Leukemia is a hematological neoplasm with abnormal genetic mutation or chromosomal translocation in the myeloblast or lymphoblast, and characterized by accumulation of immature cells and malfunction of lymphocytes and myeloid-derived cells. The prognosis of treatment depends on genetic mutation, chromosomal aberration, disease progression and age of patients. Currently, bone marrow transplantation is a useful therapeutic strategy, but the success in therapy is limited by the bone marrow of donors and life-threatening events such as immune repulsion. Although chemotherapy improves leukemia treatment, long-term chemotherapy usually leads to the production of drug-resistant cancer cells. Thus, the development of new modality in overcoming drug-resistant should be beneficial for in leukemia therapy. In this thesis, Naja nigricollis toxin £^, piceatannol, caffeine, and Bungarus multicinctus protease inhibitor-like protein 1 (PILP-1) are employed to investigate the molecular mechanisms in regulating apoptosis and invasion of leukemic cell lines K562 and U937. Hopefully, the signaling pathways elicited by these treatments may be aid in identifying new targets in treating leukemia. Toxin £^ inducing cell death is found to evoke p38 MAPK-mediated Bcl-2 down-regulation, which facilitates mitochondria dysfunction, ROS generation and cytiochrome c release. Finally, activation of caspases leads to apoptotic death of toxin £^-treated cells. Piceatannol elicits Ca2+/p38£\ MAPK- mediated c-Jun and ATF-2 phosphorylation, leading to up-regulation of Fas/FasL protein expression and autocrine Fas-mediated death pathway activation. Caffeine treatment down-regulates MMP-2/-9 down-regulation via Ca2+/ROS-mediated inactivation of ERK/c-Fos and activation of p38 MAPK/c-Jun pathway. Consequently, caffeine treatment suppresses invasion of leukemia cells. PILP-1-induced ADAM17 down-regulation suppresses Lyn-mediated Akt phosphorylation, resulting in death of PILP-1-treated leukemia cells. Taken together, the results of the present study elucidate the signaling pathways responsible for apoptosis and invasion of leukemia cells. Moreover, these findings might suggest new targets in developing therapeutic strategy in treating leukemia.

In this thesis, photocrosslinked ferrocene-based methacrylate polymers for thin-film cathodes in lithium batteries have been synthesized. Patterned thin-film electrodes of the ferrocene-based methacrylate polymers are fabricated by photocrosslinking. The structure and composition of the photocrosslinkable polymers are characterized by infrared spectra, nuclear magnetic resonances, and gel permeation chromatography. The result of quartz crystal microbalance shows that the crosslinked polymers prevent the polymers from dissolving into organic electrolytes. The cyclic voltammogram shows the photocrosslinked ferrocene-based methacrylate polymers have a redox couple. The energy capacity of the polymer for lithium batteries is about 40-50 mAh g-1 at a discharge rate of 10 C. The results show that the photocrosslinked ferrocene-based methacrylate polymers also improve the batteries.

The purpose of this study was to assess the prognostic significance and clinical correlations of cyclooxgenase-2 expression (COX) in a cohort of patients treated with radiation (RT) for post-mastectomy chest wall relapse (PMCWR). Between 1975 and 1999, 113 patients were treated for isolated PMCWR. All patients were treated with biopsy and/or excision of the CWR followed by RT. Median follow-up was 10 years. All clinical data including demographics, pathology, staging, receptor status, HER-2/neu status, and adjuvant therapy were entered into a computerized database. Paraffin-embedded CWR specimens were retrieved from 42 patients, of which 38 were evaluated, created into a tissue microarray, stained by immunohistochemical methods for COX, and graded 0-3+. A score of 2-3+ was considered positive. Overall survival from original diagnosis for the entire cohort was 44% at 10 years. Survival rate after chest wall recurrence was 28% at 10 years. The distant metastasis-free survival rate after CWR was 40% at 10 years. Local-regional control of disease was achieved in 79% at 10 years after CWR. COX was considered positive in 13 of 38 cases. COX was inversely correlated with ER (p= .045) and PR (p = .028), and positively correlated with HER-2/neu (p =.003). COX was also associated with a shorter time to PMCWR. The distant metastasis-free rate for COX negative patients was 70% at 10 years, compared with 31% at 10 years for COX-2 positive patients (p = 0.029). COX positive had a poorer local-regional progression-free rate of 19% at 10 years, compared with 81% at 10 years for COX negative (p = 0.003). Outcome following RT for PMCWR is relatively poor. Positive COX correlated with other markers of poor outcome including a shorter time to local relapse, negative ER/PR and positive Her-2/neu status. Positive COX correlated with higher distant metastasis and lower local-regional control of disease. If confirmed with larger studies, these data have implications with respect to the concurrent use of COX-2 inhibitors and radiation for PMCWR.

