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There is currently no harmonized way in Japan to manage safety data which are obtained during clinical trials supported by Government funds. There are two types of clinical trials, 'sponsored trials(sponsored by industrial companies)' and 'non-sponsored trials(funded by the Government, etc.)'. The Japanese Ministry of Health and Welfare has issued many of pharmaceutical laws(GCP, GPMSP etc.) for the regulation of sponsored trials, while none has ever established for non-sponsored trials, thus leaving the most important quality control/assurance unregulated. In this manuscript we discuss that the simple application of pharmaceutical laws to government-sponsored trials can not be a proper answer because of the different nature of the two types of trials.

Optically active peptide foldamers Tfa-[(S)-(alphaEt)Leu]-[(S)-(alphaEt)Nva]-Deg-[(S)-(alphaEt)Nle]-OEt (10) and Tfa-[(S)-(alphaEt)Val]-[(S)-(alphaEt)Leu]-[(S)-(alphaEt)Nva]-Deg-[(S)-(alphaEt)Nle]-OEt (11) composed of diverse alpha-ethylated alpha,alpha-disubstituted alpha-amino acids were synthesized. The dominant conformation of these peptides in solution was an unusual, fully extended planar conformation, and that in the crystal state was both right-handed (P) and left-handed (M) 3(10)-helical structures in 10 and a P 3(10)-helical structure in 11, respectively. The preferred planar C(5) conformation of the peptides prepared from chiral alpha-ethylated alpha,alpha-disubstituted alpha-amino acids was drastically different from the 3(10)-helical structure of the peptides prepared from chiral alpha-methylated alpha,alpha-disubstituted alpha-amino acids.

With use of diol, alkoxysilane, and a catalytic amount of trimethylsilyl trifluoromethanesulfonate (TMSOTf), carbonyl compounds are converted to acetals in good yields under mild conditions. This procedure, which was carried out without synthesizing the silylated diols, is a more convenient adaptation of Noyori's method. This acetalization applies to not only simple but also conjugated carbonyl compounds. Moreover, various TMS compounds, including solid supported compounds, are effective for this method instead of alkoxylsilane.

The design and synthesis of new 1α,25-dihydroxy-19-norvitamin D3 analogues 3a–c, which have an amide bond in the molecule instead of the diene, are described. The A-ring moiety was constructed by a (3S,5S)-3,5-dihydroxypiperidine derivative (9, 11, or 13) prepared from d -mannose, and a CD-ring carboxylic acid 16 was synthesized from Grundmann's ketone. Coupling those parts gave desired 3a–c in good yield. This strategy can be applied in combinatorial chemistry; therefore, those compounds would be applicable as useful tools in the development of new drugs.

CD uniformity and MTT (Mean to Target) control are very important in mask production for the 90nm node and beyond. Although it is well known that baking temperatures influence CD control in the CAR (chemically amplified resist) process for mask patterning, we found that 2 other process factors, which are related to acid diffusion and CA- reaction, greatly affect CD performance. We used a commercially available, negative CAR material and a 50kV exposure tool. We focused on the baking process for both PB (Pre Baking) and PEB (Post Exposure Bake). Film densification strength was evaluated from film thickness loss during PB. Plate temperature distribution was monitored with a thermocouple plate and IR camera. CA-reactions were also monitored with in-situ FTIR during PEB. CD uniformity was used to define the process influence. In conclusion, we found that airflow control and ramping temperature control in the baking process are very important factors to control CD in addition to conventional temperature control. These improvements contributed to a 30 % of reduction in CD variation.

