Aid effectiveness, Governance and Public Investment

To analyze how to make aid effective, we develop a growth model in which aid finances infrastructure investment and pro-poor spending. We assume that recipient countries are aid dependent in the early phase of development but finally become independent. In the model, donors can accelerate the independence of a recipient from aid by investing in infrastructure. We demonstrate that even a small increase in aid can improve aid effectiveness and that aid effectiveness depends more on growth rates than on the efficiency of government. This paper also evaluates Japan's aid, which has strength in economic infrastructure.

Radioprotective p53-targeting drugs

Radiation damage to normal tissues is a serious concern in radiation therapy. Advances in radiotherapeutic technology have improved the dose distribution of the target volumes and risk organs, but damage to risk organs that are located within the irradiation field still limits the allowable prescription dose. To overcome this dose-limiting toxicity, and to further improve the efficacy of radiotherapy, the development of drugs that protect normal tissues but not cancer tissues from the effects of radiation are expected to be developed based on molecular target-based drugs. p53 is a well-known transcription factor that is closely associated with radiation-induced cell death. In radiation-injured tissues, p53 induces apoptosis in hematopoietic lineages, whereas it plays a radioprotective role in the gastrointestinal epithelium. These facts suggest that p53 inhibitor would be effective for radioprotection of the hematopoietic system, and that a drug that upregulates the radioprotective functions of p53 would enhance the radioresistance of gastrointestinal tissues. In this review, we summarize recent progress regarding the prevention of radiation injury by regulating p53 and provide new strategic insights into the development of radioprotectors in radiotherapy

Non-monotonic behavior of the Binder Parameter in the discrete spin systems

We study a non-monotonic behavior of the Binder parameter, which appears in the discrete spin systems. Using the Fortuin-Kasteleyn graph representation, we find that the improved estimator of the Binder parameter consists of two terms with values only in high- and low-temperature regions. The non-monotonic behavior is found to originate from the low-temperature term. With the appropriately defined order parameter, we can reduce the influence of the low-temperature term, and as a result, the non-monotonic behavior can also be reduced. We propose new definitions of the order parameter, which reduces or eliminates the non-monotonic behavior of the Binder parameter in a system for which the improved estimator of the Binder parameter is unknown.Comment: 23 pages, 12 figures, added new result

Molecular mechanisms of acute radiation intestinal injury and its control

腸管は代表的な放射線高感受性組織であり、放射線治療においては腹部・骨盤領域の腫瘍への処方線量を制限するリスク臓器である。高線量の放射線により腸組織が損傷を受けると腸上皮幹細胞の喪失を誘発するが、この過程はp53 によって制御される陰窩細胞死過程と炎症性の免疫応答による増悪過程の2 段階のプロセスからなることが明らかにされつつある。本総説では、それぞれの過程の分子機構について概説し、急性放射線腸管障害を効果的に制御する方法について考察する。The intestinal tract is a typical radiosensitive tissue and a risk organ in radiotherapy that limits the prescribed dose to tumors in the abdominal and pelvic regions. High-dose radiation damage to intestinal tissue induces loss of intestinal stem cells, and it is becoming clear that this process consists of two steps: a crypt cell death process regulated by p53 and an exacerbation process by inflammatory immune responses. In this review, we will outline the molecular mechanisms of each process and discuss how to effectively control acute radiation intestinal injury

BMCs and periodontal tissue healing

Bone marrow-derived cells (BMCs) are considered to be a major source of mesenchymal stem cells (MSCs) in adults and are known to be effective in periodontal tissue regeneration. However, whether endogenous BMCs are involved in periodontal tissue repair process is uncertain. We therefore created periodontal tissue defects in the buccal alveolar bone of mandibular first molars in bone marrow chimeric mice, and immunohistochemically examined the expression of stromal cell derived factor-1 (SDF-1) and the mobilization of BMCs. We found that SDF-1 expression was increased around the defects at as early as 1 week after injury and that BMCs were mobilized to the defects, while GFP+/CD45+ were rarely observed. Fluorescence-activated cell sorting (FACS) analysis demonstrated that the number of platelet-derived growth factor receptor (pdgfr) α+/Sca-1+ (PαS) cells in the bone marrow decreased after injury. Taken together, these results suggest that BMCs are mobilized to the periodontal tissue defects. Recruitment of BMCs, including a subset of MSCs could be a new target of periodontal treatment

Safety and Efficacy of the Surgical Management of Hemodialysis Patients with Gastric Cancer

This retrospective study evaluated the short- and long-term outcomes after surgical management for gastric cancer in hemodialysis patients compared to non-dialysis patients. Twelve hemodialysis patients were compared with a propensity score-matched cohort of 39 gastric cancer patients who had not undergone hemodialysis. Short- and long-term outcomes along with scores estimating physiological ability and surgical stress were evaluated in both groups. The incidence of postoperative morbidity according to the Clavien-Dindo classification was higher in the hemodialysis gastric cancer group than in the non-dialysis gastric cancer group. The 5-year overall survival rate in the non-dialysis group was 69.2% after surgical resection for gastric cancer and 22.2% in the hemodialysis group. Patients with preoperative risk scores≥0.48 had significantly poorer survival outcomes compared to those with preoperative risk scores<0.48 (5-year survival rate, 83.3% vs. 39.4%, respectively). Our analyses suggest that hemodialysis patients undergoing surgery for gastric cancer have a significantly poorer postoperative prognosis and an elevated risk of postoperative complications

A Novel RNA Synthesis Inhibitor, STK160830, Has Negligible DNA-Intercalating Activity for Triggering A p53 Response, and Can Inhibit p53-Dependent Apoptosis

RNA synthesis inhibitors and protein synthesis inhibitors are useful for investigating whether biological events with unknown mechanisms require transcription or translation; however, the dependence of RNA synthesis has been difficult to verify because many RNA synthesis inhibitors cause adverse events that trigger a p53 response. In this study, we screened a library containing 9600 core compounds and obtained STK160830 that shows anti-apoptotic effects in irradiated wild-type-p53-bearing human T-cell leukemia MOLT-4 cells and murine thymocytes. In many of the p53-impaired cells and p53-knockdown cells tested, STK160830 did not show a remarkable anti-apoptotic effect, suggesting that the anti-apoptotic activity is p53-dependent. In the expression analysis of p53, p53-target gene products, and reference proteins by immunoblotting, STK160830 down-regulated the expression of many of the proteins examined, and the downregulation correlated strongly with its inhibitory effect on cell death. mRNA expression analyses by qPCR and nascent RNA capture kit revealed that STK160830 showed a decreased mRNA expression, which was similar to that induced by the RNA synthesis inhibitor actinomycin D but differed to some extent. Furthermore, unlike other RNA synthesis inhibitors such as actinomycin D, p53 accumulation by STK160830 alone was negligible, and a DNA melting-curve analysis showed very weak DNA-intercalating activity, indicating that STK160830 is a useful inhibitor for RNA synthesis without triggering p53-mediated damage responses