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Numerous variants of unknown significance (VUSs) exist in hereditary breast and ovarian cancers. Although multiple methods have been developed to assess the significance of BRCA1/2variants, functional discrepancies among these approaches remain. Therefore, a comprehensive functional evaluation system for these variants should be established. We performed conventional homologous recombination (HR) assays for 50 BRCA1and 108 BRCA2VUSs and complementarily predicted VUSs using a statistical logistic regression prediction model that integrated six in silico functional prediction tools. BRCA1/2VUSs were classified according to the results of the integrative in vitro and in silico analyses. Using HR assays, we identified 10 BRCA1and 4 BRCA2VUSs as low-functional pathogenic variants. For in silico prediction, the statistical prediction model showed high accuracy for both BRCA1and BRCA2compared with each in silico prediction tool individually and predicted nine BRCA1and seven BRCA2variants to be pathogenic. Integrative functional evaluation in this study and the American College of Medical Genetics and Genomics and the Association for Molecular Pathology (ACMG/AMP) guidelines strongly suggested that seven BRCA1variants (p.Glu272Gly, p.Lys1095Glu, p.Val1653Leu, p.Thr1681Pro, p.Phe1761Val, p.Thr1773Ile, and p.Gly1803Ser) and four BRCA2variants (p.Trp31Gly, p.Ser2616Phe, p.Tyr2660Cys, and p.Leu2792Arg) were pathogenic. This study demonstrates that integrative evaluation using conventional HR assays and optimized in silico prediction comprehensively classified the significance of BRCAVUSs for future clinical applications.

We propose a novel laser diode (LD) fabrication process that yields 100 μm-cavity GaN-based edge emitting LDs with cleaved facets. In this process, epitaxial layers for LDs are grown on a Si substrate, with a GaN layer grown using the epitaxial lateral overgrowth (ELO) technique. The ELO is finished before coalescence, resulting in multiple stripes. This configuration generates tensile stress in the direction parallel to the stripes, which originates from the difference between the thermal expansion coefficients of GaN and Si. This anisotropic tensile strain realizes automatic cleavage for laser facets without a breaking process. An array of dies manufactured through automatic cleavage are selectively transferred to a submount wafer, which is attributed to the weak connection of the ELO layers with the growth restriction mask. This wafer-level transfer technique enables the handling of tiny dies incorporating facet coating processes. The unique shape of the ELO layer, which is extremely thin and narrow in width, enables cleavage with a cavity length shorter than that of the conventional process. The fabricated device yielded lasing at 83 kA/cm2. This fabrication process can realize unique III-nitride LDs that exhibit low energy consumption for mobile applications such as augmented-reality glasses.

The first total synthesis of violaceoid A, a cytotoxic agent, and the asymmetric total synthesis of (−)- and (+)-violaceoid B are reported. The precursor was accessed by desymmetrization of a substituted quinol moiety, and the racemic secondary alcohol was kinetically resolved using a chiral nucleophilic catalyst. The asymmetric synthesis of (−)- and (+)-violaceoid B elucidated the absolute configuration of the naturally occurring violaceoid B. Synthetic violaceoid A inhibited the growth of human breast cancer cell lines MCF-7 and Hs 578T at concentrations of less than 100 μM, while (S)- and (R)-violaceoid B were inactive.

We fabricated a silicon micropore optic using deep reactive ion etching and coated by Pt with atomic layer deposition (ALD). We confirmed that a metal/metal oxide bilayer of Al_2O_3∼10  nm and Pt ∼20  nm was successfully deposited on the micropores whose width and depth are 20 μm and 300 μm, respectively. An increase of surface roughness of sidewalls of the micropores was observed with a transmission electron microscope and an atomic force microscope. X-ray reflectivity with an Al Kα line at 1.49 keV before and after the deposition was measured and compared to ray-tracing simulations. The surface roughness of the sidewalls was estimated to increase from 1.6±0.2  nm rms to 2.2±0.2  nm rms. This result is consistent with the microscope measurements. Post annealing of the Pt-coated optic at 1000°C for 2 h showed a sign of reduced surface roughness and better angular resolution. To reduce the surface roughness, possible methods such as the annealing after deposition and a plasma-enhanced ALD are discussed.

