Open Access. Powered by Scholars. Published by Universities.®

Physical Sciences and Mathematics Commons

Open Access. Powered by Scholars. Published by Universities.®

None

Discipline
Keyword
Publication Year
Publication

Articles 61 - 90 of 2377

Full-Text Articles in Physical Sciences and Mathematics

A Classroom Outsourcing Experience For Software Engineering Learning, William Honig, Tejasvini Prasad Feb 2016

A Classroom Outsourcing Experience For Software Engineering Learning, William Honig, Tejasvini Prasad

William L Honig

Outsourcing of software development is a key part of globalization, oft misunderstood by computer science students, and possibly a cause of declining enrollments in the field. The authors developed and implemented an outsourcing experience for students in an advanced software engineering course. Student teams at two universities developed game playing programs and outsourced key parts of their systems to the other university. Results show students improved their understanding of outsourcing, developed better appreciation for the importance of software engineering techniques, and created ad hoc communication protocols between teams. The paper concludes with recommendations for expanding the approach used to other …


Intelligent Systems Development In A Non Engineering Curriculum, Emily Brand, William Honig, Matthew Wojtowicz Feb 2016

Intelligent Systems Development In A Non Engineering Curriculum, Emily Brand, William Honig, Matthew Wojtowicz

William L Honig

Much of computer system development today is programming in the large - systems of millions of lines of code distributed across servers and the web. At the same time, microcontrollers have also become pervasive in everyday products, economical to manufacture, and represent a different level of learning about system development. Real world systems at this level require integrated development of custom hardware and software.

How can academic institutions give students a view of this other extreme - programming on small microcontrollers with specialized hardware? Full scale system development including custom hardware and software is expensive, beyond the range of any …


Teaching Successful "Real-World" Software Engineering To The "Net" Generation: Process And Quality Win!, William Honig Feb 2016

Teaching Successful "Real-World" Software Engineering To The "Net" Generation: Process And Quality Win!, William Honig

William L Honig

Software engineering skills are critical for students seeking careers as software developers. However, academic course content often fails to teach practical, "real-world" software engineering as it is done in large organizations. Further, the proclivities of the current generation leave students disinclined to the disciplines of process and quality. Academics seldom use the Team Software Process (TSP), a leading methodology of global industries. Four years of data indicate that student teams using TSP can achieve industry levels of productivity and reasonable quality levels. Further, results from 23 teams and over 200 students indicate that these Net-Generation students developed an understanding for …


Teaching And Assessing Programming Fundamentals For Non Majors With Visual Programming, William Honig Feb 2016

Teaching And Assessing Programming Fundamentals For Non Majors With Visual Programming, William Honig

William L Honig

Visual programming tools and mobile device applications are a natural tool to engage university students; but, are they effective in teaching quantitative thinking skills to non computer science majors? Answering this question can be based on careful assessment of the learning outcomes. This paper reports the results from teaching over 100 students mobile app development with App Inventor in a university core course. Results were measured using an assessment process motivated by Bloom's Taxonomy that included student self assessment, ratings by instructors, and comparisons of the two results. The categories in the assessment were mapped to specific levels of skills …


Preface To Electrochemistry, Past And Present, Mary Orna Feb 2016

Preface To Electrochemistry, Past And Present, Mary Orna

Sr. Mary Virgina Orna O.S.U.

No abstract provided.


The Chemical History Of Color, Mary Virginia Orna Feb 2016

The Chemical History Of Color, Mary Virginia Orna

Sr. Mary Virgina Orna O.S.U.

No abstract provided.


