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Synthesis of the A/D/E-ring core compounds of maoecrystal V was achieved. The key Diels-Alder reactions between tricyclic α-methylene lactones and Kitahara-Danishefsky dienes afforded the spirocyclic core compounds in a regioselective and stereoselective manner.Graphical AbstractSynthesis of the A/D/E-ring core compounds of maoecrystal V was achieved using Diels-Alder reactions between α-methylene lactones and Kitahara-Danishefsky dienes.

ABSTRACTAdvanced nuclear fuels are designed to offer improved performance and accident tolerance, with an emphasis on achieving higher thermal conductivity. While promising fuel candidates like uranium nitrides, carbides, and silicides have been widely studied, the majority of uranium compounds remain unexplored. To search for potential candidates among these unexplored uranium compounds, we incorporated machine learning to accelerate the material discovery process. In this study, we trained a multiclass classification model to predict a compound’s thermal conductivity based on 133 input features derived from element properties and temperature. The initial training data consist of over 160,000 processed thermal conductivity records from the Starrydata2 database, but a skewed data class distribution led the trained model to underestimate compound’s thermal conductivity. Consequently, we addressed the issue of class imbalance by applying Synthetic Minority Oversampling TEchnique and Random UnderSampling, improving the recall for materials with thermal conductivity higher than 15 W/mK from 0.64 to 0.71. Finally, our best model is used to identify 119 potential advanced fuel candidates with high thermal conductivity among 774 stable uranium compounds. Our results underscore the potential of machine learning in the field of nuclear science, accelerating the discovery of advanced nuclear materials.

Mutations of CCAAT/enhancer–binding protein alpha (CEBPAmu) are found in 10% to 15% of de novo acute myeloid leukemia (AML) cases. Double-mutated CEBPA (CEBPAdm) is associated with a favorable prognosis; however, single-mutated CEBPA (CEBPAsm) does not seem to improve prognosis. We investigated CEBPAmu for prognosis in 1028 patients with AML, registered in the Multi-center Collaborative Program for Gene Sequencing of Japanese AML. It was found that CEBPAmu in the basic leucine zipper domain (bZIP) was strongly associated with a favorable prognosis, but CEBPAmu out of the bZIP domain was not. The presence of CEBPAmu in bZIP was a strong indicator of a higher chance of achieving complete remission (P < .001), better overall survival (OS; P < .001) and a lower risk of relapse (P < .001). The prognostic significance of CEBPAmu in bZIP was also observed in the subgroup with CEBPAsm (all patients: OS, P = .008; the cumulative incidence of relapse, P = .063; patients aged ≤70 years and with intermediate-risk karyotype: OS, P = .008; cumulative incidence of relapse, P = .026). Multivariate analysis of 744 patients aged ≤70 years showed that CEBPAmu in bZIP was the most potent predictor of OS (hazard ratio, 0.3287; P < .001). CEBPAdm was validated as a cofounding factor, which was overlapping with CEBPAmu in bZIP. In summary, these findings indicate that CEBPAmu in bZIP is a potent marker for AML prognosis. It holds potential in the refinement of treatment stratification and the development of targeted therapeutic approaches in CEBPA-mutated AML.

Photodimer of 9-anthracene carboxylic acid was used as crosslinker for bisepoxides and a degradable network polymer was synthesized at 100–110 °C in the presence of a base catalyst. The resulting network polymer was thermally decrosslinked at 150 °C within 30 min and completely solubilized in an organic solvent. Detailed investigation of the thermal dissociation behavior revealed that dissociation of more than 80% of 9-AC dimer unit was required for complete solubilization of the network polymer.Photodimer of 9-anthracene carboxylic acid was used crosslinker for bisepoxides and the degradable network polymer was synthesized at 100–110 °C in the presence of the base catalyst. The resulting network polymer was thermally decrosslinked at 150 °C within 30 min and dissociation of more than 80% of 9-AC dimer unit was required for complete solubilization of the network polymer.

