Physical Sciences and Mathematics Commons^™

Mechanism Of G Protein Beta-Gamma Assembly Mediated By Phosducin-Like Protein 1, Chun Wan Jeffrey Lai

Theses and Dissertations

G-protein coupled receptor signaling (GPCR) is essential for regulating a large variety of hormonal, sensory and neuronal processes in eukaryotic cells. Because the regulation of these physiological responses is critical, GPCR signaling pathways are carefully controlled at different levels within the cascade. Phosducin-like protein 1 (PhLP1) can bind the G protein βγ dimer and participate in GPCR signaling. Recent evidence has supported the concept that PhLP1 can serve as a co-chaperone of the eukaryotic cytosolic chaperonin complex CCT/TRiC to mediate G βγ assembly. Although a general mechanism of PhLP1-mediated G βγ assembly has been postulated, many of the details about …

Its Training Update, Veronica Trammell

Veronica O. Trammell

No abstract provided.

Relating Dynamic Protein Interactions Of Metallochaperones With Metal Transfer At The Single-Molecule Level, J. J. Benítez, A. M. Keller, D. L. Huffman, Liliya A. Yatsunyk, A. C. Rosenzweig, P. Chen

Chemistry & Biochemistry Faculty Works

Metallochaperones undertake specific interactions with their target proteins to deliver metal ions inside cells. Understanding how these protein interactions are coupled with the underlying metal transfer process is important, but challenging because they are weak and dynamic. Here we use a nanovesicle trapping scheme to enable single-molecule FRET measurements of the weak, dynamic interactions between the copper chaperone Hahl and the fourth metal binding domain (MBD4) of WDP. By monitoring the behaviors of single interacting pairs, we visualize their interactions in real time in both the absence and the presence of various equivalents of Cu(1+). Regardless of the proteins' metallation …

Flexible Distributed Lag Models Using Random Functions With Application To Estimating Mortality Displacement From Heat-Related Deaths, Roger D. Peng

Johns Hopkins University, Dept. of Biostatistics Working Papers

No abstract provided.

Syntactic And Semantic Analysis And Visualization Of Unstructured English Texts, Saurav Karmakar

Computer Science Dissertations

People have complex thoughts, and they often express their thoughts with complex sentences using natural languages. This complexity may facilitate efficient communications among the audience with the same knowledge base. But on the other hand, for a different or new audience this composition becomes cumbersome to understand and analyze. Analysis of such compositions using syntactic or semantic measures is a challenging job and defines the base step for natural language processing.

In this dissertation I explore and propose a number of new techniques to analyze and visualize the syntactic and semantic patterns of unstructured English texts.

The syntactic analysis is …

Development Of A Strontium-87 Ion Interferometer, Christopher Joseph Erickson

Theses and Dissertations

I present the construction of a low-velocity intense source (LVIS) of laser-cooled neutral strontium using permanent ring magnets. The LVIS consists of a magneto-optical trap from which cold strontium is extracted in a well-collimated beam. I also present the development and implementation of a full suite of low-noise, high-bandwidth laser control electronics including a microcontroller unit. This microcontroller remotely controls and monitors the current driver, temperature controller, and PID lock circuit for each diode laser simultaneously. The current driver output is accurate to within 2 micro-amps and repeatable to with a few nano-amps. The noise spectral density of the current …

Multiple Biolgical Sequence Alignment: Scoring Functions, Algorithms, And Evaluations, Ken D. Nguyen

Computer Science Dissertations

Aligning multiple biological sequences such as protein sequences or DNA/RNA sequences is a fundamental task in bioinformatics and sequence analysis. These alignments may contain invaluable information that scientists need to predict the sequences' structures, determine the evolutionary relationships between them, or discover drug-like compounds that can bind to the sequences. Unfortunately, multiple sequence alignment (MSA) is NP-Complete. In addition, the lack of a reliable scoring method makes it very hard to align the sequences reliably and to evaluate the alignment outcomes.

