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Polymer crystallization drastically changes the physical properties of polymeric materials. However, the crystallization in polymer networks has been little explored. This study investigated the crystallization behavior of a series of poly(ethylene glycol) (PEG) networks consisting of well-defined branched precursors. The PEG networks were prepared by drying gels synthesized at various conditions. The PEG networks showed slower crystallization with lower final crystallinity than uncrosslinked PEGs with amine end groups. Surprisingly, the effect of network formation was not as significant as that of the relatively bulky end-groups introduced in the uncrosslinked polymer. The molecular weight of the precursor PEG, or equivalently the chain length between neighboring junctions, was the primary parameter that affected the crystallization of the PEG networks. Shorter network chains led to lower crystallization rates and final crystallinity. This effect became less significant as the network chain length increased. On the other hand, the spatial and topological defects formed in the gel synthesis process did not affect the crystallization in the polymer networks at all. The crystallization in the polymer networks seems insensitive to these mesoscopic defects and can be solely controlled by the chain length between junctions.

This review provides comprehensive knowledge on synthetic methods of star polymer networks – structurally controlled three-dimensional networks of polymer chains by means of end-linking between monodisperse star polymers.

Structural changes and mechanical responses of a model bottlebrush elastomer with a controlled network structure were investigated by small-angle X-ray scattering coupled with uniaxial tensile testing.

The incorporation of weak and reversible dynamic bonds is a key strategy for enhancing the mechanical properties of polymers. However, the quantitative relationship between the molecular characteri...

A structurally controlled polymer gel was synthesized by end-linking a monodisperse star polymer in which each arm was a bottlebrush (BB) polymer densely grafted with side chains. The combination of atom transfer radical polymerization and postpolymerization modification yielded a four-arm star-shaped BB polymer with a controlled polymerization degree of the backbone and side chains. The reactive end groups introduced at the end of each arm reacted with small bifunctional linkers in solution, leading to the formation of a BB polymer gel. The elasticity study on the BB polymer gel suggested its uniform network structure. Our method enables precise and uniform tuning of essential structural parameters across the entire BB polymer network, which will be beneficial for developing soft materials with desired mechanical responses.

Precise control of the crystal orientation and hierarchical crystalline morphology is essential for application of crystalline polymers, although a homogeneous morphology with a controlled crystal ...

Gels are giant single molecules that consist of a very large number (∼Avogadro’s number) of cross-linked nanometer-size polymer chains. Unlike most low-molecular-weight compounds, the extensively c...

Multidentate hydrogen bonds (H-bonds) play a pivotal role in determining the structure, dynamicity, and function of biological macromolecules, motivating many researchers to design artificial H-bon...

国民経済計算は, 国連で採択された国際基準に基づいており国際比較が可能である｡特にOECD 加盟国についてはOECD がNational Accounts のデータベースを公開している｡だが, その様式は内閣府の国民経済計算の様式とは微妙に異なっている｡そこで, 本稿では, OECD のNational Accounts の政府統計に関する諸項目が内閣府の国民経済計算の項目とどのような対応関係にあるのかを検討し, 対照表を作成した｡また, これを用いてOECD の加盟国を対象とした財政の国際比較に取り組んだ｡その際, 日本のデータについては, より新しいデータが収録されている内閣府の国民経済計算年次推計を用いた｡

Many clinical research studies evaluate a time-to-event outcome, illustrate survival functions, and conventionally report estimated hazard ratios to express the magnitude of the treatment effect when comparing between groups. However, it may not be straightforward to interpret the hazard ratio clinically and statistically when the proportional hazards assumption is invalid. In some recent papers published in clinical journals, the use of restricted mean survival time (RMST) or τ-year mean survival time is discussed as one of the alternative summary measures for the time-to-event outcome. The RMST is defined as the expected value of time to event limited to a specific time point corresponding to the area under the survival curve up to the specific time point. This article summarizes the necessary information to conduct statistical analysis using the RMST, including the definition and statistical properties of the RMST, adjusted analysis methods, sample size calculation, information fraction for the RMST difference, and clinical and statistical meaning and interpretation. Additionally, we discuss how to set the specific time point to define the RMST from two main points of view. We also provide developed SAS codes to determine the sample size required to detect an expected RMST difference with appropriate power and reconstruct individual survival data to estimate an RMST reference value from a reported survival curve.

