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Anemia, a frequently occurring condition in older patients, has no standard definition; however, in most studies, it is defined as hemoglobin level

T315I mutation found in chronic myelogenous leukemia (CML) and Ph + ALL patients is the most serious one among resistance against BCR/ABL kinase inhibitors including imatinib and is only responsive to ponatinib (PNT). However, the novel strategy is required to reduce life-threatening adverse effects of PNT including ischemic cardiovascular disease. We examined the mechanism of PNT-induced cytotoxicity against a T315I(+) Ph + ALL cell line, TccY/Sr. PNT induced apoptosis (increased sub G1 cells, and cleaved caspase3 and PARP), and suppressed protein expression of MCL1, cyclin D2 and c-myc, which were reversed by a proteasome inhibitor, MG132, suggesting enhanced proteasomal degradation by PNT. Among BCL2 family inhibitors, MCL1 inhibitors (maritoclax and AZD5991) robustly induced cell death, showing the MCL1-dependent survival of TccY/Sr cells. Decreased MCL1 and c-myc expression by PNT was also observed in T315I(+) MEGA2/STIR cells. PNT suppressed PI3K activation followed by AKT inhibition and GSK3 dephosphorylation. PI3K/AKT inhibitors mimicked PNT, suggesting that PI3K/AKT signaling is important for survival of TccY/Sr cells. Moreover, GSK3 inhibitor (SB216763) reduced PNT-induced cytotoxicity and degradation of c-myc and MCL1. AZD5991 exhibited the synergistic action with PNT, anti-cancer drugs and venetoclax (BCL2 inhibitor), suggesting the utility of MCL1 inhibitor alone or in combination as a future clinical option for Ph + leukemia patients.

Fusions of the Runt-related transcription factor 1 (RUNX1) with different partner genes have been associated with various hematological disorders. Interestingly, the C-terminally truncated form of RUNX1 and RUNX1 fusion proteins are similarly considered important contributors to leukemogenesis. Here, we describe a 59-year-old male patient who was initially diagnosed with acute myeloid leukemia, inv(16)(p13;q22)/CBFB-MYH11 (FAB classification M4Eo). He achieved complete remission and negative CBFB-MYH11 status with daunorubicin/cytarabine combination chemotherapy but relapsed 3 years later. Cytogenetic analysis of relapsed leukemia cells revealed CBFB-MYH11 negativity and complex chromosomal abnormalities without inv(16)(p13;q22). RNA-seq identified the glutamate receptor, ionotropic, kinase 2 (GRIK2) gene on 6q16 as a novel fusion partner for RUNX1 in this case. Specifically, the fusion of RUNX1 to the GRIK2 antisense strand (RUNX1-GRIK2as) generated multiple missplicing transcripts. Because extremely low levels of wild-type GRIK2 were detected in leukemia cells, RUNX1-GRIK2as was thought to drive the pathogenesis associated with the RUNX1-GRIK2 fusion. The truncated RUNX1 generated from RUNX1-GRIK2as induced the expression of the granulocyte colony-stimulating factor (G-CSF) receptor on 32D myeloid leukemia cells and enhanced proliferation in response to G-CSF. In summary, the RUNX1-GRIK2as fusion emphasizes the importance of aberrantly truncated RUNX1 in leukemogenesis.

The helix-sense reversal of poly(β-phenylpropyl l-aspartate) (3PLA) in the solid state was studied by synchrotron wide-angle X-ray diffraction and small-angle X-ray scattering. The direct determination of the characteristic helical pitch before and after the transition revealed that the transition takes place reversibly between the two α-helices having opposite screw-sense during the heating and cooling cycle. While the hexagonal packing remains unaltered, the helix-sense inversion causes discontinuous changes in the molecular arrangement and, by extension, the crystalline dimension. In this study, another transition was detected at a higher temperature from the left-handed α-helix to the π-helix, the molecular chirality being unaffected.

