The 1987 Whittier Narrows, California, earthquake: A Metropolitan shock

Just 3 hours after the Whittier Narrows earthquake struck, it became clear that a heretofore unseen geological structure was seismically active beneath metropolitan Los Angeles. Contrary to initial expectations of strike-slip or oblique-slip motion on the Whittier fault, whose north end abuts the aftershock zone, the focal mechanism of the mainshock showed pure thrust faulting on a deep gently inclined surface [Hauksson et al., 1988]. This collection of nine research reports spans the spectrum of seismological, geodetic, and geological investigations carried out as a result of the Whittier Narrows earthquake. Although unseen, the structure was not unforeseen. Namson [1987] had published a retrodeformable geologic cross section (meaning that the sedimentary strata could be restored to their original depositional position) 100 km to the west of the future earthquake epicenter in which blind, or subsurface, thrust faults were interpreted to be active beneath the folded southern Transverse Ranges. Working 25 km to the west, Hauksson [1987] had also found a surprising number of microearthquakes with thrust focal mechanisms south of the Santa Monica mountains, another clue to a subsurface system of thrust faults. Finally, Davis [1987] had presented a preliminary cross section only 18 km to the west of Whittier Narrows that identified as "fault B" the thrust that would rupture later that year. Not only was the earthquake focus and its orientation compatible with the 10–15 km depth and north dipping orientation of Davis' proposed thrust, but fault B appears to continue beneath the northern flank of the Los Angeles basin, skirting within 5 km of downtown Los Angeles, an area of dense commercial high-rise building development. These results are refined and extended by Davis et al. [this issue]

12 May 2008 M = 7.9 Wenchuan, China, earthquake calculated to increase failure stress and seismicity rate on three major fault systems

Author Posting. © American Geophysical Union, 2008. This article is posted here by permission of American Geophysical Union for personal use, not for redistribution. The definitive version was published in Geophysical Research Letters 35 (2008): L17305, doi:10.1029/2008GL034903.The Wenchuan earthquake on the Longmen Shan fault zone devastated cities of Sichuan, claiming at least 69,000 lives. We calculate that the earthquake also brought the Xianshuihe, Kunlun and Min Jiang faults 150–400 km from the mainshock rupture in the eastern Tibetan Plateau 0.2–0.5 bars closer to Coulomb failure. Because some portions of these stressed faults have not ruptured in more than a century, the earthquake could trigger or hasten additional M > 7 earthquakes, potentially subjecting regions from Kangding to Daofu and Maqin to Rangtag to strong shaking. We use the calculated stress changes and the observed background seismicity to forecast the rate and distribution of damaging shocks. The earthquake probability in the region is estimated to be 57–71% for M ≥ 6 shocks during the next decade, and 8–12% for M ≥ 7 shocks. These are up to twice the probabilities for the decade before the Wenchuan earthquake struck.S. T. and R. S. are grateful for research fellowships at EOST- Institut de Physique du Globe de Strasbourg, France. J. L. was supported by the Charles D. Hollister Endowed Fund for Support of Innovative Research at WHOI

The Escape Problem for Irreversible Systems

The problem of noise-induced escape from a metastable state arises in physics, chemistry, biology, systems engineering, and other areas. The problem is well understood when the underlying dynamics of the system obey detailed balance. When this assumption fails many of the results of classical transition-rate theory no longer apply, and no general method exists for computing the weak-noise asymptotics of fundamental quantities such as the mean escape time. In this paper we present a general technique for analysing the weak-noise limit of a wide range of stochastically perturbed continuous-time nonlinear dynamical systems. We simplify the original problem, which involves solving a partial differential equation, into one in which only ordinary differential equations need be solved. This allows us to resolve some old issues for the case when detailed balance holds. When it does not hold, we show how the formula for the mean escape time asymptotics depends on the dynamics of the system along the most probable escape path. We also present new results on short-time behavior and discuss the possibility of focusing along the escape path.Comment: 24 pages, APS revtex macros (version 2.1) now available from PBB via `get oldrevtex.sty

Stress triggering in thrust and subduction earthquakes and stress interaction between the southern San Andreas and nearby thrust and strike-slip faults

