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Articles 1 - 29 of 29
Full-Text Articles in Physical Sciences and Mathematics
Identification Of Disease-Linked Hyperactivating Mutations In Ube3a Through Large-Scale Functional Variant Analysis, Kellan P. Weston, Xiaoyi Gao, Jinghan Zhao, Kwang Soo Kim, Susan E. Maloney, Jill Gotoff, Sumit Parikh, Yen Chen Leu, Kuen Phon Wu, Marwan Shinawi, Joshua P. Steimel, Joseph S. Harrison, Jason J. Yi
Identification Of Disease-Linked Hyperactivating Mutations In Ube3a Through Large-Scale Functional Variant Analysis, Kellan P. Weston, Xiaoyi Gao, Jinghan Zhao, Kwang Soo Kim, Susan E. Maloney, Jill Gotoff, Sumit Parikh, Yen Chen Leu, Kuen Phon Wu, Marwan Shinawi, Joshua P. Steimel, Joseph S. Harrison, Jason J. Yi
College of the Pacific Faculty Articles
The mechanisms that underlie the extensive phenotypic diversity in genetic disorders are poorly understood. Here, we develop a large-scale assay to characterize the functional valence (gain or loss-of-function) of missense variants identified in UBE3A, the gene whose loss-of-function causes the neurodevelopmental disorder Angelman syndrome. We identify numerous gain-of-function variants including a hyperactivating Q588E mutation that strikingly increases UBE3A activity above wild-type UBE3A levels. Mice carrying the Q588E mutation exhibit aberrant early-life motor and communication deficits, and individuals possessing hyperactivating UBE3A variants exhibit affected phenotypes that are distinguishable from Angelman syndrome. Additional structure-function analysis reveals that Q588 forms a regulatory site …
Specific Splice Junction Detection In Single Cells With Sicilian, Roozbeh Dehghannasiri, Julia E. Olivieri, Ana Damljanovic, Julia Salzman
Specific Splice Junction Detection In Single Cells With Sicilian, Roozbeh Dehghannasiri, Julia E. Olivieri, Ana Damljanovic, Julia Salzman
All Faculty Articles - School of Engineering and Computer Science
Precise splice junction calls are currently unavailable in scRNA-seq pipelines such as the 10x Chromium platform but are critical for understanding single-cell biology. Here, we introduce SICILIAN, a new method that assigns statistical confidence to splice junctions from a spliced aligner to improve precision. SICILIAN is a general method that can be applied to bulk or single-cell data, but has particular utility for single-cell analysis due to that data’s unique challenges and opportunities for discovery. SICILIAN’s precise splice detection achieves high accuracy on simulated data, improves concordance between matched single-cell and bulk datasets, and increases agreement between biological replicates. SICILIAN …
Designed, Highly Expressing, Thermostable Dengue Virus 2 Envelope Protein Dimers Elicit Quaternary Epitope Antibodies, Stephen T. Kudlacek, Stefan Metz, Devina Thiono, Alexander M. Payne, Thanh T.N. Phan, Shaomin Tian, Lawrence J. Forsberg, Jack Mcguire, Ian Selm, Shu Zhang, Ashutosh Tripathy, Joseph S. Harrison, Nathan I. Niceley, Sandrine Soman, Michael K. Mccracken, Gregory D. Gromowski, Richard G. Jarman, Lakshmanane Premkumar, Aravinda M. De Silva, Brian Kuhlman
Designed, Highly Expressing, Thermostable Dengue Virus 2 Envelope Protein Dimers Elicit Quaternary Epitope Antibodies, Stephen T. Kudlacek, Stefan Metz, Devina Thiono, Alexander M. Payne, Thanh T.N. Phan, Shaomin Tian, Lawrence J. Forsberg, Jack Mcguire, Ian Selm, Shu Zhang, Ashutosh Tripathy, Joseph S. Harrison, Nathan I. Niceley, Sandrine Soman, Michael K. Mccracken, Gregory D. Gromowski, Richard G. Jarman, Lakshmanane Premkumar, Aravinda M. De Silva, Brian Kuhlman
College of the Pacific Faculty Articles
Dengue virus (DENV) is a worldwide health burden, and a safe vaccine is needed. Neutralizing antibodies bind to quaternary epitopes on DENV envelope (E) protein homodimers. However, recombinantly expressed soluble E proteins are monomers under vaccination conditions and do not present these quaternary epitopes, partly explaining their limited success as vaccine antigens. Using molecular modeling, we found DENV2 E protein mutations that induce dimerization at low concentrations (<100 pM) and enhance production yield by more than 50-fold. Cross-dimer epitope antibodies bind to the stabilized dimers, and a crystal structure resembles the wild-type (WT) E protein bound to a dimer epitope antibody. Mice immunized with the stabilized dimers developed antibodies that bind to E dimers and not monomers and elicited higher levels of DENV2-neutralizing antibodies compared to mice immunized with WT E antigen. Our findings demonstrate the feasibility of using structure-based design to produce subunit vaccines for dengue and other flaviviruses.