Abstract

The paper examines the products of interlingual and intralingual translanguaging and qualitatively analyzes three origin-based lexical varieties in Japanese, wago(native Japanese words), kango(Sino-Japanese words), and gairaigo(foreign loanwords other than kango) in terms of how they have been complementing, competing against, or being in conflict with each other, how they engage word-formation processes as deep as morpheme-levels, and how they are perceived and manipulated by language users, including translators. This study shows that translanguaging has been practiced recursively and multi-directionally over a long period of time, yielding the phenomenon ‘translanguaging sequel’. The qualitative study of a Japanese translation of a Korean poem reveals a translator’s ideology-driven translanguaging practice that crosses not only interlingual but also intralingual boundaries, causing an international socio-political dispute. This study supports the view that translanguaging has been shaping and reshaping the norms of languages and language use. It also suggests the benefits of analyzing the products and traces of translanguaging in translated texts as well as the process of translanguaging during translation activities that can be promoted and implemented in language classrooms.

Poly(?-glutamic acid) (PGA) is a biopolymer produced by Bacillusspp. via the ?-amide linkages of d- and/or l-glutamate. Although high-molecular-weight (HMW) PGA possesses many attractive properties, such as flocculating, wound healing, and immune-stimulating effects, no studies have reported factors useful for increasing the molecular weight of PGA during microbial production. PgsB, PgsC, and PgsA are the minimum protein sets required for PGA production in B. subtilis, and PgsE improves PGA productivity. Analysis by size-exclusion chromatography combined with multiangle laser light scattering revealed that the molecular weight of PGA was Mw?=?2,900,000?g?mol-1and predominantly Mw?=?47,000?g?mol-1in preparations derived from B. subtiliscells with and without pgsE, respectively. PgsE may be required to increase the molecular weight of PGA.

Introduction

Alternating radical copolymerization of cyclic conjugated diene monomers, i.e., cyclopentadiene and furan, with oxygen were carried out to generate degradable polyperoxides. The cyclopentadiene and furan based-polyperoxides consisted of different regiospecific structures. The regiospecificity of the alternating copolymerization was rationalized by the bond dissociation energies of the carbon-to-oxygen bond of the peroxy radicals based on density functional theory calculations. The thermal degradation behavior of the resulting cyclic conjugated diene-based polyperoxides was also investigated.Alternating radical copolymerization of cyclic conjugated diene monomers with oxygen were carried out to generate degradable polyperoxides. The cyclopentadiene and furan based-polyperoxides consisted of the different regiospecific structures, and the regiospecificity of the alternating copolymerization was rationalized by the bond dissociation energies of the carbon-to-oxygen bond of the peroxy radicals based on density functional theory calculations.

The effect of the solvent evaporation rate and solvent type on the crystal formation of poly(vinylidene fluoride) (PVDF) prepared by spin-coating was evaluated over time. In the much-solvent-remaining state, the crystalline phase of PVDF changed in the order of α, γ and β with the increasing dipole moment of the solvent. In the almost-all-solvent-evaporated state, the crystalline structure of PVDF/hexamethylphosphoramide with a higher dipole moment was dominantly dependent on the evaporation rate and varied in the order of β, γ and α with the increasing solvent evaporation rate. However, PVDF/triethyl phosphate, having a lower dipole moment, always formed the α phase, regardless of the evaporation rate. The PVDF α phase in the concentrated solution state is difficult to transform into the β and γ phases because the potential energy of each PVDF crystalline phase increases in the order of α, γ and β. The PVDF crystalline phase in the spin-coating method is strongly affected by both the polymer–solvent electrostatic interactions and the evaporation conditions. From the results of the crystal transition behavior, it was experimentally supported that the potential energy of the PVDF crystalline structure increases in the order of α, γ and β.

This paper demonstrates a simple method for the preparation of poly(vinylidene fluoride) (PVDF) films using the antisolvent addition method. The antisolvent addition method was performed by immersing PVDF solution-casted substrates into the antisolvent for PVDF at room temperature for a few minutes. After immersing and drying for a few hours, a PVDF film was easily obtained. Then, the crystalline structure of the resulting PVDF film was changed in the order of a, ?and ßphases with increasing dipole moment of the solvent.