CD-uniformity data of chemically amplified (CA) resists have been generated, by using a dynamically controlled multi-zone hotplate system, APB5000. The optimized baking procedure of the APB5000 system for Post Coat Bake (PCB) and Post Exposure Bake (PEB) is characterized by a maximum in the total temperature range on a 6025 mask substrate surface of 0.5 degree(s)C during the heat-up ramping and smaller than 0.2 degree(s)C at the set-point temperature of 90 degree(s)C. In this experiment CD-uniformity for isolated lines was improved to 7.8nm, compared to 13nm when using conventional baking systems. Additionally, a compensation method based on the baking processes is presented to further decrease the CD- uniformity range of CA-resists. Derived from CD-uniformity data measurements, a local temperature variation from the optimized baking strategy of the APB5000 system is used to compensate CD-errors caused by other process steps. In this experiment the result of such a measure showed a 40% improvement of the CD-uniformity range for dense lines from 14.2nm to 8.0nm.

We have developed a novel EB lithography simulator, which can analyze imaging quality such as Line Edge Roughness (LER), pattern distortion, and corner rounding for the mask fabrication process. The simulator has a direct Monte Carlo calculation mode with unequal mesh dividing, works on cluster PCs hardware, and installs an exact Chemically Amplification Resist (CAR) reaction model. The simulation analysis line and contact hole patterns clarify that intrinsic LER induced by electron scattering is dependent on the exposure dose below 10uC/cm2 and has strong dependence on diffusion length. Moreover, the simulation identify that there is an optimum point around 10uC/cm2 of sensitivity and 30nm of diffusion length, considering corner rounding effect. The developed simulator demonstrates that direct Monte Carlo simulation can analyze the imaging quality of mask pattern quantitatively and practically, and has the potential to be a mainstream for EB lithography simulation.

アワヨトウ幼虫の個体群密度に依存したクチクラのメラニン化は神経ホルモン, 体色黒化赤化ホルモン (MRCH) により支配されている. 一方, ゴキブリおよびバッタより単離きれ, 後腸筋に対してミオトロピック活性を示す神経ペプチド, pyrokinin 類および locustamyotropin (Lom-MT) 類はアワヨトウMRCH (Pss-MRCH) と共通のC末端配列, Phe-Xaa-Pro-Arg-Leu-NH2 (FXPRLアミド, Xaa=Thr, Val) を持つ. そこで, 3種の合成ミオトロピック神経ペプチドを用い, アワヨトウ幼虫のクチクラのメラニン化に対する効果を検討したところ, leucopyrokinin, Lom-MT-II, -IIIは, いずれも幼虫当たり1～100 pmol で濃度依存的に顕著なメラニン化誘起作用を示し, なかでも機Lom-MT-IIが最も強い活性を示した. 今回の結果は, MRCHの活性発現部位がFXPRLアミド配列に存在することを支持するものである.

Novel 2alpha-substituted 1alpha,25-dihydroxyvitamin D(3) analogues with 2alpha-alkyl and 2alpha-hydroxyalkyl groups were systematically synthesized from D-xylose. Their conformation on binding to the ligand binding domain (LBD) of the vitamin D receptor was analyzed. It has been found that the 2alpha-hydroxypropyl group best fits the cavity of the LBD, and the binding activity is three times higher than that for the natural hormone.

5-Formyl- and 5-(formylmethyl)-2'-deoxyuridines are introduced into a kappa B site instead of thymidine(s) in order to understand target sequence specificity of NF kappa B. It was found that one thymidine in the kappa B site is particularly important for the sequence specific recognition by NF kappa B.

Photolabile 6-nitrobenzo[a]pyrene (6-nitroBaP) released nitric oxide (NO) under visible-light irradiation. The generation of NO and the concomitant formation of the 6-oxyBaP radical were confirmed by ESR. BaP quinones were also detected as further oxidized products of the 6-oxyBaP radical. No such photodegradation was observed with other nitrated BaPs, such as 1-nitroBaP and 3-nitroBaP. DNA-strand breakage, caused by photoexcited 6-nitroBaP, was closely related to its NO-releasing activity. MO calculations of nitrated BaP suggest that the perpendicular conformation of the nitro substituent to the aromatic ring is important for the release of NO with light. These findings may be useful for the development of a new type of NO donor.