Mechanically Transduced Immunosorbent Assay To Measure Protein-Protein Interactions, Christopher J. Petell, Kathyrn Randene, Michael Pappas, Diego Sandoval, Brian Dstrahl, Joseph S. Harrison, Joshua P. Steimel
Mechanically Transduced Immunosorbent Assay To Measure Protein-Protein Interactions, Christopher J. Petell, Kathyrn Randene, Michael Pappas, Diego Sandoval, Brian Dstrahl, Joseph S. Harrison, Joshua P. Steimel
College of the Pacific Faculty Articles
Measuring protein-protein interaction (PPI) affinities is fundamental to biochemistry. Yet, conventional methods rely upon the law of mass action and cannot measure many PPIs due to a scarcity of reagents and limitations in the measurable affinity ranges. Here, we present a novel technique that leverages the fundamental concept of friction to produce a mechanical signal that correlates to binding potential. The mechanically transduced immunosorbent (METRIS) assay utilizes rolling magnetic probes to measure PPI interaction affinities. METRIS measures the translational displacement of protein-coated particles on a protein-functionalized substrate. The translational displacement scales with the effective friction induced by a PPI, thus …
Rna Splicing Programs Define Tissue Compartments And Cell Types At Single-Cell Resolution, Julia E. Olivieri, Roozbeh Dehghannasiri, Peter Wang, Sori Jang, Antoine De Morree, Serena Y. Tan, Jingsi Ming, Angela R. Wu, Stephen R. Quake, Mark A. Krasnow, Julia Salzman
Rna Splicing Programs Define Tissue Compartments And Cell Types At Single-Cell Resolution, Julia E. Olivieri, Roozbeh Dehghannasiri, Peter Wang, Sori Jang, Antoine De Morree, Serena Y. Tan, Jingsi Ming, Angela R. Wu, Stephen R. Quake, Mark A. Krasnow, Julia Salzman
All Faculty Articles - School of Engineering and Computer Science
The extent splicing is regulated at single-cell resolution has remained controversial due to both available data and methods to interpret it. We apply the SpliZ, a new statistical approach, to detect cell-type-specific splicing in >110K cells from 12 human tissues. Using 10x data for discovery, 9.1% of genes with computable SpliZ scores are cell-type-specifically spliced, including ubiquitously expressed genes MYL6 and RPS24. These results are validated with RNA FISH, single-cell PCR, and Smart-seq2. SpliZ analysis reveals 170 genes with regulated splicing during human spermatogenesis, including examples conserved in mouse and mouse lemur. The SpliZ allows model-based identification of subpopulations indistinguishable …
Euler's De Serie Lambertina, Translated From Latin To English With Supplementary Notes, Sam Gallagher
Euler's De Serie Lambertina, Translated From Latin To English With Supplementary Notes, Sam Gallagher
Euleriana
Originally published in 1779, Euler's De Serie Lambertina provides one of the early examples of the Lambert W function, a special function used in the solution to certain transcendental equations. Following the work of Johann Heinrich Lambert in 1759, who discussed a series solution to the general polynomial in series, and then particularly the solution of the general trinomial, Euler describes a symmetric form of the trinomial and its series solution. Euler investigates the series' special cases and general properties, and its use in solving certain transcendental equations. He provides several proofs of the validity of the series expansion to …
Translation Of Euler's Paper E421, Alexander Aycock
Translation Of Euler's Paper E421, Alexander Aycock
Euleriana
This is paper is the result of Euler’s findings on the Eulerian integral of second kind, i.e. the Γ-function: It summarises results and formulas on and properties of the integral in the title that Euler had obtained up to this point in his career and offers more elegant proofs of those before-mentioned results, formulas and properties. The results include a derivation of the integral in the title from an algebraic integral, the reflection formula for the Γ-function and finally a formula equivalent to the Gaußian multiplication formula for the Γ-function, expressed by Euler using mere integrals of algebraic functions.