Revisiting Hafemeister’S ‘Science And Society’ Tests, Robert Brecha, Rex Berney, Bruce Craver Feb 2016

Revisiting Hafemeister’S ‘Science And Society’ Tests, Robert Brecha, Rex Berney, Bruce Craver

Robert J. Brecha

We revisit a series of papers on science and society issues by David Hafemeister in the 1970s and 1980s. The emphasis in the present work is on world oil production limits and some consequences of various possible scenarios for the near future. Some of the data and scenarios used by Hafemeister are updated for U.S. oil production in the past two decades and extended to an analysis of a peak in world oil production in the future. We discuss some simple scenarios for future energy use patterns and look at the consequence of these scenarios as world oil production begins …


Emissions Scenarios In The Face Of Fossil-Fuel Peaking, Robert Brecha Feb 2016

Emissions Scenarios In The Face Of Fossil-Fuel Peaking, Robert Brecha

Robert J. Brecha

Emissions scenarios used by the Intergovernmental Panel on Climate Change (IPCC) are based on detailed energy system models in which demographics, technology and economics are used to generate projections of future world energy consumption, and therefore, of greenhouse gas emissions. We propose in this paper that it is useful to look at a qualitative model of the energy system, backed by data from short- and medium-term trends, to gain a sense of carbon emission bounds. Here we look at what may be considered a lower bound for 21st century emissions given two assumptions: first, that extractable fossil-fuel resources follow the …


Bose-Einstein Condensation Of Potassium Atoms By Sympathetic Cooling, Giovanni Modugno, Gabriele Ferrari, Giacomo Roati, Robert Brecha, A. Simoni, Massimo Inguscio Feb 2016

Bose-Einstein Condensation Of Potassium Atoms By Sympathetic Cooling, Giovanni Modugno, Gabriele Ferrari, Giacomo Roati, Robert Brecha, A. Simoni, Massimo Inguscio

Robert J. Brecha

We report on the Bose-Einstein condensation of potassium atoms, whereby quantum degeneracy is achieved by sympathetic cooling with evaporatively cooled rubidium. Because of the rapid thermalization of the two different atoms, the efficiency of the cooling process is high. The ability to achieve condensation by sympathetic cooling with a different species may provide a route to the production of degenerate systems with a larger choice of components.


Collapse Of A Degenerate Fermi Gas, Giovanni Modugno, Giacomo Roati, Francesco Riboli, Francesca Ferlaino, Robert Brecha, Massimo Inguscio Feb 2016

Collapse Of A Degenerate Fermi Gas, Giovanni Modugno, Giacomo Roati, Francesco Riboli, Francesca Ferlaino, Robert Brecha, Massimo Inguscio

Robert J. Brecha

A degenerate gas of identical fermions is brought to collapse by the interaction with a Bose-Einstein condensate. We used an atomic mixture of fermionic potassium-40 and bosonic rubidium-87, in which the strong interspecies attraction leads to an instability above a critical number of particles. The observed phenomenon suggests a direction for manipulating fermion-fermion interactions on the route to superfluidity.


Cost Optimization With Solar And Conventional Energy Production, Energy Storage, And Real Time Pricing, Ata Raziei, Kevin Hallinan, Robert Brecha Feb 2016

Cost Optimization With Solar And Conventional Energy Production, Energy Storage, And Real Time Pricing, Ata Raziei, Kevin Hallinan, Robert Brecha

Robert J. Brecha

Research is presented that investigates the potential for solar power generation with battery energy storage for reducing the effective cost of energy delivered to residential customers if real time pricing is present. A linear optimization approach is developed based upon a two-step process. In step one, given a specified solar array area and battery capacity, the optimal means to meet loads based upon grid power, solar power, and/or battery power is determined. This analysis considers an expected lifespan of the solar panel. With these results established, in the next step, the capital costs for the solar arrays and batteries are …


Dipolar Oscillations In A Quantum Degenerate Fermi–Bose Atomic Mixture, Francesca Ferlaino, Robert Brecha, Peter Hannaford, Francesco Riboli, Giacomo Roati, Giovanni Modugno, Massimo Inguscio Feb 2016

Dipolar Oscillations In A Quantum Degenerate Fermi–Bose Atomic Mixture, Francesca Ferlaino, Robert Brecha, Peter Hannaford, Francesco Riboli, Giacomo Roati, Giovanni Modugno, Massimo Inguscio

Robert J. Brecha

We study the dynamics of coupled dipolar oscillations in a Fermi–Bose mixture of 40K and 87Rb atoms. This low-energy collective mode is strongly affected by the interspecies interactions. Measurements are performed in the classical and quantum degenerate regimes and reveal the crucial role of the statistical properties of the mixture. At the onset of quantum degeneracy, we investigate the role of Pauli blocking and superfluidity for K and Rb atoms, respectively, resulting in a change in the collisional interactions.


