At-wavelength figure metrology of hard x-ray focusing mirrors

We have developed an at-wavelength wave-front metrology of a grazing-incidence focusing optical systems in the hard x-ray region. The metrology is based on numerical retrieval from the intensity profile around the focal point. We demonstrated the at-wavelength metrology and estimated the surface figure error on a test mirror. An experiment for measuring the focusing intensity profile was performed at the 1-km-long beamline (BL29XUL) of SPring-8. The obtained results were compared with the profile measured using an optical interferometer and were confirmed to be in good agreement with it. This technique is a potential method of characterizing wave-front aberrations on elliptical mirrors for sub-10-nm focusing. © 2006 American Institute of Physics.Yumoto H., Mimura H., Matsuyama S., et al. At-wavelength figure metrology of hard x-ray focusing mirrors. Review of Scientific Instruments, 77, 6, 063712 (2006) https://doi.org/10.1063/1.221687

Erythropoietin supports the survival of prostate cancer, but not growth and bone metastasis

Erythropoietin (Epo) is used in clinical settings to enhance hematopoietic function and to improve the quality of life for patients undergoing chemotherapy by reducing fatigue and the need for transfusions. However, several meta‐analyses have revealed that Epo treatments are associated with an increased risk of mortality in cancer patients. In this study, we examined the role of Epo in prostate cancer (PCa) progression, using in vitro cell culture systems and in vivo bone metastatic assays. We found that Epo did not stimulate the proliferation of PCa cell lines, but did protect PCa cells from apoptosis. In animal models of PCa metastasis, no evidence was found to support the hypothesis that Epo enhances metastasis. Together, these findings suggest that Epo may be useful for treating severe anemia in PCa patients without increasing metastatic risk. J. Cell. Biochem. 114: 2471–2478, 2013. © 2013 Wiley Periodicals, Inc.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/100159/1/jcb24592.pd

Direct determination of the wave field of an x-ray nanobeam

We present a remarkably accurate method for determining the wave field of an x-ray nanobeam. The intensity profile of a beam was directly measured over a range of three orders of magnitude while its phase distribution was successfully recovered using an iterative algorithm. The evolution of the wave field along the beam propagation direction was precisely simulated, and there was good agreement with the experimental results.Hidekazu Mimura, Hirokatsu Yumoto, Satoshi Matsuyama, Soichiro Handa, Takashi Kimura, Yasuhisa Sano, Makina Yabashi, Yoshinori Nishino, Kenji Tamasaku, Tetsuya Ishikawa, and Kazuto Yamauchi Phys. Rev. A 77, 015812 (2008)

Growth Arrest‐Specific 6 (GAS6) Promotes Prostate Cancer Survival by G1 Arrest/S Phase Delay and Inhibition of Apoptosis During Chemotherapy in Bone Marrow

Prostate cancer (PCa) is known to develop resistance to chemotherapy. Growth arrest‐specific 6 (GAS6), plays a role in tumor progression by regulating growth in many cancers. Here, we explored how GAS6 regulates the cell cycle and apoptosis of PCa cells in response to chemotherapy. We found that GAS6 is sufficient to significantly increase the fraction of cells in G1 and the duration of phase in PCa cells. Importantly, the effect of GAS6 on G1 is potentiated during docetaxel chemotherapy. GAS6 altered the levels of several key cell cycle regulators, including the downregulation of Cyclin B1 (G2/M phase), CDC25A, Cyclin E1, and CDK2 (S phase entry), while the upregulation of cell cycle inhibitors p27 and p21, Cyclin D1, and CDK4. Importantly, these changes became further accentuated during docetaxel treatment in the presence of GAS6. Moreover, GAS6 alters the apoptotic response of PCa cells during docetaxel chemotherapy. Docetaxel induced PCa cell apoptosis is efficiently suppressed in PCa cell culture in the presence of GAS6 or GAS6 secreted from co‐cultured osteoblasts. Similarly, the GAS6‐expressing bone environment protects PCa cells from apoptosis within primary tumors in vivo studies. Docetaxel induced significant levels of Caspase‐3 and PARP cleavage in PCa cells, while GAS6 protected PCa cells from docetaxel‐induced apoptotic signaling. Together, these data suggest that GAS6, expressed by osteoblasts in the bone marrow, plays a significant role in the regulation of PCa cell survival during chemotherapy, which will have important implications for targeting metastatic disease. J. Cell. Biochem. 117: 2815–2824, 2016. © 2016 Wiley Periodicals, Inc.We explored how GAS6, expressed by osteoblasts, regulates the cell cycle and apoptosis in PCa cells during chemotherapy in the bone marrow. We demonstrate that GAS6 significantly increases the number of G1 arrested cells by altering signaling networks associated with G1 arrest and S phase delay. Our results suggest that GAS6 contributes to the regulation of PCa cell survival during chemotherapy in the bone marrow microenvironment.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/134410/1/jcb25582_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/134410/2/jcb25582.pd