Variant chromosomal translocations associated with t(8;21) are observed in 3-4% of acute myeloid leukemia (AML) cases with a RUNX1-RUNX1T1 fusion gene. However, the molecular events that occur in variants of t(8;21) are not well characterized. In the present study, we report genetic features of a variant three-way translocation of t(8;12;21)(q22;p11;q22) in a patient with AML. In this patient, leukemia cells lacked azurophilic granules, which does not correspond with the classic features of t(8;21). RNA-seq analysis revealed that TM7SF3 at 12p11 was fused to VPS13B at 8q22 and VPS13B to RUNX1, in addition to RUNX1-RUNX1T1. VPS13B was located near RUNX1T1 and both were localized at the same chromosomal bands. The reading frames of TM7SF3 and VPS13B did not match to those of VPS13B and RUNX1, respectively. Disruption of VPS13B causes Cohen syndrome, which presents intermittent neutropenia with a left-shifted granulopoiesis in the bone marrow. Disruption of VPS13B may thus cause the unusual features of RUNX1-RUNX1T1 leukemia. Our case indicates that rearrangement of VPS13B may be additional genetic events in variant t(8;21).

International students come to Japan to study or conduct research; however, they should be encouraged to tour Japan as well. To this end, we have developed and operated a system to support the tourism of international students in Japan. The tourism behavior of international students have been not sufficiently studied, however. Therefore, in this study, we at first present an analysis method to analyze international students' tourism behavior using the operational data of the tourism support system and then discuss the process of analysis method from the viewpoint of data acquisition and data visualization. We conducted analysis in three contents: 1. tourism preferences and attribute analysis at the individual level, 2. comparative analysis between a plan and actual tour at the group level, and 3. comparative analysis between the tourism preferences of international students and those of foreign tourists. Based on analysis results, we were able to characterize aspects of international students' tourism behavior, such as the tendencies of visiting places, preference for types of tourism activities, and trends in understanding Japanese language and culture. As future task, we intend to improve the method to raise the accuracy of our analysis in future research. Moreover, we will attempt to automate the analysis, and increase the comprehensiveness of the tourism support system according to knowledge on tourism behavior obtained by analysis.

We fabricated electric double-layer transistors with perovskite nickelate LaNiO3 epitaxial films as a channel and an ionic liquid as a gate insulator and investigated the channel's transport behavior at negative gate bias voltages. We found that when the negative VG is low enough, the channel resistance undergoes reversible changes due to electrostatic carrier accumulation. On the other hand, with increasing VG, electrochemical decomposition of the channels due to the VG-induced instability of the unusually high Ni valence state [Ni(3+δ)+] occurs and the channels are etched, which is seen as an irreversible increase in the channel resistance. We also show that channel layers electrochemically etched to a few nanometers thick exhibit metallic transport behavior and the electrostatic carrier accumulation in the etched metallic channels results in 30% reductions in the channel resistance at 220 K, which are about twice as large as those seen for the ultra-thin insulating film channels. These observations indicate that surface defects and dangling bonds in the electrochemically etched channel layers differ from those in ultrathin films. Our results highlight that the electrochemical decomposition and etching in electric double-layer transistors is a unique approach for fabricating ultrathin oxide films and exploring electric field-induced effects on their functional properties.

In recent years, bioremediation has been used as an effective technique for the cleaning of polluted sites. However, bioremediation treatment efficacy varies considerably; thus, characterization of indigenous pollutant-degrading soil microorganisms and assessment of the changes in microbial composition by pollutants are essential for designing efficient bioremediation methods. In this study, an ecological impact evaluation method that is cost-efficient and has low contamination risk was developed to assess the indigenous microbial composition. An “in situ microcosm” was constructed using a porous ceramic arrowhead. Phenol, a common environmental pollutant, was used to assess the evaluation efficacy of this method. Our data showed that phenol gradually percolated into the soil adjacent to the arrowhead and stimulated unique indigenous microorganisms (Bacillus sp., Streptomyces sp., and Cupriavidus sp.). Furthermore, the arrowhead approach enabled efficient evaluation of the ecological impact of phenol on soil microorganisms. Thus, the arrowhead method will contribute to the development of bioremediation methods.

In recent years, the business conditions of museums in Japan have been growing increasingly severe as attendance falls and the local governments that operate them are forced to cut budgets. The same is true of open-air museums, which also face the additional pressure of maintenance and management costs for their vast sites and buildings. For this reason, there are reports from across Japan of attempts to increase numbers of visitors at such museums by making them more attractive as tourism resources, by stressing hospitality or strengthening ties with the local community. It is thought that one effective means of overcoming these challenges faced by open-air museums would be through enhancement of information services, which encourage the understanding of and connections with various stakeholders. This study attempted to create new services using wearable devices in order to improve hospitality at open-air museums located on vast sites on hilly land. We implemented an action research approach to gather knowledge on solutions to problems faced in the field, by intervening in activities on site at two open-air museums in Japan. Providing information to support visitors? tours of the museums, integrated with physical information and spatial information, added new value to existing smartphone-based systems intended to support visitors by explaining museum exhibits. Through experiments in the field by proposing ?Physical condition management and barrier-free information provision when viewing cultural heritage? at the Hiraizumi World Heritage Site and a new type of information service characterized by ?Fusion of support for viewing works of art and health promotion activities? at an open-air art museum, we elucidated the expected results and issues involved in practical operation.