Microlight-emitting diodes were fabricated using an original substrate (ELO GaN on silicon; EGOS). The EGOS substrate was fabricated by growing a GaN layer on a (111)-plane silicon substrate via the epitaxial lateral overgrowth technique. The EGOS substrate has a wide mask that formed an open area. The widths of the ELO mask and open area are 51.5 and 3.5 μm, respectively. Whole micro-LEDs could be formed within the wing area by widening its width, which has a low defect density. Because the adjacent ELO layers do not coalesce into each other, gaps are present between the ELO layers. The EGOS substrate exhibits a ridge structure that is formed via the dry-etched method, facilitating the removal of the chips from the EGOS substrate. The optimizing growth condition of the ELO GaN layer was realizing 3.2 μm in thickness even though the width of the LEO layer is over 47 μm. Cathode luminescence measurement did not show dislocations at the wing area of the ELO layer. The micro-LEDs fabricated via this method emitted at 424 nm, proving the feasibility of the method. The original substrate with an ELO layer can be used as a platform to fabricate many kinds of microlight sources with an ultralow dislocation density.

We performed evaluation of anisotropic strain relaxation in the patterned Ge1-xSnx mesa by Raman spectroscopy. For strain evaluation, several coefficients, e.g., strain shift coefficient b and phonon deformation potentials (PDPs: p and q), are indispensable. In this study, using thin Ge1-xSnx films which were epitaxially grown on Ge substrate by MOCVD, the b coefficient and PDPs were derived. From results of Raman spectroscopy and XRD, the b coefficient was -399.3+-5.6 cm-1. And, the p and q show only small variation in the Sn concentration range less than 3.2%. These derived coefficients were used to evaluate the biaxial strain in the patterned Ge1-xSnx mesa by oil-immersion Raman spectroscopy. As a result, we confirmed uniaxial strain relaxation in the Ge1-xSnx stripe pattern.

Si1-xGex is one of the prospective materials for the next-generation transistors due to its high carrier mobility, especially for high Ge concentration Si1-xGex. Inducing strain in the Si1-xGex leads to transistor performance improvement, however it is difficult to evaluate strain induced in the channel region because the strained Si1-xGex channel may be scaled down to nanosize and relaxed complicatedly. We adopted oil-immersion Raman spectroscopy to evaluate the stress in the Si1-xGex nanostructure. In this technique, the anisotropic biaxial stress state in the Si1-xGex nanostructure can be evaluated. As a result, the nanostructure size dependence of the biaxial stress states in the Si1-xGex mesa structure on the Ge substrates was obtained, which was confirmed for the Si1-xGex with 76, 85, 92% Ge concentrations.

We applied surface-enhanced Raman spectroscopy (SERS) to the excitation of transversal optical (TO) phonos in strained SiGe. The SERS technique can greatly enhance the Raman signal owing to metal-surface plasmon resonance. Furthermore, the electrical field includes a large amount of z-polarization, which can excite TO phonons. In this study, we evaluated anisotropic biaxial stress state in thin strained-SiGe layer on a Si substrate with the SERS technique.

A polarization-independent, high-index contrast grating (HCG) with a single layer of cross stripes allowing simple fabrication is proposed. Since the cross stripes structure can be suspended in air by selectively wet-etching the layer below, all the layers can be grown at once when implemented for vertical-cavity surface-emitting lasers. We optimized the structure to have a broad and high reflectivity band centered at around 1 μm using a finite difference time domain method, and obtained an 80 nm high reflectivity band centered at 0.97 μm in which the reflectivity exceeded 99.5%. We also investigated the fabrication tolerances of the structure and found that, assuming careful optimizations of electron beam lithography for the precise grating width and dry-etching for the vertical sidewall, the suggested polarization-independent HCG can be fabricated using standard technologies.

The effects of the pre-mixing method and degree of saponification poly(vinyl alcohol) (PVA) on the morphology of poly(vinyl chloride) (PVC)/PVA blends were investigated. Two pre-mixing methods were employed: a powder method and an aqueous solution method. In the powder method, both components were blended in powder form before melt kneading using a mixing roll. In the aqueous solution method, the PVC powder was added to an as-prepared PVA aqueous solution, followed by drying and then pounding before melt kneading. In the case of PVA with a degree of saponification of 98 mol%, PVA domains several hundred μm across were dispersed in the PVC matrix in the powder method system, whereas finer PVA domains with sizes ranging from sub μm to several μm were observed in the aqueous solution method. In the cases of PVA with saponification degrees of 88 and 78 mol%, domain sizes of several tens of μm were observed for both powder and solution methods. This indicates that there was no apparent influence of pre-mixing method on the domain size. When poly(methyl methacrylate) (PMMA) was added to the PVC/PVA blend, smaller PVA domains (with sizes ranging from 5 to 10 μm) were observed in both powder and solution method systems than without the PMMA. Viscoelastic properties showed specific interactions between PVC and PMMA, and between PMMA and PVA.

