Physical Sciences and Mathematics Commons^™

Determining Magnetic Nanoparticle Size Distributions From Thermomagnetic Measurements, R. Dipietro, H. Johnson, S. Bennett, T. Nummy, L. Lewis, D. Heiman

Laura H. Lewis

Thermomagnetic measurements are used to obtain the size distribution and anisotropy of magnetic nanoparticles. An analytical transformation method is described which utilizes temperature-dependent zero-field cooling (ZFC) magnetization data to provide a quantitative measurement of the average diameter and relative abundance of superparamagnetic nanoparticles. Applying this method to self-assembled MnAs nanoparticles in MnAs-GaAs composite films reveals a log-normal size distribution and reduced anisotropy for nanoparticles compared to bulk materials. This analytical technique holds promise for rapid assessment of the size distribution of an ensemble of superparamagnetic nanoparticles.

Magnetic Signature Of Symmetry Reduction In Epitaxial La₀.₆₇Sr₀.₃₃Mno₃ Films, Radhika Barua, L. Lewis, D. Heiman

Laura H. Lewis

The magnetic properties of epitaxially grown La0.67Sr0.33MnO3 perovskite thin films were investigated to elucidate an unexpected broken symmetry between orthogonal [100] and [010] inplane directions, resulting from the magnetostructural coupling between the film and the cubic SrTiO3 (001) substrate. The films were synthesized by molecular beam epitaxy with either complete or zero A-site cation disorder. Magnetization measured in [100] and [010] directions shows differences that signal a reduction of the in-plane cubic symmetry only for T < 290 K. The magnetization asymmetry is more robust in the film with complete A-site disorder. These results are attributed to a dominant Mn3+ character …

Universal Properties Of Linear Magnetoresistance In Strongly Disordered Mnas-Gaas Composite Semiconductors, H. Johnson, S. Bennett, R. Barua, L. Lewis, D. Heiman

Donald Heiman

Linear magnetoresistance (LMR) occurs in semiconductors as a consequence of strong electrical disorder and is characterized by nonsaturating magnetoresistance that is proportional to the applied magnetic field. By investigating a disordered MnAs-GaAs composite material, it is found that the magnitude of the LMR is numerically equal to the carrier mobility over a wide range and is independent of carrier density. This behavior is complementary to the Hall effect that is independent of the mobility and dependent on the carrier density. Moreover, the LMR appears to be insensitive to the details of the disorder and points to a universal explanation of …

Nonparametric Copula Density Estimation In Sensor Networks, Leming Qu, Hao Chen, Yicheng Tu

Leming Qu

Statistical and machine learning is a fundamental task in sensor networks. Real world data almost always exhibit dependence among different features. Copulas are full measures of statistical dependence among random variables. Estimating the underlying copula density function from distributed data is an important aspect of statistical learning in sensor networks. With limited communication capacities or privacy concerns, centralization of the data is often impossible. By only collecting the ranks of the data observed by different sensors, we estimate and evaluate the copula density on an equally spaced grid after binning the standardized ranks at the fusion center. Without assuming any …

Its Training Update, Veronica Trammell

Veronica O. Trammell

No abstract provided.

Using Computers To Support Children As Authors: An Examination Of Three Cases, Lisa Kervin, Jessica Mantei

Jessica Mantei

The changing nature of literacy is well documented within the literature, challenging educators to examine their pedagogies in light of the needs of learners in the current climate. The development and creation of non‐linear texts within primary classrooms is of current interest as they reflect the types of texts accessed and created by users of technology and afford children opportunities to make connections between their in and out of school literacy experiences. The authors observed children over extended periods as they collaborated with teachers and peers to author non‐linear texts for a range of purposes. Three case studies will be …

Role Of The Epididymis In Sperm Competition, Russell Jones, Jl Dacheux, Brett Nixon, Heath Ecroyd

