in Hamburg FLASH at DESY in Hamburg. This new photon diagnostic device allows to parasitically measure the spectral distribution of the FEL laser pulses on a single shot basis and therefore gives complementary spectral and temporal pulse information for user experiments and FEL operation. The spectrometer combines a plane mirror and two plane variable line spacing (VLS) gratings and is installed at the non-monochromized beamline branch at FLASH. In contrast to a standard grating the blaze angle is optimized for the zero-order radiation transferred to the experimental stations, leaving approximately 1–10% intensity for recording the wavelength in the spectrometer. The detector, an intensified CCD camera imaging the dispersed beam on a Ce:YAG crystal, can follow the focal plane of the gratings covering a wavelength ranging from 6 to 60 nm. The resolving power of the spectrometer is expected to range from 500 to 8000 depending on the FEL wavelength.

The use of a grating monochromator on a soft X-ray FEL source raises concerns about the induced pulse stretch because a diffraction grating stretches the pulse due to the optical path difference along the illuminated length. This paper describes a method for controlling the pulse stretch by matching the grating angles to the properties of the source, so that the illuminated footprint is defined. The source properties are deduced by wavefront propagation of simulations of the FEL output. The pulse stretch can be kept to about 10 fs RMS from 250 to 850 eV. The monochromator uses a single grating in the classical mount and gives high efficiency combined with flexibility to permit other operation modes such as high spectral resolving power. The gratings must be of very low line density to work at 250 eV with such low pulse stretch.

We report the use of soft X-ray resonant reflectivity at the Fe M 2,3 edges to probe the magnetic circular dichroism of non-stoichiometric Fe 3− δ O 4 thin films grown epitaxially on Al 2 O 3 . Photon energy scans of the magnetic dichroism display features that arise from the different Fe cation sites, with relative intensities that depend on the incident angle of the X-rays. Comparisons are made between the dichroism measured with this technique and X-ray magnetic circular dichroism calculated for the three Fe sites in magnetite.

This report describes the conceptual design of a proposed free electron laser test facility called CLARA that will be a major upgrade to the existing VELA accelerator test facility at Daresbury Laboratory in the UK. CLARA will be able to test a number of new free electron laser schemes that have been proposed but require a proof of principle experiment to confirm that they perform as predicted. The primary focus of CLARA will be on ultra short photon pulse generation which will take free electron lasers into a whole new regime, enabling a new area of photon science to emerge.

At the SRS at Daresbury Laboratory, we are undertaking a programme comparing the results from efficiency calculations of diffraction gratings, mainly using the GRADIF code of Neviere, with measured efficiencies. The deviations from the predicted performance are larger for higher orders than for first order. Higher order contamination is important in determining the usability of the beamline for certain types of experiments, particularly at energies below 100 eV.

There has been a recent rapid increase in interest in the measurement of soft X-ray magnetic scattering (SoXMaS) to characterize the distribution of magnetic moments in thin films and multilayers. The Daresbury Laboratory team has adapted a high-vacuum two-circle diffractometer for pioneering measurements in this field. The principal features of the diffractometer and the alignment procedure for SoXMaS measurements are presented. A flexible data acquisition system is used, which allows a wide variety of scan modes and control of the various beamlines on which the experiments have been performed.

The recent performance of the Daresbury Laboratory soft X-ray undulator beamline 5U1 is presented. The beamline resolution has been estimated from the photo-absorption of various gases. The resolution does not follow the expected trend with photon energy due to slope error problems with the optics. The flux has been measured by the drain-current from a gold photodiode and is in good agreement with the theoretical prediction. The performance of a new ellipsoidal post-focusing mirror is found to be in excellent agreement with the predictions from the ray tracing. The effect of movement of the source on photon energy calibration is considered.

FePd thin-film samples with perpendicular magnetic anisotropy (PMA) have been studied with x-ray resonant magnetic scattering, both at the Fe and at the Pd ${L}_{3}$ edges. In these samples the competition between PMA and shape anisotropy leads to the formation of highly ordered striped domain patterns with a magnetization component perpendicular to the film plane. These striped domains give rise to magnetic satellite peaks in the diffraction pattern. Magnetic diffraction rod scans of these satellites were analyzed to obtain information about the magnetic depth profile of the films. It was found that flux closure occurs in samples with a low to medium PMA, while a high PMA impedes the formation of closure domains. Data analysis gives a depth of the closure domains extending to 85 \AA{}, with approximately half the magnetic moment aligned in plane.