ETV6, which encodes an ETS family transcription factor, is frequently rearranged in human leukemias. We show here that a patient with acute myeloid leukemia with t(7;11)(p15;p15) gained, at the time of relapse, t(11;12)(q12.1;p13) with a split ETV6 FISH signal. Using 3'-RACE PCR analysis, we found that ETV6 was fused to LPXN at 11q12.1, which encodes leupaxin. ETV6-LPXN, an in-frame fusion between exon 4 of ETV6 and exon 2 of LPXN, did not transform the interleukin-3-dependent 32D myeloid cell line to cytokine independence; however, an enhanced proliferative response was observed when these cells were treated with G-CSF without inhibition of granulocytic differentiation. The 32D and human leukemia cell lines each transduced with ETV6-LPXN showed enhanced migration towards the chemokine CXCL12. We show here for the first time that LPXN is a fusion partner of ETV6 and present evidence indicating that ETV6-LPXN plays a crucial role in leukemia progression through enhancing the response to G-CSF and CXCL12.

DEK-NUP214 gene fusion in acute myeloid leukemia (AML) is associated with poor prognosis. It is most often a sole translocation and more rarely observed as complex chromosomal forms. We describe an AML case with complex karyotype abnormalities involving chromosome bands 6p23, 6q13, 7p22, and 9q34. RNA sequencing analysis revealed that exon 17 of NUP214 (9q34) was fused to exon 2 of RAC1 (7p22). We also detected that the 5′-end of intron 1 of RAC1 was fused with the antisense strand of intron 5 of COL12A1 (6q13). RT-PCR analysis confirmed the expression of DEK-NUP214, NUP214-RAC1, RAC1-COL12A1, NUP214, and RAC1. These results suggest that the 5′- and 3′-ends of NUP214 from the breakpoint in the same locus were fused to RAC1 and DEK, respectively, and the 5′-end of RAC1 was fused to COL12A1. The reading frame of NUP214 was not matched with RAC1; however, high expression of the RAC1 protein was detected by Western blotting. This study identifies the variant complex fusion genesNUP214-RAC1 and RAC1- COL12A1 in a case of AML.

The Great East Japan Earthquake that struck on March 11, 2011 caused massive damage centered on the Tohoku region of Japan, and disaster recovery efforts continue in the area even today. The region is moving forward with the development and use of the Sanriku Geopark, which uses earthquake structural remnants as part of its tourism assets, and it aims to have the facility added to the Global Geoparks Network. The goal of this study is to contribute to both tourism recovery and preventing the loss of the lessons of the earthquake by elucidating the ideal form of effective information services for a geopark that includes earthquake structural remnants. Since the Great East Japan Earthquake is a negative experience, there was a need to move forward with design of information services while ascertaining the intentions of stakeholders in the local community, who consist of a diverse range of subjects. Accordingly, we proceeded with service design based on three main policies: First, we employed the analytical methods of the Business Analysis Body of Knowledge (BABOK®) to conduct stakeholder analysis of the diverse range of stakeholders involved in preservation and use of earthquake remnants. Second, we adopted a human-centered design (HCD) process to enable participatory design, in light of the need to create new services grounded in the intentions of local residents as well as the needs of visitors. Third, we introduced the stakeholder management perspective of the Project Management Body of Knowledge (PMBOK®) in an attempt at integrated process management from stakeholder analysis through the derivation of services through the HCD process. We believe that through this approach we were able to identify the ideal forms of information service concepts and provision systems through ICT to contribute to both prevention of loss of the lessons of the earthquake and promotion of new tourism programs, while obtaining the understanding of local residents and others who were the parties actually affected by the earthquake. The knowledge obtained through this study also is likely to be useful in design of information services for other open-air museums for which diverse stakeholders support management.

