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In general, the US codes such as the UBC-97 and ASCE-7 are widely used in developing countries including Myanmar, Syria, Philippines and so on. When the current seismic design guideline based on the UBC-97 and ACI 318-99 in Myanmar is assessed, several problems can be found in the following items: firstly, the fundamental period is not checked in modeling; secondly, reduction factor R is introduced a priori for the base shear estimation. And finally, a limit state assessment is done only for Design Basic Earthquake (DBE) but not for other design earthquakes. As a result, adequate yield strength is not checked for Maximum Operational Earthquake (MOE). Then there is no way to assess the seismic safety of the ultimate limit state for Maximum Considered Earthquake (MCE). In order to solve these problems, a rationalized seismic design method for earthquake prone developing countries is proposed. A new seismic design method is developed for MOE and MCE with adequate yield acceleration and typical period of the building estimated by using pushover analysis. A simplified procedure to estimate the inelastic response for a given design spectrum is also proposed. Finally, this design procedure can provide a rational method to assess the seismic safety for the ultimate limit of the building.

The Burmese roofed turtle (

Successful restoration of Geochelone platynota to Dry Zone ecosystems in Myanmar depends on the survival of translocated tortoises and, therefore, a knowledge of predators and predation is important. We here report the loss of 28 and approximately 200 translocated G. platynota to Eurasian golden jackals (Canis aureus) and wild pigs (Sus scrofa), respectively, at Shwe Settaw Wildlife Sanctuary in central Myanmar. Measures to reduce the risk of future predation include structural reinforcement of acclimation pens to deter wild pigs and the experimental use of large cat (e.g., tiger [Panthera tigris] and leopard [Panthera pardus]) odors to repel jackals and wild pigs from the translocation area.

Inhibitors that target specific kinases or oncoproteins have become popular additions to or replacements for cytotoxic chemotherapies to treat many different types of cancer. However, many tumors lack a discernable target kinase and an amplified oncoprotein and/or rely on several cooperating mechanisms for progression. Thus, combinations of targeted therapies are essential for treating many cancers to avoid the rapid emergence of resistance. In this issue of the JCI, Ren et al. use an elegant kinase activity–profiling method and identify activity of the oncogene polo-like kinase-1 (PLK1) as an important driver of double-hit lymphoma (DHL), an aggressive subgroup of B cell lymphoma characterized by chromosomal translocations involving c-MYC and BCL2 or BCL6. Moreover, PLK1 activity was associated with MYC expression and poor prognosis in DHL patients. PLK1 inhibition with volasertib, alone and in combination with the BCL-2 inhibitor venetoclax, was efficacious in multiple DHL models, including mice harboring DHL patient–derived xenografts. Together, these data support PLK1 as a promising prognostic marker and therapeutic target for DHL.

On January 11, 2018 (18:26 UTC), a Mw 6.0 earthquake occurred approximately 30 km west of the Sagaing Fault in the Bago-Yoma Range (BYR). Using a local broadband seismic network and regional seismic stations, we refine the locations and moment tensors of the earthquake sequence. We relocate 98 earthquake epicenters and determine the focal mechanism and centroid depth of the mainshock and 20 aftershocks with Mw > 4. The relocated epicenters cluster in a NW-SE direction that is consistent with the strike of the mainshock fault plane solution and the slip distribution derived from ALOS-2 interferometric synthetic aperture radar observations. Most of the aftershocks have a pure thrust focal mechanism similar to the mainshock, except for four strike-slip aftershocks. The refined locations and moment tensors of the thrust events clearly delineate a fault dipping ∼40° to the southwest at a depth range of 3–7 km, indicating that the earthquake sequence ruptured a previously unmapped, active fault. We interpret the earthquake sequence to be associated with pre-existing faults within the BYR anticlinorium. This earthquake sequence and historical seismicity indicate that the upper crust of the BYR is highly stressed, resulting in ongoing distributed deformation between the oblique Rakhine megathrust and the dextral Sagaing Fault. The seismic hazard posed by these active faults has been increasing with the development of infrastructure such as dams within the BYR. Our study highlights the need for high-resolution earthquake source parameter and strong ground motion attenuation studies for further understanding of the neotectonics of Myanmar and its related seismic hazard. Ministry of Education (MOE) National Research Foundation (NRF) Published version This research study was supported by the Earth Observatory of Singapore via its funding from the National Research Foundation Singapore and the Singapore Ministry of Education under the Research Centres of Excellence initiative.

