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Detachment-induced cell death, or anoikis, is a type of apoptosis that occurs when epithelial cells lose their attachment to the extracellular matrix. Anoikis serves as a physiologic barrier to metastasis. Deviation from the tightly regulated mechanism of detachment-induced cell death might result in progression to metastatic cancer. Here, we investigated the function of CIIA in the regulation of anoikis. CIIA protein was upregulated in colon cancer tissue samples. Knockdown of CIIA in metastatic colorectal carcinoma SW620 and KM12SM cells promoted detachment-induced cell death through the regulation of caspase activation. Knockdown of CIIA also inhibited anchorage-independent growth in soft agar and colony formation after suspension stress. These observations suggest that CIIA is a novel negative regulator of anoikis. Cancer Res; 70(15); 6352–8. ©2010 AACR.

Supplementary Methods, Figures 1-5 from CIIA Is a Novel Regulator of Detachment-Induced Cell Death

A self-seeded X-ray free-electron laser (XFEL) is a promising approach to realize bright, fully coherent free-electron laser (FEL) sources in the hard X-ray domain that have been a long-standing issue with longitudinal coherence remaining challenging. At the Pohang Accelerator Laboratory XFEL, we have demonstrated a hard X-ray self-seeded XFEL with a peak brightness of 3.2 × 1035 photons s–1 mm–2 mrad–2 0.1% bandwidth (BW)–1 at 9.7 keV. The bandwidth (0.19 eV) is about 1/70 times as wide (close to the Fourier transform limit) and the peak spectral brightness is 40 times higher than in self-amplified spontaneous emission (SASE), with substantial improvements in the stability of self-seeding and noticeably suppressed pedestal effects. We could reach an excellent self-seeding performance at a photon energy of 3.5 keV (lowest) and 14.6 keV (highest) with the same stability as the 9.7 keV self-seeding. The bandwidth of the 14.6 keV seeded FEL was 0.32 eV, and the peak brightness was 1.3 × 1035 photons s–1 mm–2 mrad–2 0.1%BW–1. We show that the use of seeded FEL pulses with higher reproducibility and a cleaner spectrum results in serial femtosecond crystallography data of superior quality compared with data collected using SASE mode. A hard X-ray self-seeded X-ray free-electron laser at the Pohang Accelerator Laboratory provides X-ray pulses with peak brightness of 3.2 × 1035 photons s–1 mm–2 mrad–2 0.1%BW–1 at 9.7 keV and a very small shot-to-shot electron energy jitter of 0.012%.

With forming of an X-ray cavity with a set of narrow bandwidth diamond Bragg crystals and by storing and recirculating the output of an amplifier in an X- ray cavity so that the X-ray pulse can interact with following fresh electron bunches over many passes thus enabling the development of full temporal coherence, we will be able to build cavity-based X-ray FELs (CBXFELs) such as the X-ray free-electron laser oscillator (XFELO) and the X-ray regenerative amplifier free-electron laser (XRAFEL) [1, 2]. One of the key challenges to forming the X-ray cavity is the nanopositioning design and construction of the cavity mechanical system. In this paper, we present the design of the nanopositioning and mechanical system that is currently under construction for use in a proof-of-principle cavity-based X-ray free electron laser experiment at the LCLS-II at SLAC.

The ion exchange membrane (IEM) is a key component that helps achieve good performance in membrane capacitive deionization (MCDI). However, systematic researches have been limitedly conducted regarding the effect of IEM characteristics on MCDI performance. The aim of this study is to investigate the effects of the characteristics of the cation exchange membrane (CEM) on MCDI performance. Salt adsorption capacity (SAC), maximum average deionization rate (MADR), and charge efficiency were chosen to demonstrate MCDI performances. Only MADR was significantly affected by CEM characteristics. Additionally, MADR showed a positive relationship with the transport number divided by total electrical resistance (R2 = 0.83). Therefore, CEM should have a high transport number and low electrical resistance for fast rate-capable MCDI. The correlations between CEM characteristics and MCDI performances revealed through this study are expected to further develop high-performance MCDI.

