Digital Commons Network^™

The Pseudomonas Aeruginosa Magnesium Transporter Mgte Inhibits Transcription Of The Type Iii Secretion System, Gregory G. Anderson, Timothy L. Yahr, Rustin R. Lovewell, George A. O'Toole

Dartmouth Scholarship

Pseudomonas aeruginosa is an opportunistic pathogen that causes life-long pneumonia in individuals with cystic fibrosis (CF). These long-term infections are maintained by bacterial biofilm formation in the CF lung. We have recently developed a model of P. aeruginosa biofilm formation on cultured CF airway epithelial cells. Using this model, we discovered that mutation of a putative magnesium transporter gene, called mgtE, led to increased cytotoxicity of P. aeruginosa toward epithelial cells. This altered toxicity appeared to be dependent upon expression of the type III secretion system (T3SS). In this study, we found that mutation of mgtE results in increased T3SS …

H-Ns Binding And Repression Of The Ctx Promoter In Vibrio Cholerae, Emily A. Stonehouse, Robin R. Hulbert, Melinda B. Nye, Karen Skorupski, Ronald K. Taylor

Dartmouth Scholarship

Expression of the ctx and tcp genes, which encode cholera toxin and the toxin coregulated pilus, the Vibrio cholerae O1 virulence determinants having the largest contribution to cholera disease, is repressed by the nucleoid-associated protein H-NS and activated by the AraC-like transcriptional regulator ToxT. To elucidate the molecular mechanism by which H-NS controls transcription of the ctxAB operon, H-NS repression and binding were characterized by using a promoter truncation series, gel mobility shift assays, and DNase I footprinting. Promoter regions found to be important for H-NS repression correlated with in vitro binding. Four main H-NS binding regions are present at …

Salicylic Acid Diminishes Staphylococcus Aureus Capsular Polysaccharide Type 5 Expression, Lucia P. Alvarez, Maria S. Barbagelata, Mariana Gordiola, A. L. Cheung

Dartmouth Scholarship

Capsular polysaccharides (CP) of serotypes 5 (CP5) and 8 (CP8) are major Staphylococcus aureus virulence factors. Previous studies have shown that salicylic acid (SAL), the main aspirin metabolite, affects the expression of certain bacterial virulence factors. In the present study, we found that S. aureus strain Reynolds (CP5) cultured with SAL was internalized by MAC-T cells in larger numbers than strain Reynolds organisms not exposed to SAL. Furthermore, the internalization of the isogenic nonencapsulated Reynolds strain into MAC-T cells was not significantly affected by preexposure to SAL. Pretreatment of S. aureus strain Newman with SAL also enhanced internalization into MAC-T …

Uterine Epithelial Cell Regulation Of Dc-Sign Expression Inhibits Transmitted/Founder Hiv-1 Trans Infection By Immature Dendritic Cells, Daniel O. Ochiel, Christina Ochsenbauer, John C. Kappes, Mimi Ghosh, John V. Fahey, Charles R. Wira

Dartmouth Scholarship

Background:

Sexual transmission accounts for the majority of HIV-1 infections. In over 75% of cases, infection is initiated by a single variant (transmitted/founder virus). However, the determinants of virus selection during transmission are unknown. Host cell-cell interactions in the mucosa may be critical in regulating susceptibility to infection. We hypothesized in this study that specific immune modulators secreted by uterine epithelial cells modulate susceptibility of dendritic cells (DC) to infection with HIV-1.

Methodology/Principal Findings:

Here we report that uterine epithelial cell secretions (i.e. conditioned medium, CM) decreased DC-SIGN expression on immature dendritic cells via a transforming growth factor beta (TGF-β) …

Pauli Spin Blockade And Lifetime-Enhanced Transport In A Si/Sige Double Quantum Dot, C. B. Simmons, Teck Seng Koh, Nakul Shaji, Madhu Thalakulam, L. J. Klein, Hua Qin, H. Luo, D. E. Savage, M. G. Lagally, A. J. Rimberg

