Dynamics of local initiatives in land acquisition : the case of General Santos City, the Philippines

Thesis (M.C.P.)--Massachusetts Institute of Technology, Dept. of Urban Studies and Planning, 1998.Includes bibliographical references (leaves 65-69).by Akira Akazawa.M.C.P

Reconstruction of Bone Defect Using the Bone Transport Technique for a Case of Osteosarcoma of the Femur

There are few reports on skeletal reconstruction using the bone transport technique to repair bone defects caused by resections of tumors associated with osteosarcoma. We attempted to reconstruct a 23 cm bone defect after resection of an osteosarcoma of the left femur, and succeeded in gaining 17 cm by bone transport. Five years after surgery, this patient remains alive without metastasis or local recurrence.</p

Large scale genotyping study for asthma in the Japanese population

<p>Abstract</p> <p>Background</p> <p>Asthma is a complex phenotype that is influenced by both genetic and environmental factors. Genome-wide linkage and association studies have been performed to identify susceptibility genes for asthma. These studies identified new genes and pathways implicated in this disease, many of which were previously unknown.</p> <p>Objective</p> <p>To perform a large-scale genotyping study to identify asthma-susceptibility genes in the Japanese population.</p> <p>Methods</p> <p>We performed a large-scale, three-stage association study on 288 atopic asthmatics and 1032 controls, by using multiplex PCR-Invader assay methods at 82,935 single nucleotide polymorphisms (SNPs) (1^ststage). SNPs that were strongly associated with asthma were further genotyped in samples from asthmatic families (216 families, 762 members, 2^ndstage), 541 independent patients, and 744 controls (3^rdstage).</p> <p>Results</p> <p>SNPs located in the 5' region of <it>PEX19 </it>(rs2820421) were significantly associated with <it>P </it>< 0.05 through the 1^stto the 3^rdstage analyses; however, the <it>P </it>values did not reach statistically significant levels (combined, <it>P </it>= 3.8 × 10^-5; statistically significant levels with Bonferroni correction, <it>P </it>= 6.57 × 10^-7). SNPs on <it>HPCAL1 </it>(rs3771140) and on <it>IL18R1 </it>(rs3213733) were associated with asthma in the 1^stand 2^ndstage analyses, but the associations were not observed in the 3^rdstage analysis.</p> <p>Conclusion</p> <p>No association attained genome-wide significance, but several loci for possible association emerged. Future studies are required to validate these results for the prevention and treatment of asthma.</p

A low-frequency IL4R locus variant in Japanese patients with intravenous immunoglobulin therapy-unresponsive Kawasaki disease

Background: Kawasaki disease (KD) is a systemic vasculitis which may be associated with coronary artery aneurysms. A notable risk factor for the development of coronary artery aneurysms is resistance to intravenous immunoglobulin (IVIG) therapy, which comprises standard treatment for the acute phase of KD. The cause of IVIG resistance in KD is largely unknown; however, the contribution of genetic factors, especially variants in immune-related genes, has been suspected. Methods: To explore genetic variants related to IVIG-unresponsiveness, we designated KD patients who did not respond to both first and second courses of IVIG therapy as IVIG-unresponsive patients. Using genomic DNA from 30 IVIG-unresponsive KD patients, we performed pooled genome sequencing targeting 39 immune-related cytokine receptor genes. Results: The single nucleotide variant (SNV), rs563535954 (located in the IL4R locus), was concentrated in IVIG-unresponsive KD patients. Individual genotyping showed that the minor allele of rs563535954 was present in 4/33 patients with IVIG-unresponsive KD, compared with 20/1063 individuals in the Japanese genome variation database (odds ratio = 7.19, 95% confidence interval 2.43-21.47). Furthermore, the minor allele of rs563535954 was absent in 42 KD patients who responded to IVIG treatment (P = 0.0337), indicating that a low-frequency variant, rs563535954, is associated with IVIG-unresponsiveness in KD patients. Although rs563535954 is located in the 3'-untranslated region of IL4R, there was no alternation in IL4R expression associated with the mior allele of rs563535954. However, IVIG-unresponsive patients that exhibited the minor allele of rs563535954 tended to be classified into the low-risk group (based on previously reported risk scores) for prediction of IVIG-resistance. Therefore, IVIG-unresponsiveness associated with the minor allele of rs563535954 might differ from IVIG-unresponsiveness associated with previous risk factors used to evaluate IVIG-unresponsiveness in KD. Conclusion: These findings suggest that the SNV rs563535954 could serve as a predictive indicator of IVIG-unresponsiveness, thereby improving the sensitivity of risk scoring systems, and may aid in prevention of coronary artery lesions in KD patients.ArticlePEDIATRIC RHEUMATOLOGY.17:34(2019)journal articl