Specifications for advanced photomask are becoming more and more stringent as the industry shifts to smaller lithography nodes. Among various requirements for photomasks, the need for stringent mean to target (MTT) control of critical dimensions (CDs) as well as the reduction of defects is the hottest issue for current photomask manufacturers. In this paper a unique photomask manufacturing method for precise CD-MTT control is described and an approach to defect free manufacturing (DFM) is also proposed. In the new method, a two-step compensation to cancel CD errors is adopted. Its essence is the selection of metrology tools used in each step. An MTT of +/- 5nm is achieved using this method. For DFM, a cluster tool, combining the processing tools with each other by a robot handler, has been installed and avoiding human handling is proved to be a correct way.

In order to cast light on the significance of lipid peroxidation products for carcinogenesis, the lacI mutant frequency (MF), micronucleus induction and cell proliferation were analyzed in lacI transgenic mice treated with trans-4-hydroxy-2-nonenal (HNE), a typical example. Male mice were ip injected with HNE at doses of 0, 5 or 50 mg/kg bw and 48 h thereafter, peripheral blood was collected for analyzing micronucleus induction. After 14 days, the mice were sacrificed to allow tissue sampling for examination of lacI MF and cell proliferative activity. Sixty percent of the mice given 50 mg/kg HNE died within 5 days after the treatment, but no other mortalities were observed. Histopathologically, marked pulmonary hemorrhage was found in the 50 mg/kg HNE group mice that survived until day 14. Immunohistochemically, HNE-modified proteins were detected in their alveolar macrophages. The HNE treatment did not increase lacI MF in the liver, kidney and lung and no significant increase in micronucleus induction or cell proliferation in major organs was found in either treatment. Moreover, no tumors developed in the 5 mg/kg HNE-treated mice which survived until week 78. Our results thus indicate that HNE lacks in vivo genotoxicity in lacI transgenic mice even when lethal doses are applied.

The scavenging effects of (-)-epigallocatechin gallate (EGCG) and (-)-epicatechin gallate (ECG) on peroxyl radicals and their mechanisms were studied by investigating the products formed during the first stages by 2,2'-azobis(2-aminopropane) hydrochloride (AAPH)-induced oxidation, without any isolation, using LC/MS, spectrophotometry, chemiluminescence analyses, and semiempirical molecular orbital (MO) calculations. The results show that EGCG can be converted to an anthocyaninlike compound followed by cleavage of the gallate moiety by oxidation. On the other hand, ECG can be converted to an anthocyaninlike compound after cleavage of the gallate moiety. The calculated C-H bond dissociation enthalpies (BDEs) for EGCG and ECG at the C-2 position were quite low (62.7 and 66.8 kcal/mol, respectively) compared with O-H BDEs at the phenolic sites (ca. 70 kcal/mol), suggesting that the C-2 hydrogen can be abstracted by free radicals. The addition of superoxide dismutase (SOD) decreased the chemiluminescence in EGCG by one-half during the inhibitory action. Active oxygen including superoxide (O2-) would be produced in EGCG, but not in ECG. The authors proposed the antioxidative mechanisms of EGCG and ECG depending on the experimental results and theoretical calculations.

Higher resolution and accuracy are required in e-beam lithography for reticle fabrication for coping with further advances in optical lithography. The trend is to use high acceleration voltage (50 kV) e-beam to improve spatial resolution. However, in the case of high acceleration e-beam writing, a drastic critical dimension (CD) change is caused by a strong proximity effect and a large resist heating effect. The proximity effect is caused by the increase in the back- scattering radius. The back-scattering radius was estimated by two independent observations of the CD variation of a monitor and the thickness variation of a partially developed resist. It is found to be ca. 15 nm. Using the shot time modulation as a proximity correction reduced the proximity effect to a small level: CD error due to the pattern density change remained within 10 nm. On the other hand, the resist heating effect is caused by the change in resist dissolution speed by the temperature rise of the resist. In reducing this effect, multi-pass writing is found to be effective. The range of the CD error of 2 micrometer lines-and-spaces in the writing field has been reduced from 22 nm to 6 nm by changing the writing from one pass to four passes for a conventional resist. Moreover, when a chemically amplified resist (CAR) is exposed through one-pass writing, the range of the CD error is found to be 8 nm. Therefore, the use of the CAR is effective in reducing the resist heating effect. Simulation software ProBEAM/3D and TEMPTATION were used to obtain three- dimensional resist profile and the transient temperature rise of the resist, respectively. Both provided results that agreed well with those by experiment.