In this dissertation, we have designed a new scoring method for use in multiple sequence alignment. Our scoring method …

Novel Near-Infrared Cyanine Dyes For Fluorescence Imaging In Biological Systems, Nilmi T. Fernando

Chemistry Dissertations

Heptamethine cyanine dyes are attractive compounds for imaging purposes in biomedical applications because of their chemical and photophysical properties exhibited in the near-infrared region. A series of meso amino-substituted heptamethine cyanine dyes with indolenine, benz[e]indolenine and benz[c,d]indolenine heterocyclic moieties were synthesized and their spectral properties including fluorescence quntum yield were investigated in ethanol and ethanol/water mixture. Upon substitution with amines, the absorption maxima of the dyes shifted to the lower wavelength region (~600 nm), showed larger Stokes shifts and stronger fluorescence which can be attributed to an excited state intramolecular charge transfer (ICT). High quantum yields …

Nucleic Acid Substrates: Investigation Of Structural And Dynamic Features That Influence Enzyme Activity, Christopher N. Johnson

Chemistry Dissertations

The previous view of DNA as a linear sequence of bases is evolving to consider structure, topology and dynamics. Sequences surrounding damage lesions have been shown to effect enzyme recognition and processing. Here we present an in depth investigation of subtle structural and dynamical features imparted to nucleic acid duplexes by a designed modification or damage lesions. Highly restrained solution structures were generated and validated utilizing a range of NMR techniques. This allowed for the characterization of multiple features of the nucleic acid duplex; such as base pairing, backbone torsion angles, deoxyribose sugar pucker, and intra and inter nucleotide proton …

Background-Oriented Schlieren Pattern Optimization, Jeffery E. Hartberger

Theses and Dissertations

This paper describes a test series to investigate background patterns used for the Background-Oriented Schlieren field density measurement technique. Several varying background patterns were substituted under similar fluid density conditions to visualize and isolate the effects of patterns in the background images. A qualitative comparison was completed of the flow visualization results of each background pattern to categorize background conditions that improved the flow visualization image. Changes in background patterns revealed significant changes in flow visualization. Pattern contrast, spacing and sizing all played large parts in the quality of the visual density gradient imaging during the test series.

Transition Metal Complexes With Reactive Trimethylsilylchalcogenolate Ligands: Precursors For The Preparation Of Ternary Nanoclusters, Chhatra Bahadur Khadka

Electronic Thesis and Dissertation Repository

The Co²⁺ and Mn²⁺ complexes (N,N´-tmeda)Co(ESiMe₃)₂ (E = S, 1a; E = Se, 1b), (3,5-Me₂C₅H₃N)₂Co(ESiMe₃)₂ (E = S, 2a; E = Se, 2b), [Li(N,N´-tmeda)]₂[(N,N´-tmeda)Mn₅(μ-ESiMe₃)₂(ESiMe₃)₄(μ₄-E)(μ₃-E)₂] (E = S, 3a; E = Se, 3b), [Li(N,N´-tmeda)]₂[Mn(SSiMe₃)₄] (4), [Li(N,N´-tmeda)]4[Mn₄(SeSiMe₃)₄(μ_{3 …}

Study Of Malaria Transmission Dynamics By Mathematical Models, Yanyu Xiao

Electronic Thesis and Dissertation Repository

This Ph.D thesis focuses on modeling transmission and dispersal of one of the most common infectious disease, Malaria. Firstly, an integro-differential equation system is derived, based on the classical Ross-Macdonald model, toemphasize the impacts of latencies on disease dynamics. The novelty lies in the fact that different distributionfunctions are used to describe the variance of individual latencies. The theoretical results of this projectindicate that latencies reduce the basic reproduction number. Secondly, a patch model is derived to examine how travels of human beings affects the transmission and spread of Malaria. Due to coexistence of latency and dispersal, the model turns …

