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Summary: Background: Novel treatments with superior benefit‐risk profiles are needed to improve the long‐term prognosis of patients with inflammatory bowel disease (IBD). Etrolizumab—a monoclonal antibody that specifically targets β7 integrins—is currently under phase III clinical evaluation in IBD. Aim: This review summarises the available pharmacological and pharmacokinetic/pharmacodynamic data for etrolizumab to provide a comprehensive understanding of its mechanism of action (MOA) and pharmacological effects. Methods: Published and internal unpublished data from nonclinical and clinical studies with etrolizumab are reviewed. Results: Etrolizumab exerts its effect via a unique dual MOA that inhibits both leucocyte trafficking to the intestinal mucosa and retention within the intestinal epithelial layer. The gut‐selectivity of etrolizumab results from its specific targeting of the β7 subunit of α4β7 and αEβ7 integrins. Etrolizumab does not bind to α4β1 integrin, which mediates lymphocyte trafficking to tissues including the central nervous system, a characteristic underlying its favourable safety with regard to progressive multifocal leucoencephalopathy. Phase I/II studies in patients with ulcerative colitis (UC) showed linear pharmacokinetics when etrolizumab was administered subcutaneously at 100 mg or higher once every 4 weeks. This dose was sufficient to enable full β7 receptor occupancy in both blood and intestinal tissues of patients with moderate to severe UC. The phase II study results also suggested that patients with elevated intestinal expression of αE integrin may have an increased likelihood of clinical remission in response to etrolizumab treatment. Conclusion: Etrolizumab is a gut‐selective, anti‐β7 integrin monoclonal antibody that may have therapeutic potential for the treatment of IBD. [ABSTRACT FROM AUTHOR]

Nanocrystalline CeO2 samples were prepared via precipitation from aqueous cerium(IV) sulfate solution under a controlled pH. After being subjected to calcination at various temperatures to yield different particle sizes, the local structure around Ce atom was investigated by using EXAFS spectroscopy at Ce K-edge. The first shell Ce&z.sbnd;O distance was found to be slightly shorter with small CeO2 particles, indicating a contraction of the lattice. There exists a significant growth in coordination number of the second cell Ce&z.sbnd;Ce when the particle size became larger. In terms of Debye–Waller factor (σ2), the first three coordination shells showed a consistent trend, i.e. the degree of disorder increases with reduced particle size. Moreover, σ2 of the second shell was found to be smaller than that of the first shell for all samples. [ABSTRACT FROM AUTHOR]

Studies have shown that the 577R alíele of cc- actinin-3 (ACTN3) is more prevalent in sprint athletes than in the general population or in endurance athletes. We examined the distribution of ACTN3 R577X (rs 1815739) genotypes and alíeles in the Taiwanese general population (603) and in elite sprint swimmers who had participated in international/national events (168). Additionally, 50 pre-adolescent (age 11-13 years) male students and 38 adult males who completed 12-weeks of swimming training, were included in the present study. We found that the frequencies of the R alíele were significantly higher in female international sprint swimmers (67.6%) than in national sprint swimmers (50.0%) or in the general population (53.7%). Th 25-m performance was significantly improved across the genotypes after swimming training among the pre-adolescent males but not among the adult males. In addition, pre-adolescents with the RR genotype had the best performance both before and after training although not statistically significant. In conclusion, the frequencies of ACTN3 577R alíele were significantly higher in female international sprint swimmers than among national sprint swimmers or the general population. Furthermore, male pre-adolescents with either the ACTN3 RX or XX genotype showed a greater improvement in 25-meter swimming performance than those with the RR genotype. [ABSTRACT FROM AUTHOR]