The Carbon Rent Economics Of Climate Policy, Matthias Kalkuhl, Robert Brecha Jan 2016

The Carbon Rent Economics Of Climate Policy, Matthias Kalkuhl, Robert Brecha

Robert J. Brecha

By reducing the demand for fossil fuels, climate policy can reduce scarcity rents for fossil resource owners. As mitigation policies ultimately aim to limit emissions, a new scarcity for “space” in the atmosphere to deposit emissions is created. The associated scarcity rent, or climate rent (that is, for example, directly visible in permit prices under an emission trading scheme) can be higher or lower than the original fossil resource rent. In this paper, we analyze analytically and numerically the impact of mitigation targets, resource availability, backstop costs, discount rates and demand parameters on fossil resource rents and the climate rent. …


Analyzing Major Challenges Of Wind And Solar Variability In Power Systems, Falko Ueckerdt, Robert Brecha, Gunnar Luderer Jan 2016

Analyzing Major Challenges Of Wind And Solar Variability In Power Systems, Falko Ueckerdt, Robert Brecha, Gunnar Luderer

Robert J. Brecha

Ambitious policy targets together with current and projected high growth rates indicate that future power systems will likely show substantially increased generation from renewable energy sources. A large share will come from the variable renewable energy (VRE) sources wind and solar photovoltaics (PV); however, integrating wind and solar causes challenges for existing power systems. In this paper we analyze three major integration challenges related to the structural matching of demand with the supply of wind and solar power: low capacity credit, reduced utilization of dispatchable plants, and over-produced generation. Based on residual load duration curves we define corresponding challenge variables …


Global Fossil Energy Markets And Climate Change Mitigation: An Analysis With Remind, Nico Bauer, Ioanna Mouratiadou, Gunnar Luderer, Lavinia Baumstark, Robert Brecha, Ottmar Edenhofer, Elmar Kriegler Jan 2016

Global Fossil Energy Markets And Climate Change Mitigation: An Analysis With Remind, Nico Bauer, Ioanna Mouratiadou, Gunnar Luderer, Lavinia Baumstark, Robert Brecha, Ottmar Edenhofer, Elmar Kriegler

Robert J. Brecha

We analyze the dynamics of global fossil resource markets under different assumptions for the supply of fossil fuel resources, development pathways for energy demand, and climate policy settings. Resource markets, in particular the oil market, are characterized by a large discrepancy between costs of resource extraction and commodity prices on international markets. We explain this observation in terms of (a) the intertemporal scarcity rent, (b) regional price differentials arising from trade and transport costs, (c) heterogeneity and inertia in the extraction sector. These effects are captured by the REMIND model. We use the model to explore economic effects of changes …


Logistic Curves, Extraction Costs And Peak Oil, Robert Brecha Jan 2016

Logistic Curves, Extraction Costs And Peak Oil, Robert Brecha

Robert J. Brecha

Debates about the possibility of a near-term maximum in world oil production have become increasingly prominent over the past decade, with the focus often being on the quantification of geologically available and technologically recoverable amounts of oil in the ground. Economically, the important parameter is not a physical limit to resources in the ground, but whether market price signals and costs of extraction will indicate the efficiency of extracting conventional or nonconventional resources as opposed to making substitutions over time for other fuels and technologies. We present a hybrid approach to the peak-oil question with two models in which the …


