Cooperative elastic switching vs. laser heating in [Fe(phen)2(NCS)2] spin-crossover crystals excited by a laser pulse.

Spin-crossover crystals show multi-step responses to femtosecond light excitation. The local molecular photo-switching from low to high spin states occurs on sub-picosecond timescale. It is followed by additional conversion due to elastic (ns) and thermal (µs) effects. In [Fe(phen)2(NCS)2] crystals discussed herein, the thermal switching can be made unobtrusive for the investigation of cooperative elastic switching. We evidence a cooperative transformation induced by lattice expansion through elastic coupling between molecules in the crystal, where up to 3 molecules are transformed per photon.

Synchrotron Mössbauer spectroscopy using high-speed shutters.

A new method of performing Mössbauer spectroscopy with synchrotron radiation is demonstrated that involves using a high-speed periodic shutter near the focal spot of a microfocused X-ray beam. This fast microshuttering technique operates without a high-resolution monochromator and has the potential to produce much higher signal rates. It also offers orders of magnitude more suppression of unwanted electronic charge scattering. Measurement results are shown that prove the principle of the method and improvements are discussed to deliver a very pure beam of Mössbauer photons (E/ΔE ≃ 10(12)) with previously unavailable spectral brightness. Such a source will allow both Mössbauer spectroscopy in the energy domain with the many advantageous characteristics of synchrotron radiation and new opportunities for measurements using X-rays with ultra-high energy resolution.

BioCARS: a synchrotron resource for time-resolved X-ray science.

BioCARS, a NIH-supported national user facility for macromolecular time-resolved X-ray crystallography at the Advanced Photon Source (APS), has recently completed commissioning of an upgraded undulator-based beamline optimized for single-shot laser-pump X-ray-probe measurements with time resolution as short as 100 ps. The source consists of two in-line undulators with periods of 23 and 27 mm that together provide high-flux pink-beam capability at 12 keV as well as first-harmonic coverage from 6.8 to 19 keV. A high-heat-load chopper reduces the average power load on downstream components, thereby preserving the surface figure of a Kirkpatrick-Baez mirror system capable of focusing the X-ray beam to a spot size of 90 µm horizontal by 20 µm vertical. A high-speed chopper isolates single X-ray pulses at 1 kHz in both hybrid and 24-bunch modes of the APS storage ring. In hybrid mode each isolated X-ray pulse delivers up to ~4 × 10(10) photons to the sample, thereby achieving a time-averaged flux approaching that of fourth-generation X-FEL sources. A new high-power picosecond laser system delivers pulses tunable over the wavelength range 450-2000 nm. These pulses are synchronized to the storage-ring RF clock with long-term stability better than 10 ps RMS. Monochromatic experimental capability with Biosafety Level 3 certification has been retained.

IGF2BP1 controls cell death and drug resistance in rhabdomyosarcomas by regulating translation of cIAP1.

Rhabdomyosarcoma (RMS), a neoplasm characterised by undifferentiated myoblasts, is the most common soft tissue tumour of childhood. Although aggressive treatment of RMS could provide long-term benefit, resistance to current therapies is an ongoing problem. We report here that insulin-like growth factor 2-binding protein 1 (IGF2BP1), an oncofetal protein, is expressed in RMS patient-derived cell lines and in primary tumours where it drives translation of the cellular inhibitor of apoptosis 1 (cIAP1), a key regulator of the nuclear factor-κB signalling pathway and of caspase-8-mediated cell death. We demonstrate that reducing the levels of cIAP1 in RMS, either by IGF2BP1 knockdown or by IAP antagonists, sensitises these cells to tumour necrosis factor-α-mediated cell death. Finally, we show that targeting cIAP1 by IAP antagonists delays RMS tumour growth and improve survival in mice. Our results identify IGF2BP1 as a critical translational regulator of cIAP1-mediated apoptotic resistance in RMS and advocate for the combined use of IAP antagonists and tumour necrosis factor-α as a therapeutic approach for this type of cancer.