Generally, turn-to-turn fluctuations of synchrotron radiation power in a storage ring depend on the 6D phase-space distribution of the electron bunch. This effect is related to the interference of fields radiated by different electrons. Changes in the relative electron positions and velocities inside the bunch result in fluctuations in the total emitted energy per pass in a synchrotron radiation source. This effect has been previously described assuming constant and equal electron velocities before entering the synchrotron radiation source. In this paper, we present a generalized formula for the fluctuations with a non-negligible beam divergence. Further, we corroborate this formula in a dedicated experiment with undulator radiation in the Integrable Optics Test Accelerator (IOTA) storage ring at Fermilab. Lastly, possible applications in beam instrumentation are discussed.

We demonstrate a hard-X-ray self-seeded (HXRSS) free-electron laser (FEL) at Pohang Accelerator Laboratory with an unprecedented peak brightness (3.2 × 1035 photons/(s·mm2·mrad2·0.1%BW)). The self-seeded FEL generates hard X-ray pulses with improved spectral purity; the average pulse energy was 0.85 mJ at 9.7 keV, almost as high as in SASE mode; the bandwidth (0.19 eV) is about 1/70 as wide, the peak spectral brightness is 40 times higher than in self-amplified spontaneous emission (SASE) mode, and the stability is excellent with > 94% of shots exceeding the average SASE intensity. Using this self-seeded XFEL, we conducted serial femtosecond crystallography (SFX) experiments to map the structure of lysozyme protein; data-quality metrics such as Rsplit, multiplicity, and signal-to-noise ratio for the SFX were substantially increased. We precisely map out the structure of lysozyme protein with substantially better statistics for the diffraction data and significantly sharper electron density maps compared to maps obtained using SASE mode.

In a storage ring, turn-to-turn fluctuations in the intensity of spontaneous synchrotron radiation occur due to two mechanisms. The first mechanism is the quantum uncertainty in the number of emitted photons. The second mechanism is the turn-to-turn variations in the relative positions of classical pointlike electrons in the bunch. We present a unified description of both effects in the framework of quantum optics. We derive an equation for the fluctuations for an arbitrary degree of coherence, which generalizes previously reported results for temporally incoherent radiation. We compare the predictions of our calculation with a previous experiment at Brookhaven National Laboratory, where the latter mechanism was dominant and propose a new dedicated experiment in the Integrable Optics Test Accelerator (IOTA) at Fermilab, where the two mechanisms may have comparable contributions to the fluctuations. Finally, our calculation shows that the magnitude of the fluctuations is rather sensitive to the dimensions and the shape of the electron bunch, thereby indicating possible applications in beam instrumentation. In particular, the small vertical size of the flat beams in IOTA may be estimated via these fluctuations, whereas measurement by a conventional synchrotron radiation monitor is difficult due to the diffraction limit.

Wavefront-preserving x-ray diamond crystal optics are essential for numerous applications in x-ray science. Perfect crystals with flat Bragg planes are a prerequisite for wavefront preservation in Bragg diffraction. However, this condition is difficult to realize in practice because of inevitable crystal imperfections. Here we use x-ray rocking curve imaging to study the smallest achievable Bragg-plane slope errors in the best presently available synthetic diamond crystals and how they compare with those of perfect silicon crystals. We show that the smallest specific slope errors in the best diamond crystals (both freestanding or strain-free mounted) are about 0.15-0.2~$\mu$rad/mm$^2$. These errors are only a factor of two larger than the 0.05-0.1~$\mu$rad/mm$^2$ specific slope errors we measure in perfect silicon crystals. High-temperature annealing at 1450$^{\circ}$C of almost flawless diamond crystals reduces the slope errors very close to those of silicon. Further investigations are required to establish the wavefront-preservation properties of these crystals., Comment: 12 figures, 1 table

X-ray free-electron lasers in the oscillator configuration (XFELO) are future fully coherent hard X-rays sources with ultrahigh spectral purity. X-ray beams circulate in an XFELO optical cavity comprising diamond single crystals. They function as high-reflectance (close to 100%), narrowband (∼10 meV) Bragg backscattering mirrors. The average power density of the X-ray beams in the XFELO cavity is predicted to be as high as ∼10 kW mm−2. Therefore, XFELO feasibility relies on the ability of diamond crystals to withstand such a high radiation load and preserve their high reflectivity. Here the endurance of diamond crystals to irradiation with multi-kW mm−2 power density X-ray beams is studied. It is shown that the high Bragg reflectivity of the diamond crystals is preserved after the irradiation, provided it is performed at ∼1 × 10−8 Torr high-vacuum conditions. Irradiation under 4 × 10−6 Torr results in a ∼1 meV shift of the Bragg peak, which corresponds to a relative lattice distortion of 4 × 10−8, while the high Bragg reflectivity stays intact.