Economic And Environmental Impacts Of Community-Based Residential Building Energy Efficiency Investment, Jun-Ki Choi, Drew Morrison, Kevin Hallinan, Robert Brecha Jan 2016

Economic And Environmental Impacts Of Community-Based Residential Building Energy Efficiency Investment, Jun-Ki Choi, Drew Morrison, Kevin Hallinan, Robert Brecha

Robert J. Brecha

A systematic framework for evaluating the local economic and environmental impacts of investment in building energy efficiency is developed. Historical residential building energy data, community-wide economic input-output data, and emission intensity data are utilized. The aim of this study is to show the comprehensive insights and connection among achieving variable target reductions for a residential building energy use, economic and environmental impacts. Central to this approach for the building energy reduction goal is the creation of individual energy models for each building based upon historical energy data and available building data. From these models, savings estimates and cost implications can …


Cost-Availability Curves For Hierarchical Implementation Of Residential Energy-Efficiency Measures, Roman Villoria-Siegert, Philip Brodrick, Kevin Hallinan, Robert Brecha Jan 2016

Cost-Availability Curves For Hierarchical Implementation Of Residential Energy-Efficiency Measures, Roman Villoria-Siegert, Philip Brodrick, Kevin Hallinan, Robert Brecha

Robert J. Brecha

Historical residential electricity data and natural gas consumption data were collected for, respectively, 1,200 and 178 residences in a small town in the USA. These data were merged with local building and weather databases, and energy consumption models were developed for each residence, revealing substantial variation in heating and cooling intensity. After estimating approximate physical building characteristics, energy profiles for each residence were calculated, and savings from adoption of the most cost-effective energy-efficiency measures for each residence were estimated. Effectively, we wish to leverage commonly available data sets to infer characteristics of building envelopes and equipment, without the need for …


Development Without Energy? Assessing Future Scenarios Of Energy Consumption In Developing Countries, Jan Steckel, Robert Brecha, Michael Jakob, Jessica Strefler, Gunnar Luderer Jan 2016

Development Without Energy? Assessing Future Scenarios Of Energy Consumption In Developing Countries, Jan Steckel, Robert Brecha, Michael Jakob, Jessica Strefler, Gunnar Luderer

Robert J. Brecha

We analyze the relationship between economic development and energy consumption in the context of greenhouse gas mitigation. The main contribution of this work is to compare estimates of energy thresholds in the form of minimum energy requirements to reach high levels of development with output projections of per capita final energy supply from a group of integrated assessment models (IAMs). Scenarios project that reductions of carbon emissions in developing countries will be achieved not only by means of decreasing the carbon intensity, but also by making a significant break with the historically observed relationship between energy use and economic growth. …


The Ssdna Mutator Apobec3a Is Regulated By Cooperative Dimerization, Markus-Frederik Bohn, Shivender Shandilya, Tania Silvas, Ellen Nalivaika, Takahide Kouno, Brian Kelch, Sean Ryder, Nese Yilmaz, Mohan Somasundaran, Celia Schiffer Jan 2016

The Ssdna Mutator Apobec3a Is Regulated By Cooperative Dimerization, Markus-Frederik Bohn, Shivender Shandilya, Tania Silvas, Ellen Nalivaika, Takahide Kouno, Brian Kelch, Sean Ryder, Nese Yilmaz, Mohan Somasundaran, Celia Schiffer

Celia A. Schiffer

Deaminase activity mediated by the human APOBEC3 family of proteins contributes to genomic instability and cancer. APOBEC3A is by far the most active in this family and can cause rapid cell death when overexpressed, but in general how the activity of APOBEC3s is regulated on a molecular level is unclear. In this study, the biochemical and structural basis of APOBEC3A substrate binding and specificity is elucidated. We find that specific binding of single-stranded DNA is regulated by the cooperative dimerization of APOBEC3A. The crystal structure elucidates this homodimer as a symmetric domain swap of the N-terminal residues. This dimer interface …


