Element Selectivity in Second-Harmonic Generation of GaFeO_{3} by a Soft-X-Ray Free-Electron Laser.

Nonlinear optical frequency conversion has been challenged to move down to the extreme ultraviolet and x-ray region. However, the extremely low signals have allowed researchers to only perform transmission experiments of the gas phase or ultrathin films. Here, we report second harmonic generation (SHG) of the reflected beam of a soft x-ray free-electron laser from a solid, which is enhanced by the resonant effect. The observation revealed that the double resonance condition can be met by absorption edges for transition metal oxides in the soft x-ray range, and this suggests that the resonant SHG technique can be applicable to a wide range of materials. We discuss the possibility of element-selective SHG spectroscopy measurements in the soft x-ray range.

Temperature Dependence of Magnetically Active Charge Excitations in Magnetite across the Verwey Transition.

We study the electronic structure of bulk single crystals and epitaxial films of Fe_{3}O_{4}. Fe 2p core level spectra show clear differences between hard x-ray (HAX) and soft x-ray photoemission spectroscopy (PES). The bulk-sensitive spectra exhibit temperature (T) dependence across the Verwey transition, which is missing in the surface-sensitive spectra. By using an extended impurity Anderson full-multiplet model-and in contrast to an earlier peak assignment-we show that the two distinct Fe species (A and B site) and the charge modulation at the B site are responsible for the newly found double peaks in the main peak above T_{V} and its T-dependent evolution. The Fe 2p HAXPES spectra show a clear magnetic circular dichroism (MCD) in the metallic phase of magnetized 100-nm-thick films. The model calculations also reproduce the MCD and identify the contributions from magnetically distinct A and B sites. Valence band HAXPES shows a finite density of states at E_{F} for the polaronic half metal with a remnant order above T_{V} and a clear gap formation below T_{V}. The results indicate that the Verwey transition is driven by changes in the strongly correlated and magnetically active B-site electronic states, consistent with resistivity and optical spectra.

RISING beamline (BL28XU) for rechargeable battery analysis.

The newly installed BL28XU beamline at SPring-8 is dedicated to in situ structural and electronic analysis of rechargeable batteries. It supports the time range (1 ms to 100 s) and spatial range (1 µm to 1 mm) needed for battery analysis. Electrochemical apparatus for battery charging and discharging are available in experimental hutches and in a preparation room. Battery analysis can be carried out efficiently and effectively using X-ray diffraction, X-ray absorption fine-structure analysis and hard X-ray photoelectron spectroscopy. Here, the design and performance of the beamline are described, and preliminary results are presented.

Coffin-Siris syndrome is a SWI/SNF complex disorder.

Coffin-Siris syndrome (CSS) is a congenital disorder characterized by intellectual disability, growth deficiency, microcephaly, coarse facial features, and hypoplastic or absent fifth fingernails and/or toenails. We previously reported that five genes are mutated in CSS, all of which encode subunits of the switch/sucrose non-fermenting (SWI/SNF) ATP-dependent chromatin-remodeling complex: SMARCB1, SMARCA4, SMARCE1, ARID1A, and ARID1B. In this study, we examined 49 newly recruited CSS-suspected patients, and re-examined three patients who did not show any mutations (using high-resolution melting analysis) in the previous study, by whole-exome sequencing or targeted resequencing. We found that SMARCB1, SMARCA4, or ARID1B were mutated in 20 patients. By examining available parental samples, we ascertained that 17 occurred de novo. All mutations in SMARCB1 and SMARCA4 were non-truncating (missense or in-frame deletion) whereas those in ARID1B were all truncating (nonsense or frameshift deletion/insertion) in this study as in our previous study. Our data further support that CSS is a SWI/SNF complex disorder.

Electronic excitations of a magnetic impurity state in the diluted magnetic semiconductor (Ga,Mn)As.