The Burmese Roofed Turtle (Batagur trivittata Duméril & Bibron, 1835) is a large (straight-line carapace length [CL] to 620 mm; Platt et al., 2019), aquatic, herbivorous turtle endemic to the major river systems of Myanmar (Smith 1931; TTWG 2017). Although historically widespread and apparently abundant, long-term population declines resulted from chronic egg collecting, subsistence harvesting of adults, and loss of critical nesting habitat (Platt et al. 2017a). By the late 1990s B. trivittata was considered a candidate for Extinct status (Bhupathy et al. 2000) until a living specimen purchased in a Chinese wildlife market came into the possession of an American turtle collector in the early 2000s (Platt et al. 2005; W.P. McCord, pers. comm.). Shortly thereafter, field surveys “rediscovered” two remnant populations in the Dokhtawady and upper Chindwin Rivers (Platt et al. 2005; Kuchling et al. 2006). Intense ex- and in-situ recovery efforts were launched shortly thereafter and continue today (Kuchling & Tint Lwin 2004; Çilingir et al. 2017).

Open fracture is one of the common health care problems in clinical orthopedic practice. Incidence of open fracture rate is increasing, especially in working age groups in industrialized society. Treatment of open fractures is still challenging since surgeons have to tackle not only fracture and also risk of infection, soft tissue coverage and neurovascular injury. Traditionally, external fixator (EF) device was used to fix the open fracture as an emergency or definitive management. In recent years, there was the introduction of locked compression plate (LCP) as an alternative to the conventional external fixator. There are not too many studies regarding the outcome, biomechanics and complications regarding LCP as an external fixator. Based on the available resources, we have reviewed some journals. We would like to comment that usage of LCP as an external fixator in the treatment of long bone fractures shows acceptable outcome. There is no significant difference in operation time between LCP and EF. The rates of union and complication are comparable to that of the conventional external fixator. There is no enough report about a biomechanical comparison study between LCP and EF. Patient acceptance may be higher in LCP than in EF however; there is very little research for the time being. We would like to recommend further research in this area.

We conducted an interview-based survey to investigate the conservation status of large (adult carapace length >400mm) Softshell Turtles (Amyda ornata, Chitra vandijki, and Nilssonia formosa) in the Irrawaddy Dolphin Protected Area (IDPA) of Myanmar during November 2015. Our objectives were to: (1) determine which species of Softshell Turtles occur in IDPA, (2) assess threats to these populations, (3) evaluate the protected area as a release site for captive-bred Softshell Turtles, and (4) make conservation recommendations. To this end, we interviewed 180 people (mostly males) in 30 villages and verified the occurrence of all three species of Softshell Turtles in IDPA. Softshell Turtle populations appear to have undergone precipitous declines during the last 10–15 years largely driven by commercial demand from the illegal trans-boundary wildlife trade with China. Turtle hunting is no longer considered economically worthwhile, but Softshell Turtles continue to be taken as fisheries by-catch. We recommend that existing regulations designed to protect dolphins be enforced, and most importantly electro-fishing be eliminated from IDPA. We also urge authorities to revisit earlier proposals to reduce or eliminate the use of monofilament gill netting in IDPA. Implementation of a community-based fisheries plan to address these issues is warranted. In lieu of effective action, Softshell Turtle populations in IDPA face almost certain extirpation in the near future. IDPA is currently considered unsuitable as a release site for captive-bred Softshell Turtles.

Political and economic transitions have had substantial impacts on forest conservation. Where transitions are underway or anticipated, historical precedent and methods for systematically assessing future trends should be used to anticipate likely threats to forest conservation and design appropriate and prescient policy measures to counteract them. Myanmar is transitioning from an authoritarian, centralized state with a highly regulated economy to a more decentralized and economically liberal democracy and is working to end a long-running civil war. With these transitions in mind, we used a horizon-scanning approach to assess the 40 emerging issues most affecting Myanmar's forests, including internal conflict, land-tenure insecurity, large-scale agricultural development, demise of state timber enterprises, shortfalls in government revenue and capacity, and opening of new deforestation frontiers with new roads, mines, and hydroelectric dams. Averting these threats will require, for example, overhauling governance models, building capacity, improving infrastructure- and energy-project planning, and reforming land-tenure and environmental-protection laws. Although challenges to conservation in Myanmar are daunting, the political transition offers an opportunity for conservationists and researchers to help shape a future that enhances Myanmar's social, economic, and environmental potential while learning and applying lessons from other countries. Our approach and results are relevant to other countries undergoing similar transitions.

