Educational Leadership in Haiti: A Case Study of Innovative and Exemplary Leadership in a Fragile State

In this study, we consider three school leaders in Haiti who provide examples of innovative and exemplary leadership practices in the midst of challenging circumstances. Using a framework of innovative (Moolenaar, Daly, & Sleeger, 2010; Rogers, 2003) and exemplary leadership practices (Kouzes & Posner, 2006), we examine three themes that emerged from interviews with the three participants, observations of their work in the field, and interviews with other educational stakeholders in their communities. We raise considerations for leadership practices that include: The importance of social and professional networks, barriers and opportunities to innovative practice, and collaborations involving community, regional, national, and international partners. The paper provides suggestions for further exploration in examining educational leadership in fragile states such as Haiti

Spawning induction in the common carp (Cyprinus carpio) using different combinations of [D-Ser(tBu)6,Pro9-Net]-LHRHa and metoclopramide [D-Ser(tBu)6,Pro9-NEt]-LHRHa ve metoklopramidin farkli kombinasyonlarda kullanimi ile sazan (Cyprinus carpio) anaçlarinda yumurtlamanin uyarilmasi

The effects of a single administration of [D-Ser(tBu)6,Pro 9-NEt]-LHRHa at high dose alone (50 µg/kg), and at constant dose (20 µg/kg) combined with different doses of the dopamine receptor antagonist Metoclopramide (5, 10, 20, 40 mg/kg) for the induction of spawning in common carp broodstocks were determined under local hatchery conditions and compared with classic carp pituitary extract (CPE, double injection) application (water temperature 24°C). Fish injected with physiological saline (0.7% NaCl) were used as a control group. No spawning was observed in the control group or in the groups given LHRH-a combined with low (5, 10 mg/kg) doses of MET. The spawning ratio was low in the group given a high dose of LHRH-a alone (50 µg/kg), while it was high in the groups given LHRH-a combined with high (20, 40 mg/kg) doses of MET, and in the group injected with CPE. Latency period in the LHRH-a+MET groups was approximately half of that in the CPE group (14-16 and 24-26 h, respectively). There were no differences between spawned groups with respect to the spawning index of broodstocks, or the fertilization/hatching rate of eggs. It was concluded that spawning can be induced successfully in common carp broodstocks with 20 mg/kg LHRH-a+20 mg/kg MET, in a single injection, in a shorter latency period and without a negative effect on egg quality, compared to CPE treatment. This combination may be useful for more effective broodstock and hatchery management in common carp culture. © TÜB¨ITAK

Abstract 1933: Discovery of first-in-class small molecule CD99 inhibitors for targeted therapy of Ewing sarcoma

Abstract Ewing sarcoma (ES) is an aggressive bone and soft tissue malignancy that affects predominantly children and adolescents with a high propensity to metastasize and poor prognosis. CD99 is a transmembrane cell surface protein that is highly expressed on ES cells, and routinely used as a marker for histological diagnosis of ES. We screened small molecule libraries for their binding to recombinant CD99 protein and subsequent selective inhibition of ES cell growth. We identified two structurally similar FDA-approved nucleoside analogues, clofarabine and cladribine that selectively inhibited the growth of ES cells in a panel of 14 ES vs. 28 non-ES cell lines. A significant negative correlation was found in human cell lines between CD99 expression and IC50 values for clofarabine and cladribine. Both drugs inhibited CD99 dimerization and its interaction with downstream signaling components cyclophilin A and PKA-RIIα as well as led to reduced ROCK2 protein expression and migration in ES cells. A membrane-impermeable analog of clofarabine showed similar cytotoxicity in ES cells, suggesting that it can function through inhibiting CD99 alone without any effect on DNA metabolism. Clofarabine and cladribine led to a significant increase in hypodiploid DNA content of ES cells, which was diminished by suppression of CD99 expression. Both drugs drastically inhibited anchorage-independent growth of ES cells, but clofarabine was more effective in inhibiting ES xenografts. Finally, the screening of a set of chemotherapy drugs revealed a synergy for the combination of anti-CD99 drugs and dasatinib in ES cells, which may translate into increased survival and reduced toxicity. Overall, our findings suggest that clofarabine is a good candidate for early phase clinical trials in children with ES. Citation Format: Haydar Celik, Marika Sciandra, Bess Flashner, Elif Gelmez, Neslihan Kayraklıoğlu, David V. Allegakoen, Jeff R. Petro, Erin J. Conn, Sarah Hour, Jenny Han, Lalehan Oktay, Purushottam B. Tiwari, Mutlu Hayran, Maria Cristina Manara, Jeffrey A. Toretsky, Katia Scotlandi, Aykut Uren. Discovery of first-in-class small molecule CD99 inhibitors for targeted therapy of Ewing sarcoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 1933. doi:10.1158/1538-7445.AM2017-1933</jats:p

Clofarabine inhibits Ewing sarcoma growth through a novel molecular mechanism involving direct binding to CD99

Ewing sarcoma (ES) is an aggressive bone and soft tissue malignancy that predominantly affects children and adolescents. CD99 is a cell surface protein that is highly expressed on ES cells and is required to maintain their malignancy. We screened small molecule libraries for binding to extracellular domain of recombinant CD99 and subsequent inhibition of ES cell growth. We identified two structurally similar FDA-approved compounds, clofarabine and cladribine that selectively inhibited the growth of ES cells in a panel of 14 ES vs. 28 non-ES cell lines. Both drugs inhibited CD99 dimerization and its interaction with downstream signaling components. A membrane-impermeable analog of clofarabine showed similar cytotoxicity in culture, suggesting that it can function through inhibiting CD99 independent of DNA metabolism. Both drugs drastically inhibited anchorage-independent growth of ES cells, but clofarabine was more effective in inhibiting growth of three different ES xenografts. Our findings provide a novel molecular mechanism for clofarabine that involves direct binding to a cell surface receptor CD99 and inhibiting its biological activities