Efficient focusing of hard x rays to 25 nm by a total reflection mirror

Nanofocused x rays are indispensable because they can provide high spatial resolution and high sensitivity for x-ray nanoscopy/spectroscopy. A focusing system using total reflection mirrors is one of the most promising methods for producing nanofocused x rays due to its high efficiency and energy-tunable focusing. The authors have developed a fabrication system for hard x-ray mirrors by developing elastic emission machining, microstitching interferometry, and relative angle determinable stitching interferometry. By using an ultraprecisely figured mirror, they realized hard x-ray line focusing with a beam width of 25 nm at 15 keV. The focusing test was performed at the 1-km -long beamline of SPring-8. © 2007 American Institute of Physics.Hidekazu Mimura, Hirokatsu Yumoto, et al. "Efficient focusing of hard x rays to 25nm by a total reflection mirror", Appl. Phys. Lett. 90(5), 051903 (2007) https://doi.org/10.1063/1.2436469

At-wavelength figure metrology of total reflection mirrors in hard x-ray region

Hirokatsu Yumoto, Hidekazu Mimura, Satoshi Matsuyama, Soichiro Handa, Akihiko Shibatani, Keiko Katagishi, Yasuhisa Sano, Makina Yabashi, Yoshinori Nishino, Kenji Tamasaku, Tetsuya Ishikawa, and Kazuto Yamauchi "At-wavelength figure metrology of total reflection mirrors in hard x-ray region", Proc. SPIE 6317, Advances in X-Ray/EUV Optics, Components, and Applications, 631709 (29 August 2006); https://doi.org/10.1117/12.681587

Mer Tyrosine Kinase Regulates Disseminated Prostate Cancer Cellular Dormancy

Many prostate cancer (PCa) recurrences are thought to be due to reactivation of disseminated tumor cells (DTCs). We previously found a role of the TAM family of receptor tyrosine kinases TYRO3, AXL, and MERTK in PCa dormancy regulation. However, the mechanism and contributions of the individual TAM receptors is largely unknown. Knockdown of MERTK, but not AXL or TYRO3 by shRNA in PCa cells induced a decreased ratio of Pâ Erk1/2 to Pâ p38, increased expression of p27, NR2F1, SOX2, and NANOG, induced higher levels of histone H3K9me3 and H3K27me3, and induced a G1/G0 arrest, all of which are associated with dormancy. Similar effects were also observed with siRNA. Most importantly, knockdown of MERTK in PCa cells increased metastasis free survival in an intraâ cardiac injection mouse xenograft model. MERTK knockdown also failed to inhibit PCa growth in vitro and subcutaneous growth in vivo, which suggests that MERTK has specificity for dormancy regulation or requires a signal from the PCa microenvironment. The effects of MERTK on the cell cycle and histone methylation were reversed by p38 inhibitor SB203580, which indicates the importance of MAP kinases for MERTK dormancy regulation. Overall, this study shows that MERTK stimulates PCa dormancy escape through a MAP kinase dependent mechanism, also involving p27, pluripotency transcription factors, and histone methylation. J. Cell. Biochem. 118: 891â 902, 2017. © 2016 Wiley Periodicals, Inc.Escape from cellular dormancy is the process where previously dormant single disseminated tumor cells reactivate to form cancer microâ metastases, which continue to grow and ultimately make the disease incurable. Here, were show that Mer tyrosine kinase is important for prostate cancer dormancy escape through a mechanism involving MAP kinases, cell cycle inhibitors, epigenetics, and transcription factors associated with pluripotent cells.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/136285/1/jcb25768_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/136285/2/jcb25768.pd