Adsorbed layers of o -nitrophenol on single-crystal LaCoO 3 (111) have been investigated by near edge extended X-ray absorption fine structure (NEXAFS). This is the first NEXAFS study of o -nitrophenol and also of adsorption on LaCoO 3 (111). The results suggest that, at coverages of 0.3 and 0.7 monolayers, nitrophenol is dissociated to form two nitrogen-containing species, with one oriented perpendicular to the surface and the other oriented at around 44° to the surface. The ring also appears to be oriented at around 45° to the surface with bonding through a phenoxy group formed by loss of the phenol-group hydrogen.

A detailed study of the soft X-ray photochemistry occurring in some nickel dithiocarbamate and xanthate complexes has shown that soft X-ray induced photoreduction of [NiIV(S2CNEt2)3][BF4] results in a NiII square-planar species and the rate is dependent on photon flux, photon energy and ligand set, but is essentially independent of temperature. Also, it has been demonstrated that [PPh4][NiII(S2COEt)3] is photoisomerised to a NiII square-planar species on exposure to soft X-rays. The implication for experiments on third generation synchrotron sources is discussed briefly.

A combination of vanadium K- and L-edge XAFS has been used to characterise a series of monomeric oxovanadium(IV), monomeric dioxovanadium(V) and dimeric oxovanadium(V) complexes with oxyoxime and oxyoximate ligands. The K- and L-edge spectra confirm the presence of VV in the dimeric species and the L-edge spectra have been used to discriminate between six-co-ordinate V–N–O–V bridged oxovanadium(V) dimers and seven-co-ordinate phenolate bridged oxovanadium(V) dimers containing η2-N–O groups.

The first observation of soft X-ray induced excited spin state trapping has been made for [Fe(phen)2(NCS)2] and [Fe(phen)2(NCSe)2] (phen = 1,10-phenanthroline) at ca. 45 K, analogous to light induced excited spin state trapping but at much higher energy. Soft X-ray photochemistry has also been observed in the high- and low-spin states of [Fe(phen)2(NCS)2] and [Fe(phen)2(NCSe)2], resulting in the formation of a thermally irreversible low-spin state. The rate of formation of this low-spin state is greater from low than from high spin, and is also greater in [Fe(phen)2(NCSe)2] than in [Fe(phen)2(NCS)2].

We have isolated and characterized a genomic fragment encompassing the first six exons and 2.6 kbp 5' flanking sequence of the rat cystathionine beta-synthase (CBS) gene. A previously unknown exon approximately 3 kbp upstream of exon 1 was identified. The transcription start site was mapped to approximately 3 kbp upstream from the translation start codon and contains a consensus cap signal. The putative promoter region contains three GC boxes, in both orientations, and no TATA box. We have also compared a 1171-bp-long DNA sequence of the 5' end of the rat CBS gene with the homologous mouse region of 1125 bp. We found two homologous Sp1 sites in the mouse gene and an overall sequence conservation of 70% with 88-89% similarity in the 80-bp regions surrounding the intron 0 splice sites.

Using a newly developed reflectometer we have measured the reflectivity of crystalline silicon and SiO x coated float glass at the silicon K absorption edge. The reflectometer can be used without the need for ultra high vacuum. The critical angle of total reflection was determined and the reflection as function of the energy was measured below the critical angle. EXAFS analysis of the data reveals the oxygen content in the samples, and the local structure around the silicon absorbers. The measurements show the strength of ReflEXAFS as a technique to study surfaces under “real” conditions.

The problems inherent in the fabrication of short period multilayer mirrors are discussed and results of the synthesis of multilayer structures with nanometer period are presented. The shortest period observed is 13 A for WSi and WB 4 C sputtered multilayers. Measurements of near normal incidence reflectivity at λ = 31–32A are presented for WSc multilayers with a period approximately 16 A. The measured reflectivity reaches a maximum of 3.3% and is in good agreement with theoretical modeling after the inclusion of interfacial roughness.