Transient cross-links such as hydrogen bonds (H-bonds) are a central concept for creating polymers with mechanical functionalities, including toughness and self-healing properties. While conventional strong H-bonding groups are based on rigid and planar molecular motifs with multidentate intermolecular interactions, we recently discovered that a structurally simple and flexible vicinal diol (VDO) could serve as a robust yet dynamic cross-link with multiple intermolecular H-bonds between hydroxy groups. In this work, we investigated the effects of cooperativity of H-bonds in VDOs on polymer dynamics. We synthesized model polybutadienes with either VDO or monool (MO) side groups by a radical-mediated thiol-ene click reaction. The oscillatory shear rheology data were analyzed by using the sticky Rouse model. The characteristic time of a single modified segment (

The crystallization behavior of poly(e-caprolactone) (PCL) chains spatially confined in a lamellar microdomain structure (nanolamella) with the PCL layer thickness d of 15.0 nm (space confinement) was examined using synchrotron small-angle X-ray scattering (SR-SAXS), differential scanning calorimetry (DSC), and infra-red spectroscopy (IR). The PCL chains were covalently tethered to nanolamella interfaces at both chain-ends, either chain-end, or no chain-end (chain confinement) to bring an additional change in their molecular mobility. The individual effect of space confinement and chain confinement on the crystallization of PCL chains was elucidated by comparing this result with that of PCL chains confined in a smaller nanolamella (i.e., d = 10.9 nm) derived in our previous study and of bulk PCL homopolymers without any confinements. Though the crystallization rate depended significantly on the state of chain-end tethering for PCL chains confined in the nanolamella with d = 10.9 nm, it converged toward bulk PCL with the difference considerably reduced when confined in the nanolamella with d = 15.0 nm. The melting temperature and crystallinity showed similar results. We tried to convert chain confinement into space confinement on the basis of crystallization rates experimentally obtained to understand their combined effect on the crystallization.

Enhancing the mechanical reliability of thermoplastic elastomers (TPEs) is a key issue for their application as a structural material. Here we systematically investigated the effects of dynamic bonds on the mechanical properties of ABA triblock copolymer-type TPEs. We prepared a series of TPEs having strong hydrogen-bonding side groups, ureidopyrimidinone (UPy), in either or both of the hard A blocks and soft B blocks. The TPEs formed microphase-separated structures consisting of spherical hard A domains surrounded by soft B matrices. When the dynamic bonds were introduced in the hard A blocks, the mechanical stability of the hard domains was improved. The stress in the tensile tests also increased but only at relatively large strains. Dynamic bonds in the soft B block served as transient crosslinks in the soft matrix that enhanced stress across the entire range of strain. The effect of introducing dynamic bonds in both the hard domains and soft matrix was more than just the sum of the effects of the dynamic bonds in both phases: a robust synergistic interaction existed between the dynamic bonding moieties in the two phases. This synergistic interaction enhanced the rigidity of the material (tensile stress ∼13 MPa) while maintaining high tensile toughness (∼58 MJ m−3). The dynamicity of the interactions in the different phases and its effect on fatigue recoverability in the large strain regime were also discussed using the classical theory of nonlinear viscoelasticity.

We developed a network polymer with solvent-assisted self-healing ability based on vicinal tricarbonyl chemistry. A copolymer bearing vicinal tricarbonyl pendant groups was crosslinked with α,ω-alkanediol through the addition reaction between diol and vicinal tricarbonyl. The resulting hemiketal acted as a dynamic crosslink because it could undergo reversible alcohol-alcohol or water-alcohol exchange reaction in an ambient condition. Thermal and mechanical analyses showed that the polymer networks were in the rubbery state at room temperature while they became a viscoelastic liquid at elevated temperature. The mechanical property and the qualitative self-healing ability were found to depend on the crosslinker concentration. The network polymer with lower crosslinker concentration was less stiff and could be autonomously healed at room temperature. Those with higher crosslinker concentration were stiffer and could not be autonomously healed at room temperature. However, addition of the simplest monool, methanol, to the cut surfaces drastically improved the self-healing ability of the latter samples. The self-healing mechanism and the role of added methanol were discussed in terms of both the chemical and physical aspects.