Varicella, characterized by a vesicular rash, occurs primarily in young children. Although older individuals can also be affected or vaccinated, outbreaks among adults are rare. We investigated a small outbreak of varicella in B-cell lymphoma patients for elucidation of risk factor of the disease. We experienced four cases of varicella after an index herpes zoster case. All varicella cases were confirmed varicella zoster virus (VZV) infection by PCR. All varicella cases occurred in diffuse large B-cell lymphoma patients receiving rituximab-containing chemotherapy. On the other hand, only three of the 18 non-varicella patients in the same room were receiving rituximab-containing chemotherapy (P = 0.005). All varicella patients had detectable serum anti-varicella zoster virus IgG antibodies before chemotherapy. Even in the presence of neutralizing antibodies to the virus, lymphoma patients treated with rituximab-containing chemotherapy can possibly become re-infected with varicella. These findings suggest that zoster patients should be strictly isolated in hematology and oncology ward, and prophylactic acyclovir should be considered for such patients when exposed to zoster/varicella.

The dysregulation of proper transcriptional control is a major cause of developmental diseases and cancers. Polycomb proteins form chromatin-modifying complexes that transcriptionally silence genome regions in higher eukaryotes. The BCL6 corepressor (BCOR) complex comprises ring finger protein 1B (RNF2/RING1B), polycomb group ring finger 1 (PCGF1), and lysine-specific demethylase 2B (KDM2B) and is uniquely recruited to nonmethylated CpG islands, where it removes histone H3K36me2 and induces repressive histone H2A monoubiquitylation. Germline BCOR mutations have been detected in patients with oculofaciocardiodental and Lenz microphthalmia syndromes, which are inherited conditions. Recently, several variants of BCOR and BCOR-like 1 (BCORL1) chimeric fusion transcripts were reported in human cancers, including acute promyelocytic leukemia, bone sarcoma, and hepatocellular carcinoma. In addition, massively parallel sequencing has identified inactivating somatic BCOR and BCORL1 mutations in patients with acute myeloid leukemia (AML), myelodysplastic syndrome (MDS), chronic myelomonocytic leukemia, medulloblastoma, and retinoblastoma. More importantly, patients with AML and MDS with BCOR mutations exhibit poor prognosis. This perspective highlights the detection of BCOR mutations and fusion transcripts of BCOR and BCORL1 and discusses their importance for diagnosing cancer subtypes and estimating the treatment responses of patients. Furthermore, this perspective proposes the need for additional functional studies to clarify the oncogenic mechanism by which BCOR and BCORL1 are disrupted in cancers, and how this may lead to the development of novel therapeutics. Mol Cancer Res; 12(4); 479–84. ©2014 AACR.

The BCR-ABL1 fusion gene is the molecular marker of chronic myeloid leukemia (CML). The e19a2 transcript is a rare variant associated with various clinical presentations and courses of CML. We herein present a case of e19a2-positive CML who was intolerant to initial treatment with imatinib and successfully responded to subsequent nilotinib therapy. She achieved a major molecular response and has since be able to sustain it. According to the literature, achieved molecular response by imatinib monotherapy has not yet been reported in e19a2-positive CML patients. Second generation tyrosine kinase inhibitors may therefore be a more effective treatment for e19a2-positive CML patients.

The soluble protein fraction of the extremely halophilic archaeon Haloarcula japonica exhibits substantial inorganic pyrophosphate (PPi) hydrolysis activity in the presence of 2–4 M NaCl (Wakai et al, J Biol Chem 288:29247–29251, 2013), which provides high ionic strength (2–4). In this study, much higher PPi hydrolysis activity was unexpectedly detected, even with 0 M NaCl in the presence of 100–200 mM MgSO4, providing a much lower ionic strength of 0.4–0.8, in the same protein fraction. Na+ and Mg2+ ions were required for activity under high and low ionic strength conditions, respectively. A recombinant H. japonica pyrophosphatase (HjPPase) exhibited PPi hydrolysis activity with the same broad ionic strength range, indicating that the activity associated with such a broad ionic strength range could be attributed to a single enzyme. Thus, we concluded that the broad ionic strength range of HjPPase may contribute to adaptation for both Na+ and Mg2+ which are abundant but variable in the unstable living environments of H. japonica.

Wnt signaling plays an important role in hematopoietic stem cell self-renewal and proliferation. Recent studies have revealed that the strength of the Wnt signaling pathway regulates normal hematop...