Mantle cell lymphoma (MCL) and diffuse large B-cell lymphoma (DLBCL) are aggressive hematologic malignancies characterized by the accumulation of lymphoid cells defective in cell apoptosis biology and function. The anti-apoptotic B-cell lymphoma 2 (BCL-2) family proteins are pivotal regulators of the mitochondrial apoptotic pathway and genetic aberrations in these genes are associated with lymphomagenesis and chemotherapeutic resistance. Notably, the anti-apoptotic myeloid cell leukemia 1 (MCL-1) protein is recurrently highly expressed in various kinds of non-Hodgkin's B-cell lymphomas and promotes the survival of lymphoma cells by counteracting pro-apoptotic protein activity. Collectively, these data support the hypothesis that MCL-1 plays a central role in B-cell lymphoma progression and drug resistance. Pharmacologically targeting MCL-1, therefore, represents an attractive strategy to combat these lymphomas. However, previous clinical and pre-clinical data suggest that treatment with single agent anti-BCL-2 family member therapy is associated with rapid acquisition of resistance. To this end, there is a great need to develop and apply selective small molecule MCL-1 inhibitors as part of a first-line therapy or upon emergence of tumor resistance characterized by upregulation of MCL-1 for lymphoma therapy. Here, we exploited the MCL-1 dependency in MCL and DLBCL by implementing pharmacogenomic and chemical proteomic approaches to investigate the molecular drug response and resistance mechanism to MCL-1 inhibitors. In anticipation of the evolution of MCL-1 inhibitor resistance, we modeled MCL-1 inhibitor resistance mechanisms by developing S63845 resistant lines with high doses of S63845 treatment for an extended period in MCL, DLBCL and MCL-derived lines. RNA sequencing and chemical proteomics on paired parental and resistant cells demonstrated that transcriptome and kinome reprograming linked to the MEK and ERK pathways contribute to MCL-1 inhibitor resistance via regulation of the BCL-2 family profile (BCL-2 and BIM), and as such, represent a novel targetable vulnerability in MCL-1 inhibitor resistant lymphoma. Additional analyses revealed synergistic activity of MCL-1 inhibitors (S63845, AZD5991) in combinations with inhibitors of MEK (Trametinib), ERK (SCH772984) and BCR (Ibrutinib) in MCL-1 inhibitor resistant MCL/DLBCL lines and primary samples. These results provide a strong rationale for further evaluation of MCL-1 inhibitor in combination with established therapy in the clinical setting and highlight a potential strategy for overcoming MCL-1 inhibitor resistance. Disclosures Shah: NCCN: Vice-Chair, Acute Lymphoblastic Leukemia Working Group: Membership on an entity's Board of Directors or advisory committees; Kite/Gilead, Precision Biosciences, Novartis, AstraZeneca: Other: TRAVEL, ACCOMMODATIONS, EXPENSES; Kite/Gilead, Jazz, Incyte: Research Funding; Moffitt Cancer Center: Current Employment; Kite/Gilead, Celgene/Juno/BMS, Novartis, Pfizer, Amgen, Spectrum/Acrotech, Precision Biosciences, Beigene, AstraZeneca, Pharmacyclics/Jansen, Adaptive: Honoraria. Shain:AbbVie: Research Funding; GlaxoSmithKline: Speakers Bureau; Takeda: Honoraria, Speakers Bureau; Amgen: Speakers Bureau; Sanofi/Genzyme: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Adaptive: Consultancy, Honoraria; Janssen: Honoraria, Speakers Bureau; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; BMS: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Karyopharm: Research Funding, Speakers Bureau.