The lower critical solution temperature of thermo- and photo-responsive polymers, which involve coumarin units having functions for the dual-responsivity in chloroform, was controlled by the copolymerization. The cloud points of the copolymers of 7-methacryloyloxycoumarin with methacrylic acid and methyl methacrylate as solvophobic and solvophilic comonomers, respectively, were tuned below room temperature to nearly the boiling point of chloroform. The photodimerization of the coumarin units in the copolymer resulted in a decrease of the cloud points, i.e., photoresponsivity.The lower critical solution temperature of the thermo- and photo-responsive polymers, which involve the coumarin units having functions for the dual-responsivity in chloroform, were controlled by copolymerization with solvophilic and solvophobic comonomers. The photodimerization of the coumarin units in the copolymer resulted in a decrease in the cloud points.

We have demonstrated the validity of a new type of pressure-sensitive adhesion system using block copolymers containing a poly(2-ethylhexyl acrylate) (P2EHA) segment as the low glass transition temperature polymer and a poly(tert-butyl acrylate) (PtBA) or poly(isobornyl acrylate) (PIBoA) segment as the reacting polymer in the presence of a photoacid generator (PAG). This adhesion system can be easily debonded because of a change in the polymer properties of the adhesives by acid-catalyzed deprotection uniquely occurring during the photoirradiation followed by postbaking. We investigated the transformation of PtBA and PIBoA into poly(acrylic acid) using IR spectroscopy and a thermogravimetric analysis in the presence of p-toluenesulfonic acid and the PAGs. The block copolymers with a well-defined molecular structure were then synthesized by atom transfer radical polymerization, and their adhesive properties were evaluated using the 180° peel test. The block copolymers showed superior adhesion property than a random copolymer and polymer blends, due to the microphase separation of the block copolymers. A drastic change in the adhesive strength of the block copolymers was observed in response to the dual external stimuli consisting of UV irradiation and the subsequent heating.

Block copolymers consisting of readily degradable polyperoxides and non-degradable vinyl polymers as the block segments were successfully synthesized by reversible chain transfer catalyzed polymerization, which is one of living radical polymerization techniques. The block copolymers showed characteristic morphology and wettability being different from the polymer blends. When block copolymers containing polyperoxide and polymethacrylate blocks were heated below 150 °C, the polyperoxide blocks were completely degraded and the polymethacrylate blocks were recovered without degradation. Block copolymers containing a poly(2-ethylhexyl methacrylate) block were then investigated as a dismantlable adhesion material, which requires adequate bonding strength during use and easy debonding on demand. Among the several block copolymers, the one consisting of poly(2-ethylhexyl methacrylate) and polyperoxide from methyl sorbate (PPMS) (Mn= 4900) exhibited good performance as a pressure-sensitive adhesive (PSA). After heating the test specimens in a temperature range from 60 to 100 °C, PSA performance, which was evaluated by 180° peel strength and shear holding power measurements, was significantly diminished. Especially, after heating at 100 °C for 1 h, spontaneous debonding of some test specimens was observed because of the evolution of volatile acetaldehyde from PPMS.

Polyperoxides containing peroxy bonds as the main-chain repeating units are a new class of degradable polymers because of significant changes in their molecular weight and physical properties during a degradation process. In this study, the application of linear and network polyperoxides to dismantlable adhesion was investigated. When the linear polyperoxide obtained from methyl sorbate and oxygen (PP-MS) was used as a pressure-sensitive adhesive (PSA), its shear holding power and 180° peel strength immediately decreased upon heating at 70 °C or under UV irradiation. Low-molecular-weight products, which were generated by the degradation of PP-MS, behaved as a plasticizer to effectively reduce the cohesive force. The adhesive properties of two types of polyperoxides-based network polymers, the cross-linking point and main-chain degradable network polymers, were evaluated. A cross-linking point degradable network polymer was produced by the oxygen cross-linking of dienyl-functionalized poly(ethylene glycol). A main-chain degradable network polymer was formed by the diisocyanate cross-linking of a hydroxy-functionalized polyperoxide. Both network polymers showed a higher adhesive strength than PP-MS due to their three-dimensional network structure. Noteworthy, the adhesive strength of the main-chain degradable network polymer was varied from the level of PSA to structural adhesives by increasing the added amount of the diisocyanate cross-linker. After heating at 110 °C, the cohesive and adhesive strengths significantly decreased. The linear and network polyperoxides are shown to be promising materials for dismantlable adhesion.