Progression-free survival (PFS) is frequently used as a primary endpoint in late-phase clinical trials for anti-metastatic cancer agents. Previous studies have indicated that the frequency of tumor assessment affects the statistical power for PFS because progression dates are inaccurate; however, this finding may be difficult to generalize because of its unrealistic assumptions. Therefore, we re-examined this issue under realistic assumptions and various scenarios that approximate actual clinical trials. Randomized clinical trials comparing two interventions against a solid tumor were simulated under conditions where progressive disease (PD)-dominant PFS or a non-negligible number of deaths (death-competitive PFS) contributed to PFS events, which are conditions that resemble clinical trials of first-line therapy and later-line therapy, respectively. We assessed the impact of tumor assessment frequency on the statistical power. Under the PD-dominant PFS condition, even in extreme scenarios, statistical power loss was only approximately 3%. Under the death-competitive PFS condition, tumor assessment frequency affected the statistical power of PFS if the effect of the treatment on overall survival was lower than that on time to progression. In this case, loss of statistical power was often more than 10% in some realistic scenarios. In trials investigating first-line treatments (PD-dominant PFS), tumor assessment frequency has a negligible impact on statistical power, whereas in trials investigating late-line therapies (death-competitive PFS), the potential impact of tumor assessment frequency on statistical power should be carefully evaluated at the design stage.

The microscopic structure of module-assembled thermoresponsive conetworks was systematically investigated as a function of both temperature T and the mole fraction of the thermoresponsive modules r using small-angle neutron scattering (SANS). The conetworks were prepared by end-linking of hydrophilic modules and LCST-type thermoresponsive modules in water by the molar ratio of (1 – r):r. When the hydrogels with 0.02 ≤ r ≤ 0.10 were heated above certain T, nanometer-scale spherical domains were formed by aggregation of several prepolymer modules, whereas for the hydrogel with r = 0.01 such domain formation was not detected in the T range investigated. The size of spherical domains increased with increasing r and T. The observed r dependence of the domain size was theoretically explained by considering the free energy of domain formation, from which we concluded that the equilibrium domain size was determined mainly by the balance between two free energy contributions: the interfacial free energy of domain–...

Fabrication and characterization of water-resistant nacre-like polymer/clay nanocomposites, in which clay platelets and hydrophobic polymer chains are alternately stacked in parallel, are reported. Hydrophilic clay was converted by an ion-exchange reaction with a methacrylate monomer having a long alkyl chain and a quaternary ammonium salt group at the end. The subsequent in situ polymerization bound the neighboring clay surfaces, leading to the preferential orientation of the clay platelets owing to their high aspect ratio. The composites maintained excellent mechanical properties even after being immersed in water for more than a day. Strong shape stability was observed in water as well as in various organic solvents.

We examined the isothermal crystallization kinetics of poly(e-caprolactone) (PCL) homopolymers confined in a cylindrical nanodomain (nanocylinder) with 12.9 nm in diameter. The confined PCL homopolymers were prepared using the microphase separation of PCL-block-polystyrene (PCL-b-PS) diblock copolymers with a photocleavable o-nitrobenzyl group (ONB) at block junctions and the subsequent cleavage of ONB with UV light. Several PCL homopolymers with different end-groups, acetyl group (molecular weight MEG = 43 g/mol, original PCL homopolymer), adamantane (MEG = 163), cholesterol (MEG = 386), methyl 2,3,6-tri-o-benzoyl-α-d-galactopyranoside (MEG = 506), and vitrified PS (MEG = ∞, i.e., PCL blocks in PCL-b-PS), were prepared to gradually change their chain mobility in the nanocylinder. The crystallization rate of corresponding bulk PCL homopolymers (i.e., no spatial confinement imposed) decreased steadily with increasing MEG, suggesting that these end-groups had no extra effect on the crystallization but simpl...

We investigated the microscopic structure of the nonswellable hydrogel using small-angle neutron scattering (SANS). The hydrogel consisted of four-armed thermoresponsive prepolymer units embedded in a homogeneous network of four-armed poly(ethylene glycol) (Tetra-PEG). The structure of the hydrogel was similar to that of the ordinary Tetra-PEG hydrogels at temperatures below 16.6 °C, whereas discrete spherical domains were formed at temperatures above 19.5 °C. The number of prepolymer units contained in one domain was much larger than unity, indicating that multiple thermoresponsive prepolymer units as well as Tetra-PEG units gathered to form a domain. Formation of domains much larger than a single prepolymer unit led to significant frustration of the matrix polymer network outside the domains. This frustration enhanced the elastic energy of the matrix network which would cancel the osmotic pressure and induce significant macroscopic shrinking. The selection mechanism of the domain size could qualitativel...