Structure Of The Vif-Binding Domain Of The Antiviral Enzyme Apobec3g, Takahide Kouno, Elizabeth Luengas, Megumi Shigematsu, Shivender Shandilya, Jingying Zhang, Luan Chen, Mayuko Hara, Celia Schiffer, Reuben Harris, Hiroshi Matsuo Jan 2016

Structure Of The Vif-Binding Domain Of The Antiviral Enzyme Apobec3g, Takahide Kouno, Elizabeth Luengas, Megumi Shigematsu, Shivender Shandilya, Jingying Zhang, Luan Chen, Mayuko Hara, Celia Schiffer, Reuben Harris, Hiroshi Matsuo

Celia A. Schiffer

The human APOBEC3G (A3G) DNA cytosine deaminase restricts and hypermutates DNA-based parasites including HIV-1. The viral infectivity factor (Vif) prevents restriction by triggering A3G degradation. Although the structure of the A3G catalytic domain is known, the structure of the N-terminal Vif-binding domain has proven more elusive. Here, we used evolution- and structure-guided mutagenesis to solubilize the Vif-binding domain of A3G, thus permitting structural determination by NMR spectroscopy. A smaller zinc-coordinating pocket and altered helical packing distinguish the structure from previous catalytic-domain structures and help to explain the reported inactivity of this domain. This soluble A3G N-terminal domain is bound by …


Simultaneously Targeting The Ns3 Protease And Helicase Activities For More Effective Hepatitis C Virus Therapy, Jean Ndjomou, M Corby, Noreena Sweeney, Alicia Hanson, Cihan Aydin, Akbar Ali, Celia Schiffer, Kelin Li, Kevin Frankowski, Frank Schoenen, David Frick Jan 2016

Simultaneously Targeting The Ns3 Protease And Helicase Activities For More Effective Hepatitis C Virus Therapy, Jean Ndjomou, M Corby, Noreena Sweeney, Alicia Hanson, Cihan Aydin, Akbar Ali, Celia Schiffer, Kelin Li, Kevin Frankowski, Frank Schoenen, David Frick

Celia A. Schiffer

This study examines the specificity and mechanism of action of a recently reported hepatitis C virus (HCV) nonstructural protein 3 (NS3) helicase-protease inhibitor (HPI), and the interaction of HPI with the NS3 protease inhibitors telaprevir, boceprevir, danoprevir, and grazoprevir. HPI most effectively reduced cellular levels of subgenomic genotype 4a replicons, followed by genotypes 3a and 1b replicons. HPI had no effect on HCV genotype 2a or dengue virus replicon levels. Resistance evolved more slowly to HPI than telaprevir, and HPI inhibited telaprevir-resistant replicons. Molecular modeling and analysis of the ability of HPI to inhibit peptide hydrolysis catalyzed by a variety …


Structural Basis For Mutation-Induced Destabilization Of Profilin 1 In Als, Sivakumar Boopathy, Tania Silvas, Maeve Tischbein, Silvia Jansen, Shivender Shandilya, Jill Zitzewitz, John Landers, Bruce Goode, Celia Schiffer, Daryl Bosco Jan 2016

Structural Basis For Mutation-Induced Destabilization Of Profilin 1 In Als, Sivakumar Boopathy, Tania Silvas, Maeve Tischbein, Silvia Jansen, Shivender Shandilya, Jill Zitzewitz, John Landers, Bruce Goode, Celia Schiffer, Daryl Bosco

Celia A. Schiffer

Mutations in profilin 1 (PFN1) are associated with amyotrophic lateral sclerosis (ALS); however, the pathological mechanism of PFN1 in this fatal disease is unknown. We demonstrate that ALS-linked mutations severely destabilize the native conformation of PFN1 in vitro and cause accelerated turnover of the PFN1 protein in cells. This mutation-induced destabilization can account for the high propensity of ALS-linked variants to aggregate and also provides rationale for their reported loss-of-function phenotypes in cell-based assays. The source of this destabilization is illuminated by the X-ray crystal structures of several PFN1 proteins, revealing an expanded cavity near the protein core of the …


