Characterization of a Specific Region in the Hepatitis B Virus Enhancer I for the Efficient Expression of X Gene in the Hepatic Cell

AbstractHepatitis B virus (HBV) enhancer I has been shown to consist of severalcis-acting sequences for the HBV gene expression efficiently in certain types of cells. Transcriptional regulation of HBV X gene mediated by enhancer I might be one of the mechanisms by which HBV obtains hepatotropism. By mutagenesis analysis of enhancer I function in the enhancer I/X gene promoter complex, we characterized a specific transcriptional regulatory region (designated as a LSR element, nt 989–1030) of enhancer I for the X gene promoter by means of the transient transfection technique using hepatic and nonhepatic cells. Based on the analysis of protein factors interacting with the LSR element, liver-enriched transcriptional factors, HNF3 and HNF4 or retinoid X receptor α (RXRα), are probably implicated in the activity of enhancer I for the efficient expression of X gene through their interaction with the LSR element in the hepatic cell. Furthermore, the isolated LSR element was demonstrated to function alone as a specificcis-acting element and to be able to activate transcription from the X gene promoter efficiently in the hepatic cell in an orientation-independent manner

Field experiments in labor economics

In this thesis I show with three studies how field experiments can enhance our understanding of labor markets. Economists traditionally assume that individuals exclusively respond to monetary incentives. As a consequence, if workers have no prospect of future employment at the firm and pay is not contingent on their performance, a wage change should not affect effort. Some economists, however, have recognized that this narrow view of human motivation may severely limit our progress in understanding incentives. In Chapters 2 and 3, I investigate the role of psychological motives like the desire to reciprocate in the context of a real‐life work environment. The first experiment explores the impact of a wage increase on work performance when there is no economic reason for workers to change their effort. I find that workers reciprocate a generous wage with higher performance, particularly those workers who care about fairness and felt underpaid prior to the wage increase. The second experiment investigates the effects of a wage cut on performance when either all workers in a team or only some of them suffer the cut. I show that a general pay cut reduces performance, while a wage cut for only some of the workers reduces their performance more than twice as much. This finding demonstrates the powerful force of social comparison and the need to build the social nature of humans into economic theory. In Chapter 4, I examine the joint effects of monetary incentives and social interaction on work performance. Many jobs offer wage schemes that create positive or negative externalities on coworkers. Whether or not workers have the possibility to interact socially at work may distort the intended incentives of these schemes. I find that under relative incentives, when own effort imposes a negative externality on the coworker’s income, social interaction works against monetary incentives and leads to low performance due to collusion. However, the more workers differ in skills the less able they are to sustain collusive agreements. In der vorliegenden Dissertation zeige ich anhand von drei Studien wie Feldexperimente unser Verständnis von Arbeitsmärkten verbessern können. Ökonomen gehen traditionell davon aus, dass Individuen ausschliesslich auf materielle Anreize reagieren. Wenn also Arbeitskräfte keine Aussicht auf eine langfristige Anstellung haben und deren Lohn nicht von der Leistung abhängt, dann sollte eine Lohnveränderung keinen Einfluss auf die Arbeitsleistung haben. Manche Ökonomen haben jedoch erkannt, dass diese Sichtweise des menschlichen Verhaltens beschränkt ist und unseren Fortschritt im Verständnis von Anreizen bremsen kann. In den Kapiteln 2 und 3 untersuche ich die Bedeutung von psychologischen Motiven wie Fairness oder Reziprozität in echten Arbeitsumgebungen. Das erste Experiment untersucht den Einfluss einer Lohnerhöhung auf die Arbeitsleistung, wenn Arbeitskräfte keinen ökonomischen Grund haben, ihren Arbeitseinsatz zu ändern. Diese Studie zeigt, dass Arbeitskräfte einen grosszügigen Lohn mit höherer Arbeitsleistung erwidern. Dies gilt besonders für diejenigen, die Fairness als wichtig empfinden und sich vor der Lohnerhöhung unterbezahlt fühlten. Das zweite Experiment untersucht die Wirkung einer Lohnkürzung auf die Arbeitsleistung, wenn entweder das ganze Team oder nur einen Teil davon betroffen ist. Diese Studie zeigt auf, dass eine generelle Lohnkürzung die Arbeitsleistung senkt, wohingegen eine Lohnkürzung nur für einzelne Arbeitskräfte deren Leistung um mehr als das Doppelte reduziert. Diese Erkenntnis unterstreicht die Bedeutung von sozialen Motiven und die Notwendigkeit einer Veränderung des Menschenbilds in der Ökonomie. In Kapitel 4 erforsche ich den gemeinsamen Einfluss von materiellen Anreizen und sozialer Interaktion auf die Arbeitsleistung. Viele Firmen bieten Lohnsysteme an, bei welchen die eigene Leistung vor‐ oder nachteilhafte Nebeneffekte auf das Einkommen der Arbeitskollegen hat. Soziale Interaktion am Arbeitsplatz kann dabei die Anreize dieser Lohnsysteme verzerren. Diese Studie findet heraus, dass bei Entlohnung der Arbeitskräfte durch Turnieranreize, d.h. wenn die eigene Leistung sich nachteilhaft auf das Einkommen der Arbeitskollegen auswirkt, soziale Interaktion die Anreize ausser Kraft setzt und zu geheimen Absprachen führt. Wenn hingegen Arbeitskräfte sehr unterschiedliche Fähigkeiten besitzen, dann sind geheime Absprachen schwieriger aufrecht zu halten