The electronic structure of doped Mn in (Ga,Mn)As is studied by resonant inelastic x-ray scattering. From configuration-interaction cluster-model calculations, the line shapes of the Mn L3 resonant inelastic x-ray scattering spectra can be explained by d-d excitations from the Mn ground state dominated by charge-transferred states, in which hole carriers are bound to the Mn impurities, rather than a pure acceptor Mn2+ ground state. Unlike archetypical d-d excitation, the peak widths are broader than the experimental energy resolution. We attribute the broadening to a finite lifetime of the d-d excitations, which decay rapidly to electron-hole pairs in the host valence and conduction bands through the hybridization of the Mn 3d orbital with the ligand band.

An imprinted gene p57KIP2 is mutated in Beckwith-Wiedemann syndrome.

p57KIP2 is a potent tight-binding inhibitor of several G1 cyclin/Cdk complexes, and is a negative regulator of cell proliferation. The gene encoding p57KIP2 is located at 11p15.5 (ref. 2), a region implicated in both sporadic cancers and Beckwith-Wiedemann syndrome, a cancer-predisposing syndrome, making it a tumour-suppressor candidate. Several types of childhood tumours including Wilms' tumour, adrenocortical carcinoma and rhabdomyosarcoma exhibit a specific loss of maternal 11p15 alleles, suggesting that genomic imprinting is involved. Genetic analysis of the Beckwith-Wiedemann syndrome indicated maternal carriers, as well as suggesting a role of genomic imprinting. Previously, we and others demonstrated that p57KIP2 is imprinted and that only the maternal allele is expressed in both mice and humans. Here we describe p57KIP2 mutations in patients with Beckwith-Wiedemann syndrome. Among nine patients we examined, two were heterozygous for different mutations in this gene-a missense mutation in the Cdk inhibitory domain resulting in loss of most of the protein, and a frameshift resulting in disruption of the QT domain. The missense mutation was transmitted from the patient's carrier mother, indicating that the expressed maternal allele was mutant and that the repressed paternal allele was normal. Consequently, little or no active p57KIP2 should exist and this probably causes the overgrowth in this BWS patient.

Successful treatment of monomorphic primary central nervous system post-transplantation lymphoproliferative disorder 5 years after kidney transplantation.

A 31-year-old man underwent living-related kidney transplantation in 2004 as a consequence of primary focal segmental glomerulosclerosis (FSGS). Four years after the transplantation, we confirmed nephrotic syndrome caused by recurrent FSGS. We performed plasmapheresis and low-density lipoprotein adsorption. We also combined steroid therapy with a reduction in the dose of tacrolimus and an increased dose of mycophenolate mofetil. The nephrotic syndrome improved dramatically with this combined therapeutic approach. However, 10 months after these treatments, he revisited our hospital because of altered consciousness. We detected multiple tumor masses in his brain that were ring enhanced on contrast magnetic resonance imaging. Consequently, we suspected primary central nervous system post-transplantation lymphoproliferative disorder (CNS-PTLD). We performed a craniotomy to biopsy the brain tumors. The biopsy specimen showed Epstein-Barr virus-associated diffuse large B-cell lymphoma. There is no definitive treatment for CNS-PTLD. Therefore, we treated the primary CNS-PTLD successfully with whole-brain radiation and discontinuation of immunosuppression therapy.

The clinical utility of comprehensive measurement of autoimmune disease-related antibodies in patients with advanced solid tumors receiving immune checkpoint inhibitors: a retrospective study.