SUMMARY Ibrutinib, a bruton’s tyrosine kinase (BTK) inhibitor, provokes robust clinical responses in aggressive mantle cell lymphoma (MCL), yet many patients relapse with lethal Ibrutinib-resistant (IR) disease. Here, using genomic, chemical proteomic, and drug screen profiling, we report that enhancer remodeling-mediated transcriptional activation and adaptive signaling changes drive the aggressive phenotypes of IR. Accordingly, IR MCL cells are vulnerable to inhibitors of the transcriptional machinery and especially so to inhibitors of cyclin-dependent kinase 9 (CDK9), the catalytic subunit of the positive transcription elongation factor b (P-TEFb) of RNA polymerase II (RNAPII). Further, CDK9 inhibition disables reprogrammed signaling circuits and prevents the emergence of IR in MCL. Finally, and importantly, we find that a robust and facile ex vivo image-based functional drug screening platform can predict clinical therapeutic responses of IR MCL and identify vulnerabilities that can be targeted to disable the evolution of IR., In brief Zhao et al. conduct unbiased proteomic, enhancer, and transcriptional profiling in combination with high-throughput drug screening to identify super-enhancer and kinome remodeling as an Ibrutinib resistance mechanism. CDK9 and BRD4 are vulnerabilities for Ibrutinib resistance necessary to sustain super-enhancers, and inhibition of CDK9 or BRD4 prevents the emergence of resistance., Graphical Abstract

This article was migrated. The article was marked as recommended. A conducive educational environment is vital to successful learning. Perception of students about their particular educational environment may vary depending on their educational background, gender, level of study, and many other factors. Awareness and understanding of the students' perception of educational environment are a key to improve our teaching and learning environment. The aim of the study was to determine the perception of undergraduate medical students of Taylor's University, Malaysia on their educational environment. A cross sectional cohort study was conducted among preclinical and clinical students simultaneously at Taylor's University, School of Medicine in July 2019. Overall total scores of perceptions (136.55 ± 19.6) and those for the subscales were very satisfactory and similar to those of other local universities as well as international universities. There was a significant difference between preclinical and clinical students in two domains; Perception of Course Organizers and Academic Self-Perception, with higher scores among clinical students in all. There was a significant difference between students with Grade 'B' and those with Grade 'C' in the mean total score and Perceptions of Atmosphere. These results, in spite of being satisfactory, urge us to seek methods of and opportunities for further enhancement of the students' education environment.

Problem: Multiple myeloma (MM) is a treatable yet incurable hematologic cancer that lacks predictive biomarkers. Approach: Here we apply a systems biology approach to determine patient-specific mechanisms, as well as signatures of drug resistance in MM. To achieve this goal, we have combined ex vivo drug sensitivity data from 307 MM fresh primary samples tested with 162 drugs and combinations, with paired molecular data (RNAseq and mutational profiling) from a larger overlapping cohort of 606 MM samples from Moffitt's Multiple Myeloma Working Group (MMWG) repository in collaboration with M2Gen/Oncology Research Information Exchange Network (ORIEN). With the purpose of decoupling biological function from intracellular control mechanisms, we have re-constructed a MM-specific transcriptional regulatory network composed of clusters of co-expressing genes. We demonstrate how this gene cluster network regulates biology, and how different biological functions (e.g. Proteasome, Ribosome, Oxidative Phosphorylation) share common regulatory circuits. We have used gene set enrichment analysis (GSEA) to identify gene clusters with transcriptional profiles, and investigated mutations associated with drug resistance. Results: As a preliminary validation of this approach, we have confirmed established mechanisms of resistance (MOR) to targeted therapies, as well as proposed novel MOR to clinically relevant and experimental drugs in MM, as well as putative synergistic drug combinations. In addition, we have identified a list of low frequency mutations ( We have also explored evolution of drug resistance in sequential samples. Consistent with altered transcriptional programming in therapeutic escape, single sample GSEA demonstrated cumulative dysregulation of cancer-related genes with increasing lines of therapy. We have identified 60 MM-specific transcriptional core auto-regulatory circuits (CRC) correlated with ex vivo drug resistance, suggesting that characterization of transcriptional regulatory circuits is a critical approach to infer mechanisms of MM resistance, and providing a novel rationale for combination therapy. We hypothesized that identifying and targeting these transcriptional CRCs could facilitate patient-specific rational combination therapies, with the goal to overcome therapy resistance in the clinic. As proof-of-principle, we have identified a novel transcriptional network consisting of 3 of these CRCs (FOXP1, JUNB and JUN) associated with BCL2 inhibitor (BCL2i) response in MM. Our preliminary data suggests that this transcriptional regulatory circuit is associated to t(11;14) MM through CCND1 up-regulation, but is also present in non-t(11;14) BCL2i-sensitive primary samples, and can be modulated to induce BCL2i sensitivity in non-t(11;14) MM through HDAC inhibitors. Conclusion and next steps: Preliminary results confirm the potential of this combination of unsupervised and supervised, yet functionally testable approach, to infer novel, and patient-specific MOR for MM drugs. Disclosures Dai: M2Gen: Employment. Dalton:MILLENNIUM PHARMACEUTICALS, INC.: Honoraria. Shain:Bristol-Myers Squibb: Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees; Sanofi Genzyme: Membership on an entity's Board of Directors or advisory committees; AbbVie: Research Funding; Adaptive Biotechnologies: Consultancy; Janssen: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees.