Dartmouth Scholarship

We analyze electron-transport data through a Si/SiGe double quantum dot in terms of spin blockade and lifetime-enhanced transport (LET), which is transport through excited states that is enabled by long spin-relaxation times. We present a series of low-bias voltage measurements showing the sudden appearance of a strong tail of current that we argue is an unambiguous signature of LET appearing when the bias voltage becomes greater than the singlet-triplet splitting for the (2,0) electron state. We present eight independent data sets, four in the forward-bias (spin-blockade) regime and four in the reverse-bias (lifetime-enhanced transport) regime and show that all eight …

Information-Preserving Structures: A General Framework For Quantum Zero-Error Information, Robin Blume-Kohout, Hui Khoon Ng, David Poulin, Lorenza Viola

Dartmouth Scholarship

Quantum systems carry information. Quantum theory supports at least two distinct kinds of information (classical and quantum), and a variety of different ways to encode and preserve information in physical systems. A system’s ability to carry information is constrained and defined by the noise in its dynamics. This paper introduces an operational framework, using information-preserving structures, to classify all the kinds of information that can be perfectly (i.e., with zero error) preserved by quantum dynamics. We prove that every perfectly preserved code has the same structure as a matrix algebra, and that preserved information can always be corrected. We …

Type Ii Protein Arginine Methyltransferase 5 (Prmt5) Is Required For Circadian Pperiod Determination In Arabidopsis Thaliana, Sunghyun Hong, Hae-Ryoung Song, Kerry Lutz, Randall A. Kerstetter, Todd P. Michael, C. Robertson Mcclung

Dartmouth Scholarship

Posttranslational modification is an important element in circadian clock function from cyanobacteria through plants and mammals. For example, a number of key clock components are phosphorylated and thereby marked for subsequent ubiquitination and degradation. Through forward genetic analysis we demonstrate that protein arginine methyltransferase 5 (PRMT5; At4g31120) is a critical determinant of circadian period in Arabidopsis. PRMT5 is coregulated with a set of 1,253 genes that shows alterations in phase of expression in response to entrainment to thermocycles versus photocycles in constant temperature. PRMT5 encodes a type II protein arginine methyltransferase that catalyzes the symmetric dimethylation of arginine residues (Rsme2). …

Wording Effects In Moral Judgments, Ross E. O'Hara, Walter Sinnott-Armstrong, Nicholas A. Sinnott-Armstrong

Dartmouth Scholarship

As the study of moral judgments grows, it becomes imperative to compare results across studies in order to create unified theories within the field. These efforts are potentially undermined, however, by variations in wording used by different researchers. The current study sought to determine whether, when, and how variations in wording influence moral judgments. Online participants responded to 15 different moral vignettes (e.g., the trolley problem) using 1 of 4 adjectives: “wrong”, “inappropriate”, “forbidden”, or “blameworthy”. For half of the sample, these adjectives were preceded by the adverb “morally”. Results indicated that people were more apt to judge an act …

Singular Value Decomposition Metrics Show Limitations Of Detector Design In Diffuse Fluorescence Tomography, Frederic Leblond, Kenneth M. Tichauer, Brian W. Pogue

Dartmouth Scholarship

The spatial resolution and recovered contrast of images reconstructed from diffuse fluorescence tomography data are limited by the high scattering properties of light propagation in biological tissue. As a result, the image reconstruction process can be exceedingly vulnerable to inaccurate prior knowledge of tissue optical properties and stochastic noise. In light of these limitations, the optimal source-detector geometry for a fluorescence tomography system is non-trivial, requiring analytical methods to guide design. Analysis of the singular value decomposition of the matrix to be inverted for image reconstruction is one potential approach, providing key quantitative metrics, such as singular image mode spatial …

Excision Dynamics Of Vibrio Pathogenicity Island-2 From Vibrio Cholerae: Role Of A Recombination Directionality Factor Vefa, Salvador Almagro-Moreno, Michael G. Napolitano, E. Fidelma Boyd

Dartmouth Scholarship

Vibrio Pathogenicity Island-2 (VPI-2) is a 57 kb region present in choleragenic V. cholerae isolates that is required for growth on sialic acid as a sole carbon source. V. cholerae non-O1/O139 pathogenic strains also contain VPI-2, which in addition to sialic acid catabolism genes also encodes a type 3 secretion system in these strains. VPI-2 integrates into chromosome 1 at a tRNA-serine site and encodes an integrase intV2 (VC1758) that belongs to the tyrosine recombinase family. ntV2 is required for VPI-2 excision from chromosome 1, which occurs at very low levels, and formation of a non-replicative circular intermediate.

