Making the H-Cluster from Scratch

Spectroscopic data begin to elucidate the initial steps in the biosynthesis of the hydrogenase active site. [Also see Report by Kuchenreuther et al. ] </jats:p

An Agent-Based Network Simulation Model for Comprehensive Stress Testing and Understanding Systemic Risk

This paper develops an agent-based network simulation model that measures systemic risk in the U.S. banking system. It is shown that ultimate losses to a bank after an initial shock to the system is greater than the direct loss they would expect to face. Using actual balance sheet data and simulating over randomly-generated interbank networks, the model captures the feedback effects that arise from a shock to the highly connected and interdependent system. In addition to capturing these extra\u27\u27 losses that arise from bank interactions over several periods, this framework measures the different channels through which the initial risk propagates, amplifies, and transforms. The model is then employed in Monte Carlo simulations for stress tests, which are analyzed from both the perspective of a bank risk manager and a regulator. It is also implemented in a Value-at-Risk framework to demonstrate its potential to inform existing VaR models employed by banks. An important feature of the banking system that is often omitted in related models is collateral underlying the majority of interbank transactions. It is included in this model, and simulations reveal that as much as 30% of total losses due to an asset shock are due to strains in the collateralized interbank debt/repo market. The regulator stress tests highlight the extra risk faced by banks heavily involved in the securities and interbank markets. A wide variety of different scenarios can be tested in this framework, and by collecting detailed information throughout the simulation, the composition of systemic risk and its evolution through the system can be analyzed in different ways

Doctor of Philosophy

dissertationTranscription initiation is a key regulatory point of nearly every cell signaling pathway; therefore, understanding the regulation and function or transcription factors is essential for understanding physiological and pathological processes. The Myc and Mondo transcription factors heterodimerize with Max and Mlx, respectively, bind DNA, and activate transcription of many of the same promoters. Antagonizing Myc and Mondo are the Mad proteins which dimerize with either Max or Mlx to repress transcription. The regulation of Mondo subcellular localization is unique among family members as this protein localizes to the outer michondrial membrane. Mondo proteins have clear nuclear functions in regulating the transcription of key glycolytic enzymes, yet the signal(s) that cause Mondo translocation to the nucleus are not yet known. To characterize the genetic interactions of Myc superfamily members and examine the regulation of Mondo subcellular localization, we examined their orthologs in the model genetic and developmental organism, Caenorhabditis elegans. The nematode orthologs of Myc and Mondo, MML-1, and Mlx, MXL-2, heterodimerize and activate transcription similar to their mammalian counterparts. Despite a high degree of sequence conservation in subcellular localization domains, MML-1 is a nuclear protein. MML-1 and MXL-2 play roles in cell migration and behavior. These proteins act in the nonmigrating hypodermis to regulate the transcription of extracellular matrix components which control migration of ray 1 precursor cells. MML-1/MXL-2, in conjunction with Wnt/BAR-1 and semaphorin signaling, regulate the migration of ray 1 precursor cells. Further, we find that MML-1/MXL-2 regulates male attraction to hermaphrodites and antagonizes MDL-1/MXL-1 in regulating hermaphrodite avoidance. These functions of MML-1 and MXL-2 broaden the roles of Myc and Mondo proteins suggesting additional, but currently unappreciated, roles in development and disease for this highly conserved network of transcription factors

Ultrasonic Verification of the Material Processing for Uranium-Titanium Alloys

In today’s world of rapid growth in the material sciences, knowledge of a material’s mechanical properties has become increasingly important. It has also become very important that this “knowledge” be obtained by some type of nondestructive method. The mechanical properties that are of particular interest to most material scientists are the ones governing elastic behavior. These properties are primarily determined by three basic characteristics: the type of material, the method of processing, and the processing sequence for multiprocessed materials

Strategies for maximizing supply chain resilience : learning from the past to prepare for the future

Thesis (M. Eng. in Logistics)--Massachusetts Institute of Technology, Engineering Systems Division, 2003.Also issued in leaves.Includes bibliographical references (p. 113-120).The terrorist attacks undertaken by Osama bin Laden's al Qaeda organization on the morning of September 11, 2001 ushered in a new era of indiscriminate global terrorism characterized by an unprecedented focus on security, risk management, and business continuity. The probability of future attacks, coupled with government response to the threat, has introduced myriad new challenges that virtually every manufacturer, distributor, and retailer engaged in global commerce must now face. This thesis will explore and analyze the impact that the "new" terrorist threat has, and will continue to have, on the supply chains of those manufacturers, distributors, and retailers by studying relevant historical disruptions; in essence, looking to the past to glean important insights as to how enterprises can best prepare for the future. Throughout history, numerous disruptive events have occurred that bear comparison to a potential terrorist attack. These events include earthquakes, hurricanes, floods, industrial accidents, and labor strikes, as well as other terrorist attacks. By studying such events in detail and understanding the impact that they had on the supply chains of companies that were affected, important lessons can be learned regarding how best to prepare for, and react to, future disruptions. This thesis project ultimately seeks to collect, analyze, and synthesize historical data with the goal of presenting insights and conclusions that can be applied by businesses in the current operating environment to best prepare their supply chains for future disruptions, whether natural or man-made. All research results are organized and presented in terms of the nature of the specific supply chain disruption (key supplier down, transportation capability disrupted, etc.)(cont.), as opposed to the nature, location, or other defining characteristics of the disaster itself. Conclusions consist of a discussion of the unifying themes and the relevant lessons learned. The thesis then goes on to recommend ten prescriptive measures that organizations can take in today's business environment to strengthen their supply chains, minimize their exposure to future disruptions, and maximize their operational resilience.by Christopher B. Pickett.M.Eng.in Logistic