This paper describes the synthesis and assembly of multihybrid particles having a gold core, silica as an initial shell and polymethylmethacrylate (pMMA) as a second shell (Au@SiO2@pMMA). Multihybrid particles were synthesized in a stepwise manner. First, direct sol–gel coating of silica onto gold nanoparticles was carried out to prepare Au@SiO2particles. The Au@SiO2particles were modified with 3-(triethoxysilyl)propyl 2-bromo-2-methylpropanoate (BMPS), which is an initiator for atom transfer radical polymerization (ATRP) of MMA. Finally, bulk ATRP of MMA was conducted using BMPS-coated Au@SiO2particles. Au@SiO2@pMMA particles formed a closely packed monolayer at the air–water interface. The monolayer can be deposited onto a solid substrate using the Langmuir–Blodgett technique. Atomic force microscopy and scanning electron microscopy images of the deposited film show a uniform and closely packed monolayer film in an area a few tens-of-micrometers in size with no voids. Moreover, a clear Au core, silica shell and pMMA shell structure were observed in a transmission electron microscopy image of the transferred film. It is particularly interesting that the monolayer film shows no clear plasmon absorption of the gold core, as observed in the chloroform solution of the particle. Results show that a thick silica shell masked the monolayer film’s plasmon absorption.

The crystal structures have been solved and/or refined for minerals of the alunite and beudantite groups having the general formula AM3(XO4)2(OH)6: that is, Pb(Fe2Cu)(SO4)2(OH)6 [beaverite], PbFe3(SO4)(PO4)(OH)6 [corkite], KAl3(SO4)2(OH)6 [alunite], NaAl3(SO4)2(OH)6 [natroalunite], KFe3(SO4)2(OH)6 [jarosite], SrAl3(SO4)(PO4)(OH)6 [svanbergite] and CaAl3(SO4)(PO4)(OH)6 [woodhouseite]. The structure analyses revealed that the ionic radius of the M site cation affected the a axis length whereas those of the A and X site ions influenced the c axis length. Cu-bearing minerals, osarizawaite and beaverite, showed the Jahn-Teller distortion in the Cu2+ octahedra. The space group of corkite was found to be the centric R3m rather than the acentric R3m space group reported previously.

We attempted a switch of mammalian target of rapamycin (mTOR) inhibitors from sirolimus to everolimus, a derivative of sirolimus and now on the market in Japan, in two pancreatic islet transplant patients. Both patients were administered tacrolimus with sirolimus or everolimus. They had been administered 5 or 9 mg sirolimus once a day and had maintained a trough concentration of about 15 ng/mL as measured by high performance liquid chromatography with ultraviolet detection. After the switch from sirolimus to everolimus, they were given 10 or 12 mg/day of everolimus twice a day to maintain a trough concentration of 12–15 ng/mL as measured by a fluorescence polarization immunoassay (FPIA) method. Afterward, the blood concentrations of everolimus and sirolimus after the conversion were measured by high performance liquid chromatography with mass spectrometry and everolimus concentrations were found to be 5–10 ng/mL. These data show that a larger dosage is needed for everolimus than sirolimus to maintain the same trough blood concentration. Data obtained by the FPIA for everolimus should be carefully evaluated after switching from sirolimus to everolimus because of the cross-reactivity of the antibody with sirolimus.

A branched copolymer containing a degradable polyperoxide linkage at a branching point was synthesized by the radical copolymerization of dienyl‐functionalized polystyrene and polyisoprene macromonomers with molecular oxygen. The ternary mixture of the branched copolymer and the macromonomers showed phase‐separated structure after annealing at 45 and 90 °C. The adjacent spacing of the phase‐separated structure was in the order of submicron to micrometer, which is larger than that of general microphase separated structures, due to the presence of homopolymers (macromonomers). Annealing at 110 °C induced thermal decomposition of the polyperoxide followed by in‐situ collapse and a drastic morphology change in the phase‐separated structure.

