5,729 research outputs found
Fault Models for Quantum Mechanical Switching Networks
The difference between faults and errors is that, unlike faults, errors can
be corrected using control codes. In classical test and verification one
develops a test set separating a correct circuit from a circuit containing any
considered fault. Classical faults are modelled at the logical level by fault
models that act on classical states. The stuck fault model, thought of as a
lead connected to a power rail or to a ground, is most typically considered. A
classical test set complete for the stuck fault model propagates both binary
basis states, 0 and 1, through all nodes in a network and is known to detect
many physical faults. A classical test set complete for the stuck fault model
allows all circuit nodes to be completely tested and verifies the function of
many gates. It is natural to ask if one may adapt any of the known classical
methods to test quantum circuits. Of course, classical fault models do not
capture all the logical failures found in quantum circuits. The first obstacle
faced when using methods from classical test is developing a set of realistic
quantum-logical fault models. Developing fault models to abstract the test
problem away from the device level motivated our study. Several results are
established. First, we describe typical modes of failure present in the
physical design of quantum circuits. From this we develop fault models for
quantum binary circuits that enable testing at the logical level. The
application of these fault models is shown by adapting the classical test set
generation technique known as constructing a fault table to generate quantum
test sets. A test set developed using this method is shown to detect each of
the considered faults.Comment: (almost) Forgotten rewrite from 200
Optimization of carbon and energy utilization through differential translational efficiency.
Control of translation is vital to all species. Here we employ a multi-omics approach to decipher condition-dependent translational regulation in the model acetogen Clostridium ljungdahlii. Integration of data from cells grown autotrophically or heterotrophically revealed that pathways critical to carbon and energy metabolism are under strong translational regulation. Major pathways involved in carbon and energy metabolism are not only differentially transcribed and translated, but their translational efficiencies are differentially elevated in response to resource availability under different growth conditions. We show that translational efficiency is not static and that it changes dynamically in response to mRNA expression levels. mRNAs harboring optimized 5'-untranslated region and coding region features, have higher translational efficiencies and are significantly enriched in genes encoding carbon and energy metabolism. In contrast, mRNAs enriched in housekeeping functions harbor sub-optimal features and have lower translational efficiencies. We propose that regulation of translational efficiency is crucial for effectively controlling resource allocation in energy-deprived microorganisms
Immunoglobulin variable-region gene mutational lineage tree analysis: application to autoimmune diseases
Lineage trees have frequently been drawn to illustrate diversification, via somatic hypermutation (SHM), of immunoglobulin variable-region (IGV) genes. In order to extract more information from IGV sequences, we developed a novel mathematical method for analyzing the graphical properties of IgV gene lineage trees, allowing quantification of the differences between the dynamics of SHM and antigen-driven selection in different lymphoid tissues, species, and disease situations. Here, we investigated trees generated from published IGV sequence data from B cell clones participating in autoimmune responses in patients with Myasthenia Gravis (MG), Rheumatoid Arthritis (RA), and Sjögren's Syndrome (SS). At present, as no standards exist for cell sampling and sequence extraction methods, data obtained by different research groups from two studies of the same disease often vary considerably. Nevertheless, based on comparisons of data groups within individual studies, we show here that lineage trees from different individual patients are often similar and can be grouped together, as can trees from two different tissues in the same patient, and even from IgG- and IgA-expressing B cell clones. Additionally, lineage trees from most studies reflect the chronic character of autoimmune diseases
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Nicotine Blocks Brain Estrogen Synthase (Aromatase): In Vivo Positron Emission Tomography Studies in Female Baboons
The front-line tuberculosis (TB) chemotherapeutics isoniazid (INH), rifampicin (RIF), and pyrazinamide (PZA) have been labeled with carbon-11 and the biodistribution of each labeled drug has been determined in baboons using positron emission tomography (PET). Each radiosynthesis and formulation has been accomplished in 1 h, using [11C]CH3I to label RIF and [11C]HCN to label INH and PZA. Following iv administration, INH, PZA, RIF, and/or their radiolabeled metabolites clear rapidly from many tissues; however, INH, PZA, and/or their radiolabeled metabolites accumulate in the bladder while RIF and/or its radiolabeled metabolites accumulates in the liver and gall bladder, consistent with the known routes of excretion of the drugs. In addition, the biodistribution data demonstrate that the ability of the three drugs and their radiolabeled metabolites to cross the blood−brain barrier decreases in the order PZA > INH > RIF, although in all cases the estimated drug concentrations are greater than the minimum inhibitory concentration (MIC) values for inhibiting bacterial growth of Mycobacterium tuberculosis (MTB). The pharmacokinetic (PK) and drug distribution data have important implications for treatment of disseminated TB in the brain and pave the way for imaging the distribution of the pathogen in vivo.Chemistry and Chemical Biolog
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Transportation Module of Global Change Assessment Model (GCAM): Model Documentation- Version 1.0