Thermal Plume Transport From Sand And Gravel Pits Potential Thermal Impacts On Cool-Water Streams, Jeffrey M. Markle

Electronic Thesis and Dissertation Repository

Potential thermal impacts from below-water-table aggregate extraction on a cool-water stream were investigated by monitoring thermal plumes, moving through an unconfined glacial-outwash aquifer, and assessing their subsurface persistence. The growing demand for aggregate and increased pressure to pursue extraction in ecologically sensitive areas has driven the need for this work. During a 10-year period, ground and surface water temperatures were measured monthly, including two periods of intensive monitoring (22 months and 2.5 years). The aquifer hydraulic conductivity (K) is quantified at the laboratory and field scale. The mean K’s from the multi-scale tests depend on test-support volume and …

Towards Node Cooperation In Mobile Opportunistic Networks, Abderrahmen Mtibaa, Khaled Harras

Computer Science Faculty Works

Mobile devices such as smart-phones and tablets are becoming ubiquitous, with ever increasing communication capabilities. In situations where the necessary infrastructure is unavailable, costly, or overloaded, opportunistically connecting theses devices becomes a challenging area of research. Data is disseminated using nodes that store-carry-and-forward messages across the network. In such networks, node cooperation is fundamental for the message delivery process. Therefore, the lack of node cooperation (e.g., a node may refuse to act as a relay and settle for sending and receiving its own data) causes considerable degradation in the network. In order to ensure node cooperation in such networks, we …

A Horizontal Edges Bound For The Independence Number Of A Graph, Michelle Grigsby

Theses and Dissertations

The independence number alpha of a graph is the size of a maximum independent set of vertices. An independent set is a set of vertices where every pair of vertices in non-adjacent. This number is known to be hard to compute. The bound we worked with is defined as epsilon = max[e(v)-eh(v)] over all the vertices in the vertex set, V(G). e(v) is the number of vertices at even distance from v. eh(v) is the number of edges both of whose endpoints are at even distance from v. Epsilon can be calculated in polynomial time. Siemion Fajtlowicz proved that alpha …

The Sn 393-Snr Rx J1713.7-3946 (G347.3-0.5) Connection, Robert A. Fesen, Richard Kremer, Daniel Patnaude, Dan Milisavljevic

Dartmouth Scholarship

Although the connection of the Chinese "guest" star of 393 AD with the Galactic supernova remnant RX J1713.7-3946 (G347.3-0.5) made by Wang et al. in 1997 is consistent with the remnant's relatively young properties and the guest star's projected position within the "tail" of the constellation Scorpius, there are difficulties with such an association. The brief Chinese texts concerning the 393 AD guest star make no comment about its apparent brightness, stating only that it disappeared after eight months. However, at the remnant's current estimated 1-1.3 kpc distance and A _V 3, its supernova (SN) should have been a visually …

The Chernobyl Disaster : Reflection After 25 Years = 切爾諾貝爾核災難25年後的反思, Valentin Yakushik

South South Forum 南南論壇

The adverse technogenic impact of industrial accidents that have gripped the world in recent decades definitely testifies to the problem-ridden character of contemporary economic and technological development. This is especially evident on the example of nuclear industry, which proved to be a source of dangerous pollution in case of potential (and real) catastrophes, as recently borne out by the Fukushima disaster. In this regard, the issues of Chernobyl disaster once again become the part of the discourse centered on the analysis of global nuclear industry problems. Likewise, current situation in Ukraine demands deeper investigation of the problems of technological development, …

Planning Framework Options For The Massachusetts Ocean Plan (Draft), Jack Wiggin, Kristin Uiterwyk, Steve Bliven, Dan Hellin, John Duff, David Terkla, Robert E. Bowen, Andrew A. Rosenberg, Jennie Harrington, Jill H. Swasey, Suzanne Iudicello, Robert O’Boyle, Porter Hoagland, Hauke L. Kite-Powell, Di Jin, Fara Courtney, Rich Delaney, Pat Hughes, Tracey Morin Dalton, Suzanne Goulet Orenstein, Charles N. Ehler, Fannie Douvere, Les Kaufman, Charles T. Mccaffrey Jr., Nicholas Napoli, Stephanie Moura, Kim Starbuck

