Juan de Fuca subduction zone from a mixture of tomography and waveform modeling

Seismic tomography images of the upper mantle structures beneath the Pacific Northwestern United States display a maze of high-velocity anomalies, many of which produce distorted waveforms evident in the USArray observations indicative of the Juan de Fuca (JdF) slab. The inferred location of the slab agrees quite well with existing contour lines defining the slab's upper interface. Synthetic waveforms generated from a recent tomography image fit teleseismic travel times quite well and also some of the waveform distortions. Regional earthquake data, however, require substantial changes to the tomographic velocities. By modeling regional waveforms of the 2008 Nevada earthquake, we find that the uppermost mantle of the 1D reference model AK135, the reference velocity model used for most tomographic studies, is too fast for the western United States. Here, we replace AK135 with mT7, a modification of an older Basin-and-Range model T7. We present two hybrid velocity structures satisfying the waveform data based on modified tomographic images and conventional slab wisdom. We derive P and SH velocity structures down to 660 km along two cross sections through the JdF slab. Our results indicate that the JdF slab is subducted to a depth of 250 km beneath the Seattle region, and terminates at a shallower depth beneath Portland region of Oregon to the south. The slab is about 60 km thick and has a P velocity increase of 5% with respect to mT7. In order to fit waveform complexities of teleseismic Gulf of Mexico and South American events, a slab-like high-velocity anomaly with velocity increases of 3% for P and 7% for SH is inferred just above the 660 discontinuity beneath Nevada

Upper mantle P velocity structure beneath the Midwestern United States derived from triplicated waveforms

Upper mantle seismic velocity structures in both vertical and horizontal directions are key to understanding the structure and mechanics of tectonic plates. Recent deployment of the USArray Transportable Array (TA) in the Midwestern United States provides an extraordinary regional earthquake data set to investigate such velocity structure beneath the stable North American craton. In this paper, we choose an M_w5.1 Canadian earthquake in the Quebec area, which is recorded by about 400 TA stations, to examine the P wave structures between the depths of 150 km to 800 km. Three smaller Midwestern earthquakes at closer distance to the TA are used to investigate vertical and horizontal variations in P velocity between depths of 40 km to 150 km. We use a grid-search approach to find the best 1-D model, starting with the previously developed S25 regional model. The results support the existence of an 8° discontinuity in P arrivals caused by a negative velocity gradient in the lithosphere between depths of 40 km to 120 km followed by a small (∼1%) jump and then a positive gradient down to 165 km. The P velocity then decreases by 2% from 165 km to 200 km, and we define this zone as the regional lithosphere-asthenosphere boundary (LAB). Beneath northern profiles, waves reflected from the 410 discontinuity (410) are delayed by up to 1 s relative to those turning just below the 410, which we explain by an anomaly just above the discontinuity with P velocity reduced by ∼3%. The 660 discontinuity (660) appears to be composed of two smaller velocity steps with a separation of 16 km. The inferred low-velocity anomaly above 410 may indicate high water concentrations in the transition zone, and the complexity of the 660 may be related to Farallon slab segments that have yet to sink into the deep mantle

Testing of a novel web browser interface for the Chinese market

This paper compares the perspicacity, appropriateness and preference of web browser icons from leading software providers with those of a culture-specific design. This online study was conducted in Taiwan and involved 103 participants, who were given three sets of web browser icons to review, namely Microsoft Internet Explorer, Macintosh Safari, and culturally specific icons created using the Culture-Centred Design methodology. The findings of the study show that all three sets have generally high recognition rates, but that some icon functions (e.g. Go/Visit and Favourite) in all three sets have poor recognition rates and are considered inappropriate

High-throughput, Efficient, and Unbiased Capture of Small RNAs from Low-input Samples for Sequencing.

MicroRNAs hold great promise as biomarkers of disease. However, there are few efficient and robust methods for measuring microRNAs from low input samples. Here, we develop a high-throughput sequencing protocol that efficiently captures small RNAs while minimizing inherent biases associated with library production. The protocol is based on early barcoding such that all downstream manipulations can be performed on a pool of many samples thereby reducing reagent usage and workload. We show that the optimization of adapter concentrations along with the addition of nucleotide modifications and random nucleotides increases the efficiency of small RNA capture. We further show, using unique molecular identifiers, that stochastic capture of low input RNA rather than PCR amplification influences the biased quantitation of intermediately and lowly expressed microRNAs. Our improved method allows the processing of tens to hundreds of samples simultaneously while retaining high efficiency quantitation of microRNAs in low input samples from tissues or bodily fluids

Applying an enterprise architecting framework to design enterprise sales and operations planning

Thesis (M.B.A.)--Massachusetts Institute of Technology, Sloan School of Management; and, (S.M.)--Massachusetts Institute of Technology, Engineering Systems Division; in conjunction with the Leaders for Manufacturing Program at MIT, 2008.Includes bibliographical references (p. 63).Raytheon Company, a leader in aerospace and defense, has experienced tremendous growth through mergers and acquisitions. In particular, the company's Space and Airborne Systems (SAS) business unit was largely formed through acquisitions of E-Systems and Texas Instruments and a merger with Hughes Aircraft Company. To assimilate the legacy organizations, Raytheon and SAS have undertaken great efforts to work as "One Company." One such example has been to strive for an enterprise sales and operations planning process. Five years ago, Raytheon Space and Airborne Systems (SAS) Operations leaders recognized the need to be more proactive in comprehending forecasted business and subsequent impacts to SAS' manufacturing network. As a result, Program Requirements and Operations Planning (PROP) was born to enable improved supply chain planning for factory labor and capital resources. Over time, the complexity of SAS' business has proven to be a challenge for PROP to achieve its intended objectives.- This thesis considers PROP as an enterprise rather than a process and proposes re-designing it using a holistic enterprise architecting framework including a thorough examination of the current state of PROP with respect to seven architectural views (strategy, policy/external factors, process, organization, knowledge, IT, and products/services). A future state PROP design is derived from the analysis and then validated against a detailed case study of the Army's Firefinder radar product line manufactured at Raytheon's Forest, Mississippi facility.by Brandon B. Chu.S.M.M.B.A