X-ray free-electron-laser oscillators with nuclear-resonant cavity stabilization hold the promise for providing X-rays with unprecedented coherence properties that will enable interesting quantum-optical and metrologial applications. Among these are atom optics with X-ray-based optical elements providing high momentum transfer, or a frequency standard far surpassing the best state-of-the-art atomic clocks.

Surface mechanical properties of poly(urethane acrylate) (PUA)/silica hybrid interpenetrating polymer network (IPN) coating materials were investigated using several test methods including nano-indentation, nano-scratch, pencil hardness, and stretching. To prepare coated films, an organic part (urethane acrylate) was mixed with an inorganic part (silica) at various ratios. Independent crosslinking reactions were applied to form the hybrid IPN structure: UV curing and sol-gel reactions were used for the organic and inorganic parts, respectively. The prepared hybrid IPN coatings exhibited no macroscopic phase separation. As the silica content was increased, the values for indentation hardness and pencil hardness increased, while failure strain during stretching test decreased. It was found that the hybrid IPN coating with its balanced dissipative and elastic properties had better scratch resistance than that of other coatings.

The localization and transfer of carbon nanotubes (CNTs) in PA66/(PS/PPE)/CNTs nanocomposites were investigated using several methods including TEM/EDS techniques, surface energy and wetting coefficient calculations, electrical conductivity measurements, and rheological analysis. The CNTs were found to be dispersed preferentially in the polyamide 66 (PA66) phase and not in the miscible polystyrene (PS)/poly(phenylene ether) (PPE) blend phase because CNTs have a higher affinity for PA66. The electrical conductivity of the PA66/(PS/PPE)/CNTs nanocomposites significantly increased compared to the PA66/CNTs nanocomposites at the same CNT loading. The nanocomposites were prepared with three different compounding procedures. The nanocomposites prepared with sequence III (premixing PS/PPE and CNTs, and then blending the (PS/PPE)/CNTs with PA66) yielded a better CNT dispersion that resulted in a higher electrical conductivity. The CNT dispersion was determined by TEM and rheological analysis. Additionally, the nonlinear-linear viscoelastic ratio (NLR) was used to quantify the degree of CNT dispersion. Because the CNTs initially dispersed in the unfavorable PS/PPE phase were transferred as individual rods into the preferred PA66 phase during the second step of compounding sequence III, the nanocomposite prepared with sequence III had a higher NLR value, that is, a better CNT dispersion compared to the other nanocomposite prepared with different compounding sequences.

A wake monochromator based on a large-area diamond single crystal for hard X-ray self-seeding has been successfully installed and commissioned in the hard X-ray free-electron laser (FEL) at the Pohang Accelerator Laboratory with international collaboration. For this commissioning, the self-seeding was demonstrated with a low bunch charge (40 pC) and the nominal bunch charge (180 pC) of self-amplified spontaneous emission (SASE) operation. The FEL pulse lengths were estimated as 7 fs and 29.5 fs, respectively. In both cases, the average spectral brightness increased by more than three times compared with the SASE mode. The self-seeding experiment was demonstrated for the first time using a crystal with a thickness of 30 µm, and a narrow bandwidth of 0.22 eV (full width at half-maximum) was obtained at 8.3 keV, which confirmed the functionality of a crystal with such a small thickness. In the nominal bunch-charge self-seeding experiment, the histogram of the intensity integrated over a 1 eV bandwidth showed a well defined Gaussian profile, which is evidence of the saturated FEL and a minimal electron-energy jitter (∼1.2 × 10−4) effect. The corresponding low photon-energy jitter (∼2.4 × 10−4) of the SASE FEL pulse, which is two times lower than the Pierce parameter, enabled the seeding power to be maximized by maintaining the spectral overlap between SASE FEL gain and the monochromator.