Konstitutiv aktivierte Signalwege sind verantwortlich für die malignen Veränderungen in Melanozyten, die zur Entstehung des Melanoms beitragen. Im Mittelpunkt dieser Veränderungen stehen der PI3Kinase-AKT-Signalweg und der MAPK-ERK-Signalweg als wichtige Schlüsselwege in der Zellzykluskontrolle. Daher zielen viele neue Therapieversuche im Kampf gegen das Melanom auf die Kontrolle und Regulation dieser Wege. In dieser vorliegenden Arbeit wurden erstmals die Effekte eines neuen PI3K-Inhibitors, BAY-80-6946, und Wortmannin alleine und in Kombinationsbehandlungen mit den MEK1/2-Inhibitoren PD98059 und U0126 in vitro und in vivo untersucht. Zunächst wurden humane Melanomzellen auf konstitutiv aktivierte Signalwege in vitro per Western Blot untersucht und ihre Wachstumsraten im Mausmodell ermittelt. Die humane Melanomzelllinie LOX zeigte eine hohe konstitutive Expression von aktiviertem AKT und ERK, während A375 nur eine geringe Aktivität dieser beiden Signalwege aufwies. Dennoch besaßen diese beiden Zelllinien ein großes Wachstumspotential im Mausmodell im Vergleich zu anderen getesteten Zelllinien. A375 und LOX wurden in Zellkulturexperimenten mit den PI3Kinase-Inhibitoren Bay-80-6946 und Wortmannin sowie den MEK1/2-Inhibitoren PD98059 und U0126 behandelt und Tumor-relevante Zellfunktionen wie Proliferation und Apoptose gemessen. Die Zelllinien zeigten ein unterschiedliches Ansprechen auf die verschiedenen Inhibitoren und keine der Behandlungen wies eine zufriedenstellendes Ergebnis hinsichtlich der Anti-tumoralen Funktion auf. Bei dualer PI3Kinase- und MEK1/2-Hemmung zeigten sich jedoch deutliche synergistische Effekte, so dass diese Behandlungsform einen vielversprechenden Ansatz im Kampf gegen das Melanom darstellt.

Musica para dos megainstrumentos y grupo de camara (Music for two Megainstruments and Chamber Ensemble) is a six-section piece written for two violins (treated as a megaviolin), two flutes (treated as a megaflute) and chamber ensemble. Both the form and the different tempi of the piece are determined by the interaction of the two mega-instruments and the ensemble. The piece is an original contribution in its concept and use of the megainstruments. A mega-instrument is composed by two single instruments of the same kind. The main function of the mega-instrument is that of expanding the technical possibilities of the individual instruments that constitute it, as well as creating new possibilities, while keeping, at the same time, the specific characteristics or "personality" of the original instruments. In the Primer ensamble and Segundo ensamble sections the two mega-instruments are incorporated into the ensemble and treated as four individual instruments. The basic pitch structure of the piece is represented by SC [014], which is further organized in a six-note scale that is a member of SC [014589]. The six-note scale (used in the piece as an unordered set) and its three available transpositions create a universe of four pitch regions with two different modulation levels to connect them. Pitch Regions are also used simultaneously in the piece. This procedure (that I have called a multi region) includes harmonic and/or melodic intervals that are not available within single pitch regions. The piece could be defined as atonal or without pitch centers. It is characterized by an interaction of the tempered system and the pitch continuum (microtones and glissandi).

No description available.

Diss. (sammanfattning) Stockholm : Karol. inst., 2006. / Härtil 4 uppsatser.

Chemnitz, Techn. Universiẗat, Diss., 1999. / Datei im PS-Format.

Made available in DSpace on 2014-06-11T19:27:10Z (GMT). No. of bitstreams: 0 Previous issue date: 2011-10-03Bitstream added on 2014-06-13T18:07:04Z : No. of bitstreams: 1 martini_ah_me_rcla.pdf: 2016802 bytes, checksum: 99b219ef9e4367f5e8268e22828e9b81 (MD5) / Neste trabalho estudamos tópicos de cálculo diferencial para funções de várias variáveis a valor real, utilizando como ferramenta o programa livre MAXIMA / We study some topics of the differential calculus using the software as a tool MAXIMA

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