Dielectronic recombination (DR) rate coefficients for carbon-like 40Ca14+ forming nitrogen-like 40Ca13+ have been measured using the electron–ion merged-beam technique at the heavy-ion storage ring CSRm at the Institute of Modern Physics in Lanzhou, China. The measured DR rate coefficients in the energy range from 0 to 92 eV cover most of the DR resonances associated with 2s22p2 → 2s22p2 and 2s22p2 → 2s2p3 core transitions (ΔN = 0). Theoretical calculations of the DR cross sections were carried out by using two different state-of-the-art atomic theoretical techniques, multiconfiguration Breit–Pauli (MCBP) code AUTOSTRUCTURE and relativistic configuration interaction code FAC, to compare with the experimental rate coefficients. The theoretical calculations agree with the experimental results at collision energy higher than 10 eV. However, significant discrepancies of resonance energies and strengths can be found at collision energy below 8 eV. Temperature-dependent plasma recombination rate coefficients were derived from the measured DR rate coefficients in the energy range from 0.1 to 1000 eV and compared with the recommended atomic data from the literature. The theoretical data of Gu et al. and Zatsarinny et al. are 30% lower than the experimental results at the temperatures of photoionized plasmas, but have a very good agreement at the temperatures of collisionally ionized plasmas. Other previously published theoretical data of Jacobs et al. and Mazzotta et al. by using Burgess formula and LS-coupling calculations significantly underestimate the plasma rate coefficients in the low temperature range. The present results comprise a set of benchmark data suitable for astrophysical modeling. [ABSTRACT FROM AUTHOR]

The use of an electronic cooling system at the High Intensity heavy ion Accelerator Facility (HIAF) accelerator complex, which is being developed at the Institute of Modern Physics (China), to improve the efficiency of ion injection into the accelerator and reduce the spread of ion pulses in the beam has been proposed. Electron cooling of the ion beam was carried out due to the interaction of ions with a continuous electron beam with a current of up to 3 A, energy of up to 450 keV, and energy stability at the level of 10-4 or better. The electron beam energy recuperation was carried out at the expense of a power source with a power of 5-15 kW, which was located at the top of a high-voltage column—a high-voltage terminal. The operation of a prototype of power transmission system, which was based on a cascade transformer with a volumetric coil, has been considered. Such a transformer has a relatively low scattering inductance, which can significantly reduce the number of capacitors to compensate for it. It has been shown that this design made it possible to transfer power of up to 40 kW at small dimensions of the transformer and heat dissipation in it was not more than 10 kW. [ABSTRACT FROM AUTHOR]

Recovery of copper and cobalt from smelter slag using reductive-sulfurizing smelting method was performed in this study. The effects of reductive agent (coke), sulfurizing agent (pyrite), slag modifier (CaO) and smelting temperature and duration on the extractive efficiencies of Cu, Co and Fe were discussed. The phase compositions and microstructure of the materials, copper-cobalt matte and cleaned slag were determined. The results showed that copper and cobalt contents in cleaned slag could decrease averagely to 0.18% and 0.071% respectively after cleaning. 91.99% Cu and 92.94% Co and less than 38.73% Fe were recovered from the smelter slag under the optimum conditions: 6 wt.% coke, 20 wt.% pyrite and 6 wt.% CaO addition to the smelter slag, smelting temperature of 1350°C and smelting duration of 3h. The addition of CaO can increase the selectivity of Co recovery. The cleaning products were characterized by XRD and SEM-EDS analysis. The results showed that the main phases of copper-cobalt matte were iron sulfide (FeS), geerite (Cu8S5), iron cobalt sulfide (Fe0.92Co0.08S) and Fe-Cu-Co alloy. The cleaned slag mainly comprised fayalite (Fe2SiO4), hedenbergite (CaFe(Si2O6)) and magnetite (Fe3O4). [ABSTRACT FROM AUTHOR]

A modified algorithm for X-ray dynamical diffraction theory is presented for curved boundary crystals and a detailed description of the numerical procedure is given. The simulated and experimental results both show an anomalous focusing behavior in a curved multi-plate crystal cavity of silicon under the back-diffraction condition at a photon energy of 14.4388 keV. The focusing effects are analyzed, within the framework of the dynamical theory of X-ray diffraction, from the excitation of the dispersion surface and modification of the index of refraction with respect to the non-plane-parallel boundaries of a curved crystal cavity. [ABSTRACT FROM AUTHOR]

