ALBERT

Description: The destruction of the Fukushima Daiichi Nuclear Power Plant (NPP) following the March 2011 Tohoku earthquake and tsunami brought into sharp focus the susceptibility of NPPs to natural hazards. This is not a new issue—seismic hazard has affected the development of plants in the United States, and volcanic hazard was among the reasons for not commissioning the Bataan NPP in the Philippines [ Connor et al ., 2009].

Description: We present analytical closed-form expressions for the radiation patterns of 2D line sources and 3D point dipoles embedded in a general multi-layered configuration. While the former are simplified model sources, used as a preliminary analytical step toreduce derivation complexity, the latter have been shown experimentally to reproduce the electromagnetic behaviour of many elementary statistical sources. By decomposing the sources to current elements generating pure transverse electric (TE) or transverse magnetic (TM) polarized radiation, we arrive at a unified format for the radiation pattern expression for all sources considered. Analyzing the common 1D (characteristic) Green's function, we show that the normalized TE-polarized emission of model 2D electric line sources reproduces exactly the measured TE-polarized radiation of statistical (3D) dipoles with random in-plane orientation; the connection between the TM-polarized emission of the two species is discussed, and physical interpretation is provided via the unified expression. These results specify the precise relations between the 2D and 3D models, providing intuition as well as guidelines for proper usage of simplified 2D results for analysis of realistic 3D statistical configurations.

Description: Pediatric brain tumors as a group, including medulloblastomas, gliomas and atypical teratoid rhabdoid tumors (ATRT) are the most common solid tumors in children and the leading cause of death from childhood cancer. Brain tumor-derived cell lines are critical for studying the biology of pediatric brain tumors and can be useful for initial screening of new therapies. Use of the appropriate brain tumor cell line for experiments is important, as results may differ depending on tumor properties, and can thus affect the conclusions and applicability as a model. Despite reports in the literature of over 60 pediatric brain tumor cell lines, the majority of published papers utilize only a small number of these cell lines. Here we list the approximately 60 currently-published pediatric brain tumor cell lines and summarize some of their central features as a resource for scientists seeking pediatric brain tumor cell lines for their research. J. Cell. Biochem. © 2014 Wiley Periodicals, Inc.

Description: The size and thickness of organic aerosol particles collected by impaction in five field campaigns were compared to those of laboratory generated secondary organic aerosols (SOA). Scanning transmission x-ray microscopy (STXM) was used to measure the total carbon absorbance (TCA) by individual particles as a function of their projection areas on the substrate. Particles with higher viscosity/surface tension can be identified by a steeper slope on a plot of TCA vs. size because they flatten less upon impaction. The slopes of the ambient data are statistically similar indicating a small range of average viscosities/surface tensions across five field campaigns. Steeper slopes were observed for the plots corresponding to ambient particles, while smaller slopes were indicative of the laboratory generated SOA. This comparison indicates that ambient organic particles have higher viscosities/surface tensions than those typically generated in laboratory SOA studies.

Description: Protected Areas (PAs) remain central to the conservation of biodiversity. PAs were originally conceived as areas that would be set aside to maintain a natural state free from human influence. However, global environmental change, growing anthropogenic influence, and increasing globalisation of society have made it clear that PAs can no longer be thought of as 'ecological islands' that function independently of the broader social-ecological system in which they are located. For PAs to be resilient (and to contribute to broader social-ecological resilience) they must be able to adapt to changing social and ecological conditions over time in a way that supports the long-term persistence of populations, communities, and ecosystems of conservation concern. We propose a framework for understanding PAs and their long-term persistence, as a form of land-use embedded in social-ecological systems, with feedbacks from the local to the global scale. We develop approaches to thinking of PAs as multi-scale social-ecological systems in three ways. First, we combine elements of resilience analysis and the closely related social-ecological systems framework of Ostrom to develop a new conceptual outline for thinking about PA resilience. Second, we highlight the cross-scale influences and feedbacks on PAs that exist from the local to the global scale, contextualizing PAs within multi-scale social-ecological 'functional landscapes'. Such functional landscapes are integral to understanding and managing the long-term sustainability of individual PAs. Third, we illustrate our conceptual contribution with three case studies that highlight cross-scale feedbacks and social-ecological interactions in the functioning of PAs and in relation to regional resilience. Our analysis suggests that while ecological, economic and social processes are often directly relevant to PAs at finer scales, at broader scales the dominant processes that shape and alter PA resilience are primarily social and economic. # doi:10.1890/13-2113.1