Synchrotron charge-density studies in materials chemistry: 16 K X-ray charge density of a new magnetic metal-organic framework material, [Mn2(C8H4O4)2(C3H7NO)2].

A new magnetic metal-organic framework material, [Mn(2)(C(8)OH(4)(4))(2)(C(3)H(7)NO)(2)], has been synthesized. The structure consists of chains of carboxylate-bridged Mn atoms interconnected with acid linkers, giving much larger interchain than intrachain Mn...Mn distances. Magnetic susceptibility data fitted to a Curie-Weiss law give Theta = -5.7 K and a total magnetic moment of 5.96 micro(B). The heat capacity provides no evidence of magnetic ordering down to 2 K. The X-ray charge density was determined from multipole modeling of 16 (1) K single-crystal synchrotron-radiation data. The structural surroundings of the two unique Mn centers are different, but orbital population analysis reveals close to single electron occupation in all 3d orbitals of both Mn sites, in agreement with the magnetic susceptibility measurements. Bader topological analysis shows the presence of direct chemical Mn...Mn interactions only in two out of three intrachain contacts, which suggests a 'broken' chain. The topological measures and approximate energy densities at the metal-ligand bond critical points (rho, nabla(2)rho, G, V and H) indicate ionic interactions. Formal electron counting suggests mixed-valence Mn sites, but this hypothesis is not supported by the Bader atomic charges [q(Mn) = +2.035 and +2.031].

Orthosurgical teamwork.

A series of orthognathic cases illustrates the potential service that is available to young adult and adult patients. These patients have problems that are not within the therapeutic possibilities of orthodontics alone. From a variety of viewpoints--length of time, appliance wear, iatrogenic damage, and patient concern--such procedures may well be preferred and ultimately more successful and stable than alternate conventional orthodontic therapy. Surgical procedures, in combination with orthodontics and prosthetics, have now achieved a level of sophistication that permits correction of almost any type of facial deformity quickly, with minimum pain, and relatively few unfavorable sequelae.12.13.15.

Determinants controlling iatrogenic external root resorption and repair during and after palatal expansion.

The mechanisms controlling iatrogenic external root resorption (ERR) and repair were studied on 8 Macaca fascicularis monkeys. The animals were divided into short-term and long-term groups, and were treated with jackscrew, magnetic and sham palatal expansion appliances. Scanning electron microscopy morphometric analysis found major evidence of ERR in the tooth-borne jackscrew appliance, in the long-term group, in the maxillary premolars, on the buccal and furcation root surfaces, on the mesiobuccal root, and in the apical zone. Correspondingly, the ERR mechanism is controlled by the impulse (F. delta t) and the critical barrier of the periodontal ligament as primary determinants and by the environmental density as a secondary determinant. ERR is initially regulated by the force component of the impulse and, with increased duration, by the time component of the impulse. The impairment/repair dynamics were found to be regulated by three principles: ERR level of irreversibility, delayed resorption response and jiggling.

Role of magnesium in health and disease.

Appropriate intracellular and extracellular magnesium levels are necessary for proper body functioning. Imbalances of magnesium are common and are associated with a great deal of morbidity and mortality. Routine determination of serum magnesium levels in patients at risk for magnesium disorders must become the norm. As technology improves, cellular magnesium levels will become widely available and may be indicated to guide therapy and prevention of a wide variety of diseases.

X-ray pump optical probe cross-correlation study of GaAs.