Author Posting. © American Geophysical Union, 2004. This article is posted here by permission of American Geophysical Union for personal use, not for redistribution. The definitive version was published in Journal of Geophysical Research 109 (2004): B02303, doi:10.1029/2003JB002607.We argue that key features of thrust earthquake triggering, inhibition, and clustering can be explained by Coulomb stress changes, which we illustrate by a suite of representative models and by detailed examples. Whereas slip on surface-cutting thrust faults drops the stress in most of the adjacent crust, slip on blind thrust faults increases the stress on some nearby zones, particularly above the source fault. Blind thrusts can thus trigger slip on secondary faults at shallow depth and typically produce broadly distributed aftershocks. Short thrust ruptures are particularly efficient at triggering earthquakes of similar size on adjacent thrust faults. We calculate that during a progressive thrust sequence in central California the 1983 Mw = 6.7 Coalinga earthquake brought the subsequent 1983 Mw = 6.0 Nuñez and 1985 Mw = 6.0 Kettleman Hills ruptures 10 bars and 1 bar closer to Coulomb failure. The idealized stress change calculations also reconcile the distribution of seismicity accompanying large subduction events, in agreement with findings of prior investigations. Subduction zone ruptures are calculated to promote normal faulting events in the outer rise and to promote thrust-faulting events on the periphery of the seismic rupture and its downdip extension. These features are evident in aftershocks of the 1957 Mw = 9.1 Aleutian and other large subduction earthquakes. We further examine stress changes on the rupture surface imparted by the 1960 Mw = 9.5 and 1995 Mw = 8.1 Chile earthquakes, for which detailed slip models are available. Calculated Coulomb stress increases of 2–20 bars correspond closely to sites of aftershocks and postseismic slip, whereas aftershocks are absent where the stress drops by more than 10 bars. We also argue that slip on major strike-slip systems modulates the stress acting on nearby thrust and strike-slip faults. We calculate that the 1857 Mw = 7.9 Fort Tejon earthquake on the San Andreas fault and subsequent interseismic slip brought the Coalinga fault ~1 bar closer to failure but inhibited failure elsewhere on the Coast Ranges thrust faults. The 1857 earthquake also promoted failure on the White Wolf reverse fault by 8 bars, which ruptured in the 1952 Mw = 7.3 Kern County shock but inhibited slip on the left-lateral Garlock fault, which has not ruptured since 1857. We thus contend that stress transfer exerts a control on the seismicity of thrust faults across a broad spectrum of spatial and temporal scales.J. L. was supported by the National Science Foundation through grant NSFEAR0003888; R. S. gratefully acknowledges funding from Swiss Re

SmedGD: the Schmidtea mediterranea genome database

The planarian Schmidtea mediterranea is rapidly emerging as a model organism for the study of regeneration, tissue homeostasis and stem cell biology. The recent sequencing, assembly and annotation of its genome are expected to further buoy the biomedical importance of this organism. In order to make the extensive data associated with the genome sequence accessible to the biomedical and planarian communities, we have created the Schmidtea mediterranea Genome Database (SmedGD). SmedGD integrates in a single web-accessible portal all available data associated with the planarian genome, including predicted and annotated genes, ESTs, protein homologies, gene expression patterns and RNAi phenotypes. Moreover, SmedGD was designed using tools provided by the Generic Model Organism Database (GMOD) project, thus making its data structure compatible with other model organism databases. Because of the unique phylogenetic position of planarians, SmedGD (http://smedgd.neuro.utah.edu) will prove useful not only to the planarian research community, but also to those engaged in developmental and evolutionary biology, comparative genomics, stem cell research and regeneration

Clinical actionability of comprehensive genomic profiling for management of rare or refractory cancers

