172 research outputs found

    Development and Characterization of Tool Compounds Targeting the Runt Domain’s interaction With Cbfβ

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    RUNX1 and CBFβ, which encode subunits of the core binding factor, are frequent targets of chromosomal aberrations in hematological malignancies. We previously determined that CBFβ (encoded by CBFB) is important for the transforming activity of the chimeric protein AML1-ETO protein (RUNX1-RUNX1T1) generated by the t(8;21), and other studies showed that normal Runx1 functions are essential for survival and maintenance of some leukemias lacking RUNX1 or CBFB mutations. Thus, we hypothesized that we could achieve therapeutic efficacy in multiple leukemias by targeting the Runx1:CBFβinteraction with small molecules. Using the structural information of the DNA binding Runt domain (RD) of Runx1 and its interface with CBFβ, we employed a computational screen for a library of 78,000 drug-like compounds, and further optimized our leads. The Runt domain inhibitors (RDIs) bind directly to the RD and disrupt its interaction with CBFβ. We showed that the RDIs reduced growth and induced apoptosis of t(8;21) acute myeloid leukemia (AML) cell lines, and reduced the progenitor activity of mouse and human leukemia cells harboring the t(8;21), but not normal bone marrow cells. The RDIs had similar effects on murine and human T cell acute lymphocytic leukemia (T-ALL) cell lines that did not harbor the t(8;21). Furthermore, our inclusion of a structurally related and weakly active compound as a control strongly support that the efficacies we observed were due to on target inhibition of RUNX functions. Our results confirmed that the RDIs might prove efficacious in various AMLs, and that a therapeutic window is available to specifically target malignant cells. We developed a pro-drug AI-9-59 with improved solubility and pharmacokinetic properties and assessed whether it has any in vivo efficacies in mouse leukemia models. Our results showed that the pro-drug was toxic to mice at dosage above 50 mg/kg and had no observable growth inhibitory effect on leukemia cells, suggesting that the concentration of the pro-drug necessary to inhibit endogenous core binding factor activity exceeds the maximum tolerated dose in mice. However, the expansion of granulocyte macrophage progenitors, and the gastrointestinal toxicity phenotype we observed suggested that the effects could be from on-target repression of RUNX proteins functions

    The Effect of Information System on User Satisfaction and Net Benefits at Yangon Electricity Supply Corporation (Zaw Min Oo, 2024)

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    The objectives of this study are to analyze the effect of information system on user satisfaction and to analyze the effect of user satisfaction on net benefits at Yangon Electricity Supply Corporation. The sample size of the study is 133 employees calculated by using Yamane’s method from 200 employees at YESC who conduct meter reading, billing, and accounting. Simple random sampling method is used to select 133 employees among 200 employees. Questionaire survey method are used to collect the primary data. Both descriptive statistics and linear regression analyses are used to analyze the collected data. The analysis of employee perception on information quality of the AMI system at YESC shows that employees agreed that the system provided accurate, understandable, and report effectiveness, contributing to their satisfaction. They strongly agreed that system quality is effectiveness and flexible enhancing user satisfaction. In service quality, employees strongly agreed that the reliability and empathy in delivering services, enhancing user satisfaction. In the analysis of perception on user satisfaction, employees agreed that the system’s functionality, ease of use, and impact on work processes. With regard to net benefits from using the AMI system at YESC, employees strongly agreed that the benefits included easy access to power distribution, financial savings, reduced power losses and customer complaints, and preventive measures against financial abuse. When the effects of information quality on user satisfaction was analyzed, accuracy and report effectiveness have positive significant effect on user satisfaction. More over system effectiveness, and system flexibility have positive significant effect on user satisfaction. Service reliability and service empathy also positively influenced user satisfaction. User satisfaction was found to be a strong predictor of net benefits, with a significant positive relationship indicating that satisfied users contribute to organizational benefits

    Gender, ethnicity, and geography on security in Myanmar

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    The study looks at public perceptions towards public service delivery on health, education and security. Kachin State was selected to understand how the breakdown of ceasefire between the Tatmadaw and Kachin Independent Army (KIA) impacted people’s opinion on security. (Note that since publication the coup d’état, February 1, 2021, has severely halted Myanmar’s fragile democratisation). Kayin state was chosen to reflect how the ongoing ceasefire shaped public opinion on security; Chin state was selected because it was one of the least developed ethnic states. Magway provided the control case as it was a Burman-dominant state, not directly affected by armed conflict