The Artemis facility for ultrafast XUV science is constructed around a high average power carrier-envelope phasestabilised system, which is used to generate tuneable pulses across a wavelength range spanning the UV to the far infrared, few-cycle pulses at 800nm and short pulses of XUV radiation produced through high harmonic generation. The XUV pulses can be delivered to interaction stations for materials science and atomic and molecular physics and chemistry through two vacuum beamlines for broadband XUV or narrow-band tuneable XUV pulses. The novel XUV monochromator provides bandwidth selection and tunability while preserving the pulse duration to within 10 fs. Measurements of the XUV pulse duration using an XUV-pump IR-probe technique demonstrate that the XUV pulselength is below 30 fs for a 28 fs drive laser pulse. The materials science station, which contains a hemispherical electron analyser and five-axis manipulator cooled to 14K, is optimised for photoemission experiments with the XUV. The end-station for atomic and molecular physics and chemistry includes a velocity-map imaging detector and molecular beam source for gas-phase experiments. The facility is now fully operational and open to UK and European users for twenty weeks per year. Some of the key new scientific results obtained on the facility include: the extension of HHG imaging spectroscopy to the mid-infrared; a technique for enhancing the conversion efficiency of the XUV by combining two laser fields with non-harmonically related wavelengths; and observation of D3+ photodissociation in intense laser fields.

The double‐crystal monochromator on beam line 3.4 at the Daresbury synchrotron radiation source covers the energy region 0.8–4 keV, routinely using crystal pairs of beryl, quartz, InSb, Ge, and Si. The beam line has a unique system to cut off high‐energy radiation. The whole beam line has been built on a swinging arm, which allows the glancing angle on a chromium coated premirror to be varied between 0.5° and 3°. This not only reduces the heat load on fragile crystals, but also reduces the higher order contributions. We have made a thorough study of the alignment problems arising in the double‐crystal geometry. Crystal misalignment, Bragg angular offset, as well as heat‐load effects, can cause severe beam movements. A beam‐position monitor, which has recently been commissioned, is an invaluable diagnostic tool for these beam movements.The double‐crystal monochromator on beam line 3.4 at the Daresbury synchrotron radiation source covers the energy region 0.8–4 keV, routinely using crystal pairs of beryl, quartz, InSb, Ge, and Si. The beam line has a unique system to cut off high‐energy radiation. The whole beam line has been built on a swinging arm, which allows the glancing angle on a chromium coated premirror to be varied between 0.5° and 3°. This not only reduces the heat load on fragile crystals, but also reduces the higher order contributions. We have made a thorough study of the alignment problems arising in the double‐crystal geometry. Crystal misalignment, Bragg angular offset, as well as heat‐load effects, can cause severe beam movements. A beam‐position monitor, which has recently been commissioned, is an invaluable diagnostic tool for these beam movements.

We report on an environmental chamber, which is attached to a UHV beamline, in which soft x‐ray measurements can be done at atmospheric pressure in helium. X‐ray measurements in air can only be performed at energies above about 3 keV because of the strong absorption of soft x rays by oxygen and nitrogen. However, a low‐Z scatterer such as helium has a long absorption length for soft x rays even at atmospheric pressure. Thus, this new chamber allows soft x‐ray experiments to be performed on samples with physical properties that are incompatible with UHV conditions, e.g., liquid and frozen aqueous solutions, corrosive materials, etc. A helium‐tight tank has been installed behind the vacuum experimental chamber of the double crystal beamline 3.4 at the Daresbury SRS. The tank is purged with helium at atmospheric pressure and the gas in the tank is isolated from the high vacuum of the rest of the beamline by a thin mylar window which is supported on a capillary array. The tank contains a sample stage, two ion...