The aim of this study was to quantitatively evaluate the effects of intestinal and hepatic extraction on the pharmacokinetics of everolimus in rats. Everolimus was administered intravenously, intraportally or intraintestinally in order to separately evaluate the intestinal and hepatic first-pass extraction. Cyclosporine or tacrolimus was administered into rat intestines, and after 10 min everolimus pharmacokinetics were evaluated. The blood concentrations of everolimus were measured by the high-performance liquid chromatography with tandem mass spectrometry. Total body clearance of everolimus was constant in the dosage from 0.2 to 1.0 mg/kg. The bioavailability after intraportal and intraintestinal administration were 48.0% and 21.2%, respectively. Concomitantly administered cyclosporine (5 mg/kg), but not tacrolimus (1 mg/kg), significantly decreased the total body clearance of everolimus compared with the control, and also increased the bioavailabilty of everolimus after intraintestinal administration 1.75-fold. Cyclosporine significantly increased the area under the blood concentration-time curve of everolimus after the intraintestinal constant infusion 3-fold, and increased that after the intraportal constant infusion only 1.35-fold. In conclusion, the intestine as well as liver contributes to the first-pass extraction for everolimus in rats. Intestinally administered cyclosporine inhibited the intestinal extraction of everolimus more than its hepatic extraction.

Pancreatic islet transplantation is a curable treatment for type 1 diabetes and has been put into practice in various countries. In this study, we analyzed the pharmacokinetic characteristics of sirolimus and tacrolimus in six Japanese patients with pancreatic islet transplants immediately after surgery, and monitored efficacy and toxicity. The patients were treated with immunosuppressive therapy based on the Edmonton protocol, that is, sirolimus and low-dose tacrolimus. Pharmacokinetic analyses were performed using the nonlinear mixed-effects modeling program NONMEM. Large inter- and intra-individual variability was observed in the pharmacokinetics of sirolimus and tacrolimus. A model with increased apparent clearance in the postoperative period explained well the intra-individual variability in the pharmacokinetics of both drugs. The most frequent drug-induced toxicity was a decrease in the white blood cell count, and two of six patients required the administration of granulocyte colony-stimulating factor. Clinical laboratory tests immediately before the transplantation and cytochrome P450 3A5 genotype were not related to the high blood concentrations of sirolimus after the loading dose. From these results, the apparent clearance of sirolimus and tacrolimus might temporally decline immediately after pancreatic islet transplantation. A high trough concentration of sirolimus might increase the risk of hematological toxicy, and adjustment of the dosage for immunosuppressive treatment will be necessary in Japanese patients.

Highly stereospecific polymerization of a novel sulfur containing aromatic acetylenes, that is, (p‐n‐octylthiophenyl)acetylene (pOctSPA), was successfully performed using the Rh complex, [Rh(norbornadiene)Cl]2‐TEA, catalyst in the presence of various solvents under mild conditions. The resulting polymers were characterized in detail by 1H NMR, ESR, laser Raman, diffuse reflective UV‐Vis (DRUV‐Vis), and wide angle X‐ray diffraction methods. The data showed that the resulting polymers bear cis‐transoid form, which can induce the cis‐to‐trans isomerization when the cis polymers are subjected to pressure at room temperature under vacuum, breaking rotationally the cis C&dbond;C bonds in the main‐chain giving two kinds of π‐radicals, the so‐called cis radical and trans radical as the origin of a polymer magnet like a novel spin glass material. Further, the resulting cis poly(acetylene)s were found to have a helical main‐chain, which is packed in pseudohexagonal crystal called π‐conjugated columnar or nano π‐conjugated columnar as a novel color controllable material. © 2005 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 43: 2836–2850, 2005

In general, the clock (or oscillator) is central to circadian rhythms in many organisms. In the model higher plant Arabidopsis thaliana, the best candidates forclock components are CCA1 (CIRCADIAN CLOCK-ASSOCIATED 1) and LHY (LATE ELONGATED HYPOCOTYL), which are homologous Myb-related transcription factors. It is also believed that TOC1 (TIMING OF CAB EXPRESSION 1) is another component of the central oscillator. In this connection, we have been characterizing a small family of proteins, designated ARABIDOPSISPSEUDO-RESPONSE REGULATOR (PRR1, PRR3, PRR5, PRR7, and PRR9), based on the fact that one of the members (PRR1) is identical to TOC1. Nevertheless, it is not yet certain whether other PRR family members are also implicated in clock function per se. To address this issue, in this study we examined a functional interaction between the CCA1 clock component and one of the PRR family members, PRR5, by employing transgenic lines overexpressing both the CCA1and PRR5genes. Evidence will be provided that PRR5 plays an antagonistic role(s) to the putative CCA1 clock component.

