PCAIM joint inversion of InSAR and ground-based geodetic time series: Application to monitoring magmatic inflation beneath the Long Valley Caldera

This study demonstrates the interest of using a Principal Component Analysis-based Inversion Method (PCAIM) to analyze jointly InSAR and ground-based geodetic time series of crustal deformation. A major advantage of this approach is that the InSAR tropospheric biases are naturally filtered out provided they do not introduce correlated or high amplitude noise in the input times series. This approach yields source models which are well-constrained both in time and space due to the temporal resolution of the ground-based geodetic data and the spatial resolution of the InSAR data. The technique is computationally inexpensive allowing for the inversion of large datasets. To demonstrate the performance of this approach, we apply it to the 1997–98 magmatic inflation event in the Long Valley Caldera, California

Seismic and aseismic slip on the Central Peru megathrust

Slip on a subduction megathrust can be seismic or aseismic, with the two modes of slip complementing each other in time and space to accommodate the long-term plate motions. Although slip is almost purely aseismic at depths greater than about 40 km, heterogeneous surface strain suggests that both modes of slip occur at shallower depths, with aseismic slip resulting from steady or transient creep in the interseismic and postseismic periods. Thus, active faults seem to comprise areas that slip mostly during earthquakes, and areas that mostly slip aseismically. The size, location and frequency of earthquakes that a megathrust can generate thus depend on where and when aseismic creep is taking place, and what fraction of the long-term slip rate it accounts for. Here we address this issue by focusing on the central Peru megathrust. We show that the Pisco earthquake, with moment magnitude M_w = 8.0, ruptured two asperities within a patch that had remained locked in the interseismic period, and triggered aseismic frictional afterslip on two adjacent patches. The most prominent patch of afterslip coincides with the subducting Nazca ridge, an area also characterized by low interseismic coupling, which seems to have repeatedly acted as a barrier to seismic rupture propagation in the past. The seismogenic portion of the megathrust thus appears to be composed of interfingering rate-weakening and rate-strengthening patches. The rate-strengthening patches contribute to a high proportion of aseismic slip, and determine the extent and frequency of large interplate earthquakes. Aseismic slip accounts for as much as 50–70% of the slip budget on the seismogenic portion of the megathrust in central Peru, and the return period of earthquakes with M_w = 8.0 in the Pisco area is estimated to be 250  years

The Emergence of Movement Units Through Learning with Noisy Efferent Signals and Delayed Sensory Feedback

Rapid human arm movements often have velocity profiles consisting of several bell-shaped acceleration-deceleration phases, sometimes overlapping in time and sometimes appearing separately. We show how such sub-movement sequences can emerge naturally as an optimal control policy is approximated by a reinforcement learning system in the face of uncertainty and feedback delay. The system learns to generate sequences of pulse-step commands, producing fast initial sub-movements followed by several slow corrective sub-movements that often begin before the initial sub-movement has completed. These results suggest how the nervous system might efficiently control a stochastic motor plant under uncertainty and feedback delay. 1

Geochemical portray of the Pacific Ridge: New isotopic data and statistical techniques

Samples collected during the PACANTARCTIC 2 cruise fill a sampling gap from 53° to 41° S along the Pacific Antarctic Ridge (PAR). Analysis of Sr, Nd, Pb, Hf, and He isotope compositions of these new samples is shown together with published data from 66°S to 53°S and from the EPR. The recent advance in analytical mass spectrometry techniques generates a spectacular increase in the number ofmultidimensional isotopic data for oceanic basalts. Working with such multidimensional datasets generates a new approach for the data interpretation, preferably based on statistical analysis techniques. Principal Component Analysis (PCA) is a powerful mathematical tool to study this type of datasets. The purpose of PCA is to reduce the number of dimensions by keeping only those characteristics that contribute most to its variance. Using this technique, it becomes possible to have a statistical picture of the geochemical variations along the entire Pacific Ridge from 70°S to 10°S. The incomplete sampling of the ridge led previously to the identification of a large-scale division of the south Pacific mantle at the latitude of Easter Island. The PCA method applied here to the completed dataset reveals a different geochemical profile. Along the Pacific Ridge, a large-scale bell-shaped variation with an extremum at about 38°S of latitude is interpreted as a progressive change in the geochemical characteristics of the depleted matrix of the mantle. This Pacific Isotopic Bump (PIB) is also noticeable in the He isotopic ratio along-axis variation. The linear correlation observed between He and heavy radiogenic isotopes, together with the result of the PCA calculation, suggests that the large-scale variation is unrelated to the plume–ridge interactions in the area and should rather be attributed to the partial melting of a marble-cake assemblage