Ultrafast dynamics in atomic, molecular and condensed-matter systems are increasingly being studied using optical-pump, X-ray probe techniques where subpicosecond laser pulses excite the system and X-rays detect changes in absorption spectra and local atomic structure(1-3). New opportunities are appearing as a result of improved synchrotron capabilities and the advent of X-ray free-electron lasers(4,5). These source improvements also allow for the reverse measurement: X-ray pump followed by optical probe. We describe here how an X-ray pump beam transforms a thin GaAs specimen from a strong absorber into a nearly transparent window in less than 100 ps, for laser photon energies just above the bandgap. We find the opposite effect-X-ray induced optical opacity-for photon energies just below the bandgap. This raises interesting questions about the ultrafast many-body response of semiconductors to X-ray absorption, and provides a new approach for an X-ray/optical cross-correlator for synchrotron and X-ray free-electron laser applications.

Asymmetric-cut variable-incident-angle monochromator.

A novel asymmetric-cut variable-incident-angle monochromator was constructed and tested in 1997 at the Advanced Photon Source of Argonne National Laboratory. The monochromator was originally designed as a high heat load monochromator capable of handling 5-10 kW beams from a wiggler source. This was accomplished by spreading the x-ray beam out on the surface an asymmetric-cut crystal and by using liquid metal cooling of the first crystal. The monochromator turned out to be a highly versatile monochromator that could perform many different types of experiments. The monochromator consisted of two 18° asymmetrically cut Si crystals that could be rotated about 3 independent axes. The first stage (Φ) rotates the crystal around an axis perpendicular to the diffraction plane. This rotation changes the angle of the incident beam with the surface of the crystal without changing the Bragg angle. The second rotation (Ψ) is perpendicular to the first and is used to control the shape of the beam footprint on the crystal. The third rotation (Θ) controls the Bragg angle. Besides the high heat load application, the use of asymmetrically cut crystals allows one to increase or decrease the acceptance angle for crystal diffraction of a monochromatic x-ray beam and allows one to increase or decrease the wavelength bandwidth of the diffraction of a continuum source like a bending-magnet beam or a normal x-ray-tube source. When the monochromator is used in the doubly expanding mode, it is possible to expand the vertical size of the double-diffracted beam by a factor of 10-15. When this was combined with a bending magnet source, it was possible to generate an 8 keV area beam, 16 mm wide by 26 mm high with a uniform intensity and parallel to 1.2 arc sec that could be applied in imaging experiments.

NF45 functions as an IRES trans-acting factor that is required for translation of cIAP1 during the unfolded protein response.

Expression of the cellular inhibitor of apoptosis protein 1 (cIAP1) is unexpectedly repressed at the level of translation under normal physiological conditions in many cell lines. We have previously shown that the 5' untranslated region of cIAP1 mRNA contains a stress-inducible internal ribosome entry site (IRES) that governs expression of cIAP1 protein. Although inactive in unstressed cells, the IRES supports cap-independent translation of cIAP1 in response to endoplasmic reticulum stress. To gain an insight into the mechanism of cIAP1 IRES function, we empirically derived the minimal free energy secondary structure of the cIAP1 IRES using enzymatic cleavage mapping. We subsequently used RNA affinity chromatography to identify several cellular proteins, including nuclear factor 45 (NF45) as cIAP1 IRES binding proteins. In this report we show that NF45 is a novel RNA binding protein that enhances IRES-dependent translation of endogenous cIAP1. Further, we show that NF45 is required for IRES-mediated induction of cIAP1 protein during the unfolded protein response. The data presented are consistent with a model in which translation of cIAP1 is governed, at least in part, by NF45, a novel cellular IRES trans-acting factor.

Imaging nonequilibrium atomic vibrations with x-ray diffuse scattering.

We use picosecond x-ray diffuse scattering to image the nonequilibrium vibrations in the lattice following ultrafast laser excitation. We present images of nonequilibrium phonons in InP and InSb throughout the Brillouin zone which remain out of equilibrium up to nanoseconds. The results are analyzed using a Born model that helps identify the phonon branches contributing to the observed features in the time-resolved diffuse scattering. In InP this analysis shows a delayed increase in the transverse-acoustic (TA) phonon population along high-symmetry directions accompanied by a decrease in the longitudinal-acoustic phonons. In InSb the increase in TA phonon population is less directional.