This publication provides methodological detail on the new GCAM Transportation Module and contains the following: (1) Descriptions of the new transportation module in GCAM (2) Details about the data sources and methodology adopted to estimate the exogeneous input parameters (3) A summary of the region-specific transportation data for base year (2005) (4) Comparisons of these estimates across regions and modes. (5) Highlights of the uncertainty and shortcomings in our estimates The project broadly encompasses the following four refinements to the transportation sector of GCAM: 1) Increased resolution to include the full spectrum of sub-modes and technologies available in passenger and frieght transport; 2) Refined estimates of input parameters so as to better represent real-world heterogeneity in a way consistent with the latest literature on transportation; 3) Refined estimates of base year (2005) estimates of transportation demand, and disaggregation of IEA energy estimates between modes and size classes; 4) Included the non-motorized modes of walking and biking. The above refinements will not only allow us to develop better estimates of transportation energy demand and emissions, but will also enable modeling of the impact of policies that induce behavioral change and switching to different size classes within a single fuel type. Existing literature on long-term forecasts of transportation energy demand and emissions have focused on the role of advanced low-emission vehicle technologies and low-carbon energy carriers in achieving climate change goals. In GCAM, modeling the impact of policies in the form of varying levels of carbon prices has, to date, been restricted to consumer choices for different modes (e.g. rail versus personal car) and different vehicle technologies (e.g. internal combustion engine vehicles versus electric vehicle). A more detailed representation of the transportation sector – including various size classes of vehicles -- will allow us to estimate the potential for downsizing in the case of private modes (large LDV to midsize or compact LDVs), transfer to public modes (rail and bus) or to non-motorized transport (walking and biking), and adoption of energy efficient “new” modes like the electric-bikes, which have seen rapid adoption in China and other developing countries. This project aims to better represent the heterogeneity and flexibility in the transport system to allow the modeling of a broader range of transport policy intruments including subsidies to public transit, government incentives for alternative technology, transportation fuel taxes, and public investments to increase the speed, service frequency/availability, and comfort of public and nonmotorized modes
Scaling Behavior of Cyclical Surface Growth
The scaling behavior of cyclical surface growth (e.g. deposition/desorption),
with the number of cycles n, is investigated. The roughness of surfaces grown
by two linear primary processes follows a scaling behavior with asymptotic
exponents inherited from the dominant process while the effective amplitudes
are determined by both. Relevant non-linear effects in the primary processes
may remain so or be rendered irrelevant. Numerical simulations for several
pairs of generic primary processes confirm these conclusions. Experimental
results for the surface roughness during cyclical electrodeposition/dissolution
of silver show a power-law dependence on n, consistent with the scaling
description.Comment: 2 figures adde
Intermolecular Diels-Alder Cycloaddition for the Construction of Bicyclo[2.2.2]diazaoctane Structures: Formal Synthesis of Brevianamide B and Premalbrancheamide
A stereoselective intermolecular Diels-Alder cycloaddition of an intermediate pyrazinone with both achiral and chiral acrylate-derived dienophiles provides rapid access to the bicyclo[2.2.2]diazaoctane core shared among several prenylated indole alkaloids. The product derived from cydoaddition with 2-nitroacrylate required an additional five to six synthetic operations to intercept established precursors to premalbrancheamide and brevianamide B. The chemistry detailed in this manuscript constitutes a formal total synthesis (12 steps each) of these [2.2.2]diazabicyclic natural products from proline methyl ester
A Reversible Gene-Targeting Strategy Identifies Synthetic Lethal Interactions between MK2 and p53 in the DNA Damage Response In Vivo
A fundamental limitation in devising new therapeutic strategies for killing cancer cells with DNA damaging agents is the need to identify synthetic lethal interactions between tumor-specific mutations and components of the DNA damage response (DDR) in vivo. The stress-activated p38 mitogen-activated protein kinase (MAPK)/MAPKAP kinase-2 (MK2) pathway is a critical component of the DDR network in p53-deficient tumor cells in vitro. To explore the relevance of this pathway for cancer therapy in vivo, we developed a specific gene targeting strategy in which Cre-mediated recombination simultaneously creates isogenic MK2-proficient and MK2-deficient tumors within a single animal. This allows direct identification of MK2 synthetic lethality with mutations that promote tumor development or control response to genotoxic treatment. In an autochthonous model of non-small-cell lung cancer (NSCLC), we demonstrate that MK2 is responsible for resistance of p53-deficient tumors to cisplatin, indicating synthetic lethality between p53 and MK2 can successfully be exploited for enhanced sensitization of tumors to DNA-damaging chemotherapeutics in vivo.National Institutes of Health (U.S.) (Grant ES015339)National Institutes of Health (U.S.) (Grant GM60594)National Institutes of Health (U.S.) (Grant GM59281)National Institutes of Health (U.S.) (Grant CA112967)Janssen Pharmaceutical Ltd.Massachusetts Institute of Technology. Center for Environmental Health Sciences (Core Grant P30-CA14051)Massachusetts Institute of Technology. Center for Environmental Health Sciences (Core Grant ES-002109
Meson Mass Splittings in the Nonrelativistic Model
Mass splittings between isodoublet meson pairs and between and
mesons of the same valence quark content are computed in a detailed
nonrelativistic model. The field theoretic expressions for such splittings are
shown to reduce to kinematic and Breit-Fermi terms in the nonrelativistic
limit. Algebraic results thus obtained are applied to the specific case of the
linear-plus-Coulomb potential, with resultant numbers compared to experiment.Comment: 29 pages with 2 tables and 4 figures, LBL-32872 and UCB-PTH-92/3
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