We have examined the crystal orientation of poly (e-caprolactone) (PCL) chains covalently tethered to nanodomain interfaces at both chain-ends (T2-PCL), one chain-end (T1-PCL), and no chain-end (PCL homopolymers, T0-PCL) all confined in an identical lamellar nanodomain (nanolamella). In order to prepare these PCL chains, we synthesized two kinds of lamella-forming polystyrene-block-PCL-block-polystyrene (PS-b-PCL-b-PS) triblock copolymers with photocleavable o-nitrobenzyl groups (ONB) at either or both of block junctions. The chain-ends tethering significantly affected the tilt angle φ between the c axis of PCL crystals and the normal of nanolamella interfaces (ND). That is, the c axis of T2-PCL crystals oriented almost perpendicular to ND (φ ≥ 70°), whereas that of T0-PCL crystals took completely parallel orientation against ND (φ ∼ 0°) at high crystallization temperatures (>32 °C). The T1-PCL crystal showed an intermediate orientation between T2-PCL and T0-PCL crystals (35°

Hypothesis Nacre-like polymer/clay nanocomposites are a fascinating material thanks to its superior mechanical property. However, it has been a great challenge to incorporate hydrophobic polymer components due to highly hydrophilic nature of clay, which limits further improvement of water-resistance and addition of various functionalities. To overcome this problem, we developed a method to form regular nacre-like layered structure from a hydrophobic polymer and hydrophilic clay by a combination of surface modification of clay and selective click reaction between the polymer and clay surfaces. Experiments Natural clay, montmorillonite, was modified with a hydrophobic surfactant bearing an ethenyl group and subsequently reacted in situ with a thiol-functionalized hydrophobic polysiloxane. The layered structure, as well as its formation process, mechanical property, physical stability in water, and self-adhesion property of the nanocomposites were investigated. Findings In situ thiol-ene click reaction between surface-modified clay and polymer led to self-alignment of clay platelets into a regular layered structure. The resultant nacre-like nanocomposites not only showed the good mechanical property but also had excellent stability in water and self-adhesion ability, both of which originated from the characteristics of the polymer used. These findings widen the possibility of functional nacre-like nanocomposites by expanding the range of applicable polymers to hydrophobic ones.

Geometric constraint in pregel solution enables construction of a highly ordered three-dimensional polymer network., Gels are a soft elastic material consisting of a three-dimensional polymer network with nanometer-sized pores and are used in a variety of applications. However, gel networks typically have a substantial level of defects because the network formation reaction proceeds stochastically. In this study, we present a general scheme to fabricate gels with extremely low levels of defects by applying geometric constraints into pregel solution based on the “bond percolation” concept. In the formed gel, stationary laser speckles, which are an indicator of spatial defects, were not observed at all. In addition, we found that the concentration fluctuations of the polymer chains were ergodic across the whole gel network. In such a homogeneous gel, both the spatial and temporal correlations of polymer chains are the same before and after gelation.