An HPLC (high performance liquid chromatography) method with laser induced fluorescence (LIF) detection is described for the determination of 4-hydroxy-2-nonenal (HNE) formed from lipid peroxidation in rat hepatocytes. Carbonyl compounds were fluorescently labelled by incubating the hepatocyte samples with a tagging reagent, 4-(2-carbazoylpyrrolidin-1-yl)-7-nitro-2,1,3-benzoxadiazole (NBD-ProCZ), at 60°C for 10 min. The hydrazone derivatives were extracted with a C18 solid phase extraction (SPE) cartridge and separated on a reversed-phase HPLC column. The detection limit was 2.5 fmol or 0.5 nM (5 µL injection) of HNE in the cell homogenate. Method precision (C.V.) was 5% at the 5 nM level. The method has been used to determine free HNE in rat hepatocyte samples treated with several pro-oxidant toxins. A significant HNE increase (from 4 to 27.6 pmol/106 cells) was observed with the samples treated by allyl alcohol. The results were in accordance with those for malondialdehyde formation as measured by a thiobarbituric acid (TBA) assay. Copyright © 1999 John Wiley & Sons, Ltd.

The antioxidative mechanisms of catechins were studied by investigating products generated at the first stages by 2, 2'-azobis(2-aminopropane)hydrochloride (AAPH)-induced radical oxidation, without any isolation, using LC/MS, spectrophotometry, and PM3 semiempirical molecular orbital (MO) calculations. Catechins were quite effective in scavenging peroxyl radicals in a liposomal system and in an aqueous system except for (-)-epigallocatechin (EGC). EGC was the least effective among four catechins tested. From the results of LC/MS and spectroscopic studies, (-)-epicatechin (EC) would be gently converted to an anthocyanin-like compound. According to the mechanisms, the compound produced from EC by radical oxidation can also function as an antioxidant. As a result, EC has a longer inhibition period (tinh = 9360 s). On the other hand, EGC decreased shortly after oxidation (tinh = 3420 s) and was transformed to a quinone-like compound. The addition of superoxide dismutase (SOD) reduced the chemiluminescence from EGC during oxidation. Active oxygen including superoxide anion radicals (O-2) may be produced in the case of EGC, but not in the case of EC. However, EGC has a more rapid scavenging effect on peroxyl radicals (kinh/kp = 232) than EC (kinh/kp = 41). The calculated C-H bond dissociation enthalpies (BDEs) for catechins at the C-2 position were unexpectedly low (65 kcal/mol) compared to O-H BDEs at phenolic sites (70 kcal/mol), suggesting that hydrogen at the C-2 position may be abstracted by free radicals. The authors propose the tentative antioxidative mechanisms of catechins depending on the experimental results and theoretical calculations.