Heath Ecroyd

Although it is generally understood that the testes recruited kidney ducts for reproductive function during the evolution of vertebrates, little is understood of the biological significance of the adaptation. In the context of the evolution of the mammalian epididymis, this report provides evidence that a major role of the epididymis is to enhance a male's chance of achieving paternity in a competitive mating system. A unique example of sperm cooperation, in monotremes is used as evidence that the epididymis produces sperm competition proteins to form groups of 100 sperm into bundles that have a forward motility nearly thrice that of …

Tyrosine Phosphorylation Of Hsp-90 During Mammalian Sperm Capacitation, Heath Ecroyd, Russell Jones, Robert Aitken

Heath Ecroyd

The process of sperm capacitation is correlated with activation of a signal transduction pathway leading to protein tyrosine phosphorylation. Whereas phosphotyrosine expression is an essential prerequisite for fertilization, the proteins that are phosphorylated during capacitation have not yet been identified. In the present study, we observed that a major target of this signaling pathway is the molecular chaperone protein, heat shock protein (HSP)-86, a member of the HSP-90 family of HSPs. We used cross-immunoprecipitation experiments to confirm the tyrosine phosphorylation of HSP-86, a process that is not inhibited by the ansamycin antibiotic, geldanamycin. The general significance of these findings was …

Dissociation From The Oligomeric State Is The Rate-Limiting Step In Fibril Formation By Kappa-Casein, Heath Ecroyd, Tomas Koudelka, David Thorn, Danielle Williams, Glyn Devlin, Peter Hoffmann, John Carver

Heath Ecroyd

Amyloid fibrils are aggregated and precipitated forms of protein in which the protein exists in highly ordered, long, unbranching threadlike formations that are stable and resistant to degradation by proteases. Fibril formation is an ordered process that typically involves the unfolding of a protein to partially folded states that subsequently interact and aggregate through a nucleation-dependent mechanism. Here we report on studies investigating the molecular basis of the inherent propensity of the milk protein, kappa-casein, to form amyloid fibrils. Using reduced and carboxymethylated kappa-casein ( RCM kappa-CN), we show that fibril formation is accompanied by a characteristic increase in thioflavin …

The Effect Of Small Molecules In Modulating The Chaperone Activity Of Alpha B-Crystallin Against Ordered And Disordered Protein Aggregation, Heath Ecroyd, John Carver

Heath Ecroyd

Protein aggregation can proceed via disordered or ordered mechanisms, with the latter being associated with amyloid fibril formation, which has been linked to a number of debilitating conditions including Alzheimer's, Parkinson's and Creutzfeldt-Jakob diseases. Small heat-shock proteins (sHsps), such as alpha B-crystallin, act as chaperones to prevent protein aggregation and are thought to play a key role in the prevention of protein-misfolding diseases. In this study, we have explored the potential for small molecules such as arginine and guanidine to affect the chaperone activity of alpha B-crystallin against disordered (amorphous) and ordered (amyloid fibril) forms of protein aggregation. The effect …

Analysis Of The Mechanism By Which Calcium Negatively Regulates The Tyrosine Phosphorylation Cascade Associated With Sperm Capacitation, Mark Baker, Louise Hethrington, Heath Ecroyd, Shaun Roman, Robert Aitken

Heath Ecroyd

The capacitation of mammalian spermatozoa involves the activation of a cAMP-mediated signal transduction pathway that drives tyrosine phosphorylation via mechanisms that are unique to this cell type. Controversy surrounds the impact of extracellular calcium on this process, with positive and negative effects being recorded in independent publications. We clearly demonstrate that the presence of calcium in the external medium decreases tyrosine phosphorylation in both human and mouse spermatozoa. Under these conditions, a rise in intracellular pH was recorded, however, this event was not responsible for the observed changes in phosphotyrosine expression. Rather, the impact of calcium on tyrosine phosphorylation in …

The Two Faced Nature Of Milk Casein Proteins: Amyloid Fibril Formation And Chaperone-Like Activity, David Thorn, Heath Ecroyd, John Carver