The purpose of this research was to gather knowledge on the behavior characteristics of visitors when they use information services, to clarify kinds of effective information services for fostering understanding of and relationships with open-air museums, and to contribute to sustainable museum management. Here, "open-air museum" does not just refer to traditional museums where items are preserved and displayed by a specialist such as a curator. It also refers to new formats, such as the ecomuseums created in France where the region's residents actively participate in maintenance and management. The scope of this research encompasses a consideration of various configurations of open-air museums (local preservation, relocating collection, restorative construction). Three cultural institutions/regions of Japan (the Hiraizumi World Heritage Site, Kitakami City?s park for traditional houses, and an open-air art museum in Iwate) were chosen. These facilities were already using a guide system for smartphones developed using the results of our previous research. In order to analyze the behavior characteristics of the visitors, we gathered quantitative data, with the cooperation of the facility managers, from the aforementioned guide system's GPS excursion logs and information browsing logs, then attempted analysis visualization using our own original GIS-based tools. By combining this quantitative method with qualitative ones, such as field observations and interviews, we were able to acquire knowledge on behavior characteristics specific to visitors of open-air museums, which unlike mere tourist facilities have a multifaceted role in cultural dissemination, tourism promotion, and regional development. Hereafter, we will implement information service design for other open-air museums in urgent need of development (facilities to preserve/pass on relics of the Great East Japan Earthquake etc.), i.e. we will apply and verify knowledge through action research while systematizing the methodology of information service design.

Public participation geographic information systems (PPGIS) are used in regional urban development and in solving regional problems that affect local communities. In this paper, the de- velopment of a Web GIS-based regional social networking service (SNS) is described. The regional SNS employs PPGIS and supports user activities, GPS-enabled mobile phones, and a reward point system. The system has four functions: information extraction by user activity area, location-based information posting, GPS location referencing, and reward points. Furthermore, a PPGIS opera- tional model is proposed for continuously using the regional SNS. In this model, roles are assigned to local governments, nonprofit organizations, and universities. The proposed system was evaluated in Takizawa Village, Japan. The system was found to be applicable to PPGIS activities. In addition, some challenges in implementation and education were identified.

The RUNX1 locus, which encodes a transcription factor that is essential for normal hematopoiesis, is a frequent location of chromosomal rearrangements in human hematological malignancies. We report the case of a 78-year-old man with acute myeloid leukemia (AML), M1 subtype (French–American–British classification), with a t(11;21)(p14;q22). Fluorescence in situ hybridization showed a split signal for RUNX1 , which indicated that RUNX1 was involved in this translocation. Using 3′-rapid amplification of cDNA ends and reverse transcription-polymerase chain reaction analyses, we found that RUNX1 was fused to C11orf41 on 11p14 and detected two in-frame C11orf41-RUNX1 fusion transcripts. One was a fusion between exon 5 of RUNX1 and exon 13 of C11orf41 , and the other was between exon 6 of RUNX1 and exon 13 of C11orf41 . This suggested that the RUNX1 breakpoint was in intron 6 and had generated alternative fusion splice variants. A reciprocal C11orf41-RUNX1 fusion was not detected. Thus, we identified C11orf41 as a novel fusion partner of RUNX1 in AML.

The Clapeyron analysis has been performed on polyaspartate samples (–[NH–CH(CH 2 C(O)OX)C(O)] n –) carrying side chains such as X = benzyl (1PLA), phenethyl (2PLA), phenylpropyl (3PLA), and phenoxyethyl (PPOLA). In all cases examined, the unwinding and rewinding process of the helical backbone is consistent with the zippering mechanism previously elucidated for the concentrated LC solution. Variation of the PVT properties such as the volume and enthalpy changes at the transition was carefully examined. In the bulk solid state, contribution from the thermodynamic quantities associated with the redistribution of molecules in the configurational space (molecular packing) becomes substantial. It has been concluded that the characteristic features of the l-α|l-ω transition of 1PLA (140 °C) are inconsistent with the Clapeyron concept, suggesting that the phase transition may involve a non-equilibrium step. The r-α|l-ω transitions of the other polymers were found to conform to the Clapeyron relation. The screw-sense inversion seems to be reversible only when the crystalline structure (hexagonal) remains unaltered before and after the transition. The purpose of this work is to elucidate the key factor responsible for the reversibility of the solid-sate transition, thus providing a basis to understand the role of flanking side chains.

