Iron-catalysed cross-coupling of halohydrins with aryl aluminium reagents: a protecting-group-free strategy attaining remarkable rate enhancement and diastereoinduction.

Non-protected halohydrins are cross-coupled with aryl aluminium reagents to produce aryl alkanols in the presence of the iron-bisphosphine catalysts. Remarkable reaction rate enhancement and diastereoinduction are realized by the in situ generated aluminium alkoxides, offering a new method for the reactivity and selectivity control of the iron-catalysed cross-coupling reaction

N-Cadherin Expressed on Malignant T Cell Lymphoma Cells is Functional, and Promotes Heterotypic Adhesion Between the Lymphoma Cells and Mesenchymal Cells Expressing N-Cadherin

Cadherins are Ca2+-dependent cell–cell adhesion molecules, and are involved in the formation and maintenance of the organocellular architecture. Using a combination of molecular biologic and biochemical methods, we analyzed cadherins expressed on cultured human malignant lymphoma cell lines (adult T cell lymphomas, human T cell leukemia virus type 1-negative T cell lines, and thymus-derived lymphoma cell lines), and obtained evidence that N-cadherin is the major cadherin expressed on these cells. These cells were found to form cell aggregates in a Ca2+-dependent manner, and more importantly to coaggregate and adhere with cells expressing N-cadherin, suggesting that N-cadherin on lymphoma cells is functionally active. Therefore, N-cadherin expressed on lymphoma cells could underlie the frequent invasion of these cells into the mesenchymal tissue in the skin and the central nervous system

Recent Advances on the Halo- and Cyano-Trifluoromethylation of Alkenes and Alkynes

Incorporation of fluorine into organic molecules is a well-established strategy in the design of advanced materials, agrochemicals, and pharmaceuticals. Among numerous modern synthetic approaches, functionalization of unsaturated bonds with simultaneous addition of trifluoromethyl group along with other substituents is currently one of the most attractive methods undergoing wide-ranging development. In this review article, we discuss the most significant contributions made in this area during the last decade (2012−2021). The reactions reviewed in this work include chloro-, bromo-, iodo-, fluoro- and cyano-trifluoromethylation of alkenes and alkynes

Pressure-induced structural phase transition and new superconducting phase in UTe2

We report on the crystal structure and electronic properties of the heavy fermion superconductor UTe2 at high pressure up to 11 GPa, as investigated by X-ray diffraction and electrical resistivity experiments. The X-ray diffraction measurements under high pressure using a synchrotron light source reveal anisotropic linear compressibility of the unit cell up to 3.5 GPa, while a pressure-induced structural phase transition is observed above 3.5-4GPa at room temperature, where the body-centered orthorhombic crystal structure with the space group Immm changes into a body-centered tetragonal structure with the space group I4/mmm. The molar volume drops abruptly at the critical pressure, while the distance between the first-nearest neighbor of U atoms increases, implying a switch from the heavy electronic states to the weakly correlated electronic states. Surprisingly, a new superconducting phase at pressures higher than 7 GPa was detected at Tsc above 2K with a relatively low upper-critical field, Hc2(0). The resistivity above 3.5GPa, thus, in the high-pressure tetragonal phase, shows a large drop below 230 K, which may also be related to a considerable change from the heavy electronic states to the weakly correlated electronic states.Comment: 11 pages, 9 figure

Changes in conditional net survival and dynamic prognostic factors in patients with newly diagnosed metastatic prostate cancer initially treated with androgen deprivation therapy