α‐(2‐Methyl‐2‐phenylpropyl)acrylate (RS‐2) was examined as a C&bond;C bond‐cleavage type addition–fragmentation chain transfer (AFCT) agent in the benzene solution polymerizations of styrene (St), ethyl methacrylate (EMA), and cyclohexyl acrylate (CHA) with the objective of achieving efficient macromonomer synthesis by radical polymerization. The AFCT efficiency was evaluated in terms of the decrease in the number‐average molecular weight (Mn) upon the addition of the AFCT agent and the number of unsaturated end groups introduced per chain (f). The AFCT efficiency was rationalized by the consideration of the relative importance of AFCT as an end‐forming event and the competition between ‐fragmentation and crosspropagation as adduct radical reaction pathways. In St and EMA polymerizations at 60 °C, RS‐2 resulted in higher f values and lower Mn values than methyl α‐(2‐methyl‐2‐carbomethoxypropyl)acrylate (MMA‐2), and this suggested the facilitation of ‐fragmentation due to the expulsion of the more stable cumyl radical from the RS‐2 adduct radical. Higher f values were observed for MMA‐2 than for RS‐2 in CHA polymerization because of unsaturated end group formation by ‐fragmentation of midchain radicals. However, RS‐2 resulted in lower Mn values for poly(CHA) than MMA‐2 because of a smaller contribution of crosspropagation. Retardation in the presence of the AFCT agents was affected by the balance between b‐fragmentation and crosspropagation and by the addition rate of the propagating radical to the AFCT agent. © 2004 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 42: 6021–6030, 2004

Osteopontin (OPN) is an acidic phosphorylated glycoprotein found in many tissues and physiological fluids. Bovine OPN is a mature protein comprising 262 amino acids with a calculated molecular weight of 29 kDa. However, SDS-PAGE analysis reveals that the protein isolated from milk migrates to a molecular mass of 60 kDa (Sørensen & Petersen, 1993; Bayless et al. 1997). Bovine milk OPN is phosphorylated at 27 serine residues and one threonine residue (Sorensen et al. 1995); three O-glycosylated threonines were also identified, but no asparagine residues were glycosylated in spite of the presence of three putative N-glycosylation sites. In contrast, eight phosphates are recognized in bovine bone OPN (Salih et al. 1996), and 12 phosphoserines and one phosphothreonine are proposed in addition to five O-linked oligosaccharides and at most one N-linked oligosaccharide in the case of rat bone OPN (Prince et al. 1987). Thus, the possibility of tissue or species-specific differences in post-translational modification has been discussed.

Summary: The benzene solution polymerizations of tert-butyl acrylate (tBA) and 2-ethylhexyl acrylate (EHA) have been investigated with respect to the effects of mid-chain radicals (MCRs) on the rate of polymerization, the total radical concentration, the apparent rate coefficients for propagation, termination, and β-fragmentation, the contents of unsaturated end groups and branching, and the molecular weight distribution. The EHA polymerization involves a considerably higher concentration of MCR and is more significantly affected by MCR than the tBA polymerization. The MCR content as estimated by electron paramagnetic resonance (EPR) spectroscopy during photosensitized EHA polymerization was as high as 70% of the total radical concentration at 25 °C. However, no 1H and 13C NMR resonances due to unsaturated ends and branching, respectively, were detected for the poly(EHA) obtained at 25 °C. These findings indicate that a high MCR content does not directly correspond to significant MCR effects on the polymer structure. The rate constants for mutual reaction ($k'_{\rm t}$) and β-fragmentation (kf) of MCR were estimated for the two assumed cases where MCR was consumed solely by (i) mutual reaction, and (ii) β-fragmentation, based on the after-effect of the photosensitized EHA polymerization monitored by EPR spectroscopy at 25 °C; $k'_{\rm t}$ = 3.5 × 103 L · mol · s−1 and kf = 4.2 × 10−2 s−1. These rate coefficients were compared with those for reactions of structurally similar radicals.Reaction pathways of MCRs.

