An Optimality Approach to Chain Shifts : Nasal Vowel Lowering in French

This paper provides an optimality - theoretic account on lowering of nasal vowels in French from a (functional and) phonetic viewpoint. I will first claim that nasal vowel lowering in French was initiated by nasalization of a high vowel, in which the first formant (Fl) of /i/ (or/y/) was elevated by prominent nasal acoustic energy. Second, I will argue that the subsequent lowering of tense vowels le, y, 01 to [a, re, 5] is a consequence of dispersion of contrast between adjacent vowels, for which we evaluate a sequence of relevant adjacent vowels, rather than individual vowels in isolation. Third, I will discuss a case of neutralization in len, an/-+l iiI change, a challenging case to the dispersion pattern of contrast. I will argue that the final output of the nasal vowel pattern is a consequence of constraint interactions. We will also observe that there is a strong tendency that we maintain the closest formant values of the inputs in the outputs as possible. This result is also obtained by the pattern evaluation of the adjacent vowels. Fourth, I will discuss possible theoretical problems in a rule-based approach, in comparison with the consequences in our current analysis. Finally, I will add a theoretical implication of the result in relation to the functional goals of Dispersion Theory (Lindblom 1986, Flernrning 1996)

Evaluation of therapeutic effects of natural killer (NK) cell-based immunotherapy in mice using in vivo apoptosis bioimaging with a caspase-3 sensor

Natural killer (NK) cellâ based immunotherapy is a promising strategy for cancer treatment, and caspaseâ 3 is an important effector molecule in NK cellâ mediated apoptosis in cancers. Here, we evaluated the antitumor effects of NK cellâ based immunotherapy by serial noninvasive imaging of apoptosis using a caspaseâ 3 sensor in mice with human glioma xenografts. Human glioma cells expressing both a caspaseâ 3 sensor as a surrogate marker for caspaseâ 3 activation and Renilla luciferase (Rluc) as a surrogate marker for cell viability were established and referred to as D54â CR cells. Human NK92 cells were used as effector cells. Treatment with NK92 cells resulted in a timeâ and effector numberâ dependent increase in bioluminescence imaging (BLI) activity of the caspaseâ 3 sensor in D54â CR cells in vitro. Caspaseâ 3 activation by NK92 treatment was blocked by Zâ VAD treatment in D54â CR cells. Transfusion of NK92 cells induced an increase of the BLI signal by caspaseâ 3 activation in a doseâ and timeâ dependent manner in D54â CR tumorâ bearing mice but not in PBSâ treated mice. Accordingly, sequential BLI with the Rluc reporter gene revealed marked retardation of tumor growth in the NK92â treatment group but not in the PBSâ treatment group. These data suggest that noninvasive imaging of apoptosis with a caspaseâ 3 sensor can be used as an effective tool for evaluation of therapeutic efficacy as well as for optimization of NK cellâ based immunotherapy.â Lee, H. W., Singh, T. D., Lee, S.â W., Ha, J.â H., Rehemtulla, A., Ahn, B.â C., Jeon, Y.â H., Lee, J. Evaluation of therapeutic effects of natural killer (NK) cellâ based immunotherapy in mice using in vivo apoptosis bioimaging with a caspaseâ 3 sensor. FASEB J. 28, 2932â 2941 (2014). www.fasebj.orgPeer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/154541/1/fsb2fj13243014.pd

Enhanced cardiac expression of two isoforms of matrix metalloproteinase-2 in experimental diabetes mellitus.

BackgroundDiabetic cardiomyopathy (DM CMP) is defined as cardiomyocyte damage and ventricular dysfunction directly associated with diabetes independent of concomitant coronary artery disease or hypertension. Matrix metalloproteinases (MMPs), especially MMP-2, have been reported to underlie the pathogenesis of DM CMP by increasing extracellular collagen content.PurposeWe hypothesized that two discrete MMP-2 isoforms (full length MMP-2, FL-MMP-2; N-terminal truncated MMP-2, NTT-MMP-2) are induced by high glucose stimulation in vitro and in an experimental diabetic heart model.MethodsRat cardiomyoblasts (H9C2 cells) were examined to determine whether high glucose can induce the expression of the two isoforms of MMP-2. For the in vivo study, we used the streptozotocin-induced DM mouse heart model and age-matched controls. The changes of each MMP-2 isoform expression in the diabetic mice hearts were determined using quantitative real-time polymerase chain reaction (qRT-PCR). Immunohistochemical stains were conducted to identify the location and patterns of MMP-2 isoform expression. Echocardiography was performed to compare and analyze the changes in cardiac function induced by diabetes.ResultsQuantitative RT-PCR and immunofluorescence staining showed that the two MMP-2 isoforms were strongly induced by high glucose stimulation in H9C2 cells. Although no definite histologic features of diabetic cardiomyopathy were observed in diabetic mice hearts, left ventricular systolic dysfunction was determined by echocardiography. Quantitative RT-PCR and IHC staining showed this abnormal cardiac function was accompanied with the increases in the mRNA levels of the two isoforms of MMP-2 and related to intracellular localization.ConclusionTwo isoforms of MMP-2 were induced by high glucose stimulation in vitro and in a Type 1 DM mouse heart model. Further study is required to examine the role of these isoforms in DM CMP