Euler And The Multiplication Formula For The Gamma Function, Alexander Aycock
Euler And The Multiplication Formula For The Gamma Function, Alexander Aycock
Euleriana
We show that an apparently overlooked result of Leonhard Euler (1707-1783) from [E421] is essentially equivalent to the general multiplication for- mula for the Γ-function that was proven by Carl Friedrich Gauss (1777-1855) in [Ga28].
On The Rectilinear Motion Of Three Bodies Mutually Attracting Each Other, Sylvio R. Bistafa
On The Rectilinear Motion Of Three Bodies Mutually Attracting Each Other, Sylvio R. Bistafa
Euleriana
This is an annotated translation from Latin of E327 -- De motu rectilineo trium corporum se mutuo attrahentium (“On the rectilinear motion of three bodies mutually attracting each other”). In this publication, Euler considers three bodies lying on a straight line, which are attracted to each other by central forces inversely proportional to the square of their separation distance (inverse-square law). Here Euler finds that the parameter that controls the relative distances among the bodies is given by a quintic function.
Euler's Three-Body Problem, Sylvio R. Bistafa
Euler's Three-Body Problem, Sylvio R. Bistafa
Euleriana
In physics and astronomy, Euler's three-body problem is to solve for the motion of a body that is acted upon by the gravitational field of two other bodies. This problem is named after Leonhard Euler (1707-1783), who discussed it in memoirs published in the 1760s. In these publications, Euler found that the parameter that controls the relative distances among three collinear bodies is given by a quintic equation. Later on, in 1772, Lagrange dealt with the same problem, and demonstrated that for any three masses with circular orbits, there are two special constant-pattern solutions, one where the three bodies remain …
Euler's Miracle, William Dunham
Euler's Miracle, William Dunham
Euleriana
This article features some genuine Eulerian magic. In 1748, Leonhard Euler considered a modification of the harmonic series in which negative signs were attached to various terms by a rule that was far from self-evident. With his accustomed flair, he determined its sum, and the result was utterly improbable. There are a few occasions in mathematics when the term “breathtaking” is not too strong. This is one of them.
Spotlight On The Euler Archive, Cynthia J. Huffman Ph.D.
Spotlight On The Euler Archive, Cynthia J. Huffman Ph.D.
Euleriana
A spotlight on the Euler Archive with a special emphasis on contributions by Dr. C. Edward Sandifer.
Ed Sandifer: An Eulerian Marathoner, Robert E. Bradley
Ed Sandifer: An Eulerian Marathoner, Robert E. Bradley
Euleriana
Ed Sandifer was the founding secretary of the Euler Society. He published a remarkable quantity of Euler scholarship at the time of Euler’s Tercentenary in 2007.
Review: A History Of Mathematics In The United States And Canada (Vol. 1), By David Zitarelli, Lawrence D'Antonio
Review: A History Of Mathematics In The United States And Canada (Vol. 1), By David Zitarelli, Lawrence D'Antonio
Euleriana
This is a review of the 2019 text by David ZItarelli, A History of Mathematics in the United States and Canada. Volume 1: 1492 - 1900
Sharing Contributions To Euler Scholarship, Erik R. Tou, Christopher Goff
Sharing Contributions To Euler Scholarship, Erik R. Tou, Christopher Goff
Euleriana
A summary of this issue's contents.