Requirement For Golgi-Localized Pi(4)P In Fusion Of Copii Vesicles With Golgi Compartments, Andres Lorente-Rodriguez, Charles Barlowe

Dartmouth Scholarship

The role of specific membrane lipids in transport between endoplasmic reticulum (ER) and Golgi compartments is poorly understood. Using cell-free assays that measure stages in ER-to-Golgi transport, we screened a variety of enzyme inhibitors, lipid-modifying enzymes, and lipid ligands to investigate requirements in yeast. The pleckstrin homology (PH) domain of human Fapp1, which binds phosphatidylinositol-4-phosphate (PI(4)P) specifically, was a strong and specific inhibitor of anterograde transport. Analysis of wild type and mutant PH domain proteins in addition to recombinant versions of the Sac1p phosphoinositide-phosphatase indicated that PI(4)P was required on Golgi membranes for fusion with coat protein complex II (COPII) …

Building Graphs From Colored Trees, Rachel M. Esselstein, Peter Winkler

Dartmouth Scholarship

We will explore the computational complexity of satisfying certain sets of neighborhood conditions in graphs with various properties. More precisely, fix a radius $\rho$ and let $N(G)$ be the set of isomorphism classes of $\rho$-neighborhoods of vertices of $G$ where $G$ is a graph whose vertices are colored (not necessarily properly) by colors from a fixed finite palette. The root of the neighborhood will be the unique vertex at the "center" of the graph. Given a set S of colored graphs with a unique root, when is there a graph G with N (G) = S? Or N (G) ⊂ …

Resistive Mhd Reconstruction Of Two-Dimensional Coherent Structures In Space, W L. Teh, B U. Sonnerup, J Birn, R E. Denton

Dartmouth Scholarship

We present a reconstruction technique to solve the steady resistive MHD equations in two dimensions with initial inputs of field and plasma data from a single space- craft as it passes through a coherent structure in space. At least two components of directly measured electric fields (the spacecraft spin-plane components) are required for the reconstruction, to produce two-dimensional (2-D) field and plasma maps of the cross section of the structure. For con- venience, the resistivity tensor η is assumed diagonal in the reconstruction coordinates, which allows its values to be es- timated from Ohm’s law, E+v×B=η·j. In the present paper, …

Supply Sensitive Services In Swiss Ambulatory Care: An Analysis Of Basic Health Insurance Records For 2003-2007, André Busato, Pius Matter, Beat Künzi, David C. Goodman

Dartmouth Scholarship

Swiss ambulatory care is characterized by independent, and primarily practice-based, physicians, receiving fee for service reimbursement. This study analyses supply sensitive services using ambulatory care claims data from mandatory health insurance. A first research question was aimed at the hypothesis that physicians with large patient lists decrease their intensity of services and bill less per patient to health insurance, and vice versa: physicians with smaller patient lists compensate for the lack of patients with additional visits and services. A second research question relates to the fact that several cantons are allowing physicians to directly dispense drugs to patients ('self-dispensation') whereas …

Carhsp1 Is Required For Effective Tumor Necrosis Factor Alpha Mrna Stabilization And Localizes To Processing Bodies And Exosomes, Jason R. Pfeiffer, Bethany L. Mcavoy, Ryan E. Fecteau, Kristen M. Deleault, Seth A. Brooks

Dartmouth Scholarship

Tumor necrosis factor alpha (TNF-α) is a critical mediator of inflammation, and its production is tightly regulated, with control points operating at nearly every step of its biosynthesis. We sought to identify uncharacterized TNF-α 3' untranslated region (3'UTR)-interacting proteins utilizing a novel screen, termed the RNA capture assay. We identified CARHSP1, a cold-shock domain-containing protein. Knockdown of CARHSP1 inhibits TNF-α protein production in lipopolysaccharide (LPS)-stimulated cells and reduces the level of TNF-α mRNA in both resting and LPS-stimulated cells. mRNA stability assays demonstrate that CARHSP1 knockdown decreases TNF-α mRNA stability from a half-life (t(1/2)) of 49 min to a t(1/2) …