We developed a new positive E-beam resist, 'ERB'-900 MX for fabrication of advanced masks for the next generation. 'ERB'-900 MX is a non-chemically amplified resist based on novolak and naphthoquinonediazide. A newly designed additive and modification of the novolak resin contributed to improvement of sensitivity and resolution. There are two types of 'ERB'-900 MX, 'ERB'-900 MX(alpha) and MX(beta) whose solvents are different. Most important feature of 'ERB'-900 MX is highly sensitive. Especially, 'ERB'-900 MX(beta) showed excellent sensitivity of 3.5 (mu) C/cm 2 at 20 keV and 12 (mu) C/cm 2 at 50 keV. Stability of 'ERB'-900 MX after EB exposure was quite good. No practical change in sensitivity was observed for 12 hours in air and in vacuum. CD linearity of 'ERB'-900 MX(alpha) was around 0.75 micrometers for isolated patterns. CD bias for dry-etch process of 'ERB'-900 MX(alpha) is around 0.1micrometers which is comparable to that of 'ERB'-900 M-1. We confirmed that 'ERB'-900 MX has excellent performance suitable for fabrication of advanced masks.

A positive-tone, chemically amplified resist (CAR) has been evaluated in comparison with non-CARs in its applicability to fabrication of reticles to be used for 180-nm-rule devices. The evaluated CAR is found to have better performance than the non-CARs. It has high sensitivity and high contrast enough to be used with e-beam writing systems, and good dry-etch durability. Its characteristics when exposed with e-beam writing system with different acceleration voltages is studied. The CD linearity is maintain down to 400 nm for all patterns by adoption of a 50 kV e-beam system and a proximity effect correction. The resolution limit is 150 nm for lines-and-space pattern. The allowance of the baking conditions is examined and the use of a highly temperature-controllable hot-plate yields good CD uniformity. The influence of the ammonia concentration in the process environment of the post exposure delay stability is investigated. The CAR should be used under a concentration of ammonia less than ca. 5 ppb, which is obtainable by use of a chemical filter. In conclusion, it is demonstrated that the CAR meets our requirements for resist for 180-nm-rule reticle fabrication.

Both diastereomeric right-handed (P) and left-handed (M) 310-helices exist in homopeptides having twelve chiral centers at the side-chain bicyclic skeletons.

A convenient —and quick to realize— approach for the synthesis of an ultrathin overlayer of CaCO3 on TiO2 thin films is suggested. Since dye-sensitized photoelectrochemical investigations on CaCO3-...

Breast cancer is the leading cause of cancer death in women. Most of the primary breast cancers express estrogen receptor α (ERα) and they show estrogen-dependent proliferation. Since tamoxifen antagonizes estrogen in breast cancers, it is widely used to treat the primary breast cancers. However, tamoxifen also shows a partial agonistic activity in different tissues and cellular context, which sometimes causes a detrimental effect. An alternative strategy to kill the estrogen signaling is to downregulate ERα protein. We have developed a protein knockdown system to induce degradation of target proteins via the ubiquitin-proteasome system (UPS) in cells. The molecules for protein knockdown, which we named SNIPER (Specific and Non-genetic IAP-dependent Protein ERaser), are composed of two different ligands connected by a linker; one is a ligand for cellular inhibitor of apoptosis protein 1 (cIAP1) and the other is a ligand for a target protein. Accordingly, SNIPER is expected to crosslink a ubiquitin ligase cIAP1 and the target protein in the cells, thereby inducing the cIAP1-mediated ubiquitylation and proteasomal degradation of the target protein. By using tamoxifen as a ligand for ERα, we developed novel SNIPER to knockdown ERα protein. SNIPER(ER) induced degradation of ERα and inhibited estrogen-dependent expression of pS2 gene in an estrogen-dependent breast cancer MCF-7 cells. Intriguingly, after the ERα degradation, the SNIPER(ER)-treated MCF-7 cells undergo rapid cell death. Detailed analysis indicated that SNIPER(ER) caused necrotic cell death accompanied by a release of HMGB1, and reactive oxygen species (ROS) mediate the necrotic cell death in the SNIPER(ER)-treated MCF-7 cells. These results indicate that SNIPER(ER) induces ERα degradation, ROS production and necrotic cell death, implying a therapeutic potential of SNIPER(ER) as a lead for the treatment of ERα-positive breast cancers. Citation Information: Mol Cancer Ther 2013;12(11 Suppl):B255. Citation Format: Keiichiro Okuhira, Yosuke Demizu, Takayuki Hattori, Nobumichi Ohoka, Norihito Shibata, Tomoko Nishimaki-Mogami, Haruhiro Okuda, Masaaki Kurihara, Mikihiko Naito. Development of hybrid small molecules that induce degradation of estrogen receptor-alpha and necrotic cell death in breast cancer cells. [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2013 Oct 19-23; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2013;12(11 Suppl):Abstract nr B255.