Volociximab is a chimeric IgG4 that is being developed as a novel first-in-class anti-angiogenic, α5β1 integrin inhibitor for the treatment of solid tumors. A mechanism-based pharmacokinetic (PK)/pharmacodynamic (PD) model was developed to investigate the dynamic interaction between volociximab concentrations and free monocyte α5β1 integrin levels in cancer patients. Twenty-one cancer patients from six dose cohorts (0.5, 1.0, 2.5, 5.0, 10, and 15 mg/kg) were included in the analysis. The fully integrated receptor-binding PK/PD model was developed and fit simultaneously to the PK/PD data. A Monte-Carlo parametric expectation-maximization method implement in S-ADAPT program was used to obtain estimates of population parameters and inter- and intra-subject variability. The PK/PD time profiles were well described by the model and the parameters were estimated with good precision. The model was used to simulate PK/PD time profiles for multiple dose regimens at various dose levels, and the results suggested that the monocyte α5β1 integrin binding was saturated (≤5% free) at week 16 in the majority of patients treated with volociximab doses ≥10 mg/kg IV every 2 weeks. The developed model is useful for anticipating the drug exposures and extent of volociximab binding to peripheral monocyte α5β1 integrin in untested regimens and for optimizing the design of future clinical trials. [ABSTRACT FROM AUTHOR]

Abstract: Electromagnetic transitions within nuclei reflect specific aspects of nuclear structure. This is particularly true for metastable excited states, or isomers, like 178Hf m2 ( years, excitation energy 2446 keV). The interaction of external radiation with isomers can be used to study atomic and nuclear properties and, perhaps, to induce a release of the stored energy. Some experiments indicated that low-energy photons near the L3 edge (9.561 keV) of hafnium could cause this to occur for 178Hf m2, but the lack of a viable physical model and null experiments by other groups have left these claims in doubt. The present work describes a new experiment to examine this process by closely duplicating the irradiation conditions in positive studies, but using a more advanced multi-detector γ array. No support for an induced depletion of 178Hf m2 by low-energy photons was obtained, with an upper limit for the integral cross section that is eight orders-of-magnitude below the reported value. [Copyright &y& Elsevier]

Abstract: A new X-ray diffraction technique is developed to probe structural variations at the interfaces between epitaxy thin films and single-crystal substrates. The technique utilizes three-wave Bragg-surface diffraction, where a symmetric Bragg reflection and an asymmetric surface reflection are involved. The propagation of the latter along the interfaces conveys structural information about the interfacial region between the substrate and epi-layers. The sample systems of Au/GaAs(001) are subject to the three-wave diffraction investigation using synchrotron radiation. The GaAs three-wave Bragg-surface diffractions, (006)/(11¯3) and (006)/(1¯1¯3), are employed. The images of the surface diffracted waves are recorded with an image plate. The obtained images show relative positions of diffraction spots near the image of the interfacial boundary, which give the variation of lattice constant along the surface normal and in-plane directions. With the aid of grazing-incidence diffraction, three-dimensional mapping of strain field at the interfaces is possible. Details about this diffraction technique and the analysis procedures are discussed. [Copyright &y& Elsevier]

We present a structural investigation of self-assembled InGaAs quantum dots on GaAs(0 0 1) substrates grown by molecular-beam epitaxy. The grazing incidence X-ray scattering measurements were performed at BL17B of Taiwan Light Source and BL12B2 of SPring-8. The strain field, composition distribution, and shape of the dots are determined. We found that In concentration was less than the nominal composition, 50% near the dot/substrate interface and exceeded 50% near the top of the dots, indicating In surface segregation. In addition, the relation between the strain and the composition did not obey Vegard’s law. [Copyright &y& Elsevier]