Aim The phase II/III GATSBY study (NCT01641939) showed that trastuzumab emtansine did not have an efficacy benefit over taxane in patients with previously treated, human epidermal growth factor receptor 2 (HER2)-positive advanced or metastatic gastric or gastroesophageal junction cancer. We evaluated patients from Japanese centers within GATSBY. Methods In stage one, patients (randomized 2:2:1) received trastuzumab emtansine 3.6 mg/kg every 3 weeks, trastuzumab emtansine 2.4 mg/kg weekly, or physician's choice of taxane (docetaxel 75 mg/m² every 3 weeks or paclitaxel 80 mg/m² weekly). In stage two, patients (randomized 2:1) received trastuzumab emtansine 2.4 mg/kg weekly or taxane. Eligible patients had centrally assessed HER2-positive disease and progression during or after first-line therapy. Primary endpoint was overall survival. We present the 2.4 mg/kg weekly data. Results Eighty-two patients were randomized (intention-to-treat: 48 to trastuzumab emtansine 2.4 mg/kg weekly, 23 to taxane; September 2012-August 2014) at 19 sites. Median overall survival was 11.8 months (95% confidence interval [CI], 9.3-16.3) with trastuzumab emtansine 2.4 mg/kg weekly and 10.0 months (95% CI, 7.1-18.2) with taxane (unstratified hazard ratio = 0.94, 95% CI, 0.52-1.72). Trastuzumab emtansine 2.4 mg/kg weekly, versus taxane, was associated with fewer grade ≥3 adverse events (AEs; 52.1% vs 68.2%) and serious AEs (14.6% vs 18.2%). There were no fatal AEs. Conclusions Efficacy in Japanese patients within GATSBY was consistent with the overall population; overall survival was not prolonged with trastuzumab emtansine 2.4 mg/kg weekly versus taxane. The safety profile of trastuzumab emtansine was similar to the overall population.

Purpose Ipatasertib is a selective inhibitor of Akt, a frequently activated protein kinase in human cancers. The current study assessed the safety, tolerability, and pharmacokinetics of ipatasertib in Japanese patients with solid tumors. Methods This was a phase I, open-label, 3 + 3 dose-escalation study conducted in two stages. In stage I, Japanese patients with solid tumors were administered ipatasertib 200, 400, or 600 mg/day for 21 days of a 28-day cycle. In stage II, Japanese patients with castration-resistant prostate cancer were administered ipatasertib 200 or 400 mg/day in combination with abiraterone and prednisolone in 28-day cycles. Dose-limiting toxicity (DLT) was assessed at each dose before enrolling patients at a higher dose; DLT was used to determine the maximum tolerated dose (MTD) and maximum administered dose (MAD). Pharmacokinetic parameters were assessed after a single dose and at steady state. Results Fifteen patients were enrolled in Stage I and six in Stage II. The ipatasertib MTD was 600 mg as monotherapy and MAD was 400 mg in combination with abiraterone and prednisolone. Ipatasertib plasma exposure was dose proportional across the dose range, and was not markedly affected by concurrent administration of abiraterone plus prednisolone. Stable disease (SD) was observed in eight patients treated with ipatasertib monotherapy (53.3%); four patients had SD and one had complete response with ipatasertib plus abiraterone and prednisolone. Conclusions Ipatasertib, at the monotherapy MTD of 600 mg/day and MAD of 400 mg/day in combination with abiraterone and prednisolone, was safe and tolerable in Japanese patients with solid tumors. Electronic supplementary material The online version of this article (10.1007/s00280-019-03882-7) contains supplementary material, which is available to authorized users.

Economics of national security or international security is so immense a topic as to be intimidating. As in most of economics it has both positive and normative components. The goal of this chapter is to offer examples of both. Positive analyses, attempt to understand the economic origins of conflicts among nations and the economic foundations of success or failure in these conflicts.

The purpose of this chapter is twofold. First, we theoretically analyze simultaneous optimization of both self-protection and self-insurance by two countries facing the common risk of a disastrous event to derive simple analytical rules in the distribution of contributions. In this analysis, we provide a new perspective from the theory of collective risk management to reveal how allies share the burden of self-insurance and self-protection public goods. Second, we utilize our model to conduct numerical simulations of burden sharing in NATO from 1970 to 2010. In this simulation, we show that whether the conventional exploitation hypothesis holds depends on the risk profile that NATO faces. Our calculated results closely simulate the actual development of the military spending to GDP ratio.

Based on Ihori and McGuire (2007), this chapter first investigates the impact of self-protection on alliances and then, based on Ihori and McGuire (2010), considers the impact of self-insurance as well as self-protection on security spending. We extend existing analyses of self-insurance and self-protection that countries may implement at a national level in pursuit of their security. That is, we provide an analysis of odds-improving self-protection and cost-reducing self-insurance when they yield collective benefits to allied groups, such as alliances of nations, for whom risks of loss are public bads and prevention of loss is a public good.

This chapter investigates how the cooperation of members of an allied bloc influences their welfare when that bloc opposes another bloc. This question is related to cooperative and non-cooperative defense spending in the confronting blocs such as the NATO and the WTO in the Cold War. By addressing this question, we can explore how voluntary provision of an international public good within allied countries protects against national emergency from the adversarial alliance.