The proposed 4GLS is a suite of temporally synchronised accelerator based light sources, including a low-Q cavity free electron laser operating in the energy range 3 - 10 eV (the VUV-FEL), a seeded XUV-FEL designed to operate in the range 8 - 100 eV, an infra-red cavity FEL (the IR-FEL), as well as spontaneous radiation sources. The output from these sources is summarized. With respect to radiation damage, the two main areas of concern are the high average power from the VUV-FEL and the high peak power from the XUV-FEL. The suitability of different materials for the cavity mirror for the VUV-FEL and beamline optics is investigated. Beamline design strategies to militate against radiation damage are described and an example of a high throughput beamline in the XUV-FEL is given. The need for accurate optical constants in the VUV region, as well as damage threshold measurements, is highlighted and we outline a program of experimental measurements to be undertaken in the near future.

4GLS is a suite of accelerator-based light sources planned to provide state-of-the-art radiation in the low energy photon regime. Superconducting energy recovery linac (ERL) technology will be utilised in combination with a variety of free electron lasers (IR to XUV), undulators and bending magnets. The 4GLS undulators will generate spontaneous high flux, high brightness radiation, of variable polarisation from 3 - 800 eV, optimised in the lower harmonics up to about 200 eV. Viable radiation at energies up to several keV may be provided from multipole wiggler magnet radiation. The ERL technology of 4GLS will allow shorter bunches and higher peak photon fluxes than possible from storage ring sources. It will also give users the added bonuses of pulse structure flexibility and effectively an infinite beam lifetime. VUV and XUV FELs will be used to generate short pulses (in the fs regime) of extreme ultraviolet light that is broadly tuneable and more than a million times more intense than the equivalent spontaneous undulator radiation. A strong feature of the scientific programme planned for 4GLS is dynamics experiments in a wide range of fields. Pump probe experiments will allow the study of chemical reactions and short-lived intermediates on the timescale of bond breaking and bond making, even for very dilute species. The high intensity of the FEL radiation will allow very high resolution in imaging applications. Funding for the first three years of the 4GLS project was announced by the UK Government in April 2003. This includes the research and development work necessary to produce a design study report, with the construction of an ERL-prototype. Additional funds have recently been awarded that will enable a study of the production of ultra-short pulsed X-rays from the ERL-prototype via Thomson scattering. It is anticipated that the full 4GLS facility will be available to users in 2011.

We report on the extension of resonant magnetic diffraction into the soft X-ray region (500-1500eV). We conducted soft X-ray diffraction from a bulk single crystal of La2-2xSr1+2xMn2O7 using an in-vacuum diffractometer. We demonstrate that the resonant enhancement diffraction of the (001) magnetic peak at the manganese L-III and L-II absorption edges is extremely large. Measurements taken on samples with different strontium dopings demonstrate that the shape of the energy resonance is also dependent on the sample stoichiometry. We have applied this technique to the study of other materials such as UAs1-xSex where incommensurate magnetic diffraction has been observed at the uranium N-IV and N-V edges. (C) 2003 Elsevier B.V. All rights reserved.

Photon beam diagnostics for vacuum‐ultraviolet free electron lasers (VUV FEL) are critical to monitoring and understanding their performance characteristics. Due to the shot‐to‐shot fluctuations inherent in FELs based on the self amplified spontaneous emission (SASE) process, it is mandatory to use pulse‐resolved diagnostics. We have designed a spectrograph based on a variable‐line‐spacing (VLS) plane grating and a phosphor/CCD to monitor single shot spectra of the free electron laser at DESY. The basic concept is to allow most of the beam to be reflected towards an experimental station while the first order light is dispersed and focused by the VLS grating onto the CCD. The spectrograph will cover the wavelength range 6.4–60 nm with the CCD accepting a bandwidth of ∼10%. The grazing angle of incidence on the grating is 2°, the central line density is 1200 l/mm, and the distance grating‐CCD is approximately 2 m. The linear variation of the grating line spacing combined with positioning the detector at the focal curve, allows zeroing the defocus in the full spectrograph wavelength range. The correction of higher order grating aberrations yields a theoretical resolving power greater than 20000 over the full length of the 20 mm CCD when the CCD is positioned tangent to the focal plane. Based on power considerations, a shallow blazed grating is the preferred profile. Efficiency calculations over the spectrograph range show that with a carbon coating the absolute efficiency for zeroth order is higher than 0.85 and the first order efficiency varies between 0.5% and 8%.