Phase I/II trial of preoperative carbon ion therapy for patients with localized, resectable adenocarcinoma of the pancreas

We examined the effect of preoperative carbon ion therapy in terms of reducing the rate of local recurrence in patients undergoing resection for adenocarcinoma of the pancreas. Eighteen patients were enrolled into this trial. Median age was 62 years. Carbon ion therapy was given once daily, 4days a week, for a fixed 16 fractions in 4 weeks. The dose was set to 44.8GyE and escalated to 48.0GyE at 5% increments. All patients completed the scheduled treatment course. Three grade3 acute reactions occurred among 12 of the patients treated with a dose of 48.0GyE. Only one grade 3 portal vein reaction of them was estimated to be caused by carbon ion therapy. Of 18 patients, 12(67%) had resection. All tumor specimens pathologically revealed evidence of grade 2 treatment effects with significant fibrosis, hyalinization, and necrosis (Pathological grade2 is defined as a less than 33% active cancer cells.). Remarkable antitumor effects were observed. The overall actuarial local control rates were 100% and 100% at 1 year and at 2 years of follow-up respectively. No local failure was observed in any of the 18 enrolled patients. The above results suggest the superior usefulness of heavy ion radiotherapy in the treatment of pancreatic carcinoma to conventional photon radiotherapy.\nHCPBM 2003(9th Workshop on Heavy Charged Particles in Biology and Medicine 2003) and ENLIGHT 2003(General Meeting of the European Network for Light Ion Hadrontherapy

Carbon ion therapy for patients with localized, resectable adenocarcinoma of the pancreas

2005 Gastrointestinal Cancers Symposiu

Phase I/II trial of preoperative carbon ion therapy for patients with localized, resectable adenocarcinoma of the pancreas

European Society for Therapeutic Radiology and Oncology 23rd Annual Congres

Carbon-ion Radiotherapy for patients with locally advanced pancreas cancer

Propose: Carbon ion radiotherapy (CIRT) offers the potential advantages of improved dose localization and enhanced biological effect. We examined the effect of CIRT in terms of reducing the rate of local recurrence in patients with locally advanced adenocarcinoma of the pancreas.Methods: Between April 2003 and February 2007, 46 patients with locally advanced pancreas cancer were eligible for this analysis. Patients eligible for study entry had histologically or cytologically confirmed with invasive ductal adenocarcinoma of the pancreas. Eligibility criteria were confirmation of invasive ductal carcinoma by CT findings, age of 80 years or younger, ECOG performance score 0, 1, or 2, and adequate hepatic, renal and cardiopulmonary function sufficient for undergoing surgery. The criteria of the CT findings for non-resectability of the tumor included tumor encasement of the celiac trunk and/or superior mesenteric artery. CIRT was given once daily, 4 days a week, for fixed 12 fractions in 3 weeks. The dose was set at 38.4GyE and escalated to 52.8GyE at 5% increments. Toxicity on organs such as the skin, digestive tract and liver was assessed according to the NCI-CTC classifications. Tumor response was defined by the RECIST scoring system as the maximum tumor response observed during the first 6 months after the initiation of CIRT. Local recurrence was defined in terms of lesions occurring in the tumor bed. Results:All patients completed the scheduled treatment course. Seven grade 3 acute and two grade 3 late toxicities were observed. Six of 7 grade 3 acute toxicities were anorexia and one was cholangitis. Complete response (CR) was observed in one lesion, partial response (PR) in 7,stable disease (SD) in 37, and progressive disease (PD) was observed in one lesion. The local control rates at one year in the 46 analyzed patients and in the patients receiving 45.6GyE or more were 85% and 95% respectively. The one year overall survival rate were 44% at all patients, and 47% at higher than 45.6GyE respectively. Conclusion:CIRT for locally advanced pancreas cancer seems to be safe and effective, however we could not get sufficient survival benefit. We started a phase I/II clinical trial of gemcitabine combined with CIRT for patients with locally advanced pancreas cancer from April 2007. At present we are trying to give 1000mg/m2 combined with 48GyE of carbon ion. All patients completed the scheduled treatment course with no major toxicity. This trial is still going.第49回粒子線治療世界会