A new fabrication process for halftone phase-shift masks (HPSMs) with electron beam writers has been developed for mass production. It has a resist critical dimension (CD) measurement step before dry etching and it gives the determination of etching time using the relationships between CD shift (Chrome CD - resist CD) and overetch ratio. As a result, it shows a good mean CD controllability within a range of 0.03 μm for over 90% of our production HPSMs.

Cell-free production of bombykol was done by incubating a pheromone gland homogenate in the presence of NADPH, ATP, and CoA. Addition of n-hexane to the reaction mixture stimulated bombykol production, resulting in production of 238 ng of bombykol from the homogenate equivalent to 2 pheromone glands after 23 h. Removal of either NADPH, ATP, or CoA resulted in no stimulation of bombykol production, suggesting that the final step of the bombykol biosynthetic pathway is done by acyl CoA synthetase and reductase, sequentially. Incubation first with ATP or high concentrations of ATP suppressed the production of bombykol. Since incubation with ATP also inhibited conversion of [1-14C]palmitoyl CoA into 1-hexadecanol, the inhibitory action of ATP seemed attributable to inactivation of the acyl CoA reductase by phosphorylation, as mediated by a protein kinase in the homogenate. Our results suggest that the activity of acyl CoA reductase in bombykol biosynthesis is regulated by phosphorylation/dephosphorylation, and that the activation occurs by dephosphorylation as mediated by phosphoprotein phosphatase.

Pheromone biosynthesis activating neuropeptide (PBAN) regulates sex pheromone production in the pheromone glands of many species of female moths. In order to probe the biochemical steps as well as underlying mechanisms regulated by PBAN, we have tested the effects of pharmacological agents on sex pheromone production of the common cutworm, Spodoptera litura, using an in vitro assay. Among the pharmacological agents we tested, ionomycin (calcium ionophore) alone stimulated sex pheromone production, while LaCl3 (calcium channel blocker), W-7, trifluoperazine (calmodulin inhibitor), NaF, and p-nitrophenyl phosphate (phosphatase inhibitor) suppressed the pheromone production by a pheromonotropic peptide, TKYFSPRLamide. By contrast, forskolin (adenylate cyclase activator), phorbol 12-myristate 13-acetate (protein kinase C activator), and cyclic nucleotides alone failed to stimulate sex pheromone production. These results suggest that Ca2+/calmodulin complex and phosphoprotein phosphatase are involved in the signal transduction of PBAN action in S. litura.

Characteristics of four chemically-amplified (CA), negative EB resists have been evaluated and compared with the requirements to resists for 64 Mb-DRAM reticles The four resists satisfy the requirements on sensitivity, side-wall angle, corner roundness, edge roughness, and dry- etch rate. In a wet-etch process three resists (resists B, C and D) have good CD linearity down to 0.5 micrometers whereas one resist (resist A) has a poor linearity owing to a large etching shift. A dry-etch process could extend CD linearity and resolution limits for all the resists. Storage of a resist-coated blank in a box with silica gel is found to be effective in extending the life of the blank after coating. Thus, the lives after coating for all the resists are long enough for practical use (CD deviation less than 0.1 micrometers per month) under the above storage conditions. Only two resists (resists A and D) have lives after exposure long enough for practical use (CD deviation less than 0.1 micrometers per 10h). Reducing the contribution of post-exposure bake to CD uniformity is achieved by the use of a hot-plate that can give good uniformity in the surface temperature of a Cr/Qz-substrate. In conclusion, CA resists can meet the requirements to resists for 64 Mb-DRAM reticles.