Heath Ecroyd

Molecular chaperones are a diverse group of proteins that stabilise partially folded target proteins to prevent their misfolding, aggregation and potential precipitation under conditions of cellular stress, e.g. elevated temperature. Protein aggregation, particularly the formation of highly ordered protein aggregates termed amyloid fibrils, is of considerable research interest because of its intimate association with a wide range of debilitating diseases, including Alzheimer's, Parkinson's and Huntington's diseases and type II diabetes. In this review, we discuss the ability of the milk casein proteins to act in a chaperone-like manner. This property is of biological importance since at least two of the …

Post-Testicular Sperm Environment And Fertility, Jean-Luc Gatti, Sandrine Castella, Francoise Dacheux, Heath Ecroyd, S Metayer, Veronique Thimon, Jean-Louis Dacheux

Heath Ecroyd

When mammalian spermatozoa exit the testis, they show a highly specialized morphology; however, they are not yet able to carry out their task: to fertilize an oocyte. This property, that includes the acquisition of motility and the ability to recognize and to fuse with the oocyte investments, is gained only after a transit through the epididymis during which the spermatozoa from the testis travel to the vas deferens. The exact molecular mechanisms that turn these cells into fertile gametes still remain mysterious, but surface-modifying events occurring in response to the external media are key steps in this process. Our laboratory …

Testicular Descent, Sperm Maturation And Capacitation. Lessons From Our Most Distant Relatives, The Monotremes, Russell Jones, Heath Ecroyd, Jean-Louis Dacheux, Brett Nixon

Heath Ecroyd

The present review examines whether monotremes may help to resolve three questions relating to sperm production in mammals: why the testes descend into a scrotum in most mammals, why spermatozoa are infertile when they leave the testes and require a period of maturation in the specific milieu provided by the epididymides, and why ejaculated spermatozoa cannot immediately fertilise an ovum until they undergo capacitation within the female reproductive tract. Comparisons of monotremes with other mammals indicate that there is a need for considerable work on monotremes. It is hypothesised that testicular descent should be related to epididymal differentiation. Spermatozoa and …

Adjusting Medicare Capitation Payments Using Prior Hospitalization Data, Arlene Ash, Frank Porell, Leonard Gruenberg, Eric Sawitz, Alexa Beiser

Frank Porell

The diagnostic cost group approach to a reimbursement model for health maintenance organizations is presented. Diagnostic information about previous hospitalizations is used to create empirically determined risk groups, using only diagnoses involving little or no discretion in the decision to hospitalize. Diagnostic cost group and other models (including Medicare's current formula and other prior-use models) are tested for their ability to predict future costs, using R2 values and new measures of predictive performance. The diagnostic cost group models perform relatively well with respect to a range of criteria, including administrative feasibility, resistance to provider manipulation, and statistical accuracy.

Web 2.0 Publishing And Happy 1.0, Computing Now!, George Thiruvathukal

George K. Thiruvathukal

In this special issue, we take a look at Web 2.0 and publishing and extend a special happy first birthday greeting to Computing Now, the online member engagement initiative of the IEEE Computer Society.

Novel Architectures And Accelerators, George Thiruvathukal

George K. Thiruvathukal

Computing Now special issue on novel architectures (GPGPU, FPGA, etc.)

Promise Of Advances In Simulation Methods For Protein Crystallography: Implicit Solvent Models, Time-Averaging Refinement, And Quantum Mechanical Modeling, Celia Schiffer, Jan Hermans

Celia A. Schiffer

No abstract provided.

Competition Between Ski And Creb-Binding Protein For Binding To Smad Proteins In Transforming Growth Factor-Beta Signaling, Weijun Chen, Suvana Lam, Hema Srinath, Celia Schiffer, William Royer, Kai Lin

Celia A. Schiffer

The family of Smad proteins mediates transforming growth factor-beta (TGF-beta) signaling in cell growth and differentiation. Smads repress or activate TGF-beta signaling by interacting with corepressors (e.g. Ski) or coactivators (e.g. CREB-binding protein (CBP)), respectively. Specifically, Ski has been shown to interfere with the interaction between Smad3 and CBP. However, it is unclear whether Ski competes with CBP for binding to Smads and whether they can interact with Smad3 at the same binding surface on Smad3. We investigated the interactions among purified constructs of Smad, Ski, and CBP in vitro by size-exclusion chromatography, isothermal titration calorimetry, and mutational studies. Here, …