In the aftermath of World War II and height of the Cold War, the normative approach to the economics of alliances seemed paramount. Historically, an alliance formed when academic economics strived to assist the beleaguered civil and uniformed servants who were trying to formulate and execute policy. However, due in part to the Vietnam War and especially by the end of the Cold War, the gap between academic economics and policy implementation widened. This book develops a theory of risk management with public goods, integrating the likelihood of loss, magnitude of loss, and isolation from loss into a consolidated model of alliances. It extends existing concepts of individual risk management by a single person to decision theory for an entire country, managed by a government bureaucracy and lodged in a universe of overlapping alliances.

An interesting application of non-cooperative private funding of public goods arises in international security and national defense. In their classical article on the economic theory of alliances, Olson and Zeckhauser (1966) demonstrated that countries may allocate some fraction of national income to international (or regional) public goods (for example, special trading agreements, formation of international organizations, military preparedness, active international diplomacy, foreign aid) to reduce regional and international tension and to avoid random emergency costs.

In this chapter, we investigate the impacts on collective risk management of mistakes made in estimating the severity of a threat. In general, in the real world, it is difficult for policymakers to make precise estimates of threats to their country. Although the governments intend to collect precise information on threats, the collected information can contain significant errors and is also often biased in bureaucratic administrative processes. Moreover, interest groups try to influence the evaluation of the information and the policymaking process through lobbying. Using the alliance model developed in this book, we examine how misestimation of a threat affects burden-sharing among allies. Allies may “over”-estimate the threat so that the estimated level is higher than the true level of the threat. We will show that if an ally overestimates the threat to an alliance, it may contribute more to the public goods than when its estimates are accurate.

The isothermal crystallization kinetics of poly(e-caprolactone) (PCL) blocks confined in cylindrical microdomain structures (nanocylinders) formed by the microphase separation of PCL-block-polystyrene (PCL-b-PS) copolymers were examined as a function of nanocylinder diameter D and molecular weight of PCL blocks Mn. Small amounts of polystyrene oligomers (PSO) were gradually added to PCL blocks in PCL-b-PS to achieve small and continuous decreases in D. The time evolution of PCL crystallinity during isothermal crystallization at −42 °C showed a first-order kinetic process with no induction time for all the samples investigated, indicating that homogeneous nucleation controlled the crystallization process of confined PCL blocks. The half-time of crystallization t1/2 (inversely proportional to the crystallization rate) of PCL blocks with Mn ∼ 14 000 g/mol showed a 140-fold increase (from 0.48 to 69 min) by a 16% decrease in D (from 18.6 to 15.6 nm). Another set of PCL-b-PS/PSO blends involving slightly longe...

Background In the randomised Phase 3 IMpassion130 trial, atezolizumab combined with nab-paclitaxel (atezo + nab-P) in 902 patients with triple-negative breast cancer (TNBC) showed prolonged progression-free survival (PFS) in both the intention-to-treat (ITT) population and programmed death-ligand 1 (PD-L1)–positive subgroup compared with placebo plus nab-P (plac + nab-P). This study assessed the efficacy and safety of atezo + nab-P in the IMpassion130 Japanese subpopulation. Methods Eligible patients had unresectable locally advanced or metastatic TNBC previously untreated with chemotherapy for metastatic disease. Patients were randomised 1:1 to receive either atezo + nab-P or plac + nab-P. Co-primary endpoints were investigator-assessed PFS and overall survival (ITT population and PD-L1–positive subgroup). These were also assessed in the Japanese subpopulation. Results There were 65 Japanese patients (34 atezo + nab-P; 31 plac + nab-P). The PD-L1–positive subgroup included 25 patients (12 atezo + nab-P; 13 plac + nab-P). Median PFS was 7.4 months (atezo + nab-P) versus 4.6 months (plac + nab-P; hazard ratio [HR], 0.47; 95% CI, 0.25–0.90). In the PD-L1–positive subgroup, median PFS was 10.8 months (atezo + nab-P) versus 3.8 months (plac + nab-P; HR, 0.04; 95% CI, The efficacy of atezolizumab plus nab-paclitaxel in Japanese patients with triple-negative breast cancer was consistent with the overall IMpassion130 population. No new safety signals were observed.