Pheromone biosynthesis activating neuropeptide (PBAN) regulates sex pheromone production in the pheromone glands of many species of female moths. In order to probe the biochemical steps as well as underlying mechanisms regulated by PBAN, we have tested the effect of chemicals on sex pheromone production by using an in vitro assay. Among the chemicals we tested here, compactin, a specific 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase inhibitor, clearly inhibited the pheromone biosynthesis in the silkworm, Bombyx mori, and the common cutworm, Spodoptera litura. Since the activation of HMG CoA reductase occurs by dephosphorylation mediated by a specific phosphatase and the biochemical step regulated by PBAN in bombykol biosynthesis is similar to the one catalyzed by HMG-CoA reductase in cholesterol biosynthesis, the present results support the idea that phosphoprotein phosphatase has a significant role to regulate bombykol production in the intracellular transduction of PBAN action in B. mori.

The performance of EBR900 (Toray) as a resist used for e-beam and laser beam lithographies has been investigated. EBR900 has high sensitivity to both e-beam and laser beam exposures. It has high resolution and good dry-etch durability. The e-beam process was optimized by designing a new type of developer, MA50, which is composed of an amine and an aqueous solution of potassium hydroxide. The addition of the amine was found to be effective in improving the performance with regard to profile, CD uniformity, and defect quality. Its performance is stable (e.g., CD deviation is less than 0.03 micrometers for a shelf time of a month); this makes CD control easier. Its CD linearity in the laser beam process is down to 0.6 micrometers , being better than that in the e-beam one (down to 1.0 micrometers ). Its dissolution rate and conversion yield of the photosensitizer were estimated in order to explain the superiority of the laser process. A comparison of its performance between e-beam and laser beam processes for next generation photomask fabrication was presented. In conclusion, EBR900 meets the requirements for 64 Mb DRAM reticles for the use in e- beam and laser beam lithographies.

Hereditary vitamin D-resistant rickets (HVDRR) is a genetic disorder caused by mutations in the vitamin D receptor, which lead to resistance to 1alpha,25-dihydroxyvitamin D(3) [1alpha,25(OH)(2)D(3)]. We found that the A ring-modified analogues, 2alpha-(3-hydroxypropyl)- and 2alpha-(3-hydroxypropoxy)-1alpha,25(OH)(2)D(3), (O1C3 and O2C3) can bind better than the natural hormone to the mutant VDR (R274A), which similar to the HVDRR mutant, R274L, had lost the hydrogen bond to the 1alpha-hydroxyl group of 1alpha,25(OH)(2)D(3).

A half-tone phase shift mask process has been developed. The writing and process for normal masks are found to be applicable to HT-PSMs. A dry etch process has been adopted to etch the shifter. Several characteristics of HT-PSMs such as CD uniformity, CD linearity, edge roughness and corner rounding, positional accuracy in the EB process, selectivity in dry etch, pattern profile, durability against cleaning, pelliclization and a blind pattern are evaluated. The process shows a good performance sufficient for first generation 64 MDRAM mask making. The EB writing causes no charge-up problem. The selectivity of HT-shifter to an i-line resist and an new type EB resist in dry etch is satisfactory and the selectivity to a fused silica substrate is more than 300. An exposure test was conducted with our HT-PSM. Coherency factor ((sigma) ) of a stepper is found to strongly affect the defocus range and exposure latitude.