The Atlas of Blood Cancer Genomes (ABCG) Project: A Comprehensive Molecular Characterization of Leukemias and Lymphomas

Abstract Introduction Blood cancers are collectively common and strikingly heterogeneous diseases both clinically and molecularly. According to the WHO taxonomy, there are over 100 distinct myeloid and lymphoid neoplasms. Genomic profiling of blood cancers has been applied in a somewhat ad hoc fashion using diverse sequencing approaches including the use of targeted panels, whole exome sequencing, whole genome sequencing, RNA sequencing, etc. The lack of data uniformity has made it difficult to comprehensively understand the clinical and molecular spectrum within and across diseases. Systematic genomic approaches can address the central challenges in the diagnosis and treatment of blood cancers. For the diagnosis of blood cancers, the incorporation of genomics could greatly enhance the accuracy and speed of clinical diagnostics. Genomics could also inform their pathology classification. However, these applications must be preceded by a clear understanding of the particular genetic aberrations and expression profiles that unite and distinguish different leukemias and lymphomas. Therapeutic development can also be aided by genomic approaches through identification of new targets and establishing the relevance of existing targets and treatments. Targeted therapies including those directed at specific surface markers (e.g. CD19, CD30 and CD123) or molecular targets (e.g. BCR-ABL fusions, IDH1 mutations and EZH2 mutations) are rarely restricted to a single disease, with most occurring in multiple blood cancers. A systematic understanding of the presence or overlap of these targets within or across blood cancers would significantly expand the therapeutic possibilities and better enable the use of existing therapies in both common and rare cancers. However, such therapeutic possibilities need to be established through a rigorous, data-driven approach. We initiated the Atlas of Blood Cancers Genomes (ABCG) project to systematically elucidate the molecular basis of all leukemias and lymphomas by building upon advances in genomic technologies, our capabilities for data analysis and economies of scale. Using a uniform approach to systematically profile all blood cancers through DNA and RNA sequencing at the whole exome/whole transcriptome level, we aim to link genomic events with clinical outcomes, disease categories and subcategories, thereby providing a complete molecular blueprint of blood cancers. Methods/Results The ABCG project consists of collaborators from 25 institutions around the world who have collectively contributed samples from 10,481 patients comprising every type of blood cancer in the current WHO classification. The samples include thousands of myeloid leukemias and mature B cell lymphomas, hundreds of Hodgkin lymphoma and plasma cell myeloma, as well as every rare type of hematologic malignancy (along with case-matched normal tissue). All cases were de-identified and their associated pathology and detailed clinical information entered into a purpose-built web-based system that included disease-specific data templates. All cases were subjected to centralized pathology review and clinical data review by experienced hematopathologists and oncologists. All 10,481cases are being sequenced at the DNA and RNA level, and are being profiled to define the genetic alterations and expression changes that are characteristic of each disease. Analysis will include translocations, copy number alterations, and viral status. These molecular features will be examined in conjunction with genetic events, pathologic factors, and the clinical features. We have already generated results for ALK-negative anaplastic large B cell lymphoma and primary mediastinal B cell lymphomas (N=210). These data demonstrate novel subgroup and molecular discoveries that are enabled by integrative DNA and RNA sequencing analysis and the examination of molecular features across different diseases as well as within individual entities. In addition, other disease entities and the collective data will be presented in the meeting. Conclusion The ABCG project will comprehensively study the genetic and clinicopathological features of all blood cancers using systematic genomic approaches. We anticipate our data, approaches and results will serve as a lasting resource for the molecular classification and therapeutic development for leukemias and lymphomas. Disclosures McKinney: Novartis: Research Funding; Nordic Nanovector: Research Funding; Molecular Templates: Consultancy, Research Funding; Kite/Gilead: Honoraria, Speakers Bureau; Incyte: Research Funding; Genetech: Consultancy, Honoraria, Research Funding; Epizyme: Consultancy; Celgene: Consultancy, Research Funding; BTG: Consultancy; Beigene: Research Funding; ADC Therapeutics: Consultancy, Speakers Bureau; Pharmacyclics: Consultancy; Verastem: Consultancy. Behdad: Lilly: Speakers Bureau; Roche/Foundation Medicine: Speakers Bureau; Thermo Fisher: Speakers Bureau