David G. Terkla

The Massachusetts Ocean Partnership (MOP) Planning Frameworks Team, in consultation with the Massachusetts Executive Office of Energy and Environmental Affairs (EEA), and based on collective experience and a review of ocean, coastal and resource management programs from the US and other countries, suggests that nine elements are essential components of the framework for the Massachusetts Ocean Plan and its implementation. While management plans and programs generally have these elements in common, there are a range of options for carrying out each program component. These options were presented to structure and inform the development of the Massachusetts Ocean Plan. For the …

2010 Massachusetts Recreational Boater Survey: Final Report Submitted To The Massachusetts Ocean Partnership, Dan Hellin, Jack Wiggin, Kristin Uiterwyk, Kim Starbuck, Nicholas Napoli, David Terkla, Chris Watson, Anthony Roman, Leona Roach, Tim Welch

David G. Terkla

The Massachusetts Ocean Management Plan (Plan) completed in 2009 recognized recreational boating as an activity with “significant actual and prospective conflicts among multiple waterway uses in Massachusetts” and included the economic value of recreational boating as a key socio-economic indicator that will be used to inform coastal management. At the time of Plan completion, statistically robust recreational boating data were identified as an important need for comprehensive ocean planning. To fill this data gap, the 2010 Massachusetts Recreational Boater Survey gathered information on boating activity in Massachusetts’ coastal and ocean waters directly from recreational boaters. Researchers sent 10,000 surveys to …

Paleomagnetic Constraints On Deformation Of Superfast-Spread Oceanic Crust Exposed At Pito Deep Rift, Andrew J. Horst, R. J. Varga, J. S. Gee, J. A. Karson

Natural Resources and Earth Sciences Faculty Research

The uppermost oceanic crust produced at the superfast spreading (∼142 km Ma −1, full‐spreading rate) southern East Pacific Rise (EPR) during the Gauss Chron is exposed in a tectonic window along the northeastern wall of the Pito Deep Rift. Paleomagnetic analysis of fully oriented dike (62) and gabbro (5) samples from two adjacent study areas yield bootstrapped mean remanence directions of 38.9° ± 8.1°, −16.7° ± 15.6°, n = 23 (Area A) and 30.4° ± 8.0°, −25.1° ± 12.9°, n = 44 (Area B), both are significantly distinct from the Geocentric Axial Dipole expected direction at 23° S. Regional tectonics …

A Perceptual Metric For Photo Retouching, Eric Kee, Hany Farid

Dartmouth Scholarship

In recent years, advertisers and magazine editors have been widely criticized for taking digital photo retouching to an extreme. Impossibly thin, tall, and wrinkle- and blemish-free models are routinely splashed onto billboards, advertisements, and magazine covers. The ubiquity of these unrealistic and highly idealized images has been linked to eating disorders and body image dissatisfaction in men, women, and children. In response, several countries have considered legislating the labeling of retouched photos. We describe a quantitative and perceptually meaningful metric of photo retouching. Photographs are rated on the degree to which they have been digitally altered by explicitly modeling and …

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 …

Model For Amorphous Aggregation Processes, Samual Stranks, Heath Ecroyd, Steve Van Sluyter, Elizabeth J. Waters, John A. Carver, Lorenz Von Smekal

Heath Ecroyd

The amorphous aggregation of proteins is associated with many phenomena, ranging from the formation of protein wine haze to the development of cataract in the eye lens and the precipitation of recombinant proteins during their expression and purification. While much literature exists describing models for linear protein aggregation, such as amyloid fibril formation, there are few reports of models which address amorphous aggregation. Here, we propose a model to describe the amorphous aggregation of proteins which is also more widely applicable to other situations where a similar process occurs, such as in the formation of colloids and nanoclusters. As first …