X-ray free-electron lasers in the oscillator configuration (XFELO) are future fully coherent hard X-rays sources with ultrahigh spectral purity. X-ray beams circulate in an XFELO optical cavity comprising diamond single crystals. They function as high-reflectance (close to 100%), narrowband (∼10 meV) Bragg backscattering mirrors. The average power density of the X-ray beams in the XFELO cavity is predicted to be as high as ∼10 kW mm

We report the electrical and optical properties of structurally simple refractive-index-matched indium tin oxide (IM-ITO) films prepared on high-refractive index hard-coated polyethylene terephthalate (KM-V2) substrates by using a pilot scale roll to roll magnetron sputtering system for implementation in touch screen panels. We found that the ITO thin films are polycrystalline with a preferred (222) orientation. We determined the appropriate conditions for the deposition of simple-structure IM-ITO films on KM-V2 substrates for touch screen panels with an invisible electrode pattern. Moreover, the outgassing of the polymer substrate is very important in the roll-to-roll sputtering fabrication of high-quality IM-ITO films with the required electrical and optical properties.

RC3/neurogranin is a postsynaptic protein and plays pivotal roles in spatial learning and emotional anxiety as well as synaptic plasticity. The expression level of RC3 is dynamically changed during developmental stages, but the function of RC3 in brain development is not well understood yet. Neurotrophins interact with tropomyosin-related kinase receptors to activate Ras-extracellular signal-regulated kinase (ERK) pathway and can also induce neuronal differentiation. In this study, we demonstrate that RC3 inhibits Ras-ERK pathway by interaction with Ras and controls neurite outgrowth induced by neurotrophins. In PC12 cells, RC3 inhibits nerve growth factor (NGF)-induced activation of Ras and thereby ERK1/2 signaling cascade as well as neurite outgrowth induced by NGF. We found Ras is the target of the inhibitory function of RC3, because RC3 interacts with Ras and suppresses the elevated affinity of Ras to Ras-binding domain of Raf-1. Meanwhile, already activated Raf-1 by Ras activity is not affected by RC3. Furthermore, depletion of RC3 by RNA interference drastically enhances the stimulation of ERK1/2 and neurite outgrowth induced by brain-derived neurotrophic factor in hippocampal neurons. These findings suggest that RC3 is a novel natural inhibitor of Ras-ERK1/2 signaling axis, leading to negatively regulate neuronal differentiation induced by neurotrophins.

Performance tests of parabolic beryllium refractive lenses, considered as X-ray focusing elements in the future X-ray free-electron laser oscillator (XFELO), are reported. Single and double refractive lenses were subject to X-ray tests, which included: surface profile, transmissivity measurements, imaging capabilities and wavefront distortion with grating interferometry. Optical metrology revealed that surface profiles were close to the design specification in terms of the figure and roughness. The transmissivity of the lenses is >94% at 8 keV and >98% at 14.4 and 18 keV. These values are close to the theoretical values of ideal lenses. Images of the bending-magnet source obtained with the lenses were close to the expected ones and did not show any significant distortion. Grating interferometry revealed that the possible wavefront distortions produced by surface and bulk lens imperfections were on the level of ∼λ/60 for 8 keV photons. Thus the Be lenses can be succesfully used as focusing and beam collimating elements in the XFELO.

Learn about the latest advances in high-brightness X-ray physics and technology with this authoritative text. Drawing upon the most recent theoretical developments, pre-eminent leaders in the field guide readers through the fundamental principles and techniques of high-brightness X-ray generation from both synchrotron and free-electron laser sources. A wide range of topics is covered, including high-brightness synchrotron radiation from undulators, self-amplified spontaneous emission, seeded high-gain amplifiers with harmonic generation, ultra-short pulses, tapering for higher power, free-electron laser oscillators, and X-ray oscillator and amplifier configuration. Novel mathematical approaches and numerous figures accompanied by intuitive explanations enable easy understanding of key concepts, whilst practical considerations of performance-improving techniques and discussion of recent experimental results provide the tools and knowledge needed to address current research problems in the field. This is a comprehensive resource for graduate students, researchers and practitioners who design, manage or use X-ray facilities.