BACKGROUND: The comprehensive measurement of autoimmune disease-related antibodies (Abs) before immune checkpoint inhibitor (ICI) treatment may be useful for predicting the development of immune-related adverse events (irAEs); however, the clinical utility is not well known. MATERIALS AND METHODS: We retrospectively analyzed patients with advanced solid tumors treated with ICI monotherapy or doublet combination therapy between July 2014 and December 2020 at single institute. Anti-nuclear antibody (ANA), anti-thyroglobulin (Tg) Ab, anti-thyroid peroxidase (TPO) Ab, anti-glutamic acid decarboxylase (GAD) Ab, anti-acetylcholine esterase receptor (AchR) Ab, and platelet-associated immunoglobulin G (PA-IgG) Ab were comprehensively measured for the screening before ICI therapy. RESULTS: Of 275 registered patients (median age, 70 years; male, 64.4%; Eastern Cooperative Oncology Group performance status of 0 or 1, 88.7%; and prior regimen of 0-1/≥2, 88.7%/11.3%), 128 non-small-cell lung cancer, 35 gastric cancer, 33 head and neck cancer, 24 melanoma, 19 renal cell carcinoma, 13 urothelial carcinoma, 12 esophageal cancer, 5 malignant mesothelioma of pleura, 2 endometrial cancer, and 4 other cancer were included. The number of patients with positive ANA, Tg, TPO, PA-IgG, GAD, and AchR Abs was 52 (24.9%), 38 (14.5%), 11 (10.1%), 6 (3.5%), 5 (2.0%), and 1 (0.5%), respectively. There was no association between the development of any irAEs and Abs positivity, while thyroid dysfunction developed more frequently among patients with than without Tg Ab or TPO Ab (39.5% versus 12.5%, P < 0.01; 45.5% versus 14.3%, P = 0.02). CONCLUSIONS: The clinical utility of comprehensive measurement of autoimmune disease-related Abs before introduction of ICI therapy was limited for predicting irAE. However, Tg and TPO Abs were risk factors as regards the development of ICI-induced thyroid dysfunction.

A prospective dose-finding trial using a modified continual reassessment method for optimization of fludarabine plus melphalan conditioning for marrow transplantation from unrelated donors in patients with hematopoietic malignancies.

BACKGROUND: Because of the less graft-facilitating effect by bone marrow (BM), we need to assess a dosage of conditioning more accurately particularly in combination with reduced-intensity conditioning. Thus we examined that modified continual reassessment method (mCRM) is applicable for deciding appropriate conditioning of allogeneic BM transplantation. PATIENTS AND METHODS: The conditioning regimen consisted of i.v. fludarabine (125 mg/m2) plus an examination dose of i.v. melphalan. The primary endpoint was a donor-type T-cell chimerism at day 28 with successful engraftment defined as >90% donor cells. Five patients per dose level were planned to be accrued and chimerism data were used to determine the next dose. RESULTS: Seventeen patients were enrolled at doses between 130 and 160 mg/m2. The dose was changed from 160 to 130 mg/m(2) (second level) after five full-donor chimerisms. With one patient of 0% chimera in the second level, the dose was increased to 135 mg/m2 (third level). Following five full-donor chimerisms in the third level, the study was complete as projected. CONCLUSIONS: mCRM was shown to be a relevant method for dose-finding of conditioning regimen. The melphalan dose of 135 mg/m2 was determined as the recommended phase II dose to induce initial full-donor chimerism.

Second-order autocorrelation of XUV FEL pulses via time resolved two-photon single ionization of He.

Second-order autocorrelation spectra of XUV free-electron laser pulses from the Spring-8 Compact SASE Source (SCSS) have been recorded by time and momentum resolved detection of two-photon single ionization of He at 20.45 eV using a split-mirror delay-stage in combination with high-resolution recoil-ion momentum spectroscopy (COLTRIMS). From the autocorrelation trace we extract a coherence time of 8 ± 2 fs and a mean pulse duration of 28 ± 5 fs, much shorter than estimations based on electron bunch-length measurements. Simulations within the partial coherence model [Opt. Lett. 35, 3441 (2010)] are in agreement with experiment if a pulse-front tilt across the FEL beam diameter is taken into account that leads to a temporal shift of about 6 fs between both pulse replicas.

Enhanced nonlinear double excitation of He in intense extreme ultraviolet laser fields.

Nonlinear, three-photon double excitation of He in intense extreme ultraviolet free-electron laser fields (∼24.1 eV, ∼5 TW/cm2) is presented. Resonances to the doubly excited states converging to the He+ N=3 level are revealed by the shot-by-shot photoelectron spectroscopy and identified by theoretical calculations based on the time-dependent Schrödinger equation for the two-electron atom under a laser field. It is shown that the three-photon double excitation is enhanced by intermediate Rydberg states below the first ionization threshold, giving a greater contribution to the photoionization yields than the two-photon process by more than 1 order of magnitude.