Prognosis according to the timing of percutaneous coronary intervention in non-ST segment elevation myocardial infarction, based on the Korean Acute Myocardial Infarction Registry (KAMIR)

Background: Patients with acute coronary syndrome without ST-segment elevation (ACS- -NSTE) are at risk for adverse cardiac events. Based on data in the Korean Acute Myocardial Infarction Registry (KAMIR), we analyzed the prognosis according to the timing of percutaneous coronary intervention (PCI) in patients with NSTEMI in Korea. Methods and results: 2,455 patients with NSTEMI in KAMIR were classified according to the time interval from the onset of cardiac symptoms to PCI. Patients in Group I underwent PCI within 24 hours of the onset of symptoms; in Group II between 24 and 48 hours; and in Group III after 48 hours. Major adverse cardiac events (MACEs) are defined as cardiac death, non-cardiac death, myocardial infarction, revascularization and coronary-artery bypass graft surgery. The MACEs were compared between groups. Of the 2,455 patients, 743 (30.2%) were assigned to Group I, 583 (23.7%) to Group II, and 1,129 (45.9%) to Group III. The total incidence of MACEs was higher in Group I than Group III, and similar between Groups I and II (Group I: 15.1%, Group II: 14.4%, Group III: 11.6%, p = 0.053). The incidence of MACEs in the intermediate TIMI risk score group had decreased as the intervention time was delayed. Conclusions: The prognosis according to the timing of PCI in patients with NSTEMI was similar based on the data in KAMIR. TIMI risk score was related to a high incidence of MACEs. (Cardiol J 2011; 18, 4: 421–429

Salinomycin enhances doxorubicin-induced cytotoxicity in multidrug resistant MCF-7/MDR human breast cancer cells via decreased efflux of doxorubicin

Salinomycin is a monocarboxylic polyether antibiotic, which is widely used as an anticoccidial agent. The anticancer property of salinomycin has been recognized and is based on its ability to induce apoptosis in human multidrug resistance (MDR). The present study investigated whether salinomycin reverses MDR towards chemotherapeutic agents in doxorubicin-resistant MCF-7/MDR human breast cancer cells. The results demonstrated that doxorubicin-mediated cytotoxicity was significantly enhanced by salinomycin in the MCF-7/MDR cells, and this occurred in a dose-dependent manner. This finding was consistent with subsequent observations made under a confocal microscope, in which the doxorubicin fluorescence signals of the salinomycin-treated cells were higher compared with the cells treated with doxorubicin alone. In addition, flow cytometric analysis revealed that salinomycin significantly increased the net cellular uptake and decreased the efflux of doxorubicin. The expression levels of MDR-1 and MRP-1 were not altered at either the mRNA or protein levels in the cells treated with salinomycin. These results indicated that salinomycin was mediated by its ability to increase the uptake and decrease the efflux of doxorubicin in MCF-7/MDR cells. Salinomycin reversed the resistance of doxorubicin, suggesting that chemotherapy in combination with salinomycin may benefit MDR cancer therapyopen

Takayasu's Arteritis Involving the Ostia of Three Large Coronary Arteries

Takayasu's arteritis can involve the ostia of coronary arteries. We report a patient with Takayasu's arteritis involving the ostia of three large coronary arteries who was successfully treated by percutaneous coronary intervention (PCI) with a drug-eluting stent (DES) and had a good clinical outcome after 12 months. A 37-year-old male with unstable angina was admitted to our cardiovascular center. The patient had Takayasu's arteritis and an aortic valve replacement with a metallic valve due to severe aortic regurgitation 7 years previously. Coronary angiography (CAG) showed a 95% discrete eccentric luminal narrowing at the ostia of the large left anterior descending (LAD) and left circumflex (LCX) arteries, and a 99% discrete eccentric luminal narrowing at the ostium of the large right coronary artery (RCA). The patient was treated with prednisolone for 14 days. Two large paclitaxel-eluting stents (PES) were then implanted in the distal left main coronary artery using the kissing stent technique. After 6 months, a CAG did not reveal restenosis or recurrent coronary artery disease. Thus, PCI with a DES for patients with significant coronary involvement secondary to Takayasu's arteritis is an effective and an alternative treatment when coronary bypass grafting is not option

Benefits of Recurrent Colonic Stent Insertion in a Patient with Advanced Gastric Cancer with Carcinomatosis Causing Colonic Obstruction

Malignant obstruction develops frequently in advanced gastric cancer. Although it is primarily the gastric outlet that is obstructed, there are occasional reports of colonic obstruction. Treating intestinal obstruction usually requires emergency surgery or stent insertion. There are several kinds of complications with stent insertion, such as bowel perforation, stent migration, bleeding, abdominal pain and reobstruction. Nevertheless, endoscopic stent insertion could be a better treatment than emergency surgery in cases of malignant bowel obstruction in cancer patients with poor performance status. We report a case of advanced gastric cancer with carcinomatosis in which a recurrent colonic stent was inserted at the same site because of cancer growth into the stent. The patient maintained a good condition for chemotherapy, thus improving their chances for survival