Co-Evolutionary Analysis Suggests A Role For Tlr9 In Papillomavirus Restriction, Kelly King, Brendan B. Larsen, Sophie Gryseeis, Cécile Richet, Simona Kraberger, Robert Jackson, Michael Worobey, Joseph S. Harrison, Arvind Varsani, Koenraad Van Doorslaer
Co-Evolutionary Analysis Suggests A Role For Tlr9 In Papillomavirus Restriction, Kelly King, Brendan B. Larsen, Sophie Gryseeis, Cécile Richet, Simona Kraberger, Robert Jackson, Michael Worobey, Joseph S. Harrison, Arvind Varsani, Koenraad Van Doorslaer
College of the Pacific Faculty Articles
Upon infection, DNA viruses can be sensed by pattern recognition receptors (PRRs) leading to the activation of type I and III interferons, aimed at blocking infection. Therefore, viruses must inhibit these signaling pathways, avoid being detected, or both. Papillomavirus virions are trafficked from early endosomes to the Golgi apparatus and wait for the onset of mitosis to complete nuclear entry. This unique subcellular trafficking strategy avoids detection by cytoplasmic PRRs, a property that may contribute to establishment of infection. However, as the capsid uncoats within acidic endosomal compartments, the viral DNA may be exposed to detection by toll-like receptor (TLR) …
The Rock 2021, School Of Engineering And Computer Science
The Rock 2021, School Of Engineering And Computer Science
The Rock
No abstract provided.
Euler In Wartime: Publishing In The Seven Years' War, Erik R. Tou
Euler In Wartime: Publishing In The Seven Years' War, Erik R. Tou
Euleriana
At the outbreak of the Seven Years' War in 1756, Leonhard Euler (1707-1783) was a successful and prolific scholar at the Berlin Academy of Sciences, well on his way to producing many significant contributions to 18th century science and mathematics. However, once the war began his opportunities were sharply curtailed. Most of the war did not go well for Prussia, and Euler's place in the midst of this conflict limited his ability to publish his work. With the Euler Archive available online, Gustaf Eneström's index may be analyzed more deeply to uncover the effects of the conflict on Euler's life …
Euler Archive Spotlight, Cynthia J. Huffman Ph.D.
Euler Archive Spotlight, Cynthia J. Huffman Ph.D.
Euleriana
A spotlight on the Euler Archive, including recent translations.
Euler’S Theories Of Musical Tuning With An English Translation Of Du Véritable Caractère De La Musique Moderne, Larry G. Blaine, Susan Ferré
Euler’S Theories Of Musical Tuning With An English Translation Of Du Véritable Caractère De La Musique Moderne, Larry G. Blaine, Susan Ferré
Euleriana
Du Véritable Caractère de la Musique Moderne (E315), a work almost unknown to musical scholars, is an extremely interesting document in the history of tuning systems. A tuning system is simply an arrangement of sound frequencies for use in music. A just tuning is an arrangement in which the ratios of these frequencies are all ratios of whole numbers- preferably small ones. Classically, these ratios involve only factors of 2, 3, and 5. In particular, a very fundamental chord in music of many genres, the so-called major triad, Has frequency ratios 4:5:6. Euler proposes introducing the prime 7, …
Principles For Determining The Motion Of Blood Through Arteries, Sylvio R. Bistafa
Principles For Determining The Motion Of Blood Through Arteries, Sylvio R. Bistafa
Euleriana
Translation of Principia pro motu sanguinis per arterias determinando (E855). This work of 1775 by L. Euler is considered to be the first mathematical treatment of circulatory physiology and hemodynamics.
Euler, Father Of Haemodynamics, Sylvio R. Bistafa
Euler, Father Of Haemodynamics, Sylvio R. Bistafa
Euleriana
This article is being published in conjunction with the translation and synopsis of E855. Principia pro motu sanguinis per arterias determinando of 1775 - view the translation and synopsis by clicking here.
A History And Translation Of Lagrange's "Sur Quelques Problèmes De L'Analyse De Diophante'', Christopher Goff, Michael Saclolo
A History And Translation Of Lagrange's "Sur Quelques Problèmes De L'Analyse De Diophante'', Christopher Goff, Michael Saclolo
Euleriana
Among Lagrange's many achievements in number theory is a solution to the problem posed and solved by Fermat of finding a right triangle whose legs sum to a perfect square and whose hypotenuse is also a square. This article chronicles various appearances of the problem, including multiple solutions by Euler, all of which inadequately address completeness and minimality of solutions. Finally, we summarize and translate Lagrange's paper in which he solves the problem completely, thus successfully proving the minimality of Fermat's original solution.