We have investigated the effects of chain-ends tethering at nanodomain interfaces on the crystallization behavior of poly(e-caprolactone) (PCL) chains spatially confined in lamellar nanodomains. The PCL chains tethered at both chain-ends (T2-PCL), one chain-end (T1-PCL), and no chain-end (i.e., PCL homopolymers) (T0-PCL) were prepared from polystyrene-block-PCL-block-polystyrene (PS-b-PCL-b-PS) triblock copolymers having a photocleavable o-nitrobenzyl (ONB) group at either or both of block junctions. The lamellar nanodomain was provided by the microphase separation of PS-b-PCL-b-PS copolymers, in which T2-PCL was inherently confined. Subsequently, the ONB group was cleaved by the irradiation of ultraviolet light to yield T1-PCL or T0-PCL from T2-PCL without perturbing the lamellar nanodomain. T2-PCL showed an extremely low melting temperature and crystallinity as compared with T1-PCL and T0-PCL, indicating that the crystallization was significantly affected by chain mobility imposed by chain tethering at ...

Recent experimental studies are extensively reviewed on the crystallization of polymer chains spatially confined in small domains with their dimension on the order of 10 nm (nanodomains), with a particular emphasis on unique features of crystallization behavior and crystal orientation of confined chains. The nanodomains employed here (such as nanospheres, nanocylinders, or nanolamellae) are mainly provided by the microphase separation of diblock copolymers, and therefore we introduce the crystallization of block chains (i.e., polymer chains with one of chain-ends always tethered at nanodomain interfaces). The crystallization of confined blocks is very complicated and hence interesting as compared with that of bulk homopolymers, because it depends significantly on the shape, size, and hardness of nanodomains as well as the crystalline nature of block chains. Furthermore, we discuss a substantial difference in the crystallization behavior and crystal orientation between block chains and homopolymers (i.e., polymer chains with both chain-ends free) spatially confined in identical nanodomains.

Introduction Atezolizumab, an anti–programmed death-ligand 1 (PD-L1) agent, is effective and well tolerated in patients with pretreated advanced non–small-cell lung cancer (NSCLC). We assessed its efficacy and safety in Japanese patients through subgroup analyses of the phase 3 OAK study ( NCT02008227 ). Patients and Methods Key eligibility criteria of this randomized, controlled, open-label, international study include locally advanced/metastatic NSCLC, ≥ 1 prior platinum-based chemotherapy, age ≥ 18 years, measurable disease (Response Evaluation Criteria in Solid Tumors v1.1), and Eastern Cooperative Oncology Group performance status 0 or 1. Atezolizumab 1200 mg or docetaxel 75 mg/m2 was provided intravenously every 3 weeks. Co-primary end points were overall survival (OS) in the intention-to-treat (ITT) population and those with ≥ 1% PD-L1 expression on tumor cells (TC) or tumor-infiltrating immune cells (IC; TC1/2/3 or IC1/2/3). Results Sixty-four ITT patients were Japanese; 19 had TC1/2/3 or IC1/2/3 status. In Japanese ITT patients, median OS in the atezolizumab arm (n = 36) was longer than the docetaxel arm (n = 28; 21.3 months [95% confidence interval (CI), 11.0-not estimable (NE)] versus 17.0 months [95% CI, 12.5-NE], respectively; hazard ratio 0.80 [95% CI, 0.41-1.57]). In the TC1/2/3 or IC1/2/3 population, median OS was 21.3 months (95% CI, 15.0-NE) and NE in the atezolizumab (n = 11) and docetaxel (n = 8) groups, respectively (hazard ratio, 0.81 [95% CI, 0.22-3.05]). Atezolizumab was generally well tolerated, with no treatment-related deaths. Conclusion Atezolizumab was effective and well tolerated in pretreated Japanese patients with NSCLC. Results are consistent with the primary analysis of OAK.