Mass Spectrometry Analysis Of Hiv-1 Vif Reveals An Increase In Ordered Structure Upon Oligomerization In Regions Necessary For Viral Infectivity, Jared Auclair, Karin Green, Shivender Shandilya, James Evans, Mohan Somasundaran, Celia Schiffer

Celia A. Schiffer

HIV-1 Vif, an accessory protein in the viral genome, performs an important role in viral pathogenesis by facilitating the degradation of APOBEC3G, an endogenous cellular inhibitor of HIV-1 replication. In this study, intrinsically disordered regions are predicted in HIV-1 Vif using sequence-based algorithms. Intrinsic disorder may explain why traditional structure determination of HIV-1 Vif has been elusive, making structure-based drug design impossible. To characterize HIV-1 Vif's structural topology and to map the domains involved in oligomerization we used chemical cross-linking, proteolysis, and mass spectrometry. Cross-linking showed evidence of monomer, dimer, and trimer species via denaturing gel analysis and an additional …

Viral Protease Inhibitors, Jeffrey Anderson, Celia Schiffer, Sook-Kyung Lee, Ronald Swanstrom

Celia A. Schiffer

This review provides an overview of the development of viral protease inhibitors as antiviral drugs. We concentrate on HIV-1 protease inhibitors, as these have made the most significant advances in the recent past. Thus, we discuss the biochemistry of HIV-1 protease, inhibitor development, clinical use of inhibitors, and evolution of resistance. Since many different viruses encode essential proteases, it is possible to envision the development of a potent protease inhibitor for other viruses if the processing site sequence and the catalytic mechanism are known. At this time, interest in developing inhibitors is limited to viruses that cause chronic disease, viruses …

Mutation Patterns And Structural Correlates In Human Immunodeficiency Virus Type 1 Protease Following Different Protease Inhibitor Treatments, Thomas Wu, Celia Schiffer, Matthew Gonzales, Jonathan Taylor, Rami Kantor, Sunwen Chou, Dennis Israelski, Andrew Zolopa, W. Jeffrey Fessel, Robert Shafer

Celia A. Schiffer

Although many human immunodeficiency virus type 1 (HIV-1)-infected persons are treated with multiple protease inhibitors in combination or in succession, mutation patterns of protease isolates from these persons have not been characterized. We collected and analyzed 2,244 subtype B HIV-1 isolates from 1,919 persons with different protease inhibitor experiences: 1,004 isolates from untreated persons, 637 isolates from persons who received one protease inhibitor, and 603 isolates from persons receiving two or more protease inhibitors. The median number of protease mutations per isolate increased from 4 in untreated persons to 12 in persons who had received four or more protease inhibitors. …

Curling Of Flap Tips In Hiv-1 Protease As A Mechanism For Substrate Entry And Tolerance Of Drug Resistance, Walter Scott, Celia Schiffer

Celia A. Schiffer

BACKGROUND: The human immunodeficiency virus type 1 (HIV-1) protease is an essential viral protein that is a major drug target in the fight against Acquired Immune Deficiency Syndrome (AIDS). Access to the active site of this homodimeric enzyme is gained when two large flaps, one from each monomer, open. The flap movements are therefore central to the function of the enzyme, yet determining how these flaps move at an atomic level has not been experimentally possible.

RESULTS: In the present study, we observe the flaps of HIV-1 protease completely opening during a 10 ns solvated molecular dynamics simulation starting from …

Exploring The Role Of The Solvent In The Denaturation Of A Protein: A Molecular Dynamics Study Of The Dna Binding Domain Of The 434 Repressor, Celia Schiffer, Volker Dötsch, Kurt Wuthrich, Wilfred Van Gunsteren

Celia A. Schiffer

Molecular dynamics simulations of the DNA binding domain of 434 repressor are presented which aim at unraveling the role of solvent in protein denaturation. Four altered solvent models, each mimicking various possible aspects of the addition of a denaturant to the aqueous solvent, were used in the simulations to analyze their effects on the stability of the protein. The solvent was altered by selectively changing the Coulombic interaction between water and protein atoms and between different water molecules. The use of a modified solvent model has the advantage of mimicking the presence of denaturant without having denaturant molecules present in …