A case of leukemia escape from an HLA-specific cytotoxic T lymphocyte (CTL) response in a recipient of bone marrow transplantation is presented. Only the expression of HLA-B51, which was a mismatched HLA locus in the graft-versus-host direction, was down-regulated in post-transplant leukemia blasts compared with that in pre-transplant blasts. All CTL clones, that were isolated from the recipient’s blood when acute graft-versus-host disease developed, recognized the mismatched B ∗ 51:01 molecule in a peptide-dependent manner. The pre-transplant leukemia blasts were lysed by CTL clones, whereas the post-transplant leukemia blasts were not lysed by any CTL clones. The IFN-γ ELISPOT assay revealed that B ∗ 51:01-reactive T lymphocytes accounted for the majority of the total alloreactive T lymphocytes in the blood just before leukemia relapse. These data suggest that immune escape of leukemia blasts from CTL pressure toward a certain HLA molecule can lead to clinical relapse after bone marrow transplantation.

Liquid crystal polymer (LCP) nanofibers were prepared by electrospinning from isotropic and biphasic poly(γ-benzyl-L-glutamate) (PBLG)/dichloromethane-pyridine solutions. The as-spun PBLG fiber from the isotropic solutions had an undulating orientation of closed packed α-helices like a serpentine trajectory. The as-spun fibers from the biphasic solutions containing the LC phase, on the other hand, had uniaxially oriented hexagonal lattices of α-helices along the fiber axis. These results indicated that the orientation of the ordered structure of the electrospun lyotropic LCP fibers can be controlled by the initial microstructure of the spinning solution.

Internal tandem duplication of FMS-like receptor tyrosine kinase 3 (FLT3/ITD) within its juxtamembrane domain is a frequent mutation in adult acute myeloid leukaemia (AML). This mutation causes constitutive activation of FLT3 and is associated with poor prognosis. The high relapse rate of FLT3/ITD-positive AML might be partly because of insufficient eradication of slow-cycling leukaemic stem cells in the bone marrow microenvironment. β1 integrin mediates haematopoietic stem and progenitor cell homing along with their retention in the bone marrow and also inhibits haematopoietic proliferation and differentiation. Here, we demonstrate that inhibition of FLT3/ITD kinase activity by a FLT3 selective inhibitor named FI-700 decreases affinity of α4β1 integrin to soluble VCAM-1. α4β1 integrin deactivation by FI-700 is independent of Rap1, which is the critical regulator of integrin inside-out signalling. In addition, selective inhibition of FLT3/ITD induces Pyk2 dephosphorylation together with the inhibition of phosphatidylinositol-3-kinase (PI3K)/Akt pathway. Both wild-type and ITD-FLT3 proteins co-immunoprecipitated with β1 integrin and Pyk2 indicating the signal crosstalk between FLT3, β1 integrin and Pyk2. These results collectively indicated that the inhibition of FLT3 kinase might contribute not only to the induction of apoptosis, but also to the leukaemia cell detachment from the bone marrow microenvironment in the treatment of AML.

Poly( l -aspartic acid ester)s are known to form an α-helix in either the right(r)- or left(l)-handed screw depending on the chemical constitution of the ester group in the side chain. While poly(β-benzyl l -aspartate) (PBLA) normally remains in the l-form in conventional helicoidal solution at all temperatures, poly(β-phenethyl l -aspartate) (PPLA) exhibits transformation from the r- to l-form with increasing temperature. In this work, random copolymers comprising residues of the two opposite screw-sense preferences, BLA and PLA, were chosen to investigate the stability of the α-helical hydrogen-bond array in a helix-forming solvent such as chloroform or 1,1,2,2-tetrachloroethane. Sharp S-shape transitions of the helix sense were observed for copolymers in the range PLA > 50%. The minor component BLA strictly obeys the majority rule in these copolymers. 2 H NMR studies of partially deuterated samples in the nematic liquid-crystalline (LC) state have proved that the thermally induced r ↔ l helix-sense inversion takes place highly cooperatively along the α-helical backbone: i.e., the cooperativity of the transition was not much affected by the inclusion of substantial amount of weaker points along the chain. These observations unambiguously suggest a zipper-type propagation process for PPLA starting from one terminal to the other. For given copolymer samples, the transition temperatures determined in dilute isotropic solution are nearly identical to those observed in the LC state, suggesting that the transition mechanism remains also similar. In the succeeding paper, relevant experimental data will be interpreted according to the theory consistent with these observations.