    Decentralization of the police and its performance in four ethnic states of Myanmar

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    Along with democratic reforms started in 2011, police sector decentralization moved towards being a more gender and ethnic sensitive institution. Drawing on a survey, focus group discussions, and in-depth key informant interviews undertaken in Chin, Kayin, Kachin and Magway, the paper investigates effects of police force decentralization on service delivery performance in these four regions. Findings reveal that the police sector is only partially decentralized, and state governments have limited capability to manage police sectors even under limited decentralization. Challenges include resource and capacity constraints, political instability, and armed conflicts in the regions

    Fabrication of Titanium Dioxide Nanotubes Array For Photoanode in Mesoscopic Solar Cells

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    One dimensional (1D) nanostructures have been attracting the research interest and have many potential applications including mesoscopic solar cells. In this work, 1D titanium dioxide (TiO2) nanotubes array have been fabricated by the electrochemical anodization of Ti foils in electrolyte. Focus was placed on the morphology and size control of TiO2 nanotubes by varying fluoride content in electrolyte (0.3-0.6 Wt%). Fluoride contents of 0.4 and 0.5 Wt% are optimum for production of well-defined nanotubes array with uniform size distribution (tube diameter of 100 - 140 nm). It is also observed that higher the fluoride concentration, the larger is the anodization current across the sample. The tube morphology and size are strongly sensitive to the fluoride content in electrolyte

    Incidence of Typhoid and Paratyphoid Fevers Among Adolescents and Adults in Yangon, Myanmar

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    Background. Accurate estimates of typhoid disease burden are needed to guide policy decisions, including on vaccine use. Data on the incidence of enteric fever in Myanmar are scarce. We estimated typhoid and paratyphoid fever incidence among adolescents and adults in Yangon, Myanmar, by combining sentinel hospital surveillance with a healthcare utilization survey. Methods. We conducted a population-based household health care utilization survey in the Yangon Region 12 March through 5 April 2018. Multipliers derived from this survey were then applied to hospital-based surveillance of Salmonella Typhi and Paratyphi A bloodstream infections from 5 October 2015 through 4 October 2016 at Yangon General Hospital (YGH) to estimate the incidence of typhoid and paratyphoid fevers among person &ge;12 years of age. Results. A total of 336 households representing 1598 persons were enrolled in the health care utilization survey, and multipliers were derived based on responses to questions about healthcare seeking in the event of febrile illness. Of 671 Yangon residents enrolled over a 1-year period at YGH, we identified 33 (4.9%) with Salmonella Typhi and 9 (1.3%) with Salmonella Paratyphi A bloodstream infection. After applying multipliers, we estimated that the annual incidence of typhoid was 391 per 100 000 persons and paratyphoid was 107 per 100 000 persons. Conclusions. Enteric fever incidence is high in Yangon, Myanmar, warranting increased attention on prevention and control, including consideration of typhoid conjugate vaccine use as well as nonvaccine control measures. Research on incidence among infants and children, as well as sources and modes of transmission is needed. Keywords. incidence studies; Myanmar; paratyphoid fever; typhoid fever; typhoid vaccine</p

    Taming age mortality in semi-captive Asian elephants

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    Understanding factors preventing populations of endangered species from being self-sustaining is vital for successful conservation, but we often lack sufficient data to understand dynamics. The global Asian elephant population has halved since the 1950s, however >25% currently live in captivity and effective management is essential to maintain viable populations. Here, we study the largest semi-captive Asian elephant population, those of the Myanma timber industry (~20% global captive population), whose population growth is heavily limited by juvenile mortality. We assess factors associated with increased mortality of calves aged 4.0–5.5 years, the taming age in Myanmar, a process affecting ~15,000 captive elephants to varying degrees worldwide. Using longitudinal survival data of 1,947 taming-aged calves spanning 43 years, we showed that calf mortality risk increased by >50% at the taming age of four, a peak not seen in previous studies on wild African elephants. Calves tamed at younger ages experienced higher mortality risk, as did calves with less experienced mothers. Taming-age survival greatly improved after 2000, tripling since the 1970’s. Management should focus on reducing risks faced by vulnerable individuals such as young and first-born calves to further improve survival. Changes associated with reduced mortality here are important targets for improving the sustainability of captive populations.</p

    Confirmation of Skywalker Hoolock Gibbon (Hoolock tianxing) in Myanmar Extends Known Geographic Range of an Endangered Primate