Background The purpose of this study was to identify predictive factors associated with conditional net survival in patients with metastatic hormone-naive prostate cancer (mHNPC) initially treated with androgen deprivation therapy (ADT). Methods At nine hospitals in Tohoku, Japan, the medical records of 605 consecutive patients with mHNPC who initially received ADT were retrospectively reviewed. The Pohar Perme estimator was used to calculate conditional net cancer-specific survival (CSS) and overall survival (OS) for up to 5 years subsequent to the diagnosis. Using multiple imputation, proportional hazard ratios for conditional CSS and OS were calculated with adjusted Cox regression models. Results During a median follow up of 2.95 years, 208 patients died, of which 169 died due to progressive prostate cancer. At baseline, the 5-year CSS and OS rates were 65.5% and 58.2%, respectively. Conditional 5-year net CSS and OS survival gradually increased for all the patients. In patients given a 5-year survivorship, the conditional 5-year net CSS and OS rates improved to 0.906 and 0.811, respectively. Only the extent of disease score (EOD) >= 2 remained a prognostic factor for CSS and OS up to 5 years; as survival time increased, other variables were no longer independent prognostic factors. Conclusions The conditional 5-year net CSS and OS in patients with mHNPC gradually increased; thus, the risk of mortality decreased with increasing survival. The patient\u27s risk profile changed over time. EOD remained an independent prognostic factor for CSS and OS after 5-year follow-up. Conditional net survival can play a role in clinical decision-making, providing intriguing information for cancer survivors

Prognostic significance of early changes in serum biomarker levels in patients with newly diagnosed metastatic prostate cancer

We evaluated the impact of early changes in serum biomarker levels on the survival of patients with metastatic hormone-sensitive prostate cancer (mHSPC) who were initially treated with androgen deprivation therapy (ADT). We retrospectively investigated 330 patients with mHSPC whose serum maker levels were at baseline and at 2-4 months. An optimal Cox regression model was established with the highest optimism-corrected concordance index based on 10-fold cross-validation. The median cancer-specific survival (CSS) and overall survival (OS) were 7.08 and 6.47 years (median follow-up, 2.53 years), respectively. In the final optimal Cox model with serum biomarker levels treated as time-varying covariates, prostate-specific antigen (PSA), hemoglobin (Hb), and alkaline phosphatase (ALP) significantly increased the risk of poor survival in the context of both CSS and OS. Kaplan-Meier curves stratified by the three risk factors of high PSA, low Hb and high ALP desmondtated that median OS were not reached with none of these factors, 6.47 years with one or two factors, and 1.76 years with all three factors. Early changes in serum biomarker levels after ADT may be good prognostic markers for the survival of patients with mHSPC

チタンメッシュトレーとPCBMによる下顎骨再建を施行した類腱型エナメル上皮腫の1例

類腱型のエナメル上皮腫(desmoplastic ameloblastoma:DA)は,エナメル上皮腫の一亜型で,豊富な膠原線維の増生からなる間質と石鹸泡状のエックス線透過像を特徴とする.DAは,X線学的に境界不明瞭で,腫瘍周囲の被膜がないため切除範囲の設定が困難で,典型的なエナメル上皮腫と比較して,再発の割合が高いと考えられている.2006年9月,58歳の男性が,下顎右側臼歯部歯肉の腫脹と顎骨の膨隆にて近医より当科を紹介受診した.画像所見において,腫瘍の境界は不明瞭で,腫瘍は下顎骨下縁にまで及んでいた.生検の結果,組織学的に類腱型のエナメル上皮腫と診断された.下顎区域切除術ならびにチタンメッシュトレーと腸骨からのPCBMによる下顎骨再建を施行した.術後4年経過した現在,再発はみられていない.Desmoplastic ameloblastoma (DA) is a variant of ameloblastoma, characterized by foamy radiolucency and desmoplastic stroma. The recurrence rate of DA is thought to be higher than that of usual ameloblastoma because the fibrous capsule surrounding the tumour is not present and decision of the resection area is difficult, corresponding to the radiographically poorly-defined tumour margin. A 58-year-old man was referred to our clinic in September 2006 because of swelling of the mandible on the right side. Radiography indicated a poorly-defined lesion that expanded to the inferior border of the mandible. We carried out a biopsy and a diagnosis of DA was made histopathologically. Then, we carried out segmental mandibulectomy and mandibular reconstruction using a titanium mesh tray and PCBM from iliac bone. No signs of recurrence have been seen for 4 years after surgery

The Constrained Maximal Expression Level Owing to Haploidy Shapes Gene Content on the Mammalian X Chromosome.