Clinical activity of ASP8273 in Asian patients with non‐small‐cell lung cancer with EGFR activating and T790M mutations

Epidermal growth factor receptor (EGFR)‐activating mutations confer sensitivity to tyrosine kinase inhibitor (TKI) treatment for non‐small‐cell lung cancer (NSCLC). ASP8273 is a highly specific, irreversible, once‐daily, oral, EGFR TKI that inhibits both activating and resistance mutations. This ASP8273 dose‐escalation/dose‐expansion study (NCT02192697) was undertaken in two phases. In phase I, Japanese patients (aged ≥20 years) with NSCLC previously treated with ≥1 EGFR TKI received escalating ASP8273 doses (25‐600 mg) to assess safety/tolerability and to determine the maximum tolerated dose (MTD) and/or the recommended phase II dose (RP2D) by the Bayesian Continual Reassessment Method. In phase II, adult patients with T790M‐positive NSCLC in Japan, Korea, and Taiwan received ASP8273 at RP2D to further assess safety/tolerability and determine antitumor activity, which was evaluated according to Simon's two‐stage design (threshold response = 30%, expected response = 50%, α = 0.05, β = 0.1). Overall, 121 (n = 45 [33W/12M] phase I, n = 76 [48W/28M]) phase 2) patients received ≥1 dose of ASP8273. In phase I, RP2D and MTD were established as 300 and 400 mg, respectively. As 27 of the 63 patients treated with ASP8273 300 mg achieved a clinical response, ASP8273 was determined to have antitumor activity. The overall response rate at week 24 in all patients was 42% (n = 32/76; 95% confidence interval, 30.9‐54.0). Median duration of progression‐free survival was 8.1 months (95% confidence interval, 5.6, upper bound not reached). The most commonly reported treatment‐related adverse event in phase II was diarrhea (57%, n = 43/76). ASP8273 300 mg was generally well tolerated and showed antitumor activity in Asian patients with both EGFR‐activating and T790M mutations

Survey of Period Variations of Superhumps in SU UMa-Type Dwarf Novae. II: The Second Year (2009-2010)

As an extension of the project in Kato et al. (2009, arXiv:0905.1757), we collected times of superhump maxima for 61 SU UMa-type dwarf novae mainly observed during the 2009-2010 season. The newly obtained data confirmed the basic findings reported in Kato et al. (2009): the presence of stages A-C, as well as the predominance of positive period derivatives during stage B in systems with superhump periods shorter than 0.07 d. There was a systematic difference in period derivatives for systems with superhump periods longer than 0.075 d between this study and Kato et al. (2009). We suggest that this difference is possibly caused by the relative lack of frequently outbursting SU UMa-type dwarf novae in this period regime in the present study. We recorded a strong beat phenomenon during the 2009 superoutburst of IY UMa. The close correlation between the beat period and superhump period suggests that the changing angular velocity of the apsidal motion of the elliptical disk is responsible for the variation of superhump periods. We also described three new WZ Sge-type objects with established early superhumps and one with likely early superhumps. We also suggest that two systems, VX For and EL UMa, are WZ Sge-type dwarf novae with multiple rebrightenings. The O-C variation in OT J213806.6+261957 suggests that the frequent absence of rebrightenings in very short-Porb objects can be a result of sustained superoutburst plateau at the epoch when usual SU UMa-type dwarf novae return to quiescence preceding a rebrightening. We also present a formulation for a variety of Bayesian extension to traditional period analyses.Comment: 63 pages, 77 figures, 1 appendix, Accepted for publication in PASJ, data correctio