The paper presents theoretical treatment of a screw-sense reversal of tightly hydrogen-bonded α-helical polypeptide chains. The transition is triggered by the conformational free-energy difference (s) of the side chain flanking the chiral (right(r)- or left(l)-handed) backbone. The two-parameter scheme (s, σ) corresponding to a zipper-type transition model starting from one terminal has been constructed and applied to the thermally-induced helix–helix transition characteristic of polyaspartic acid esters observed in the helicoidal solution. The weighting parameter σ takes care of the instability associated with the l/r junction, i.e., the unfolded site where at least three successive hydrogen-bonds should become free to change their partner. The enthalpy of transition (ca. 2 kJ/mol) of poly(β-phenethyl l -aspartate) (PPLA) (Mv = 6 × 104) observed in the lyotropic liquid crystalline state in 1,1,2,2-tetrachloroethane has been reproduced with the instability parameter σ = 0.001–0.0001. Attempts were further extended to interpret the thermally-induced helix–helix transition behaviors of the PPLA homopolymers and random copolymers involving benzyl l -aspartate residues observed under various conditions.

The ETS variant gene 6 (ETV6) gene is located at 12p13, and is frequently involved in translocations in various human neoplasms, resulting in the expression of fusion proteins consisting of the amino-terminal part of ETV6 and unrelated transcription factors or protein tyrosine kinases. Leukemia with t(1;12)(q21;p13) was previously described in a 5-year-old boy with acute myeloblastic leukemia (AML-M2) who exhibited a novel ETV6-aryl hydrocarbon receptor nuclear translocator (ARNT) fusion protein. We herein report the case of a 2-year-old boy with T-cell lymphoblastic leukemia (T-ALL) harboring t(1;12)(q21;p13). Fluorescence in situ hybridization (FISH) with a ETV6 dual-color DNA probe revealed that the split signals of the ETV6 gene in 96.7% of bone marrow cells, indicating rearrangement of the ETV6 gene. Therefore, we performed a FISH analysis with bacterial artificial chromosome (BAC) probes containing the ARNT, BCL9, and MLLT11 genes located at 1q21, and these results indicated that the ARNT gene might be involved in the t(1;12)(q21;p13). Reverse transcriptase-polymerase chain reaction analysis disclosed the existence of a ETV6-ARNT fusion gene. To our knowledge, the current report is novel in its report of the ETV6-ARNT fusion in childhood T-ALL. The ETV6-ARNT fusion is associated not only with AML but also with T-ALL.

This paper is dedicated to the memory of Professor N.A. Plate for his outstanding contributions to polymer science and his extraordinary leadership in the world scientific community. The long-lasting personal and professional relationship with Nikolai came to the end rather untimely, but his enthusiasm for science and people will always be remembered. The rotational isomeric state treatment has been extended to elucidate conformation and conformation-dependent properties of chain molecules occurring under the condition for which some special care is required. Examples include the odd-even effect of n-alkane chains, dipole moment of polymethylmathacrylate (PMMA), enhancement of optical rotation of vinyl polymers, screw-sense reversal of polyaspartates, and the anisotropy of a flexible spacer involved in the main-chain liquid crystal. Major conclusions are as follows: (1) The distinct odd-even effect is a peculiar character of the methylene sequence -(CH2)n-attributable to its bond angle (tetrahedral) and rotational preference (trans). In the other chains including carbonate linkages or oxyethylene units, the correlation along the chain unnecessarily accompany the odd-even phenomenon. (2) When the meso dyad of the PMMA chain takes the trans-trans conformation, the two adjacent ester groups are situated at a separation of only ca. 0.27 nm. The strong dipole-dipole interaction between the two polar ester groups may be alleviated by taking a staggered arrangement. The importance of such neighbor-dependent correlation in treating dielectric properties has been pointed out. (3) The amplification of conformational asymmetry has been discussed for two seemingly dissimilar examples: i.e., flexible vinyl polymers having asymmetric side chains and tightly hydrogen-bonded α-helical polypeptides. The conformation of the side chain has been elucidated for each of the enantiomeric forms of the backbone. The small free-energy difference between the two forms may cooperatively trigger a drastic effect in these polymeric systems. (4) A long oxyethylene spacer carrying mesogenic units on both terminals can be rather easily accommodated in the nematic LC phase. The nematic conformation of the spacer was found to play a crucially important role in determining the orientational order and the packing entropy of the nematic state.