Importance Of Phase Unwrapping For The Reconstruction Of Microwave Tomographic Images, Tomasz M. Grzegorczyk, Paul M. Meaney, Soon Ik Jeon, Shireen D. Geimer, Keith D. Paulsen

Dartmouth Scholarship

Microwave image reconstruction is typically based on a regularized least-square minimization of either the complex-valued field difference between recorded and modeled data or the logarithmic transformation of these field differences. Prior work has shown anecdotally that the latter outperforms the former in limited surveys of simulated and experimental phantom results. In this paper, we provide a theoretical explanation of these empirical findings by developing closed form solutions for the fie

Micrornas Reveal The Interrelationships Of Hagfish, Lampreys, And Gnathostomes And The Nature Of The Ancestral Vertebrate, Alysha M. Heimberg, Richard Cowper-Sal{Middle Dot}Lari, Marie Semon, Philip C. J. Donoghue, Kevin J. Peterson

Dartmouth Scholarship

Hagfish and lampreys are the only living representatives of the jawless vertebrates (agnathans), and compared with jawed vertebrates (gnathostomes), they provide insight into the embryology, genomics, and body plan of the ancestral vertebrate. However, this insight has been obscured by controversy over their interrelationships. Morphological cladistic analyses have identified lampreys and gnathostomes as closest relatives, whereas molecular phylogenetic studies recover a monophyletic Cyclostomata (hagfish and lampreys as closest relatives). Here, we show through deep sequencing of small RNA libraries, coupled with genomic surveys, that Cyclostomata is monophyletic: hagfish and lampreys share 4 unique microRNA families, 15 unique paralogues of more …

Identifying Functional Relationships Within Sets Of Co-Expressed Genes By Combining Upstream Regulatory Motif Analysis And Gene Expression Information, Viktor Martyanov, Robert H. Gross

Dartmouth Scholarship

Existing clustering approaches for microarray data do not adequately differentiate between subsets of co-expressed genes. We devised a novel approach that integrates expression and sequence data in order to generate functionally coherent and biologically meaningful subclusters of genes. Specifically, the approach clusters co-expressed genes on the basis of similar content and distributions of predicted statistically significant sequence motifs in their upstream regions.

On The Evidence For Species Coexistence: A Critique Of The Coexistence Program, Adam M. Siepielski, Mark A. Mcpeek

Dartmouth Scholarship

A major challenge in ecology is to understand how the millions of species on Earth are organized into biological communities. Mechanisms promoting coexistence are one such class of organizing processes, which allow multiple species to persist in the same trophic level of a given web of species interactions. If some mechanism promotes the coexistence of two or more species, each species must be able to increase when it is rare and the others are at their typical abundances; this invasibility criterion is fundamental evidence for species coexistence regardless of the mechanism. In an attempt to evaluate the level of empirical …

Aminoglycoside Resistance Of Pseudomonas Aeruginosa Biofilms Modulated By Extracellular Polysaccharide, Wajiha Khan, Steve P. Bernier, Sherry L. Kuchma, John H. Hammond, Fariha Hasan, George A. O'Toole

Dartmouth Scholarship

Pseudomonas aeruginosa is an opportunistic pathogen that produces sessile communities known as biofilms that are highly resistant to antibiotic treatment. Limited information is available on the exact role of various components of the matrix in biofilm-associated antibiotic resistance. Here we show that the presence of extracellular polysaccharide reduced the extent of biofilm-associated antibiotic resistance for one class of antibiotics. Minimal bactericidal concentration (MBC) for planktonic and biofilm cells of P. aeruginosa PA14 was measured using a 96 well microtiter plate assay. The MBC of biofilm-grown ΔpelA mutant, which does not produce the Pel polysaccharide, was 4-fold higher for tobramycin and …

Automated Classification Of Breast Pathology Using Local Measures Of Broadband Reflectance, Ashley M. Laughney, Venkataramanan Krishnaswamy, Pilar Beatriz Garcia-Allende, Olga M. Conde, Wendy A. Wells, Keith D. Paulsen, Brian W. Pogue