Background. The frequency with which targeted tumor sequencing results will lead to implemented change in care is unclear. Prospective assessment of the feasibility and limitations of using genomic sequencing is critically important. Methods. A prospective clinical study was conducted on 100 patients with diverse-histology, rare, or poor-prognosis cancers to evaluate the clinical actionability of a Clinical Laboratory Improvement Amendments (CLIA)-certified, comprehensive genomic profiling assay (FoundationOne), using formalin-fixed, paraffin-embedded tumors. The primary objectives were to assess utility, feasibility, and limitations of genomic sequencing for genomically guided therapy or other clinical purpose in the setting of a multidisciplinary molecular tumor board. Results. Of the tumors from the 92 patients with sufficient tissue, 88 (96%) had at least one genomic alteration (average 3.6, range 0–10). Commonly altered pathways included p53 (46%), RAS/RAF/MAPK (rat sarcoma; rapidly accelerated fibrosarcoma; mitogen-activated protein kinase) (45%), receptor tyrosine kinases/ligand (44%), PI3K/AKT/mTOR (phosphatidylinositol-4,5-bisphosphate 3-kinase; protein kinase B; mammalian target of rapamycin) (35%), transcription factors/regulators (31%), and cell cycle regulators (30%). Many low frequency but potentially actionable alterations were identified in diverse histologies. Use of comprehensive profiling led to implementable clinical action in 35% of tumors with genomic alterations, including genomically guided therapy, diagnostic modification, and trigger for germline genetic testing. Conclusion. Use of targeted next-generation sequencing in the setting of an institutional molecular tumor board led to implementable clinical action in more than one third of patients with rare and poor-prognosis cancers. Major barriers to implementation of genomically guided therapy were clinical status of the patient and drug access. Early and serial sequencing in the clinical course and expanded access to genomically guided early-phase clinical trials and targeted agents may increase actionability. Implications for Practice: Identification of key factors that facilitate use of genomic tumor testing results and implementation of genomically guided therapy may lead to enhanced benefit for patients with rare or difficult to treat cancers. Clinical use of a targeted next-generation sequencing assay in the setting of an institutional molecular tumor board led to implementable clinical action in over one third of patients with rare and poor prognosis cancers. The major barriers to implementation of genomically guided therapy were clinical status of the patient and drug access both on trial and off label. Approaches to increase actionability include early and serial sequencing in the clinical course and expanded access to genomically guided early phase clinical trials and targeted agents

Machine studies for the development of storage cells at the ANKE facility of COSY

We present a measurement of the transverse intensity distributions of the COSY proton beam at the target interaction point at ANKE at the injection energy of 45 MeV, and after acceleration at 2.65 GeV. At 2.65 GeV, the machine acceptance was determined as well. From the intensity distributions the beam size is determined, and together with the measured machine acceptance, the dimensions of a storage cell for the double-polarized experiments with the polarized internal gas target at the ANKE spectrometer are specified. An optimum storage cell for the ANKE experiments should have dimensions of 15mm x 20mm x 390mm (vertical x horizontal x longitudinal), whereby a luminosity of about 2.5*10^29 cm^-2*s^-1 with beams of 10^10 particles stored in COSY could be reached.Comment: 18 pages, 13 figures, 4 table

Multi-Attribute Tradespace Exploration for Survivability

Multi-Attribute Tradespace Exploration for Survivability is a system design and analysis methodology that incorporates survivability considerations into the tradespace exploration process (i.e., a solution-generating and decision-making framework that applies decision theory to model-based design). During the concept generation phase of tradespace exploration, the methodology applies seventeen empirically validated survivability design principles spanning susceptibility reduction, vulnerability reduction, and resilience enhancement. During subsequent concept evaluation, the methodology adds value-based survivability metrics to traditional architectural evaluation criteria of mission utility and lifecycle cost. Applied to a satellite radar mission, the methodology allowed operational survivability to be statistically evaluated across representative distributions of naturally occurring disturbances in the space environment and for survivability to be incorporated as a decision factor earlier in the design process. Constellations in the illustrative example are shown to be the most survivable, mitigating disturbances architecturally, rather than through additive features.Massachusetts Institute of Technology (Systems Engineering Advancement Research Initiative (SEAri))Massachusetts Institute of Technology. Program on Emerging Technologie

Structure–activity relationship study of beta-carboline derivatives as haspin kinase inhibitors

Haspin is a serine/threonine kinase that phosphorylates Thr-3 of histone H3 in mitosis that has emerged as a possible cancer therapeutic target. High throughput screening of approximately 140,000 compounds identified the beta-carbolines harmine and harmol as moderately potent haspin kinase inhibitors. Based on information obtained from a structure–activity relationship study previously conducted for an acridine series of haspin inhibitors in conjunction with in silico docking using a recently disclosed crystal structure of the kinase, harmine analogs were designed that resulted in significantly increased haspin kinase inhibitory potency. The harmine derivatives also demonstrated less activity towards DYRK2 compared to the acridine series. In vitro mouse liver microsome stability and kinase profiling of a representative member of the harmine series (42, LDN-211898) are also presented