The nitroxide free radical trapping technique in connection with HPLC and electrospray ionization mass spectrometry has been employed to study reactions of tert-butoxy radicals with methyl α-(2-methyl-2-carbomethoxypropyl)acrylate (methyl methacrylate dimer (MMAD)) and methyl α-(2,2,2-tris(carbomethoxy)ethyl)acrylate (M(TM)EA). It has been shown that the adduct radical derived from MMAD undergoes β-fragmentation and expels the 2-carbomethoxy-2-propyl radical. No fragmentation was detected in the case of M(TM)EA. Rate coefficients of trapping and β-fragmentation of the tert-butoxy radical in the literature have enabled estimations of absolute rate coefficients for additions of the tert-butoxy radical and the methyl radical to monomer, hydrogen abstraction from monomer by the tert-butoxy radical, and β-fragmentation of the adduct radical (MMAD only). The reactions of tert-butoxy radicals with M(TM)EA are slower than with MMAD due to the steric hindrance of the α-substituent. Copyright © 2003 Society of Chemical Industry

The reactivities of ω-unsaturated methacrylate oligomers (RMA-n; n = 2–5) toward tert-butoxy radicals (t-BuO^·) as a model of the addition step in addition-fragmentation chain transfer (AFCT) have been investigated by the nitroxide trapping technique in combination with HPLC and electrospray ionization mass spectrometry. The ratio of the rate coefficients for the addition of ω-unsaturated methyl methacrylate oligomers (MMA-n) to t-BuO^· to the β-fragmentation of t-BuO^· (kadd/kβ), where kβ can be treated as a constant, has been shown to decrease with increasing n due to increased steric hindrance of the α-substituents. However, the value of kadd/kβ reaches a constant value at n = 3–4, and the greatest extent of suppression of the addition rate compared with MMA is less than a factor of four. Comparison of the values of kadd/kβ for ω-unsaturated cyclohexyl methacrylate oligomers (CHMA-n; n = 2 and 3) with MMA-n revealed that the extent of suppression increased with increasing n without regard to the ester alkyl group. Hydrogen abstraction by t-BuO^· from RMA-n appears to occur mainly at the ester alkyl groups, and the extent is much greater from CHMA-n than from MMA-n.

The complete genome sequence of Arabidopsis thalianarevealed that this higher plant has a tremendous number of protein kinases. We recently isolated a novel type of protein kinase, named AtWNK1, which shows an in vitroability to phosphorylate the APRR3 member of the APRR1/TOC1 quintet that has been implicated in a mechanism underlying circadian rhythms in Arabidopsis.We here address two issues, one general and one specific, as to this novel protein kinase. We first asked the general question of how many WNK family members are present in this higher plant, then whether or not other members are also relevant to circadian rhythms. The results of our analyses showed that Arabidopsishas at least 9 members of the WNK1 family of protein kinases (designated here as WNK1 to WNK9), the structural design of which is clearly distinct from those of other known protein kinases, such as receptor-like kinases and mitogen-activated protein kinases. They were examined with special reference to the circadian-related APRR1/TOC1 quintet. It was found that not only the transcription of the WNK1gene, but also those of three other members (WNK2, WNK4, and WNK6) are under the control of circadian rhythms. These results suggested that certain members of the WNK family of protein kinases might play roles in a mechanism that generates circadian rhythms in Arabidopsis.

Mutations of CCAAT/enhancer binding protein alpha (CEBPAmu) are found in 10-15% of de novoacute myeloid leukemia (AML) cases. Double-mutated CEBPA(CEBPAdm) is associated with a favorable prognosis; however, single-mutated CEBPA(CEBPAsm) does not appear to improve prognosis. We investigated the CEBPAmu for prognosis in 1028 AML patients, registered in the Multi-center Collaborative Program for Gene Sequencing of Japanese AML. It was found that CEBPAmu in the basic leucine zipper domain (bZIP) was strongly associated with a favorable prognosis, but CEBPAmu out of the bZIP domain was not. The presence of CEBPAmu in bZIP was a strong indicator of a higher chance of achieving complete remission (p<0.001), better overall survival (OS; p<0.001) and a lower risk of relapse (p<0.001). The prognostic significance of CEBPAmu in bZIP was also observed in the subgroup with CEBPAsm(all patients, OS: p=0.008; the cumulative incidence of relapse (CIR): p=0.063. patients aged ≤70 years and withintermediate-risk karyotype, OS: p=0.008; CIR: p=0.026). Multivariate analysis of 744 patients aged ≤70 years showed that CEBPAmu in bZIP was the most potent predictor of OS (hazard ratio: 0.3287; p<0.001). CEBPAdm was validated as a cofounding factor, which was overlapping with CEBPAmu in bZIP. In summary, these findings indicate that CEBPAmu in bZIP is a potent marker for AML prognosis. It holds potential in the refinement of treatment stratification and the development of targeted therapeutic approaches in CEBPAmutated AML.