Background/aim Tolerability and safety of trastuzumab emtansine (T-DM1) was investigated in Japanese patients with HER2-positive advanced breast cancer who were previously treated with chemotherapy and trastuzumab. Patients and methods Patients with inoperable or recurrent breast cancer who were previously treated with chemotherapy and trastuzumab in adjuvant and/or metastatic disease were included. T-DM1 3.6 mg/kg was administered intravenously every 21 days. The administration dosage or schedule of T-DM1 was modified based on laboratory tests on the administration day. Results Among 232 patients analyzed, adverse events were reported in 228 patients (98.3%); five patients (2.2%) discontinued due to adverse events and twenty patients (8.6%) had serious adverse events. The most commonly reported grade ≥3 adverse event of special interest was thrombocytopenia (69 patients; 29.7%), followed by hepatotoxicity (26 patients; 11.2%). Conclusion T-DM1 was well tolerated in Japanese patients with HER2-positive advanced breast cancer and no new safety signals were observed.

The crystallization behavior of poly(e-caprolactone) (PCL) homopolymers and PCL blocks confined in identical lamellar nanodomains (L-domains) has been examined using differential scanning calorimetry and synchrotron small-angle X-ray scattering as a function of PCL layer thickness d and crystallization temperature. The PCL homopolymers confined in the L-domains with d = 8.7 nm (small L-domain) and 15.8 nm (large L-domain) were prepared using microphase separation of PCL- block -polystyrene (PCL- b -PS) copolymers with a photocleavable o -nitrobenzyl group (ONB) between PCL and PS blocks, followed by the photocleavage of ONB with UV-irradiation. The PCL crystallinity showed a conventional sigmoidal evolution both for PCL blocks and PCL homopolymers confined in the large L-domain. However, it increased monotonously with no induction time for PCL blocks but sigmoidally for PCL homopolymers confined in the small L-domain. The substantial differences in crystallization mechanism between PCL blocks and PCL homopolymers confined in the small L-domain are discussed on the basis of chain mobility during crystallization.

This paper investigates the effects of a change in environmental abatement technology on the accumulation of capital stock and on the global environment in a two-country overlapping-generations model. Among other issues, we focus on a situation where abatement improves in only one country. With comparative static analysis, we derive the sufficient and necessary condition in the initial steady states for unilateral improvement in abatement technology to improve the two-country global environment. In addition, we examine the effects of changes in several technologies on capital stock and on the global environment.

In this paper the emphasis is focused upon nitriding effect on corrosion fatigue strength of Cr-Mo low alloy steel in 1% HCl aqueous solution.Corrosion fatigue strength enhancement of Cr-Mo low alloy steel by nitriding is discussed on the basis of the corrosion fatigue testing results on gas and ion nitrided Cr-Mo low alloy steel plate specimen with 3.5mm thickness in 1%HCl aqueous solution. It can be concluded that residual compressive stress distributed on the nitrided specimen surface caused improvement of corrosion fatigue strength of Cr-Mo low alloy steel.

Introduction The phase II JO28638 study evaluated first-line onartuzumab plus erlotinib in patients with MET-positive advanced, metastatic, or post-operative recurrent non-small-cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) mutations. The study was stopped following termination of the global METLung study (OAM4971g), which showed lack of efficacy in the onartuzumab/erlotinib arm. We present immature efficacy and safety data from JO28638. Materials and Methods Chemotherapy-naive patients aged ≥ 20 years were enrolled. Patients received onartuzumab (15 mg/kg every 3 weeks) plus erlotinib (150 mg once daily) until progression or unacceptable toxicity. The co-primary endpoints were investigator (INV)-assessed progression-free survival (PFS) and safety. Secondary endpoints: overall response rate (ORR), disease control rate (DCR), overall survival (OS), duration of response (DOR), and pharmacokinetics. Exploratory biomarker analyses were also conducted. Results 61 patients received treatment. Median age was 67 years and most patients had stage IV NSCLC (71%), MET-IHC score 2 (87%), and exon 19 deletion EGFR mutation (53%). Median PFS (INV) was 8.5 months (95% confidence interval [CI] 6.8–12.4); median OS was 15.6 months (95% CI 15.6–not evaluable); ORR was 68.9% (95% CI 55.7–80.1); median DOR was not reached; DCR was 88.5% (95% CI 77.8–95.3). Pharmacokinetics were similar to previous studies. All patients experienced an adverse event (AE); 26 patients discontinued treatment due to AEs; no grade 5 AEs were reported. No significant correlation was found between biomarkers and efficacy outcomes. Conclusion The results presented are inconclusive due to the early termination of the study.