The once abundant Burmese star tortoise (Geochelone platynota) was functionally extirpated from Myanmar largely due to exploitation for wildlife trade markets. Geochelone platynota is ende...

In matriculation examinations at age 16, girls achieved greater score than boys. It is still uncertain whether gender gap in examination achievement reflects sex difference in fundamental cognitive domains or not. This cross sectional comparative study was undertaken to determine the cognitive ability in 62 male and 62 female medical students between 16-22 years of age attending in University of Medicine (2) Yangon with body mass index within 18.5-24.9 kg/m2. Blood haemoglobin concentration was determined by cyamet-haemoglobin method. Serum ferritin concentration was measured by enzyme linked immunoassay method.

The novel Bruton's tyrosine kinase inhibitor ibrutinib has demonstrated high response rates in B-cell lymphomas; however, a growing number of ibrutinib-treated patients relapse with resistance and fulminant progression. Using chemical proteomics and an organotypic cell-based drug screening assay, we determine the functional role of the tumour microenvironment (TME) in ibrutinib activity and acquired ibrutinib resistance. We demonstrate that MCL cells develop ibrutinib resistance through evolutionary processes driven by dynamic feedback between MCL cells and TME, leading to kinome adaptive reprogramming, bypassing the effect of ibrutinib and reciprocal activation of PI3K-AKT-mTOR and integrin-β1 signalling. Combinatorial disruption of B-cell receptor signalling and PI3K-AKT-mTOR axis leads to release of MCL cells from TME, reversal of drug resistance and enhanced anti-MCL activity in MCL patient samples and patient-derived xenograft models. This study unifies TME-mediated de novo and acquired drug resistance mechanisms and provides a novel combination therapeutic strategy against MCL and other B-cell malignancies., Ibrutinib has demonstrated high response rates in B-cell lymphomas but a lot of ibrutinib-treated patients relapse with resistance. This study unified TME-mediated de novo and acquired drug resistance through B-cell receptor signalling and PI3K-AKT-mTOR axis and provides a combination therapeutic strategy against B-cell malignancies.

Summary Drug-tolerant "persister" tumor cells underlie emergence of drug-resistant clones and contribute to relapse and disease progression. Here we report that resistance to the BCL-2 targeting drug ABT-199 in models of mantle cell lymphoma and double-hit lymphoma evolves from outgrowth of persister clones displaying loss of 18q21 amplicons that harbor BCL2. Further, persister status is generated via adaptive super-enhancer remodeling that reprograms transcription and offers opportunities for overcoming ABT-199 resistance. Notably, pharmacoproteomic and pharmacogenomic screens revealed that persisters are vulnerable to inhibition of the transcriptional machinery and especially to inhibition of cyclin-dependent kinase 7 (CDK7), which is essential for the transcriptional reprogramming that drives and sustains ABT-199 resistance. Thus, transcription-targeting agents offer new approaches to disable drug resistance in B-cell lymphomas.