Structural Analysis Of Human Immunodeficiency Virus Type 1 Crf01_Ae Protease In Complex With The Substrate P1-P6., Rajintha Bandaranayake, Moses Prabu-Jeyabalan, Junko Kakizawa, Wataru Sugiura, Celia Schiffer

Celia A. Schiffer

The effect of amino acid variability between human immunodeficiency virus type 1 (HIV-1) clades on structure and the emergence of resistance mutations in HIV-1 protease has become an area of significant interest in recent years. We determined the first crystal structure of the HIV-1 CRF01_AE protease in complex with the p1-p6 substrate to a resolution of 2.8 A. Hydrogen bonding between the flap hinge and the protease core regions shows significant structural rearrangements in CRF01_AE protease compared to the clade B protease structure.

Non-Redundant Sequential Rules,Theory And Algorithm, David Lo, Siau-Cheng Khoo, Limsoon Wong

David LO

A sequential rule expresses a relationship between two series of events happening one after another. Sequential rules are potentially useful for analyzing data in sequential format, ranging from purchase histories, network logs and program execution traces. In this work, we investigate and propose a syntactic characterization of a non-redundant set of sequential rules built upon past work on compact set of representative patterns. A rule is redundant if it can be inferred from another rule having the same support and confidence. When using the set of mined rules as a composite filter, replacing a full set of rules with a …

Matching Dependence-Related Queries In The System Dependence Graph., Xiaoyin Wang, David Lo, Jiefeng Cheng, Lu Zhang, Hong Mei, Jeffrey Xu Yu

David LO

In software maintenance and evolution, it is common that developers want to apply a change to a number of similar places. Due to the size and complexity of the code base, it is challenging for developers to locate all the places that need the change. A main challenge in locating the places that need the change is that, these places share certain common dependence conditions but existing code searching techniques can hardly handle dependence relations satisfactorily. In this paper, we propose a technique that enables developers to make queries involving dependence conditions and textual conditions on the system dependence graph …

Mining Iterative Generators And Representative Rules For Software Specification Discovery, David Lo, Jinyan Li, Limsoon Wong, Siau-Cheng Khoo

David LO

Billions of dollars are spent annually on software-related cost. It is estimated that up to 45 percent of software cost is due to the difficulty in understanding existing systems when performing maintenance tasks (i.e., adding features, removing bugs, etc.). One of the root causes is that software products often come with poor, incomplete, or even without any documented specifications. In an effort to improve program understanding, Lo et al. have proposed iterative pattern mining which outputs patterns that are repeated frequently within a program trace, or across multiple traces, or both. Frequent iterative patterns reflect frequent program behaviors that likely …

Extracting Paraphrases Of Technical Terms From Noisy Parallel Software Corpus, Xiaoyin Wang, David Lo, Jing Jiang, Lu Zhang, Hong Mei

David LO

In this paper, we study the problem of extracting technical paraphrases from a parallel software corpus, namely, a collection of duplicate bug reports. Paraphrase acquisition is a fundamental task in the emerging area of text mining for software engineering. Existing paraphrase extraction methods are not entirely suitable here due to the noisy nature of bug reports. We propose a number of techniques to address the noisy data problem. The empirical evaluation shows that our method significantly improves an existing method by upto 58%

Mining Message Sequence Graphs, Sandeep Kumar, Siau-Cheng Khoo, Abhik Roychoudhury, David Lo

David LO

Dynamic specification mining involves discovering software behavior from traces for the purpose of program comprehension and bug detection. However, in concurrent/distributed programs, the inherent partial order relationships among events occurring across processes pose a big challenge to specification mining. In this paper, we propose a framework for mining partial orders so as to understand concurrent program behavior. Our miner takes in a set of concurrent program traces, and produces a message sequence graph (MSG) to represent the concurrent program behavior. An MSG represents a graph where the nodes of the graph are partial orders, represented as Message Sequence Charts. Mining …