Relative angle determinable stitching interferometry for hard x-ray reflective optics

Metrology plays an important role in surface figuring with subnanometer accuracy. We have developed relative angle determinable stitching interferometry for the surface figuring of elliptical mirrors, in order to realize hard x-ray nanofocusing. In a stitching system, stitching angles are determined not by the general method using a common area between neighboring shots, but by the new method using the mirror's tilt angles measured at times when profile data are acquired. The high measurement accuracy of approximately 4 nm (peak-to-valley) was achieved in the measurement of a cylindrical surface having the same curvature as the elliptically designed shape to enable hard x-ray nanofocusing. © 2005 American Institute of Physics.Hidekazu Mimura, Hirokatsu Yumoto, Satoshi Matsuyama, Kazuya Yamamura, Yasuhisa Sano, Kazumasa Ueno, Katsuyoshi Endo, Yuzo Mori, Makina Yabashi, Kenji Tamasaku, Yoshinori Nishino, Tetsuya Ishikawa and Kazuto Yamauchi, "Relative angle determinable stitching interferometry for hard x-ray reflective optics", Review of Scientific Instruments 76(4), 045102 (2005) https://doi.org/10.1063/1.186847

Wavefield characterization of nearly diffraction-limited focused hard x-ray beam with size less than 10 nm

In situ wavefront compensation is a promising method to realize a focus size of only a few nanometers for x-ray beams. However, precise compensation requires evaluation of the wavefront with an accuracy much shorter than the wavelength. Here, we characterized a one-dimensionally focused beam with a width of 7 nm at 20 keV using a multilayer mirror. We demonstrate that the wavefront can be determined precisely from multiple intensity profiles measured around the beamwaist. We compare the phase profiles recovered from intensity profiles measured under the same mirror condition but with three different aperture sizes and find that the accuracy of phase retrieval is as small as 12. © 2010 American Institute of Physics.Takashi Kimura, Hidekazu Mimura, Soichiro Handa, Hirokatsu Yumoto, Hikaru Yokoyama, Shota Imai, Satoshi Matsuyama, Yasuhisa Sano, Kenji Tamasaku, Yoshiki Komura, Yoshinori Nishino, Makina Yabashi, Tetsuya Ishikawa, and Kazuto Yamauchi , "Wavefield characterization of nearly diffraction-limited focused hard x-ray beam with size less than 10 nm", Review of Scientific Instruments 81(12), 123704 (2010) https://doi.org/10.1063/1.3509384

Fabrication of elliptically figured mirror for focusing hard x rays to size less than 50 nm

In this study, we designed, fabricated, and evaluated a hard x-ray focusing mirror having an ideally focused beam with a full width at half maximum in the intensity profile of 36 nm at an x-ray energy of 15 keV. The designed elliptically curved shape was fabricated by a computer-controlled fabrication system using plasma chemical vaporization machining and elastic emission machining, on the basis of surface profiles accurately measured by combining microstitching interferometry with relative angle determinable stitching interferometry. A platinum-coated surface was employed for hard x-ray focusing with a large numerical aperture. Line-focusing tests on the fabricated elliptical mirror are carried out at the 1-km -long beamline of SPring-8. A full width at half maximum of 40 nm was achieved in the focused beam intensity profile under the best focus conditions. © 2005 American Institute of Physics.Hirokatsu Yumoto, Hidekazu Mimura, Satoshi Matsuyama, Hideyuki Hara, Kazuya Yamamura, Yasuhisa Sano Kazumasa Ueno, Katsuyoshi Endo Yuzo Mori, Makina Yabashi, Yoshinori Nishino, Kenji Tamasaku, Tetsuya Ishikawa and Kazuto Yamauchi, "Fabrication of elliptically figured mirror for focusing hard x rays to size less than 50nm", Review of Scientific Instruments 76(6), 063708 (2005) https://doi.org/10.1063/1.1922827