Inhibition Of Apobec3g Activity Impedes Double-Stranded Dna Repair, Ponnandy Prabhu, Shivender Shandilya, Elena Britan-Rosich, Adi Nagler, Celia Schiffer, Moshe Kotler Jan 2016

Inhibition Of Apobec3g Activity Impedes Double-Stranded Dna Repair, Ponnandy Prabhu, Shivender Shandilya, Elena Britan-Rosich, Adi Nagler, Celia Schiffer, Moshe Kotler

Celia A. Schiffer

The cellular cytidine deaminase APOBEC3G (A3G) was first described as an anti-HIV-1 restriction factor, acting by directly deaminating reverse transcripts of the viral genome. HIV-1 Vif neutralizes the activity of A3G, primarily by mediating degradation of A3G to establish effective infection in host target cells. Lymphoma cells, which express high amounts of A3G, can restrict Vif-deficient HIV-1. Interestingly, these cells are more stable in the face of treatments that result in double-stranded DNA damage, such as ionizing radiation and chemotherapies. Previously, we showed that the Vif-derived peptide (Vif25-39) efficiently inhibits A3G deamination, and increases the sensitivity of lymphoma cells to …


Rediii: A Pipeline For Automated Structure Solution, Markus-Frederik Bohn, Celia Schiffer Jan 2016

Rediii: A Pipeline For Automated Structure Solution, Markus-Frederik Bohn, Celia Schiffer

Celia A. Schiffer

High-throughput crystallographic approaches require integrated software solutions to minimize the need for manual effort. REdiii is a system that allows fully automated crystallographic structure solution by integrating existing crystallographic software into an adaptive and partly autonomous workflow engine. The program can be initiated after collecting the first frame of diffraction data and is able to perform processing, molecular-replacement phasing, chain tracing, ligand fitting and refinement without further user intervention. Preset values for each software component allow efficient progress with high-quality data and known parameters. The adaptive workflow engine can determine whether some parameters require modifications and choose alternative software strategies …


Modulation Of Hiv Protease Flexibility By The T80n Mutation, Hao Zhou, Shangyang Li, John Badger, Ellen Nalivaika, Yufeng Cai, Jennifer Foulkes-Murzycki, Celia Schiffer, Lee Makowski Jan 2016

Modulation Of Hiv Protease Flexibility By The T80n Mutation, Hao Zhou, Shangyang Li, John Badger, Ellen Nalivaika, Yufeng Cai, Jennifer Foulkes-Murzycki, Celia Schiffer, Lee Makowski

Celia A. Schiffer

The flexibility of HIV protease (HIVp) plays a critical role in enabling enzymatic activity and is required for substrate access to the active site. While the importance of flexibility in the flaps that cover the active site is well known, flexibility in other parts of the enzyme is also critical for function. One key region is a loop containing Thr 80, which forms the walls of the active site. Although not situated within the active site, amino acid Thr80 is absolutely conserved. The mutation T80N preserves the structure of the enzyme but catalytic activity is completely lost. To investigate the …


A Direct Interaction With Rna Dramatically Enhances The Catalytic Activity Of The Hiv-1 Protease In Vitro, Marc Potempa, Ellen Nalivaika, Debra Ragland, Sook-Kyung Lee, Celia Schiffer, Ronald Swanstrom Jan 2016

A Direct Interaction With Rna Dramatically Enhances The Catalytic Activity Of The Hiv-1 Protease In Vitro, Marc Potempa, Ellen Nalivaika, Debra Ragland, Sook-Kyung Lee, Celia Schiffer, Ronald Swanstrom

Celia A. Schiffer

Though the steps of human immunodeficiency virus type 1 (HIV-1) virion maturation are well documented, the mechanisms regulating the proteolysis of the Gag and Gag-Pro-Pol polyproteins by the HIV-1 protease (PR) remain obscure. One proposed mechanism argues that the maturation intermediate p15NC must interact with RNA for efficient cleavage by the PR. We investigated this phenomenon and found that processing of multiple substrates by the HIV-1 PR was enhanced in the presence of RNA. The acceleration of proteolysis occurred independently from the substrate's ability to interact with nucleic acid, indicating that a direct interaction between substrate and RNA is not …