Mantle cell lymphoma (MCL) is an aggressive and incurable B-cell malignancy. Prognosis remains poor due to emergence of drug resistance and MCL progression. Ibrutinib is a novel B-cell receptor (BCR) downstream bruton's tyrosine kinase (BTK) inhibitor with high response rates reported in MCL patients. The initial success of ibrutinib is likely attributed to attenuation of BCR-dependent lymphoma-tumor microenvironment (TME) interactions. Moreover, despite the dramatic responses to ibrutinib, ibrutinib resistance (IR) inevitably develops. Remarkably, once patients relapse after ibrutinib treatment, MCL patients experience disease progression and die within 12 months. Thus, there is an urgent need to define mechanisms of ibrutinib resistance (IR) and to identify novel targets to bring forward novel treatment options with real curative potential for this fatal complication. Currently the mechanisms driving IR are poorly understood and no recurrent driver mutations have been identified in MCL. We have modeled acquired resistance to ibrutinib and implemented chemical proteomics and a cell-based drug screen approaches in IR MCL lines and primary samples, we have shown that MCL cells become resistant to ibrutinib through a kinome-adaptive reprogramming mechanism that lead to constitutive activation of the PI3K/AKT/mTOR pathway with increased levels of Myc and sustained transcription activation. Significantly, the acquired IR MCL cells have increased rates of growth and augmented adhesion to stromal cells. Collectively, our published and preliminary studies indicate that IR MCL relies on global transcriptome remodeling and subsequent kinome reprogramming, leading to molecularly and clinically aggressive phenotype and resistance to ibrutinib therapy. Rather than there being a single mechanism of acquired IR, kinase networks are rewired in a plethora of ways in MCL cells as they become resistant to ibrutinib treatment. Adaptive remodeling of the kinome creates therapeutic challenges, where even combination targeted kinase inhibitor treatments are unlikely to be successful. We reasoned instead that global adaptive kinome as a whole must be blocked for overcoming IR. Sustained transcriptional activation and associated adaptive signaling changes drive the malignant phenotype of IR and, accordingly, that targeting the transcriptional machinery responsible for conferring IR triggers synthetic lethality in MCL. We leveraged powerful genomic and pharmacoproteomic approaches available to our laboratory and IR model to identify the key upstream genetic and epigenetic driver for IR. Ultimately, we designed transcription activation based combination therapy to overcome drug resistance and hinder MCL progression. In addition, performing cell-based drug screen assay on primary MCL cells of MCL patients allowed us to predict drug response and tailor therapeutic drugs for individual patients, thus, creating a personalized therapeutic strategy for MCL patients Disclosures No relevant conflicts of interest to declare.

Background: c-MYC is a transcription factor that promotes oncogenesis by activating and repressing its target genes that control cell growth, metabolism, and proliferation. MYC is deregulated in a large proportion of aggressive B-cell lymphomas. A typical example is the Double-Hit Lymphoma (DHL) and Double-Expression Lymphoma (DEL) which present with a rapidly progressing clinical course, refractory to treatment, poor clinical outcome, and currently considered incurable. Nevertheless, MYC is considered as an "undruggable" target since it has no "active site" amenable to binding by conventional small molecule inhibitors. Moreover, MYC has a broad spectrum of functions in cell proliferation, survival, metabolism, and others, so direct inhibition would likely cause severe side effects. Besides direct inhibition, another practical strategy is to target druggable proteins that are essential for the viability of MYC-driven tumors, inducing MYC-dependent "synthetic lethality". The advantage of such approach is a capability of killing tumor cells discriminately, while leaving non-tumor cells intact or less influenced. This study is designed to identify such targets and explore practical novel strategies to treat MYC-driven lymphomas, especially DHL/DEL. Methods and Results: By integrating activity-based proteomic profiling and drug screens in isogenic MYC on/off lymphoma cells, we identified polo-like kinase-1 (PLK1) as an essential regulator of the MYC-dependent kinome in DHL/DEL. Notably, PLK1 was expressed at high levels in DHL, correlated with MYC expression and connoted poor outcome. Further, PLK1 is directly activated by MYC on transcriptional level and in turn, PLK1 signaling augmented MYC protein stability by promoting its phosphorylation and suppressing its degradation. Thus, MYC and PLK1 form a feed-forward circuit in lymphoma cells. Finally, both in vitro and in vivo studies demonstrated that inhibition of PLK1 triggered degradation of MYC and of the anti-apoptotic protein MCL1, and PLK1 inhibitors showed synergy with BCL-2 antagonists in blocking DHL/DEL cell growth, survival, and tumorigenicity. These data support that PLK1 is a promising therapeutic target in MYC-driven lymphomas. Brief summary: Functional pharmacoproteomics identified PLK1 as a therapeutic vulnerability for MYC-driven lymphoma, which was a synthetic lethal for DHL/DEL when targeted with BCL-2 inhibitors. Disclosures Vose: Roche: Honoraria; Merck Sharp & Dohme Corp.: Research Funding; Acerta Pharma: Research Funding; Seattle Genetics, Inc.: Research Funding; Novartis: Honoraria, Research Funding; Kite Pharma: Research Funding; Bristol Myers Squibb: Research Funding; Epizyme: Honoraria; Legend Pharmaceuticals: Honoraria; Abbvie: Honoraria; Celgene: Research Funding; Incyte Corp.: Research Funding.