X chromosomes are unusual in many regards, not least of which is their nonrandom gene content. The causes of this bias are commonly discussed in the context of sexual antagonism and the avoidance of activity in the male germline. Here, we examine the notion that, at least in some taxa, functionally biased gene content may more profoundly be shaped by limits imposed on gene expression owing to haploid expression of the X chromosome. Notably, if the X, as in primates, is transcribed at rates comparable to the ancestral rate (per promoter) prior to the X chromosome formation, then the X is not a tolerable environment for genes with very high maximal net levels of expression, owing to transcriptional traffic jams. We test this hypothesis using The Encyclopedia of DNA Elements (ENCODE) and data from the Functional Annotation of the Mammalian Genome (FANTOM5) project. As predicted, the maximal expression of human X-linked genes is much lower than that of genes on autosomes: on average, maximal expression is three times lower on the X chromosome than on autosomes. Similarly, autosome-to-X retroposition events are associated with lower maximal expression of retrogenes on the X than seen for X-to-autosome retrogenes on autosomes. Also as expected, X-linked genes have a lesser degree of increase in gene expression than autosomal ones (compared to the human/Chimpanzee common ancestor) if highly expressed, but not if lowly expressed. The traffic jam model also explains the known lower breadth of expression for genes on the X (and the Z of birds), as genes with broad expression are, on average, those with high maximal expression. As then further predicted, highly expressed tissue-specific genes are also rare on the X and broadly expressed genes on the X tend to be lowly expressed, both indicating that the trend is shaped by the maximal expression level not the breadth of expression per se. Importantly, a limit to the maximal expression level explains biased tissue of expression profiles of X-linked genes. Tissues whose tissue-specific genes are very highly expressed (e.g., secretory tissues, tissues abundant in structural proteins) are also tissues in which gene expression is relatively rare on the X chromosome. These trends cannot be fully accounted for in terms of alternative models of biased expression. In conclusion, the notion that it is hard for genes on the Therian X to be highly expressed, owing to transcriptional traffic jams, provides a simple yet robustly supported rationale of many peculiar features of X's gene content, gene expression, and evolution

Regio- and stereoselective multisubstituted olefin synthesis via hydro/carboalumination of alkynes and subsequent iron-catalysed cross-coupling reaction with alkyl halides

This article is part of themed collection: Celebrating the 80th Birthday of Professor Ei-ichi Negishi.A new synthetic route towards multisubstituted olefins, which are recurring core units in various pharmaceutical and bioactive compounds, was developed based on the direct cross coupling of alkenylaluminium reagents which were prepared in situ by the hydro- and carbometalation of alkynes, with non-activated alkyl halides in the presence of an iron catalyst. For the first time, alkenylaluminium reagents participated in an iron-catalysed cross-coupling reaction, following the activation of the aluminium reagents by a metal fluoride. The hydro- and carboalumination of alkynes and the subsequent cross-coupling reactions could be conducted in a one-pot manner and proceeded regio- and stereoselectively to give a variety of di-, tri-, and tetrasubstituted alkenes in good to excellent yields

精密有機合成を目指した有機アルミニウム, マグネシウムおよび亜鉛反応剤を用いる鉄触媒クロスカップリング反応の開発

京都大学0048新制・課程博士博士(工学)甲第17585号工博第3744号新制||工||1571(附属図書館)30351京都大学大学院工学研究科物質エネルギー化学専攻(主査)教授 中村 正治, 教授 辻 康之, 教授 年光 昭夫学位規則第4条第1項該当Doctor of Philosophy (Engineering)Kyoto UniversityDA