Description: Key Points CYR61/CCN1 is a bone marrow microenvironmental biomarker for myeloma progression and for transformation of MGUS and asymptomatic disease to overt myeloma. CCN1 reduces myeloma bone disease and tumor growth and is a potential therapeutic target for myeloma.

Description: Key Points Jumping translocations of 1q12 (JT1q12) provide a mechanism for the deletion of 17p in cytogenetically defined high-risk myeloma. Sequential JT1q12s introduce unexpected copy number gains and losses in receptor chromosomes during subclonal evolution.

Description: Multiple myeloma (MM) is a B-cell malignancy stratified in part by cytogenetic aberrations including the high-risk copy number alterations (CNAs) of 17p- and +1q21. CNAs of 1q21 are known to occur as a result of jumping translocations of 1q (JT1q12) which increase the copy number (CN) of 1q21, while at the same time causing collateral genomic damage including deletions and amplifications in some receptor chromosomes (RC). We have previously reported the decondensation of the 1q12 region and triradial chromosomes in the bone marrow specimens of patients with aggressive disease, and have speculated that hypomethylation of the pericentromeric region of 1q12 may play a role in the origin of 1q21 CNAs. To test the hypothesis that 1q12 hypomethylation induces CN gains of 1q21, we used the hypomethylating agent 5-azacytidine to treat blood lymphocyte cultures of five myeloma patients with balanced constitutional 1q12 aberrations as well as five normal control subjects. The patients with constitutional aberrations of 1q12 were selected based on their potential to show either novel CN gains of regions translocated distal to 1q12 or CN gains of 1q21 when 1q12 was translocated to a non-homologous chromosome. The constitutional aberrations included two patients with pericentromeric inversions of chromosome 1 inv(1)(p11q12), and one patient each with a balanced translocation of t(1;2)(q12;p11), t(1;2)(q12;q34), or t(1;9)(q12;q11). These particular aberrations should provide a unique model for testing the association between the hypomethylation of 1q12 and the origin of CN gains of 1q21. In vitro blood lymphocyte cultures of patients and controls were treated for 72 hours with 5-azacytidine at a final concentration of 10uM. 5-azacytidine is known to cause site-specific hypomethylation and chromatin decondensation in the 1q12 region. Utilizing FISH probes for 1q12 (satII/III) and 1q21(CKS1B), we analyzed 100 metaphase cells from each patient and each control for CN gains for 1q21 and any novel region translocated distal to 1q12. To fully characterize the induced rearrangements of 1q12, we also applied inverse G-banding and spectral karyotyping in selected cells. Remarkably, all patients with the balanced constitutional 1q12 rearrangements showed CN gains of chromosome regions on the derivative chromosomes distal to the inverted or translocated 1q12 regions. Recurring aberrations of 1q12 included pericentromeric decondensation and triradials of chromosome arms 1q, 1p, and 2p, in addition to localized pulverizations distal to 1q12 of these same arms. Specifically, in both patients with inv(1), whole-arm CN gains of 1p were identified in 2-3% of cells, while in the patient with t(1;2)(q12;p11), whole-arm gains of 2p (MYCN) were identified in 3% of cells. In these same three patients, on the derivative chromosomes where the 1q12 region was separated from 1q21 by an inversion or translocation, no CN gains of the 1q21 occurred. In the patients with 1q12 translocated to a non-homologous chromosome, 1q21 was amplified on the RC in 4% of the cells in the patient with t(1;2)(q12;q34), and in 3% in the patient with t(1;9)(q12;q11). Control subjects showed CN gains of 1q21on both chromosomes 1 in the range of 3-13%. Whole-arm JT1q12s to RC16q were identified in three patients and three controls. This JT1q12 results in a CN gain of 1q21, and a whole-arm CN loss in RC16q, identical to those found in the bone marrow specimens of MM patients. Interestingly, one control showed JT1q12s to two different RCs, 9q and 12q, causing whole-arm deletions in the long arms of both. The key structural aberration responsible for the generation of CN gains of 1q21 and subsequent JT1q12s is the formation of a triradial involving the 1q12 region. The novel finding in this study is the induction of triradials and CN gains for chromosome arms of 1p and 2p, which demonstrates that epigenetic modifications to 1q12 can amplify non-homologous chromosome regions juxtaposed to it. Furthermore, the CN gains induced here occurred only distal to 1q12 on all normal and derivative chromosomes and mimic the triradials and JT1q12s reported in the bone marrow of patients with aggressive disease. These findings demonstrate for the first time that the hypomethylation of the 1q12 region can potentially amplify any genomic region distal to it, and provide evidence for an epigenetic origin of the high-risk 1q21 CNAs found in the progression of MM. Disclosures No relevant conflicts of interest to declare.