We report the first direct resonant soft x-ray scattering observations of orbital ordering. We have studied the low temperature phase of ${\mathrm{L}\mathrm{a}}_{0.5}{\mathrm{S}\mathrm{r}}_{1.5}{\mathrm{M}\mathrm{n}\mathrm{O}}_{4}$, a compound that displays charge and orbital ordering. Previous claims of orbital ordering in such materials have relied on observations at the manganese $K$ edge. These claims have been questioned in several theoretical studies. Instead we have employed resonant soft x-ray scattering at the manganese ${L}_{\mathrm{I}\mathrm{I}\mathrm{I}}$ and ${L}_{\mathrm{I}\mathrm{I}}$ edges which probes the orbital ordering directly. Energy scans at constant wave vector are compared to theoretical predictions and suggest that at all temperatures there are two separate contributions to the scattering: direct orbital ordering and strong cooperative Jahn-Teller distortions of the ${\mathrm{M}\mathrm{n}}^{3+}$ ions.

We have conducted the first soft x-ray diffraction experiments from a bulk single crystal, studying the bilayer manganite ${\mathrm{L}\mathrm{a}}_{2\ensuremath{-}2x}{\mathrm{S}\mathrm{r}}_{1+2x}{\mathrm{M}\mathrm{n}}_{2}{\mathrm{O}}_{7}$ with $x=0.475$ in which we were able to access the (002) Bragg reflection using soft x rays. The Bragg reflection displays a strong resonant enhancement at the ${L}_{\mathrm{I}\mathrm{I}\mathrm{I}}$ and ${L}_{\mathrm{I}\mathrm{I}}$ manganese absorption edges. We demonstrate that the resonant enhancement of the magnetic diffraction of the (001) is extremely large, indeed so large that it exceeds that of the nonresonant Bragg diffraction. Resonant soft x-ray scattering of $3d$ transition metal oxides is the only technique for the atomic selective measurement of spin, charge, and orbital correlations in materials, such as high temperature superconductors, colossal magnetoresistance manganites, and charge stripe nickelates.

We report the first direct resonant soft x-ray scattering observations of orbital ordering. We have studied the low temperature phase of La0.5Sr1.5MnO4, a compound that displays charge and orbital ordering. Previous claims of orbital ordering in such materials have relied on observations at the manganese K edge. These claims have been questioned in several theoretical studies. Instead we have employed resonant soft x-ray scattering at the manganese L(III) and L(II) edges which probes the orbital ordering directly. Energy scans at constant wave vector are compared to theoretical predictions and suggest that at all temperatures there are two separate contributions to the scattering: direct orbital ordering and strong cooperative Jahn-Teller distortions of the Mn3+ ions.

Replication-defective, highly purified retroviral vectors (Retrovector), at titers of 10(8) colony forming units/mL, were prepared that conferred either beta-galactosidase or herpes simplex thymidine kinase (HSV-TK) activity. 9L gliosarcoma cells, transduced efficiently in vitro, were highly sensitive to ganciclovir (GCV). The mean frequency of in situ transduction, measured by flow cytometry of single-cell tumor suspensions isolated from rat brains, was 3.2 +/- 0.6%; similar assessments were made by staining of beta-galactosidase or by immunohistochemistry with anti-HSV-TK. In vitro HSV-TK-transduced and G418-selected 9L-TK gliosarcoma tumors treated with GCV were eradicated in approximately 53% of the animals (10/19) at day 26, however, 89% (17/19) histologically showed1% tumor volume. Histologic evaluation at day 26 of animals with established 9L tumors treated with intralesional injection of HSV-TK vector followed by GCV treatment showed that 29% (4/14) had no tumor; 50% (7/14) had1% tumor volume. Regression of tumors proceeded over the time since the complete rate was increased at day 60. Neither HSV-TK vector particles nor GCV alone altered the histological profile of 9L tumors, but substantial numbers of CD4+ and CD8+ lymphocytes infiltrated the tumors of animals treated with both. In cured animals, the former tumor bed contained cell debris, immune cells, and fibroblasts and was without damage to adjacent brain. The efficacy of suicide gene therapy for rat gliosarcoma using highly purified virion vectors approaches that of packaging cell lines.