On The Surface Area Of Scalene Cones And Other Conical Bodies, Daniel J. Curtin
On The Surface Area Of Scalene Cones And Other Conical Bodies, Daniel J. Curtin
Euleriana
This paper first appeared in the Novi Commentarii academiae scientiarum Petropolitanae vol. 1, 1750, pp. 3-19 and is reprinted in the Opera Omnia: Series 1, Volume 27, pp. 181–199. Its Eneström number is E133. This translation and the Latin original are available from the Euler Archive.
The Surface Area Of A Scalene Cone As Solved By Varignon, Leibniz, And Euler, Daniel J. Curtin
The Surface Area Of A Scalene Cone As Solved By Varignon, Leibniz, And Euler, Daniel J. Curtin
Euleriana
In a 1727 mathematical compendium, Pierre Varignon (1654-1722) published his solution to the problem of finding the surface area of a scalene (oblique) cone, one whose base is circular but whose vertex is off-center. The article after Varignon's in that publication was by Gottfried Leibniz (1646-1716), who proposed improvements and even extended the solution to a base with any curve. When Leonhard Euler (1707-1783) published on the subject [E133] in 1750, he gently pointed out an error in Leibniz's solution, which he corrected, after extending Varignon's solution in the case of circular base. Euler then used Leibniz's approach to solve …
Collecting Works: A History Of The Euler Archive, Erik R. Tou, Christopher Goff, Michele Gibney
Collecting Works: A History Of The Euler Archive, Erik R. Tou, Christopher Goff, Michele Gibney
Euleriana
We give a brief history of the Euler Archive, an online database of the published works of Leonhard Euler (1707-1783). Furthermore, we describe the Archive's recent move to an academic repository, and the added functionality such a move allows.
A New Look At Euler And His Contemporaries, Christopher Goff, Erik Tou
A New Look At Euler And His Contemporaries, Christopher Goff, Erik Tou
Euleriana
Introducing Euleriana: Volume 1, Issue 1.
Bayesian-Derived Vancomycin Auc24h Threshold For Nephrotoxicity In Special Populations, Dan Ho
Bayesian-Derived Vancomycin Auc24h Threshold For Nephrotoxicity In Special Populations, Dan Ho
University of the Pacific Theses and Dissertations
A Bayesian-derived 24-hour area under the concentration-time curve over minimum inhibitory concentration from broth microdilution (AUC24h/MICBMD) ratio of 400 to 600 is recommended as the new monitoring parameter for vancomycin to optimize efficacy and minimize nephrotoxicity. The AUC24h threshold of 600 mg*h/L for nephrotoxicity was extrapolated from studies that assessed the general population. It is unclear if this upper threshold is consistent or varies when used in special populations such as critically ill patients, obese patients, patients with preexisting renal disease, and patients on concomitant nephrotoxins.The purpose of this study is to investigate the generalizability of the proposed vancomycin AUC24h …
Synthesis And Conformational Study Of Triazolylcyclohexanols And Trans-2-(Azaarylsulfanyl)-Cyclohexanols, Mulinde R. Ruyonga
Synthesis And Conformational Study Of Triazolylcyclohexanols And Trans-2-(Azaarylsulfanyl)-Cyclohexanols, Mulinde R. Ruyonga
University of the Pacific Theses and Dissertations
Amino-cyclohexanol derivatives have been successful models for pH-triggered conformational switches. By changing the groups on the amine nitrogen, these models provide a wide pH-range in which a switch can occur. The pH-induced switch of conformation can be monitored by 1H NMR.In this work, structurally similar trans-2-(azaarylsulfanyl)-cyclohexanol derivatives (Scheme 1) and trans-2-triazolylcyclohexanol derivatives (Scheme 2) have been explored for the first time as compounds with a potential for the analogous pH-induced conformational switch. The azaarylsulfanyl groups showed selective conformational flexibility while the triazolyl group showed a strong preference for the equatorial position. Further, conformational studies were done on a series of …