Description: Background: The definition of high risk smoldering multiple myeloma (HR-SMM) is in flux. There are several models using serologic, bone marrow and radiologic data that predict for time to progression (TTP) to clinical myeloma (CMM). Lenalidomide and Dexamethasone in HR-SMM is reported to delay onset of end organ damage and improve overall survival, stressing the clinical utility of early intervention. We previously reported a GEP70 based score cutoff (-0.26, serum M spike ≥3g/dL, and involved SFLC 〉25 mg/dL identified a subset of patients with 67% risk of progression at 2 years. With longer follow up, we now examine whether unique gene probe sets can be identified at the AMM stage that portend an earlier time to therapy (TTT). Patients and Methods: We identified 105 patients with AMM who had baseline GEP data on our S0120 protocol, after IRB approval for retrospective data review, and evaluated each of 54,675 Affymetrix gene probes for their potential to predict TTT. Probes were ranked by their q-values; we found 40 probes with q-value 〈 0.05 and 7 probes with q-value 〈 0.01; the top probe had a q-value of 0.00066. Scores based on the number of significant probes at these cut-points were computed by subtracting the sum of the expressions of the up-regulated probes from the sum of the expressions of the down-regulated probes, then dividing by the total number of probes. Results: In the GEP40 model, an optimal cut-point for risk of progression was identified at 7.05. The 3-year TTT probability was 83% with scores 〉=7.05 and only 11% for patients with values under this threshold (Figure 1A; p65 (HR: 2.3), Albumin3g/dl (HR: 4.99), BM plasmacytosis〉=10% (HR: 12.2), GEP70〉-0.26 (HR: 3.4), GEP40〉=7.05 (HR: 16.41), GEP proliferation index 〉 -0.26 (HR: 2.8), GEP PR subgroup (HR: 9.4) and GEP PolyPC 〉11.6 (HR: 0.22) to be significant. In the multivariate model, GEP40〉=7.05 was the most significant (HR: 13.7), followed by SFLC〉10mg/dl and M-protein〉3g/dl. GEP40 score positively correlated with proliferation index (R: 0.804), and showed no correlation with GEP polyPC score (R: -0.156). Next, we used recursive partitioning on data from 72 patients and identified 23 patients with GEP40 score 〉=7.05 of whom 22 suffered TTT by 3 years (87%). Among the remaining 49 patients with GEP40 59 years identified 24 patients, of whom 11 suffered progression with a 3 year TTT estimate of 25%. In the 25 patients with GEP40

Description: Intra-tumoral heterogeneity is a hindrance to curing malignant disease. By employing all MM-active drugs upfront, TT was designed to overcome such obstacle by targeting all potential MM sub-clones broadly. We are reporting on long-term results of phase-2 TT1, phase-3 TT2 and phase-2 TT3a trials, with median follow-up times of 21yr, 12yr and 9yr, respectively. Five year estimates of OS, PFS and CR duration (CRD) increased from 58%, 28% and 40% with TT1 to 65%, 42% and 50% with TT2’s control arm (TT2-), to 68%, 56% and 58% with TT2’s thalidomide arm (TT2+), and to 74%, 65% and 74% with TT3a (all p