A Balance Between Inhibitor Binding And Substrate Processing Confers Influenza Drug Resistance, Li Jiang, Ping Liu, Claudia Bank, Nicholas Renzette, Kristina Prachanronarong, L. Yilmaz, Daniel Caffrey, Konstantin Zeldovich, Celia Schiffer, Timothy Kowalik, Jeffrey Jensen, Robert Finberg, Jennifer Wang, Daniel Bolon Jan 2016

A Balance Between Inhibitor Binding And Substrate Processing Confers Influenza Drug Resistance, Li Jiang, Ping Liu, Claudia Bank, Nicholas Renzette, Kristina Prachanronarong, L. Yilmaz, Daniel Caffrey, Konstantin Zeldovich, Celia Schiffer, Timothy Kowalik, Jeffrey Jensen, Robert Finberg, Jennifer Wang, Daniel Bolon

Celia A. Schiffer

The therapeutic benefits of the neuraminidase (NA) inhibitor oseltamivir are dampened by the emergence of drug resistance mutations in influenza A virus (IAV). To investigate the mechanistic features that underlie resistance, we developed an approach to quantify the effects of all possible single-nucleotide substitutions introduced into important regions of NA. We determined the experimental fitness effects of 450 nucleotide mutations encoding positions both surrounding the active site and at more distant sites in an N1 strain of IAV in the presence and absence of oseltamivir. NA mutations previously known to confer oseltamivir resistance in N1 strains, including H275Y and N295S, …


Structural And Thermodynamic Effects Of Macrocyclization In Hcv Ns3/4a Inhibitor Mk-5172, Djade Soumana, Nese Yilmaz, Kristina Prachanronarong, Cihan Aydin, Akbar Ali, Celia Schiffer Jan 2016

Structural And Thermodynamic Effects Of Macrocyclization In Hcv Ns3/4a Inhibitor Mk-5172, Djade Soumana, Nese Yilmaz, Kristina Prachanronarong, Cihan Aydin, Akbar Ali, Celia Schiffer

Celia A. Schiffer

Recent advances in direct-acting antivirals against Hepatitis C Virus (HCV) have led to the development of potent inhibitors, including MK-5172, that target the viral NS3/4A protease with relatively low susceptibility to resistance. MK-5172 has a P2-P4 macrocycle and a unique binding mode among current protease inhibitors where the P2 quinoxaline packs against the catalytic residues H57 and D81. However, the effect of macrocyclization on this binding mode is not clear, as is the relation between macrocyclization, thermodynamic stabilization, and susceptibility to the resistance mutation A156T. We have determined high-resolution crystal structures of linear and P1-P3 macrocyclic analogs of MK-5172 bound …


Explicating A Mechanism For Conceptual Learning: Elaborating The Construct Of Reflective Abstraction, Martin Simon, Ron Tzur, Karen Heinz, Margaret Kinzel Jan 2016

Explicating A Mechanism For Conceptual Learning: Elaborating The Construct Of Reflective Abstraction, Martin Simon, Ron Tzur, Karen Heinz, Margaret Kinzel

Ron Tzur

We articulate and explicate a mechanism for mathematics conceptual learning that can serve as a basis for the design of mathematics lessons. The mechanism, reflection on activity-effect relationships, addresses the learning paradox (Pascual-Leone, 1976), a paradox that derives from careful attention to the construct of assimilation (Piaget, 1970). The mechanism is an elaboration of Piaget's (2001) reflective abstraction and is potentially useful for addressing some of the more intractable problems in teaching mathematics. Implications of the mechanism for lesson design are discussed and exemplified. (Contains 2 figures and 9 footnotes.)