Torus fibrations and localization of index II

We give a framework of localization for the index of a Dirac-type operator on an open manifold. Suppose the open manifold has a compact subset whose complement is covered by a family of finitely many open subsets, each of which has a structure of the total space of a torus bundle. Under an acyclic condition we define the index of the Dirac-type operator by using the Witten-type deformation, and show that the index has several properties, such as excision property and a product formula. In particular, we show that the index is localized on the compact set.Comment: 47 pages, 2 figures. To appear in Communications in Mathematical Physic

Thickness and Orientation Dependence of Plastic Behaviors of Iron Whiskers

Stress-strain curves of iron whiskers, of which thickness ranges from 5 to 80μ, have been measured using an Instron-type tensile machine at room temperature. All of the whiskers show "work softening" of which softening rate decreases with increasing thickness. "The lower yield stress" decrease with increasing thickness in and whiskers thinner than about 35μ. Marked thickness and orientation dependence of the stress-strain curve have been found. The whiskers thinner than about 8μ show no appreciable plastic deformation after the sharp yielding, as already known in very thin whiskers. Those, 8～17μ in thickness, show nearly flat regions in their stress-strain curves after yielding and those thicker than about 17μ reveal "work hardening" after about 5% strain

Novel HER2 selective tyrosine kinase inhibitor, TAK-165, inhibits bladder, kidney and androgen-independent prostate cancer in vitro and in vivo

金沢大学医学部附属病院泌尿器科Purpose: TAK-165 is a new potent inhibitor of human epidermal growth factor receptor 2 (HER2) tyrosine kinase. Several reports suggest HER2 expression in bladder cancer, renal cell carcinoma (RCC) and androgen-independent prostate cancer. We therefore investigated the antitumor effect of TAK-165 on these urological cancer cells. Materials and methods: Western blot analysis was performed to confirm HER2 expression in cell lines. To study in vitro efficacy, cells were treated with TAK-165 at various concentrations for 72 h and then counted using a hemocytometer. Then the IC50 value was calculated. In the xenograft model, after the tumor reached 200-300 mm3 in volume, mice were orally administered TAK-165 10 mg/kg per day or 20 mg/kg per day or saline for 14 consecutive days (n = 6-8). Results: HER2 expression was observed in HT1376, UMUC3, T24 (bladder), ACHN (kidney), DU145, LNCaP, LN-REC4 (prostate), although the expression level in these cells was weak compared with BT474 (a breast cancer cell line which expresses HER2 strongly). IC50 was varied from 0.09 to greater than 25 μmol/L in the bladder cancer cell line. ACHN cells were less sensitive in vitro. The prostate cancer cell lines studied were all sensitive (IC50 0.053-4.62 μmol/L). In the xenograft model, treatment with TAK-165 significantly inhibited growth of UMUC-3, ACHN, and LN-REC4. The antitumor effect (T/C [%] = growth of TAK-165 treated tumor/average growth of control tumor × 100) after 14 days treatment were 22.9%, 26.0%, and 26.5% in UMUC3, ACHN and LN-REC4, respectively. Conclusions: TAK-165 may be a hopeful new agent for bladder, kidney and androgen-independent prostate cancer

Human cord blood-MNC transplantation improves PH

Objectives : To investigate the effects of human umbilical cord blood-derived mononuclear cell (hUCB-MNC) transplantation on pulmonary hypertension (PH) induced by monocrotaline (MCT) in immunodeficient mice and their distribution. Methods :MCT was administered to BALB/c Slc-nu/nu mice, and PH was induced in mice 4 weeks later. Fresh hUCB-MNCs harvested from a human donor after her delivery were injected intravenously into those PH mice. The medial thickness of pulmonary arterioles, ratio of right ventricular to septum plus left ventricular weight (RV/S+LV), and ratio of acceleration time to ejection time of pulmonary blood flow waveform (AT/ET) were determined 4 weeks after hUCB-MNC transplantation. To reveal the incorporation into the lung, CMTMR-labeled hUCB-MNCs were observed in the lung by fluorescent microscopy. DiR-labeled hUCB-MNCs were detected in the lung and other organs by bioluminescence images. Results : Medial thickness, RV/S+ LV and AT/ET were significantly improved 4 weeks after hUCB-MNC transplantation compared with those in mice without hUCB-MNC transplantation. CMTMR-positive hUCB-MNCs were observed in the lung 3 hours after transplantation. Bioluminescence signals were detected more strongly in the lung than in other organs for 24 hours after transplantation. Conclusions : The results indicate that hUCB-MNCs are incorporated into the lung early after hUCB-MNC transplantation and improve MCT-induced PH