Two lithographic processes for phase-shift mask (PSM) manufacturing have been investigated. In particular, processes in E-beam (electron beam) lithography by use of a charge-dissipating layer of a conductive polymer are studied. Two commercial conductive polymers, TQV and ESPACER100, are found to work well for charge-dissipation. Three new resists along with CMS and EBR9 are evaluated regarding their properties necessary for patterning a shifter layer. Among them two new resists are demonstrated to be excellent. The effect of the number of data-blocks on the alignment accuracy is examined in delineation with a Hitachi HL-600, where each data-block has four fine-alignment marks. The examination suggests that the use of one or two data-blocks is practical. As to combination of writers for the Cr level and the shifter level, HL-600 - HL-600 gave better alignment accuracy than the other combinations, WW6000 - HL-600 and MEBES III - HL-600, did. The comparison between the E-beam and the laser writers is summarized.

Asymmetric induction was observed in radical cross-coupling reactions of silyl enol ethers using chiral oxovanadium generated in situ from 8-phenylmenthol and vanadium oxytrichloride in the presence of MS4A (molecular sieves-4A).

Superoxide anion (O2•−) was generated via an electron-transfer oxidation of catechin dianion, which was produced in the reaction of catechin with two equivalents of methoxide anion, by molecular oxygen in acetonitrile. From the detailed spectroscopic and kinetic analyses was determined the rate constant for the formation of O2•− to be 5.8 × 10−2 mol−1 dm3 s−1.

Antisticking layers (ASLs) on UV nanoimprint lithography (UV-NIL) molds were characterized by scanning probe microscopies (SPMs) in addition to macroscopic analyses of work of adhesion and separation force. Local physical properties of the ASLs were measured by atomic force microscopy (AFM) and friction force microscopy (FFM). The behavior of local adhesive forces measured with AFM on several surfaces was consistent with that of work of adhesion obtained from contact angle. The ASLs were coated by two different processes, i.e., one is a vapor-phase process and the other a spin-coating process. The homogeneity of the ASLs prepared by the vapor-phase process was better than that of those prepared by the spin-coating process. In addition, we measured the thicknesses of ASL patterns prepared by a lift-off method to investigate the effect of the ASL thicknesses on critical dimensions of the molds with ASLs and found that this effect is not negligible.

Most problems in photomask fabrication such as pattern collapse, haze, and cleaning damage are related to the behavior of surfaces and interfaces of resists, opaque layers, and quartz substrates. Therefore, it is important to control the corresponding surface and interface energies in photomask fabrication processes. In particular, adhesion analysis in microscopic regions is strongly desirable to optimize material and process designs in photomask fabrication. We applied the direct peeling (DP) method with a scanning probe microscope (SPM) tip and measured the adhesion of resist patterns on Cr and quartz surfaces for photomask process optimization. We also studied the effect of tip shape on the reproducibility of adhesion measurements and the dependence of collapse behavior on the resist profile. We measured lateral forces between the resulting collapsed resist pillar and the Cr or the quartz surface before and after the sliding and related these observed lateral forces to the static and kinetic frictional forces, respectively. We also studied the effect of surface modification of the Cr and quartz surfaces with silanization reagents on adhesion measured with the DP method. Resist adhesion could be controlled by surface modification using silanes. We also discuss the relationship between the adhesion observed with the DP method and the properties of the modified surfaces including water contact angles and local adhesive forces measured from force–distance curves with an SPM.

Erythro α-amino epoxide, an important intermediate for synthesis of protease inhibitors, was synthesized from propargylic alcohol in a highly enantio- and diastereoselective manner.

The stereselective oxidation of acyclic allylic silyl ethers with dioxiranes generated in situ from Oxone® and ketones provided erythro epoxides.

In the presence of sec- or tert-alkoxysilane and a catalytic amount of trimethylsilyl trifluoromethanesulfonate (TMSOTf), carbonyl compounds react with various diols to give acetals in high yields.

(Z, E)-9, 12-tetradecadienyl acetate and (Z)-9-tetradecenyl acetate were identified chemically in sex pheromone gland extracts of female Spodoptera depravata (BUTLER). A laboratory wind-tunnel experiment showed that the former compound acts as an attractant-pheromone to the male but the latter compound has no pheromonal activity by itself or in combination with the former compound.