We report on the trapping of 14 keV photons in periods of 1.11–1.67 ps by the 12 4 0 backdiffraction in two- and multiplate silicon single-crystal cavities of a few hundred micrometer size. The formation of standing waves inside the cavities ensures better coherence for the x rays. We anticipate that the transmitted x rays through this type of cavities can be used as a quasicoherent x-ray source for probing the dynamic structures of solids, liquids, and biological substances. [ABSTRACT FROM AUTHOR]

Cubic phase yttrium-doped HfO2 (YDH) ultrathin films were grown on Si (111) substrates by molecular beam epitaxy. Thorough structural and morphological investigations by x-ray scattering and transmission electron microscopy reveal that the YDH thin films are epitaxially grown on the Si substrates with (111)YDH∥(111)Si and [101]YDH∥[110]Si. The interface between YDH and Si is atomistic sharp and free of interfacial layer. We have also determined the yttrium content of YDH films to be 19% by using anomalous x-ray diffraction (AXD) across Y k edge and angle resolved x-ray photoelectron spectroscopy (AR-XPS). The agreement between the AXD and AR-XPS results manifests that the incorporated Y atoms homogeneously substitute Hf atoms in the crystalline lattice and form a substitutional solid solution. [ABSTRACT FROM AUTHOR]

The authors report a general methodology for probing the depth profile of alloying extent and composition in bimetallic nanoparticles (NPs) by a combined in situ x-ray absorption spectroscopy (XAS) and electrochemical strategy. The XAS results of Pt-richcore–Ru-richshell NPs during methanol electro-oxidation revealed that the alloying extent of Pt (JPt) and Ru (JRu) is higher in the core region compared to those in the shell region. An average decrease in the JPt and JRu is observed when the cluster undergoes reduction. By controlling the cluster oxidation degree it is possible to probe the depth profile of the alloying extent in bimetallic NPs. [ABSTRACT FROM AUTHOR]

A generic x-ray diffraction method, using three-wave Bragg-surface diffraction, is developed to measure strains at the interface of molecular beam epitaxial Au/GaAs(001), where grazing-incidence diffraction cannot be applied due to the difference in refractive index between Au and GaAs. Changes in diffraction images of the surface reflection (1-13) of GaAs(006)/(1-13) three-wave Bragg-surface diffraction and the (-1-13) of GaAs(006)/(-1-13) at different azimuth and Bragg angles give the depth penetration of 2 Å resolution and variations of lattice constant, -49%, -27%, and 2%, along the surface normal [001] and in-plane directions [-1-10] and [1-10] within the depths of 18, 72, and 72 Å, respectively. [ABSTRACT FROM AUTHOR]

The electronic and atomic structures of quasi-one-dimensional blue bronze K0.3MoO3 were investigated by polarization-dependent O K-edge x-ray absorption near-edge structure (XANES) and Mo K-edge extended x-ray absorption fine structure (EXAFS) measurements at various temperature and applied voltages. The O K-edge XANES spectra suggest that the number of unoccupied O 2p–Mo 4d hybridized states increases and decreases with temperature, respectively, below and above a critical temperature of 180 K. The along b-axis electric current measurements show a threshold applied voltage, beyond which the current increases rapidly. The Mo K-edge EXAFS measurements show that the Mo–O bond lengths are insensitive to the temperature even beyond 180 K. [ABSTRACT FROM AUTHOR]

In this study, a distributed charge storage with GeO2 nanodots is demonstrated. The mean size and aerial density of the nanodots embedded in SiO2 are estimated to be about 5.5 nm and 4.3×1011 cm-2, respectively. The composition of the dots is also confirmed to be GeO2 by x-ray absorption near-edge structure analyses. A significant memory effect is observed through the electrical measurements. Under the low voltage operation of 5 V, the memory window is estimated to ∼0.45 V. Also, a physical model is proposed to demonstrate the charge storage effect through the interfacial traps of GeO2 nanodots. © 2004 American Institute of Physics. [ABSTRACT FROM AUTHOR]