Endogenous Redox Activity In Mouse Spermatozoa And Its Role In Regulating The Tyrosine Phosphorylation Events Associated With Sperm Capacitation, Heath W. Ecroyd, Russell C. Jones, Robert J. Aitken

Heath Ecroyd

We investigated the role of endogenous redox activity in regulating the signal transduction pathway leading to tyrosine phosphorylation in mouse spermatozoa. Endogenous redox activity was monitored using a luminol-peroxidase chemiluminescent probe. Chemiluminescence increased in spermatozoa that were actively undergoing cAMP-mediated tyrosine phosphorylation events associated with capacitation and was inhibited in a dose-dependent manner by addition of catalase or diphenylene iodonium, both of which also inhibited tyrosine phosphorylation within the cell at points downstream of cAMP. Excluding bicarbonate from the incubation medium reduced the redox activity of sperm by 80-90% and dramatically reduced tyrosine phosphorylation. This study provides the first evidence …

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 …

Carboxymethylated-K-Casein: A Convenient Tool For The Identification Of Polyphenolic Inhibitors Of Amyloid Fibril Formation, John A. Carver, Peter J. Duggan, Heath Ecroyd, Yanqin Liu, Adam G. Meyer, C E. Tranberg

Heath Ecroyd

Reduced and carboxymethylated-κ-casein (RCM-κ-CN) is a milk-derived amyloidogenic protein that readily undergoes nucleation-dependent aggregation and amyloid fibril formation via a similar pathway to disease-specific amyloidogenic peptides like amyloid beta (Aβ), which is associated with Alzheimer’s disease. In this study, a series of flavonoids, many known to be inhibitors of Aβ fibril formation, were screened for their ability to inhibit RCM-κ-CN fibrilisation, and the results were compared with literature data on Aβ inhibition. Flavonoids that had a high degree of hydroxylation and molecular planarity gave good inhibition of RCM-κ-CN fibril formation. IC50 values were between 10- and 200-fold higher with RCM-κ-CN …

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 …

An Epididymal Form Of Cauxin, A Carboxylesterase-Like Enzyme, Is Present And Active In Mammalian Male Reproductive Fluids, Heath W. Ecroyd, Maya Belghazi, Jl Dacheux, M Miyazaki, T Yamashita, Jl Gatti

Heath Ecroyd

Mass spectrometric analysis of a prion protein (PrP)-containing complex isolated from ram cauda epididymal fluid revealed a protein that showed homology to a carboxylesterase-like protein previously identified in cat urine (cauxin). Using anticauxin antibodies, immunoreactive bands were detected in corpus and cauda epididymal fluid from all mammals tested (ram, boar, mouse, and cat). In the ram, the protein was also present in seminal fluid but not found to be associated with sperm. The bands reacting with the anti-cauxin antibody coincided with those having esterase activity in a zymographic assay and its levels paralleled the esterase activity of native epididymal fluids. …

The Dissociated Form Of Kappa-Casein Is The Precursor To Its Amyloid Fibril Formation, Heath Ecroyd, David Thorn, Yanqin Liu, John Carver

Heath Ecroyd

Bovine milk kappa-casein forms a self-associating oligomeric micelle-like species, in equilibrium with dissociated forms. In its native form, intra- and inter-molecular disulfide bonds lead to the formation of multimeric species ranging from monomers to decamers. When incubated under conditions of physiological pH and temperature, both reduced and non-reduced kappa-casein form highly structured beta-sheet amyloid fibrils. We investigated whether the precursor to kappa-casein fibril formation is a dissociated state of the protein or its oligomeric micelle-like form. We show that reduced kappa-casein is capable of forming fibrils well below its critical micelle concentration, i.e. at concentrations where only dissociated forms of …