Summary We investigated the transcriptional and epigenetic repression of miR-29 by MYC , HDAC3 , and EZH2 in mantle cell lymphoma and other MYC -associated lymphomas. We demonstrate that miR-29 is repressed by MYC through a corepressor complex with HDAC3 and EZH2. MYC contributes to EZH2 upregulation via repression of the EZH2 targeting miR-26a, and EZH2 induces MYC via inhibition of the MYC targeting miR-494 to create positive feedback. Combined inhibition of HDAC3 and EZH2 cooperatively disrupted the MYC-EZH2-miR-29 axis, resulting in restoration of miR-29 expression, downregulation of miR-29-targeted genes, and lymphoma growth suppression in vitro and in vivo. These findings define a MYC-mediated miRNA repression mechanism, shed light on MYC lymphomagenesis mechanisms, and reveal promising therapeutic targets for aggressive B-cell malignancies.

B-cell lymphoma 6 (BCL6) and PR domain containing 1 (PRDM1) are considered as master regulators for germinal center (GC) formation and terminal B-cell differentiation. Dysregulation of BCL6 and PRDM1 has been associated with lymphomagenesis. Here, we show for the first time that direct cell–cell contact between follicular dendritic cells (FDC) and B-lymphocytes, by influencing the expression of a set of microRNAs (miRNAs), regulates the expression of BCL6 and PRDM1. We identify that, on cell adhesion to FDC, FDC induces upregulation of PRDM1 expression through downregulation of miR-9 and let-7 families and induces downregulation of BCL-6 through upregulation of miR-30 family in B-lymphocytes and lymphoma cells. We further demonstrate that the miR-30 family directly controls BCL-6 expression and miR-9-1 and let-7a directly control PRDM-1 expression through targeting their 3′UTR, mediating the FDC effect. Our studies define a novel regulatory mechanism in which the FDC, through induction of miRNAs in B-lymphocytes, orchestrates the regulation of transcription factors, promotes germinal center B-cell survival and differentiation. Dysregulation of miRNAs may interfere with B-cell survival and maturation, thus representing a novel molecular mechanism, as well as a potential therapeutic target in B-cell lymphomas.

Myanmar, lying in a major seismic belt, is indeed earthquake-prone and is vulnerable to hazards from moderate and large magnitude earthquakes, including tsunami hazards along its long coastal areas. The seismotectonics of the region indicates that earthquakes in Myanmar mostly have originated along an active subduction zone (Andaman Megathrust Zone) in the west and along a large transform fault zone (Sagaing Fault Zone) in the middle part of the country. In the past, at least two large magnitude earthquakes along that subduction zones were tsunamigenic. Of course, the tsunami generated by the giant 2004 Sumatra Earthquake also caused moderate damage in some parts of the Myanmar Coast. Thus, it is evident that Myanmar is vulnerable to hazards from moderate and large magnitude earthquakes, including tsunami hazards along its long coastline.The active fault studies (from paleoseismological survey through tectonic geodesy), upgrade and newly installation of seismic station networks, public awareness and curriculum development, building code development and technical training program are priority requirements in the country. Recently, researchers on tectonic geology recognize some active segments of the Sagaing, Kyaukkyan and Kabaw faults, as well as marine and fluvial terraces which seemed to be associated with subduction of India and Burma (Myanmar) plates along the Bengal tectonic boundary. Their study should be extended by providing some instrumentation schemes like global positioning system (GPS) network. Myanmar Earthquake Committee (MEC) has developed a seismic zone map of Myanmar in deterministic approach in 2006, for the sake of providing general information to the user for various purposes, and for public information. Technical development is needed for the completeness of the next generation of seismic zone map of Myanmar which is to be incorporated in Building Code, which in turn requires researches and findings on tectonics of Myanmar.