Dartmouth Scholarship

We demonstrate that morphological features pertinent to a tissue's pathology may be ascertained from localized measures of broadband reflectance, with a mesoscopic resolution (100-μm lateral spot size) that permits scanning of an entire margin for residual disease. The technical aspects and optimization of a k-nearest neighbor classifier for automated diagnosis of pathologies are presented, and its efficacy is validated in 29 breast tissue specimens. When discriminating between benign and malignant pathologies, a sensitivity and specificity of 91 and 77% was achieved. Furthermore, detailed subtissue-type analysis was performed to consider how diverse pathologies influence scattering response and overall classification efficacy. The …

Image Guided Near-Infrared Spectroscopy Of Breast Tissue In Vivo Using Boundary Element Method, Subhadra Srinivasan, Colin M. Carpenter, Hamid R. Ghadyani, Senate J. Taka, Peter A. Kaufman, Roberta M. Diflorio-Alexander, Wendy A. Wells, Brian W. Pogue, Keith D. Paulsen

Dartmouth Scholarship

We demonstrate quantitative functional imaging using image-guided near-infrared spectroscopy (IG-NIRS) implemented with the boundary element method (BEM) for reconstructing 3-D optical property estimates in breast tissue in vivo. A multimodality MRI-NIR system was used to collect measurements of light reflectance from breast tissue. The BEM was used to model light propagation in 3-D based only on surface discretization in order to reconstruct quantitative values of total hemoglobin (HbT), oxygen saturation, water, and scatter. The technique was validated in experimental measurements from heterogeneous breast-shaped phantoms with known values and applied to a total of seven subjects comprising six healthy individuals …

Dynamic Evolution Of Precise Regulatory Encodings Creates The Clustered Site Signature Of Enhancers, Justin Crocker, Nathan Potter, Albert Erives

Dartmouth Scholarship

Concentration gradients of morphogenic proteins pattern the embryonic axes of Drosophila by activating different genes at different concentrations. The neurogenic ectoderm enhancers (NEEs) activate different genes at different threshold levels of the Dorsal (Dl) morphogen, which patterns the dorsal/ventral axis. NEEs share a unique arrangement of highly constrained DNA-binding sites for Dl, Twist (Twi), Snail (Sna) and Suppressor of Hairless (Su(H)), and encode the threshold variable in the precise length of DNA that separates one well-defined Dl element from a Twi element. However, NEEs also possess dense clusters of variant Dl sites. Here, we show that these increasingly variant sites …

Quantum Equivalent Magnetic Fields That Are Not Classically Equivalent, Carolyn Gordon, William Kirwin, Dorothee Schueth, David Webb

Dartmouth Scholarship

We construct pairs of compact Kähler-Einstein manifolds (Mi,gi,ωi)(i=1,2) of complex dimension n with the following properties: The canonical line bundle Li=⋀ⁿT∗M_i has Chern class [ω_i/2π], and for each positive integer k the tensor powers L^⊗k₁ and L^⊗k₂ are isospectral for the bundle Laplacian associated with the canonical connection, while M₁ and M₂ – and hence T∗M₁ and T∗M₂ – are not homeomorphic. In the context of geometric quantization, we interpret these examples as magnetic fields which are quantum equivalent but not classically equivalent. Moreover, we construct many …

Deletion Of The Cel48s Cellulase From Clostridium Thermocellum, Daniel G. Olson, Shital A. Tripathi, Richard J. Giannone, Jonathan Lo, Nicky C. Caiazza, David A. Hogsett, Robert L. Hettich, Adam M. Guss, Genia Dubrovsky, Lee R. Lynd

Dartmouth Scholarship

Clostridium thermocellum is a thermophilic anaerobic bacterium that rapidly solubilizes cellulose with the aid of a multienzyme cellulosome complex. Creation of knockout mutants for Cel48S (also known as CelS, S(S), and S8), the most abundant cellulosome subunit, was undertaken to gain insight into its role in enzymatic and microbial cellulose solubilization. Cultures of the Cel48S deletion mutant (S mutant) were able to completely solubilize 10 g/L crystalline cellulose. The cellulose hydrolysis rate of the S mutant strain was 60% lower than the parent strain, with the S mutant strain also exhibiting a 40% reduction in cell yield. The cellulosome produced …