We report on the evaluation and characterization of micro-electromechanical system (MEMS) X-ray optics produced by silicon dry etching and hot plastic deformation. Sidewalls of micropores formed by etching through a silicon wafer are used as X-ray reflecting mirrors. The wafer is deformed into a spherical shape to focus parallel incidence X-rays. We quantitatively evaluated a mirror alignment error using an X-ray pencil beam (Al Ka line at 1.49 keV). The deviation angle caused only by the deformation was estimated from angular shifts of the X-ray focusing point before and after the deformation to be 2.7 +- 0.3 arcmin on average within the optics. This gives an angular resolution of 12.9 +- 1.4 arcmin in half-power diameter (HPD). The surface profile of the deformed optics measured using a NH-3Ns surface profiler (Mitaka Kohki) also indicated that the resolution was 11.4 +- 0.9 arcmin in HPD, suggesting that we can simply evaluate the alignment error caused by the hot plastic deformation.

The strain-free Raman shift of the Ge-Ge mode, $\omega _{0}^{\text{Ge--Ge}}$, of Ge-rich Si1[?] x Ge x (x: Ge fraction) was determined accurately from the bulk Ge-rich Si1[?] x Ge x samples fabricated by the Czochralski (Cz) method. Using the obtained $\omega _{0}^{\text{Ge--Ge}}$, the phonon deformation potentials (PDPs), p and q, and the strain-shift coefficient b LO of isotropic biaxial strained Ge-rich Si1[?] x Ge x thin films were extracted by oil-immersion Raman spectroscopy using Raman peak shifts of longitudinal and transverse optical (LO and TO) phonon modes. As a result, it was confirmed that these parameters are almost constant with small variations and that the strain-shift coefficient b LO is in good agreement with ab initio calculations. The parameters determined in this work are essential to realize accurate strain measurements using Raman spectroscopy for Ge-rich Si1[?] x Ge x devices.

Uniaxial strain states in a Ge epitaxial film were evaluated by oil-immersion Raman spectroscopy. The Ge epitaxial film used in this study was fabricated using a SiGe stressor template grown on a Ge substrate by selective ion implantation. The one-dimensional strain distribution in the Ge epitaxial film was evaluated by Raman spectroscopy, and large compressive strains and strain relaxations in implanted and unimplanted areas were confirmed, respectively. For further analysis of the strain states in the Ge epitaxial film in the unimplanted area, we obtained transversal optical phonon (TO1 and TO2) peaks by liquid-immersion Raman spectroscopy with a high-numerical-aperture objective lens. The stress states calculated from these peaks were clearly anisotropic. A uniaxially strained Ge epitaxial film, which is an appropriate high-performance transistor channel material, was achieved by using a SiGe template epitaxially grown on a selectively implanted Ge substrate.

We report the fabrication and characterization of high-verticality sidewalls by deep reactive ion etching (DRIE). We quantitatively evaluated the verticality of the sidewalls with a width of 20 um and a depth of 300 um by using an X-ray beam (1.49 keV). To the best of our knowledge, we succeeded in constraining the verticality and smoothness of the DRIE-fabricated sidewalls with the highest accuracy. The verticality of the sidewalls against the wafer surface was estimated from the shifts of the X-ray focus to be 8.7 +- 3.2 arcmin on average within the wafer, while the resolution of the X-ray focus was 21.1 +- 2.7 arcmin in half-power diameter. Although the verticality and resolution require further improvements, we verified that the X-ray imaging technique is valid for quantifying the sidewall properties.

Biaxial stress states in SiGe stripes on Si substrates fabricated by a novel selective Ar+ ion implantation technique were evaluated by oil-immersion Raman spectroscopy. The oil-immersion technique is appropriate for the measurement of strain induced in nanostructure devices, because it has a higher spatial resolution than conventional Raman spectroscopy and can evaluate anisotropic stress states owing to the excitation of multiple optical phonon modes. Results indicate that quasi-uniaxial stress states exist in SiGe layers in unimplanted Si areas, which depends on the stripe-width ratio of implanted and unimplanted areas, and that quasi-uniaxial stress states are successfully induced in SiGe by the present technique, which can be considered as the channel materials of high-performance transistors.

GeSn is being paid much attention as a next-generation channel material. In this work, we performed the excitation of forbidden transverse optical (TO) phonons from strained GeSn, as well as longitudinal optical (LO) phonons, under the backscattering geometry from the (001) surface by oil-immersion Raman spectroscopy. Using the obtained LO/TO phonons, we derived the phonon deformation potentials (PDPs), which play an important role in the stress evaluation, of the strained Ge1[?] x Sn x for the first time. The results suggest that PDPs are almost constant for the Ge1[?] x Sn x (x < 0.032). Biaxial stress calculated using the derived PDPs reasonably indicated the isotropic states.