This study focuses on explaining differences in soft X-ray reflectivity observed for Mo/Si multilayers produced by e-beam evaporation with two different additional methods: ion etching of the Si layer and optimization of the substrate temperature during deposition. A 32-period multilayer made with ion etching has a near normal incidence reflectivity of 50%, while the one made at an optimum deposition temperature shows only 41%. The values for the interface roughness or layer thickness errors obtained from the analysis of small angle reflectivity measurements cannot explain this difference, but a different morphology of the Si and Mo layers could. Extended X-ray absorption fine structure (EXAFS) experiments have been carried out at the Si-K and the Mo-K edge to obtain information on the multilayer structure and chemical composition. The results of these EXAFS measurements on the two types of multilayers indicate that both the Si and the Mo have an amorphous structure and that no Mo-Si compounds are formed at the interfaces. However, it is found that multilayers made with ion etching have a reduced fraction of oxygen (less than or equal to 0.5%) in the Si layer compared to layers produced without etching (4.7%). The latter fraction of oxygen, originating from the background gas in the deposition system, results in higher absorption of soft X-ray radiation and therefore affects the near normal incidence reflectivity. Although both the Si and Mo layers produced with the three different deposition methods are amorphous, some structural differences have been found using the EXAFS analysis.

We elucidated the structure and alternative splicing patterns of the rat cystathionine beta-synthase gene. The gene is 20-25 kilobase pairs long, and its coding region is divided into 17 exons. These are alternatively spliced, forming four distinct mRNAs (types I through IV). The predicted open reading frames encode proteins of 61.5, 39, 60, and 52.5 kDa, respectively. Exons 13 and 16 are used alternatively and mutually exclusively. Exon 13 includes a stop codon and encodes the unique carboxyl-terminal sequence found in types II and IV. Exon 16 is present only in type I. Types I and III, which differ by 42 nucleotides (exon 16), are the predominant synthase mRNA forms in rat liver. Seventeen arginine peptides from pure liver synthase matched the deduced amino acid sequences of types I and III. These two polypeptides are detectable in liver extracts; each exhibits enzymatic activity when expressed in transfected Chinese hamster cells. Synthase shows substantial sequence similarity with pyridoxal 5'-phosphate dependent enzymes from lower organisms. Similarity of synthase to Escherichia coli O-acetylserine (thiol)-lyase (cysK) is 52%; E. coli tryptophan synthase beta chain (trpB), 36%; yeast serine deaminase, 33%. Lysine 116 in synthase aligns with the established pyridoxyllysine residue of these enzymes suggesting that it is the pyridoxal 5'-phosphate binding residue.

A variety of 6- and 8-substituted analogs of cAMP (cyclic adenosine 3:5-monophosphate) have been tested for their ability to increase activity of tyrosine aminotransferase (EC 2.6.1.5) in cultured Reuber H35 hepatoma cells. Some analogs, particularly the 8-thio-substituted ones, produced effects approximately equivalent to those generated by N-6, O2'-dibutyryl cAMP. In contrast, cAMP and its O-2-monobutyryl derivative were relatively ineffective even at very high concentrations, whereas three other analogs actually depressed the activity of the aminotransferase. Changes in enzyme activity generated by the various analogs were paralleled closely by changes in the relative rate of aminotransferase synthesis. An excellent correlation was found to exist between the ability of any given analog to influence the activity of tyrosine aminotransferase and that of phosphoenolpyruvate carboxykinase (EC 4.1.1.32). A similar correlation was found to exist between the ability of various analogs to evelate the activity of these enzymes and to inhibit reversibly the growth of H35 cells. Only one of five inhibitors of cAMP phosphodiesterase activity tested produce any increase in aminotransferase activity when added alone. All of the 6- and 8-substituted analogs tested, including noniducers, stimulated f1 histone phosphorylation in crude rat liver extracts with approximately equal potencies. On the other hand, dibutyryl cAMP was only a weak activator of protein kinase in vitro, even though it is a potent enzyme inducer. A possible resolution of this apparent discrepancy has been provided by preliminary analyses of site-specific f1 histone phosphorylation in whole cells. Only compounds active as aminotransferase inducers are capable of stimulating phosphorylation of the serine-37 residue of endogenous f1 histone (3- to 10-fold).