The Anticonvulsant Ethosuximide Disrupts Sensory Function to Extend C. elegans Lifespan

Ethosuximide is a medication used to treat seizure disorders in humans, and we previously demonstrated that ethosuximide can delay age-related changes and extend the lifespan of the nematode Caenorhabditis elegans. The mechanism of action of ethosuximide in lifespan extension is unknown, and elucidating how ethosuximide functions is important for defining endogenous processes that influence lifespan and for exploring the potential of ethosuximide as a therapeutic for age-related diseases. To identify genes that mediate the activity of ethosuximide, we conducted a genetic screen and identified mutations in two genes, che-3 and osm-3, that cause resistance to ethosuximide-mediated toxicity. Mutations in che-3 and osm-3 cause defects in overlapping sets of chemosensory neurons, resulting in defective chemosensation and an extended lifespan. These findings suggest that ethosuximide extends lifespan by inhibiting the function of specific chemosensory neurons. This model is supported by the observation that ethosuximide-treated animals displayed numerous phenotypic similarities with mutants that have chemosensory defects, indicating that ethosuximide inhibits chemosensory function. Furthermore, ethosuximide extends lifespan by inhibiting chemosensation, since the long-lived osm-3 mutants were resistant to the lifespan extension caused by ethosuximide. These studies demonstrate a novel mechanism of action for a lifespan-extending drug and indicate that sensory perception has a critical role in controlling lifespan. Sensory perception also influences the lifespan of Drosophila, suggesting that sensory perception has an evolutionarily conserved role in lifespan control. These studies highlight the potential of ethosuximide and related drugs that modulate sensory perception to extend lifespan in diverse animals

EPR detection and characterisation of a paramagnetic Mo(III) dihydride intermediate involved in electrocatalytic hydrogen evolution

EPR spectroscopy and theoretical data show that the slow heterogeneous electron-transfer kinetics associated with the reduction of an 18-electron Mo(IV) acetato dihydride are a consequence of an η2−η1 rearrangement of the carboxylate ligand which gives a unique paramagnetic 17-electron Mo(III) dihydride

Cluster Multi-spacecraft Determination of AKR Angular Beaming

Simultaneous observations of AKR emission using the four-spacecraft Cluster array were used to make the first direct measurements of the angular beaming patterns of individual bursts. By comparing the spacecraft locations and AKR burst locations, the angular beaming pattern was found to be narrowly confined to a plane containing the magnetic field vector at the source and tangent to a circle of constant latitude. Most rays paths are confined within 15 deg of this tangent plane, consistent with numerical simulations of AKR k-vector orientation at maximum growth rate. The emission is also strongly directed upward in the tangent plane, which we interpret as refraction of the rays as they leave the auroral cavity. The narrow beaming pattern implies that an observer located above the polar cap can detect AKR emission only from a small fraction of the auroral oval at a given location. This has important consequences for interpreting AKR visibility at a given location. It also helps re-interpret previously published Cluster VLBI studies of AKR source locations, which are now seen to be only a subset of all possible source locations. These observations are inconsistent with either filled or hollow cone beaming models.Comment: 5 pages, 4 figures. Geophys. Res. Letters (accepted

Influenza research database: an integrated bioinformatics resource for influenza research and surveillance.

BackgroundThe recent emergence of the 2009 pandemic influenza A/H1N1 virus has highlighted the value of free and open access to influenza virus genome sequence data integrated with information about other important virus characteristics.DesignThe Influenza Research Database (IRD, http://www.fludb.org) is a free, open, publicly-accessible resource funded by the U.S. National Institute of Allergy and Infectious Diseases through the Bioinformatics Resource Centers program. IRD provides a comprehensive, integrated database and analysis resource for influenza sequence, surveillance, and research data, including user-friendly interfaces for data retrieval, visualization and comparative genomics analysis, together with personal log in-protected 'workbench' spaces for saving data sets and analysis results. IRD integrates genomic, proteomic, immune epitope, and surveillance data from a variety of sources, including public databases, computational algorithms, external research groups, and the scientific literature.ResultsTo demonstrate the utility of the data and analysis tools available in IRD, two scientific use cases are presented. A comparison of hemagglutinin sequence conservation and epitope coverage information revealed highly conserved protein regions that can be recognized by the human adaptive immune system as possible targets for inducing cross-protective immunity. Phylogenetic and geospatial analysis of sequences from wild bird surveillance samples revealed a possible evolutionary connection between influenza virus from Delaware Bay shorebirds and Alberta ducks.ConclusionsThe IRD provides a wealth of integrated data and information about influenza virus to support research of the genetic determinants dictating virus pathogenicity, host range restriction and transmission, and to facilitate development of vaccines, diagnostics, and therapeutics