4-Phenyl­Sulfon­Yl-2-(P-Tolyl­Sulfon­Yl)-1h,8h-Pyrrolo­[2,3-B]Indole, Jeanese C. Badenock, Jason A. Jordan, Erin T. Pelkey, Gordon W. Gribble, Jerry P. Jasinski

Dartmouth Scholarship

The title compound, C23H18N2O4S2, contains a pyrrolo group fused onto the plane of an indole ring with phenylsulfonyl and p-toluenesulfonyl groups bonded to the indole and pyrrolo rings. The angles between the mean planes of the pyrrolo- indole ring and the phenylsulfonyl and p-toluenesulfonyl rings are 73.7 (6) and 80.6 (0)􏰈, respectively. The dihedral angle between the mean planes of the two benzene rings is 78.7 (4)􏰈. In the crystal, both classical N—H􏰇 􏰇 􏰇O and non-classical C— H􏰇 􏰇 􏰇O intermolecular hydrogen-bonding interactions are observed, as well as weak 􏰁–􏰁 interactions [centroid–centroid distances = 3.6258 (8) and 3.9298 (8) …

Put Your Money Where Your Butt Is: A Commitment Contract For Smoking Cessation, Xavier Giné, Dean Karlan, Jonathan Zinman

Dartmouth Scholarship

We designed and tested a voluntary commitment product to help smokers quit smoking. The product (CARES) offered smokers a savings account in which they deposit funds for six months, after which they take a urine test for nicotine and cotinine. If they pass, their money is returned; otherwise, their money is forfeited to charity. Of smokers offered CARES, 11 percent took up, and smokers randomly offered CARES were 3 percentage points more likely to pass the 6-month test than the control group. More importantly, this effect persisted in surprise tests at 12 months, indicating that CARES produced lasting smoking cessation. …

Interferon Regulatory Factor 3-Dependent Pathways Are Critical For Control Of Herpes Simplex Virus Type 1 Central Nervous System Infection, Vineet D. Menachery, Tracy J. Pasieka, David A. Leib

Dartmouth Scholarship

The initiation of the immune response at the cellular level relies on specific recognition molecules to rapidly signal viral infection via interferon (IFN) regulatory factor 3 (IRF-3)-dependent pathways. The absence of IRF-3 would be expected to render such pathways inoperative and thereby significantly affect viral infection. Unexpectedly, a previous study found no significant change in herpes simplex virus (HSV) pathogenesis in IRF-3^−/− mice following intravenous HSV type 1 (HSV-1) challenge (K. Honda, H. Yanai, H. Negishi, M. Asagiri, M. Sato, T. Mizutani, N. Shimada, Y. Ohba, A. Takaoka, N. Yoshida, and T. Taniguchi, Nature 434:772-777, 2005). In contrast, the …

The Trilinear Hamiltonian: A Zero-Dimensional Model Of Hawking Radiation From A Quantized Source, Paul D. Nation, Miles P. Blencowe

Dartmouth Scholarship

We investigate a quantum parametric amplifier with dynamical pump mode, viewed as a zero-dimensional model of Hawking radiation from an evaporating black hole. We derive the conditions under which the spectrum of particles generated from vacuum fluctuations deviates from the thermal spectrum predicted for the conventional parametric amplifier. We find that significant deviations arise when the pump mode (black hole) has emitted nearly half of its initial energy into the signal (Hawking radiation) and idler (in-falling particle) modes. As a model of black hole dynamics, this finding lends support to the view that late-time Hawking radiation contains information about the …

Optical Discovery Of An Apparent Galactic Supernova Remnant G159.6+7.3, Robert A. Fesen, Dan Milisavljevic

Dartmouth Scholarship

Deep Hα images of portions of a faint 3° × 4° Hα shell centered at l = 1596, b = 73 seen on the Virginia Tech Spectral Line Survey images revealed the presence of several thin emission filaments along its eastern limb. Low-dispersion optical spectra of two of these filaments covering the wavelength range of 4500-7500 Å show narrow Hα line emissions with velocities around –170 ± 30 km s^–1. Both the morphology and spectra of these filaments are consistent with a Balmer-dominated shock interpretation and we propose that these optical filaments indicate that the large Hα emission …