We performed evaluation of anisotropic strain relaxation in the patterned Ge1-xSnxmesa by Raman spectroscopy. For strain evaluation, several coefficients, e.g., strain shift coefficient band phonon deformation potentials (PDPs: pand q), are indispensable. In this study, using thin Ge1-xSnxfilms which were epitaxially grown on Ge substrate by MOCVD, the bcoefficient and PDPs were derived. From results of Raman spectroscopy and XRD, the bcoefficient was -399.3±5.6 cm-1. And, the p and qshow only small variation in the Sn concentration range less than 3.2%. These derived coefficients were used to evaluate the biaxial strain in the patterned Ge1-xSnxmesa by oil-immersion Raman spectroscopy. As a result, we confirmed uniaxial strain relaxation in the Ge1-xSnxstripe pattern.

Additional broad peaks in Raman spectra from thin Ge-rich SiGe films were examined in detail. The broad peak on the low-wavenumber side of first-order optical phonon was also present for pure Ge, which indicates that the localized mode is not the reason for the broad peaks. Furthermore, other factors, e.g., strain, defect, phonon confinement effect, Fano effect, and fluorescence from oil, were excluded from the origin of the broad peaks. We assigned the broad peaks to surface optical phonon modes. The dependence of this surface mode on Ge concentration in Ge-rich SiGe was also investigated and the behavior was discussed.

We report on novel X-ray mirrors fabricated with a focused ion beam for future astronomical missions. We fabricated a test sample from a silicon wafer by forming six slits whose sidewalls were used as X-ray reflection surfaces. The six slits were designed with a size of 25 x 300 x 170 um3 and with different inclination angles of 0 and +-1deg. We examined X-ray reflection using three slits with different inclination angles at Al Ka 1.49 keV. Consequently, we demonstrated X-ray reflection from all the three slits. All the sidewalls have multiangular components with a microroughness of [?]1 nm rms. [?]30-45% of the total surface area is effective for X-ray reflection. We confirmed that the inclination angles are consistent with the designed values.

The phonon deformation potentials (PDPs), p and q, of Si1[?]xGex with the whole range of the Ge concentration x were examined in detail in pursuit of accurate strain measurements by Raman spectroscopy. An oil-immersion Raman technique was adopted to extract the PDPs of Si1[?]xGex, in which a complex sample preparation process or a stress-introduction device is not necessary. The strain-shift coefficients bLO and bTO, which can be calculated using the obtained PDPs, were compared with the values in the literature, and we suggested which values were best for application to accurate strain measurements. Ab initio calculation was also performed to understand the behavior of the PDPs throughout the whole range of x in Si1[?]xGex.

Anisotropic biaxial stress states in the high-Ge concentration Si1-xGex/Ge nanostructures were evaluated by oil-immersion Raman spectroscopy. Phonon deformation potentials (PDPs) are indispensable to convert the Raman frequency shift to stress in the Si1-xGex. Therefore, we investigated the accurate PDPs (pandq) of the Si1-xGexwith the high Ge concentration by oil-immersion Raman spectroscopy. Using the derived PDPs, the clear uniaxial stress relaxation in the strained Si1-xGexnanostructure was observed.

Si1-xGexis one of the prospective materials for the next-generation transistors due to its high carrier mobility, especially for high Ge concentration Si1-xGex. Inducing strain in the Si1-xGexleads to transistor performance improvement, however it is difficult to evaluate strain induced in the channel region because the strained Si1-xGexchannel may be scaled down to nanosize and relaxed complicatedly. We adopted oil-immersion Raman spectroscopy to evaluate the stress in the Si1-xGexnanostructure. In this technique, the anisotropic biaxial stress state in the Si1-xGexnanostructure can be evaluated. As a result, the nanostructure size dependence of the biaxial stress states in the Si1-xGexmesa structure on the Ge substrates was obtained, which was confirmed for the Si1-xGexwith 76, 85, 92% Ge concentrations.

We applied surface-enhanced Raman spectroscopy (SERS) to the excitation of transversal optical (TO) phonos in strained SiGe. The SERS technique can greatly enhance the Raman signal owing to metal-surface plasmon resonance. Furthermore, the electrical field includes a large amount of z-polarization, which can excite TO phonons. In this study, we evaluated anisotropic biaxial stress state in thin strained-SiGe layer on a Si substrate with the SERS technique.