Takaku: Bristol-Myers Squibb: Honoraria, Speakers Bureau; Novartis Pharma K.K.: Honoraria, Speakers Bureau. Tokuhira:Mitsubishi Tanabe Pharma Corporation: Speakers Bureau; Bristol-Myers Squibb: Speakers Bureau; AYUMI Pharmaceutical Corporation: Speakers Bureau; Chugai: Speakers Bureau. Asou:Eisai Co., Ltd.: Research Funding; SRL Inc.: Consultancy; Yakult Honsha Co., Ltd.: Speakers Bureau; Kyowa Hakko Kirin Co., Ltd.: Speakers Bureau; Asahi Kasei Pharma Co., Ltd.: Research Funding; Astellas Pharma Inc.: Research Funding; Sumitomo Dainippon Pharma Co., Ltd.: Research Funding; Chugai Pharmaceutical Co., Ltd.: Research Funding. Kizaki:Nippon Shinyaku,: Research Funding, Speakers Bureau; Celgene: Research Funding, Speakers Bureau; Bristol-Myers Squibb: Research Funding, Speakers Bureau; Novartis: Speakers Bureau. Kawaguchi:Novartis Pharma K.K.: Honoraria, Speakers Bureau; Bristol-Myers Squibb: Honoraria, Speakers Bureau; Alexion: Honoraria, Speakers Bureau; Pfizer: Honoraria, Speakers Bureau.

Background and Aim:Treatment with a tyrosine kinase inhibitor (TKI) is the standard of care for patients with chronic myeloid leukemia (CML). Based on the results of the ENESTnd and DASISION studies, the European LeukemiaNet 2013 guidelines now recommend the use of TKIs, imatinib (400 mg once daily), nilotinib (300 mg twice daily), and dasatinib (100 mg once daily) as first-line treatment for patients with CML in the chronic phase (CML-CP). Compared to imatinib, the new generation TKIs, nilotinib and dasatinib, were found to have deeper and faster treatment response rates with acceptable toxicities. However, a direct comparison between nilotinib and dasatinib has never been reported previously. Our study aims to compare the outcomes and molecular responses achieved following the first-line use of these two agents in patients with CML-CP.

Iriyama: Novartis: Honoraria, Speakers Bureau; Bristol-Myers Squibb: Honoraria, Speakers Bureau. Takaku:Bristol: Honoraria, Speakers Bureau; Novartis: Honoraria, Speakers Bureau. Nakazato:Mundipharma KK: Research Funding. Fujita:Chugai Pharmaceutical Co.,LTD: Honoraria. Tokuhira:Bristol Myers Squibb Co., Ltd: Honoraria; Pfizer Co., Ltd: Honoraria; Eizai Co., Ltd: Honoraria. Kawaguchi:Novartis: Honoraria.

Background and Aim:Therapy-related chronic myeloid leukemia (TR-CML), which is defined as CML that developed after exposure to cytotoxic chemotherapy and/or radiotherapy, rarely exists in clinical practice, although its incidence rates are relatively lower than those of acute myeloid leukemia or myelodysplastic syndromes, accounting for 1.2-30.4% of secondary leukemias. The clinical behavior of TR-CML, including patient outcome, is reportedly not different from that of de novoCML before the era of imatinib treatment. While the recent advancement of CML treatment by the introduction of tyrosine kinase inhibitors (TKIs) has dramatically improved treatment outcomes in patients with CML, little is known about the treatment response and outcomes in patients with TR-CML treated with TKI. In this regard, we investigated the clinical entity of TR-CML in the era of TKIs, including treatment response to TKI and prognosis, in patients enrolled to the CML Cooperative Study Group.