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    Characterizing genetically distinct populations of primates is important for protecting biodiversity and effectively allocating conservation resources. Skywalker gibbons (Hoolock tianxing) were first described in 2017, with the only confirmed population consisting of 150 individuals in Mt. Gaoligong, Yunnan Province, China. Based on river geography, the distribution of the skywalker gibbon has been hypothesized to extend into Myanmar between the N’Mai Kha and Ayeyarwaddy Rivers to the west, and the Salween River (named the Thanlwin River in Myanmar and Nujiang River in China) to the east. We conducted acoustic point-count sampling surveys, collected noninvasive samples for molecular mitochondrial cytochrome b gene identification, and took photographs for morphological identification at six sites in Kachin State and three sites in Shan State to determine the presence of skywalker gibbons in predicted suitable forest areas in Myanmar. We also conducted 50 semistructured interviews with members of communities surrounding gibbon range forests to understand potential threats. In Kachin State, we audio-recorded 23 gibbon groups with group densities ranging between 0.57 and 3.6 group/km2. In Shan State, we audio-recorded 21 gibbon groups with group densities ranging between 0.134 and 1.0 group/km2. Based on genetic data obtained from skin and saliva samples, the gibbons were identified as skywalker gibbons (99.54–100% identity). Although these findings increase the species’ known population size and confirmed distribution, skywalker gibbons in Myanmar are threatened by local habitat loss, degradation, and fragmentation. Most of the skywalker gibbon population in Myanmar exists outside protected areas. Therefore, the IUCN Red List status of the skywalker gibbon should remain as Endangered

    Fluctuations in Serum magnesium and Systemic Arterial Blood Pressures during the Menstrual Cycle in young reproductive women

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    Introduction: The menstrual cycle involves a sequence of structural, functional, and hormonal changes in the reproductive system. This is linked and controlled by cyclical fluctuations in the levels of FSH, LH, estrogen, and progesterone. Because of these cyclical fluctuations, there might also be associated cyclical changes of magnesium and systemic arterial blood pressures during the menstrual cycle. Purpose: To assess the changes in serum magnesium level and systemic arterial blood pressures during the menstrual cycle in young reproductive women. Methodology: the sample population is 40 apparently healthy young reproductive-aged 18- 25years female students from the University of Medicine, Magway participated in this study. Systemic arterial blood pressures were measured by indirect method. The serum magnesium level was measured by spectrophotometry. These measurements were done in the early follicular phase (EF), the peri-ovulatory phase (PO), and the midluteal phase (ML) of the menstrual cycle. The serum magnesium levels were significantly (p <0.001) lower, and the systolic blood pressures were significantly higher (p <0.05) in the PO than the EF and the ML. In the EF, there was a significant negative correlation between serum magnesium level and diastolic blood pressure (r= - 0.374, p <0.05) and mean arterial pressure (r = -0.354, p < 0.05) but no significant correlation with systolic blood pressure. In the PO, there was no significant correlation between serum magnesium level and systemic arterial blood pressures. In the ML, there was significant negative correlation between serum magnesium level and systolic blood pressure (r = -0.651, p <0.001), diastolic blood pressure (r = -0.607, p <0.001), and mean arterial pressure (r = -0.661, p <0.001). Conclusion: The study concludes that serum magnesium level has a negative effect on blood pressure changes and the blood pressure-lowering effect of magnesium. These changes are related to the fluctuation of estrogen levels during the menstrual cycle. KEYWORDS: Serum magnesium, systemic arterial blood pressures, menstrual cycle reproductive syste

    Late prehistoric and early historic chronology of Myanmar: a four-millennia sequence from Halin

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    Myanmar is located within an important geographic corridor of prehistoric demographic and technological exchange, yet relatively few archaeological sites have been securely dated. Here, the authors present a new radiocarbon chronology for Halin, a UNESCO-listed complex in the north-central Sagaing Division of Myanmar, which contributes to the generation of nuanced regional chronologies and to improving the temporal resolution of Southeast Asia more generally. Discussion of 94 radiocarbon determinates, together with site stratigraphy and pottery traditions, provides a chronological sequence from the early third millennium BC to the early second millennium AD. Corroboration of the beginning of this sequence would place Halin as the oldest currently dated Neolithic site in Mainland Southeast Asia and would provide support for the two-layer model of Neolithic migration
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