Pre-melt-season sediment plume variability at Jökulsárlón, Iceland, a preliminary evaluation using in-situ spectroradiometry and satellite imagery

High-latitude atmospheric warming is impacting freshwater cycling, requiring techniques for monitoring the hydrology of sparsely-gauged regions. The submarine runoff of tidewater glaciers presents a particular challenge. We evaluate the utility of Moderate Resolution Imaging Spectroradiometer (MODIS) imagery for monitoring turbid meltwater plume variability in the glacier lagoon Jökulsárlón, Iceland, for a short interval before the onset of the main melt season. Total Suspended Solids concentrations (TSS) of surface waters are related to remotely-sensed reflectance via empirical calibration between in-situ-sampled TSS and reflectance in a MODIS band 1-equivalent wavelength window. This study differs from previous ones in its application to an overturning tidewater glacier plume, rather than one derived from river runoff. The linear calibration improves on previous studies by facilitating a wider range of plume metrics than areal extent, notably pixel-by-pixel TSS values. Increasing values of minimum plume TSS over the study interval credibly represent rising overall turbidity in the lagoon as melting accumulates. Plume extent responds principally to consistently-strong offshore winds. Further work is required to determine the temporal persistence of the calibration, but remote plume observation holds promise for monitoring hydrological outputs from ungauged or ungaugeable systems

Suppression of Exosomal PD-L1 Induces Systemic Anti-tumor Immunity and Memory.

PD-L1 on the surface of tumor cells binds its receptor PD-1 on effector T cells, thereby suppressing their activity. Antibody blockade of PD-L1 can activate an anti-tumor immune response leading to durable remissions in a subset of cancer patients. Here, we describe an alternative mechanism of PD-L1 activity involving its secretion in tumor-derived exosomes. Removal of exosomal PD-L1 inhibits tumor growth, even in models resistant to anti-PD-L1 antibodies. Exosomal PD-L1 from the tumor suppresses T cell activation in the draining lymph node. Systemically introduced exosomal PD-L1 rescues growth of tumors unable to secrete their own. Exposure to exosomal PD-L1-deficient tumor cells suppresses growth of wild-type tumor cells injected at a distant site, simultaneously or months later. Anti-PD-L1 antibodies work additively, not redundantly, with exosomal PD-L1 blockade to suppress tumor growth. Together, these findings show that exosomal PD-L1 represents an unexplored therapeutic target, which could overcome resistance to current antibody approaches

UniPlonk: Plonk with Universal Verifier

We propose UniPlonK, a modification of the PlonK protocol that uniformizes the Verifier’s work for families of circuits. Specifically, a single fixed-cost “Universal Verifier” can check proofs for circuits of different: sizes, public input lengths, selector polynomials, copy constraints, and even different custom gate sets. UniPlonK therefore extends the universality of PlonK beyond the SRS; it enables a single “Universal Verifier Circuit” capable of verifying proofs from different PlonK circuits. The Universal Verifier’s marginal cost over the ordinary Plonk verifier is small: for circuits using only the vanilla Plonk gate, the Universal Verifier performs a number of additional field multiplications proportional to the logarithm of the maximum supported circuit size; it incurs no additional elliptic curve operations. For circuits using custom gates, the Universal Verifier incurs additional elliptic curve arithmetic only when verifying proofs from circuits that do not use all supported gate types. For circuits that use all supported gates, the Universal Verifier’s additional cost consists only of field multiplications proportional to the logarithm of the maximum supported circuit size, the number of custom gate types, and the number of witness variables used by these gates. In both settings (vanilla-only and custom gates) the marginal cost to the prover is a fixed-base MSM of size ℓ, the length of the public input vector

Menthol stereoisomers exhibit different effects on α4β2 nAChR upregulation and dopamine neuron spontaneous firing

Menthol contributes to poor cessation rates among smokers, in part because menthol enhances nicotine reward and reinforcement. Mentholated tobacco products contain (−)-menthol and (+)-menthol, in varying proportions. We examined these two menthol stereoisomers for their ability to upregulate α4β2 nAChRs and to alter dopamine neuron firing frequency using long-term, low-dose (≤ 500 nM) exposure that is pharmacologically relevant to smoking. We found that (−)-menthol upregulates α4β2 nAChRs while (+)-menthol does not. We also found that (−)-menthol decreases dopamine neuron baseline firing and dopamine neuron excitability, while (+)-menthol exhibits no effect. We then examined both stereoisomers for their ability to inhibit α4β2 nAChR function at higher concentrations (>10 µM) using the Xenopus oocyte expression system. To probe for the potential binding site of menthol, we conducted flooding simulations and site-directed mutagenesis. We found that menthol likely binds to the 9’ position on the TM2 helix. We found that menthol inhibition is dependent on the end-to-end distance of the side chain at the 9’ residue. Additionally, we have found that (−)-menthol is only modestly (∼25%) more potent than (+)-menthol at inhibiting wildtype α4β2 nAChRs and a series of L9’ mutant nAChRs. These data reveal that menthol exhibits a stereoselective effect on nAChRs and that the stereochemical effect is much greater for long-term, sub µM exposure in mice than for acute, higher level exposure. We hypothesize that of the two menthol stereoisomers, only (−)-menthol plays a role in enhancing nicotine reward through nAChRs on dopamine neurons