Tryptophan oxygenase activity follows a characteristic developmental pattern in the young rat, being absent until about 2 weeks of life, then attaining adult levels by the 3rd week. We have investigated the factors which control this process and determined that the increase in enzymatic activity results from increased glucocorticoid release between the 14th and 21st days. This conclusion was based on our observation that adrenalectomy completely arrests the development of the enzymatic activity. Twenty-one-day-old animals which were adrenalectomized on the 10th day, and thus possess no demonstrable enzymatic activity, could respond to cortisol treatment with an elevation of tryptophan oxygenase activity. Administration of either cycloheximide or actinomycin D completely inhibited this response, suggesting that both protein synthesis and RNA synthesis were requisite for the development of the enzyme. Immunochemical studies revealed that the enzyme found in the young animal was identical with that extracted from the adult rat; furthermore, the increase in activity observed in the developing rat is the result of increased enzyme protein levels. Direct measurement of the synthetic and degradative rates showed the accumulation of enzyme protein to depend upon increased synthetic activity, and not upon decreased enzyme degradation.

Tryptophan oxygenase activity follows a characteristic developmental pattern in the young rat, being absent until about 2 weeks of life, then attaining adult levels by the 3rd week. We have investigated the factors which control this process and determined that the increase in enzymatic activity results from increased glucocorticoid release between the 14th and 21st days. This conclusion was based on our observation that adrenalectomy completely arrests the development of the enzymatic activity. Twenty-one-day-old animals which were adrenalectomized on the 10th day, and thus possess no demonstrable enzymatic activity, could respond to cortisol treatment with an elevation of tryptophan oxygenase activity. Administration of either cycloheximide or actinomycin D completely inhibited this response, suggesting that both protein synthesis and RNA synthesis were requisite for the development of the enzyme. Immunochemical studies revealed that the enzyme found in the young animal was identical with that extracted from the adult rat; furthermore, the increase in activity observed in the developing rat is the result of increased enzyme protein levels. Direct measurement of the synthetic and degradative rates showed the accumulation of enzyme protein to depend upon increased synthetic activity, and not upon decreased enzyme degradation.

A variety of 6- and 8-substituted analogs of cAMP (cyclic adenosine 3:5-monophosphate) have been tested for their ability to increase activity of tyrosine aminotransferase (EC 2.6.1.5) in cultured Reuber H35 hepatoma cells. Some analogs, particularly the 8-thio-substituted ones, produced effects approximately equivalent to those generated by N-6, O2'-dibutyryl cAMP. In contrast, cAMP and its O-2-monobutyryl derivative were relatively ineffective even at very high concentrations, whereas three other analogs actually depressed the activity of the aminotransferase. Changes in enzyme activity generated by the various analogs were paralleled closely by changes in the relative rate of aminotransferase synthesis. An excellent correlation was found to exist between the ability of any given analog to influence the activity of tyrosine aminotransferase and that of phosphoenolpyruvate carboxykinase (EC 4.1.1.32). A similar correlation was found to exist between the ability of various analogs to evelate the activity of these enzymes and to inhibit reversibly the growth of H35 cells. Only one of five inhibitors of cAMP phosphodiesterase activity tested produce any increase in aminotransferase activity when added alone. All of the 6- and 8-substituted analogs tested, including noniducers, stimulated f1 histone phosphorylation in crude rat liver extracts with approximately equal potencies. On the other hand, dibutyryl cAMP was only a weak activator of protein kinase in vitro, even though it is a potent enzyme inducer. A possible resolution of this apparent discrepancy has been provided by preliminary analyses of site-specific f1 histone phosphorylation in whole cells. Only compounds active as aminotransferase inducers are capable of stimulating phosphorylation of the serine-37 residue of endogenous f1 histone (3- to 10-fold).

We report on a study of grazing incidence absorption and reflection spectra of NiO in the region of the Ni 2p edge. The aim is to evaluate the distortion of the near edge spectrum by the critical angle behavior of individual components within the spectrum. This can be used to improve the separation of multiplets and enhance low spectral weight line shapes like charge transfer satellites. The measured spectra have been compared with calculations using an optical model.