Role of Ti 3d carriers in mediating the ferromagnetism of Co∶TiO2 anatase thin films.

We study the surface and bulk electronic structure of the room-temperature ferromagnet Co∶TiO(2) anatase films using soft- and hard-x-ray photoemission spectroscopy with probe sensitivities of ∼1 and ∼10 nm, respectively. We obtain direct evidence of metallic Ti(3+) states in the bulk, which get suppressed to give a surface semiconductor, thus indicating the difference in electronic structure between surface and bulk. X-ray absorption and resonant photoemission spectroscopy reveal Ti(3+) electrons at the Fermi level (E(F)) and high-spin Co(2+) electrons occurring away from E(F). The results show the importance of the charge neutrality condition: Co(2+)+V(O)(2-)+2Ti(4+)↔Co(2+)+2Ti(3+) (V(O) is oxygen vacancy), which gives rise to the elusive Ti 3d carriers mediating ferromagnetism via the Co 3d-O 2p-Ti 3d exchange interaction pathway of the occupied orbitals.

Wavefront analysis of nonlinear self-amplified spontaneous-emission free-electron laser harmonics in the single-shot regime.

The single-shot spatial characteristics of the vacuum ultraviolet self-amplified spontaneous emission of a free electron laser (FEL) is measured at different stages of amplification up to saturation with a Hartmann wavefront sensor. We show that the fundamental radiation at 61.5 nm tends towards a single-mode behavior as getting closer to saturation. The measurements are found in good agreement with simulations and theory. A near diffraction limited wavefront was measured. The analysis of Fresnel diffraction through the Hartmann wavefront sensor hole array also provides some further insight for the evaluation of the FEL transverse coherence, of high importance for various applications.

Novel and recurrent TRPV4 mutations and their association with distinct phenotypes within the TRPV4 dysplasia family.

BACKGROUND: Mutations in TRPV4, a gene that encodes a Ca(2+) permeable non-selective cation channel, have recently been found in a spectrum of skeletal dysplasias that includes brachyolmia, spondylometaphyseal dysplasia, Kozlowski type (SMDK) and metatropic dysplasia (MD). Only a total of seven missense mutations were detected, however. The full spectrum of TRPV4 mutations and their phenotypes remained unclear. OBJECTIVES AND METHODS: To examine TRPV4 mutation spectrum and phenotype-genotype association, we searched for TRPV4 mutations by PCR-direct sequencing from genomic DNA in 22 MD and 20 SMDK probands. RESULTS: TRPV4 mutations were found in all but one MD subject. In total, 19 different heterozygous mutations were identified in 41 subjects; two were recurrent and 17 were novel. In MD, a recurrent P799L mutation was identified in nine subjects, as well as 10 novel mutations including F471del, the first deletion mutation of TRPV4. In SMDK, a recurrent R594H mutation was identified in 12 subjects and seven novel mutations. An association between the position of mutations and the disease phenotype was also observed. Thus, P799 in exon 15 is a hot codon for MD mutations, as four different amino acid substitutions have been observed at this codon; while R594 in exon 11 is a hotspot for SMDK mutations. CONCLUSION: The TRPV4 mutation spectrum in MD and SMDK, which showed genotype-phenotype correlation and potential functional significance of mutations that are non-randomly distributed over the gene, was presented in this study. The results would help diagnostic laboratories establish efficient screening strategies for genetic diagnosis of the TRPV4 dysplasia family diseases.

Activity of pegylated liposomal doxorubicin for extragenital mullerian adenosarcoma with sarcomatous overgrowth: a case report and a review of the literature.

A 47-year-old woman was diagnosed with extragenital mullerian adenosarcoma with sarcomatous overgrowth. One month after her initial surgery, the patient developed pelvic recurrence, which was completely excised by surgery. However, one month later, the patient developed further recurrences in her pelvis and upper abdomen. A clinical complete response was achieved with three cycles of liposomal doxorubicin and is currently clinically free of disease. So far, including the present case, 23 cases of extragenital mulleian adenosarcoma have been reported in the English literature. Because of the rarity of the reported cases, there are no treatment guidelines based on a good level of evidence. In the current report, through a literature review, we provide information on the activity of pegylated liposomal doxorubicin for extragenital mullerian adenosarcoma with sarcomatous overgrowth.

