Wang-Landau molecular dynamics technique to search for low-energy conformational space of proteins

Multicanonical molecular dynamics (MD) is a powerful technique for sampling conformations on rugged potential surfaces such as protein. However, it is notoriously difficult to estimate the multicanonical temperature effectively. Wang and Landau developed a convenient method for estimating the density of states based on a multicanonical Monte Carlo method. In their method, the density of states is calculated autonomously during a simulation. In this paper we develop a set of techniques to effectively apply the Wang-Landau method to MD simulations. In the multicanonical MD, the estimation of the derivative of the density of states is critical. In order to estimate it accurately, we devise two original improvements. First, the correction for the density of states is made smooth by using the Gaussian distribution obtained by a short canonical simulation. Second, an approximation is applied to the derivative, which is based on the Gaussian distribution and the multiple weighted histogram technique. A test of this method was performed with small polypeptides, Met-enkephalin and Trp-cage, and it is demonstrated that Wang-Landau MD is consistent with replica exchange MD but can sample much larger conformational space.Comment: 8 pages, 7 figures, accepted for publication in Physical Review

核酸分子に対する主鎖二面角力場の開発と分子動力学法による動的挙動解析

学位の種別: 課程博士審査委員会委員 : (主査)東京大学教授 児玉 龍彦, 東京大学特任教授 藤谷 秀章, 東京大学教授 浜窪 隆雄, 東京大学教授 津本 浩平, 東京大学特任准教授 山下 雄史University of Tokyo(東京大学

Surgically treated genital chronic graft‐versus‐host disease in women: A report of three cases

Hematopoietic stem cell transplantation (HSCT) is a crucial treatment for hematological malignancy. Gonadal dysfunction occurs at an early stage after this treatment, and such patients may require hormone replacement therapy. Genital chronic graft-versus-host disease is a lesser-known complication of HSCT that begins with vulvar discomfort and dysuria and progresses to sexual dysfunction and retention of menstrual blood due to vaginal stenosis and obstruction; thus, significantly impairing the patient's quality of life. We describe three women who underwent vaginal reconstruction because of genital chronic graft-versus-host disease. We discuss the surgical techniques, including double cross plasty that were performed in each case. Surgical interventions enabled the continuation of HRT and facilitated sexual intercourse. In conclusion, gynecologists should be aware that genital chronic graft-versus-host disease can occur after HSCT, and that surgical treatment options are available to improve patients' symptoms and quality of life

A case of subclinical Cushing's syndrome in pregnancy with superimposed preeclampsia

When we see preexistent hypertension in pregnancy, subclinical Cushing's syndrome should be considered in the differential diagnosis since this disorder can cause perinatal complications. MRI can be useful for identifying adrenal incidental tumors during pregnancy

迷走神経切離が腸管リンパ装置に及ぼす影響に関する基礎的研究

学位の種別: 課程博士審査委員会委員 : （主査）東京大学教授 山田 芳嗣, 東京大学教授 森屋 恭爾, 東京大学准教授 藤城 光弘, 東京大学准教授 内田 寛治, 東京大学講師 金子 順一University of Tokyo(東京大学

Post-traumatic diaphragmatic herniation of the liver, examined by positron emission tomography: case report

We present a case of post-traumatic diaphragmatic herniation of the liver, which mimicked an intrathoracic tumor. After an automobile accident, the patient underwent thoracotomies for hemothorax and lung cancer in the right chest. Seven months later, computed tomography (CT) demonstrated a round tumor in the thorax adjacent to the right diaphragm with a higher density than the liver parenchyma. An intrathoracic tumor including a primary or metastatic lung cancer was suspected. However, positron emission tomography (PET) showed that the uptake of fluorine-18-fluorodeoxyglucose (FDG) was identical to that in the liver, and the tumor appeared to be contiguous with the liver. Thus, we suspected liver herniation. Core needle biopsy revealed liver cells without neoplastic tissue. Upon surgical exploration, herniation of the liver was found and repaired. PET was helpful in providing morphological and functional information leading to accurate diagnosis of liver herniation in this unusual case

Clinical Course of 60 Cesarean Scar Pregnancies

Early diagnosis and therapy are important in a cesarean scar pregnancy (CSP), which can cause uterine rupture with resultant massive bleeding. However, there are some reports of CSPs continued to term. The optimal management of CSPs remains unclear; therefore, we investigated the clinical courses of CSPs diagnosed and treated at perinatal institutions in the Chugoku and Shikoku regions of Japan. We enrolled 60 women diag-nosed with CSP at 21 institutions from January 2006 to December 2015. Of the 60 women diagnosed with CSP, 57 were treated. Pregnancy was terminated in 48 women and continued in 9. Thirteen women underwent transabdominal hysterectomy; they experienced no postoperative complications or allogeneic blood transfu-sion. Nine women received therapies such as dilation and curettage, and 26 received non-surgical therapies such as methotrexate and topical administration of potassium chloride. Among 9 women who chose to con-tinue with their CSP, 7 successfully delivered newborns, 2 had uterine ruptures in the second trimester, and all women required transabdominal hysterectomy. Diagnosis and therapy in the first trimester of pregnancy are important in the management strategy of a CSP. When continuing a CSP, the risk of uterine rupture and trans-abdominal hysterectomy must be considered

Upregulation of Angiogenic Factors via Protein Kinase C and Hypoxia-induced Factor-1α Pathways under High-glucose Conditions in the Placenta

Abnormal glucose metabolism during pregnancy is an established risk factor for preeclampsia (PE). Disruption of the balance between placental angiogenic factors is linked to PE pathophysiology. We examined whether hypoxia-induced factor-1α (HIF-1α) and protein kinase Cβ (PKCβ) are involved in the regulation of placental angiogenic factors under high-glucose conditions in vitro. The human choriocarcinoma cell lines BeWo and JEG-3, and the human trophoblast cell line HTR-8/SVneo were cultured with 10 and 25 mmol/L glucose [control glucose group (CG) and high-glucose group (HG), respectively]. We examined the changes in HIF-1α, soluble fms-like tyrosine kinase-1 (sFlt-1), placental growth factor (PlGF), and vascular endothelial growth factor (VEGF) expression in the CG and HG by real-time PCR and ELISA. PKC activation was also measured by ELISA. The expressions of HIF-1α, sFlt-1, PlGF, and VEGF were significantly higher in the HG than in the CG. PKC activity was significantly increased in the HG. High glucose affected the expression of angiogenic factors in choriocarcinoma cells via the PKCβ and HIF-1α pathways, suggesting their involvement in PE pathogenesis