Survey of Period Variations of Superhumps in SU UMa-Type Dwarf Novae. VIII: The Eighth Year (2015-2016)

Continuing the project described by Kato et al. (2009, arXiv:0905.1757), we collected times of superhump maxima for 128 SU UMa-type dwarf novae observed mainly during the 2015-2016 season and characterized these objects. The data have improved the distribution of orbital periods, the relation between the orbital period and the variation of superhumps, the relation between period variations and the rebrightening type in WZ Sge-type objects. Coupled with new measurements of mass ratios using growing stages of superhumps, we now have a clearer and statistically greatly improved evolutionary path near the terminal stage of evolution of cataclysmic variables. Three objects (V452 Cas, KK Tel, ASASSN-15cl) appear to have slowly growing superhumps, which is proposed to reflect the slow growth of the 3:1 resonance near the stability border. ASASSN-15sl, ASASSN-15ux, SDSS J074859.55+312512.6 and CRTS J200331.3-284941 are newly identified eclipsing SU UMa-type (or WZ Sge-type) dwarf novae. ASASSN-15cy has a short (~0.050 d) superhump period and appears to belong to EI Psc-type objects with compact secondaries having an evolved core. ASASSN-15gn, ASASSN-15hn, ASASSN-15kh and ASASSN-16bu are candidate period bouncers with superhump periods longer than 0.06 d. We have newly obtained superhump periods for 79 objects and 13 orbital periods, including periods from early superhumps. In order that the future observations will be more astrophysically beneficial and rewarding to observers, we propose guidelines how to organize observations of various superoutbursts.Comment: 123 pages, 162 figures, 119 tables, accepted for publication in PASJ (including supplementary information

Nkx3.2 Promotes Primary Chondrogenic Differentiation by Upregulating Col2a1 Transcription

Background: The Nkx3.2 transcription factor promotes chondrogenesis by forming a positive regulatory loop with a crucial chondrogenic transcription factor, Sox9. Previous studies have indicated that factors other than Sox9 may promote chondrogenesis directly, but these factors have not been identified. Here, we test the hypothesis that Nkx3.2 promotes chondrogenesis directly by Sox9-independent mechanisms and indirectly by previously characterized Sox9-dependent mechanisms. Methodology/Principal Findings: C3H10T1/2 pluripotent mesenchymal cells were cultured with bone morphogenetic protein 2 (BMP2) to induce endochondral ossification. Overexpression of wild-type Nkx3.2 (WT-Nkx3.2) upregulated glycosaminoglycan (GAG) production and expression of type II collagen a1 (Col2a1) mRNA, and these effects were evident before WT-Nkx3.2-mediated upregulation of Sox9. RNAi-mediated inhibition of Nkx3.2 abolished GAG production and expression of Col2a1 mRNA. Dual luciferase reporter assays revealed that WT-Nkx3.2 upregulated Col2a1 enhancer activity in a dose-dependent manner in C3H10T1/2 cells and also in N1511 chondrocytes. In addition, WT-Nkx3.2 partially restored downregulation of GAG production, Col2 protein expression, and Col2a1 mRNA expression induced by Sox9 RNAi. ChIP assays revealed that Nkx3.2 bound to the Col2a1 enhancer element. Conclusions/Significance: Nkx3.2 promoted primary chondrogenesis by two mechanisms: Direct and Sox9-independen