Out-of-plane nesting driven spin spiral in ultrathin Fe/Cu(001) films.

Epitaxial ultrathin Fe films on fcc Cu(001) exhibit a spin spiral (SS), in contrast to the ferromagnetism of bulk bcc Fe. We study the in-plane (IP) and out-of-plane (OP) Fermi surfaces (FSs) of the SS in 8 monolayer Fe/Cu(001) films using energy-dependent soft-x-ray momentum-resolved photoemission spectroscopy. We show that the SS originates in nested regions confined to OP FSs, which are drastically modified compared to IP FSs. From precise reciprocal-space maps in successive zones, we obtain the associated real space compressive strain of 1.5+/-0.5% along c axis. An autocorrelation analysis quantifies the incommensurate ordering vector q=(2pi/a)(0,0, approximately 0.86), favoring a SS and consistent with magneto-optic Kerr effect experiments. The results reveal the importance of IP and OP FS mapping for ultrathin films.

Multiphoton double ionization of Ar in intense extreme ultraviolet laser fields studied by shot-by-shot photoelectron spectroscopy.

Photoelectron spectroscopy has been performed to study the multiphoton double ionization of Ar in an intense extreme ultraviolet laser field (hν ∼ 21 eV, ∼ 5 TW/cm²), by using a free electron laser (FEL). Three distinct peaks identified in the observed photoelectron spectra clearly show that the double ionization proceeds sequentially via the formation of Ar(+): Ar+hν→Ar (+) + e⁻ and Ar²(+) + 2hν→Ar(+) + e⁻. Shot-by-shot recording of the photoelectron spectra allows simultaneous monitoring of FEL spectrum and the multiphoton process for each FEL pulse, revealing that the two-photon ionization from Ar(+) is significantly enhanced by intermediate resonances in Ar(+).

Evidence for a correlated insulator to antiferromagnetic metal transition in CrN.

We investigate the electronic structure of chromium nitride (CrN) across the first-order magnetostructural transition at T(N)∼286 K. Resonant photoemission spectroscopy (PES) shows a gap in the 3d partial density of states at the Fermi level and an on-site Coulomb energy U∼4.5 eV, indicating strong electron-electron correlations. Bulk-sensitive high-resolution (6 meV) laser PES reveals a clear Fermi edge indicating an antiferromagnetic metal below T(N). Hard x-ray Cr 2p core-level PES shows T-dependent changes across T(N) which originate from screening due to coherent states as substantiated by cluster model calculations using the experimentally observed U. Electrical resistivity confirms an insulator above T(N) (E(g)∼70 meV) becoming a disordered metal below T(N). Thus, CrN transforms from a correlated insulator to an antiferromagnetic metal, coupled to the magnetostructural transition.

Anomalous state sandwiched between Fermi liquid and charge ordered Mott-insulating phases of Ti4O7.

The Magnéli phase Ti(4)O(7) exhibits two sharp jumps in resistivity with coupled structural transitions as a function of temperature at T(c1) approximately 142 K and T(c2) = 154 K. We have studied electronic structure changes across the two transitions using 7 eV laser, soft x-ray, and hard x-ray (HX) photoemission spectroscopy (PES). Ti 2p-3d resonant PES and HX PES show a clear metallic Fermi edge and mixed valency above T(c2). The low temperature phase below T(c1) shows a clear insulating gap of approximately 100 meV. The intermediate phase between T(c1) and T(c2) indicates a pseudogap coexisting with remnant coherent states. HX PES and complementary calculations have confirmed the coherent screening in the strongly correlated intermediate phase. The results suggest the existence of a highly anomalous state sandwiched between the mixed-valent Fermi liquid and charge ordered Mott-insulating phase in Ti(4)O(7).