1,100 research outputs found
Fixing education for the AI age: Conrad Wolfram
No full textConrad Wolfram is the CEO and co-founder of Wolfram Research Europe and Strategic Director of Wolfram Research. He is a leading advocate for mathematics education reform and author of “The Math(s) Fix: An Education Blueprint for the AI Age”. He recently gave a public lecture at LSE on this topic. The following is an edited version of an interview by Neil Olver in the Mathematics Department
Who are the Disciples and Admirers of an Author?
No full textWebcast sponsored by the Irving K. Barber Learning Centre and hosted by SLAIS. Recitation (the act of citing a given author or her/his works multiple times) provides an indication of the influence of a cited author. This study investigated patterns of citation and recitation across frequently cited authors' works to better understand how broadly citers have been influenced by cited authors and their publications. Dietmar Wolfram is Interim Dean & Professor School of Information Studies, University of Wisconsin-Milwaukee.Arts, Faculty ofLibrary, Archival and Information Studies (SLAIS), School ofUnreviewedFacult
Interest rate convexity and the volatility smile
No full textWhen pricing the convexity effect in irregular interest rate derivatives such as, e.g., Libor-in-arrears or CMS, one often ignores the volatility smile, which is quite pronounced in the interest rate options market. This note solves the problem of convexity by replicating the irregular interest flow or option with liquidly traded options with different strikes thereby taking into account the volatility smile. This idea is known among practitioners for pricing CMS caps. We approach the problem on a more general scale and apply the result to various examples. --interest rate options,volatility smile,convexity,,option replication
Comprehensive overview of disease models for Wolfram syndrome : toward effective treatments
No full textWolfram syndrome (OMIM 222300) is a rare autosomal recessive disease with a devastating array of symptoms, including diabetes mellitus, optic nerve atrophy, diabetes insipidus, hearing loss, and neurological dysfunction. The discovery of the causative gene, WFS1, has propelled research on this disease. However, a comprehensive understanding of the function of WFS1 remains unknown, making the development of effective treatment a pressing challenge. To bridge these knowledge gaps, disease models for Wolfram syndrome are indispensable, and understanding the characteristics of each model is critical. This review will provide a summary of the current knowledge regarding WFS1 function and offer a comprehensive overview of established disease models for Wolfram syndrome, covering animal models such as mice, rats, flies, and zebrafish, along with induced pluripotent stem cell (iPSC)-derived human cellular models. These models replicate key aspects of Wolfram syndrome, contributing to a deeper understanding of its pathogenesis and providing a platform for discovering potential therapeutic approaches
Algebraic properties and the finite rank problem for Toeplitz operators on the Segal–Bargmann space
No full textAbstractWe study three different problems in the area of Toeplitz operators on the Segal–Bargmann space in Cn. Extending results obtained previously by the first author and Y.L. Lee, and by the second author, we first determine the commutant of a given Toeplitz operator with a radial symbol belonging to the class Sym>0(Cn) of symbols having certain growth at infinity. We then provide explicit examples of zero-products of non-trivial Toeplitz operators. These examples show the essential difference between Toeplitz operators on the Segal–Bargmann space and on the Bergman space over the unit ball. Finally, we discuss the “finite rank problem”. We show that there are no non-trivial rank one Toeplitz operators Tf for f∈Sym>0(Cn). In all these problems, the growth at infinity of the symbols plays a crucial role
A calcium-dependent protease as a potential therapeutic target for Wolfram syndrome
No full textFull author list omitted for brevity. For the full list of authors, see article.Wolfram syndrome is a genetic disorder characterized by diabetes and neurodegeneration and considered as an endoplasmic reticulum (ER) disease. Despite the underlying importance of ER dysfunction in Wolfram syndrome and the identification of two causative genes, Wolfram syndrome 1 (WFS1) and Wolfram syndrome 2 (WFS2), a molecular mechanism linking the ER to death of neurons and β cells has not been elucidated. Here we implicate calpain 2 in the mechanism of cell death in Wolfram syndrome. Calpain 2 is negatively regulated by WFS2, and elevated activation of calpain 2 by WFS2-knockdown correlates with cell death. Calpain activation is also induced by high cytosolic calcium mediated by the loss of function of WFS1. Calpain hyperactivation is observed in the WFS1 knockout mouse as well as in neural progenitor cells derived from induced pluripotent stem (iPS) cells of Wolfram syndrome patients. A small-scale small-molecule screen targeting ER calcium homeostasis reveals that dantrolene can prevent cell death in neural progenitor cells derived from Wolfram syndrome iPS cells. Our results demonstrate that calpain and the pathway leading its activation provides potential therapeutic targets for Wolfram syndrome and other ER diseases
THE COVALENT STRUCTURE OF THE ELASTASE INHIBITOR FROM ANEMONIA-SULCATA - A NONCLASSICAL KAZAL-TYPE PROTEIN
No full textTschesche H, KOLKENBROCK H, BODE W. THE COVALENT STRUCTURE OF THE ELASTASE INHIBITOR FROM ANEMONIA-SULCATA - A NONCLASSICAL KAZAL-TYPE PROTEIN. BIOLOGICAL CHEMISTRY HOPPE-SEYLER. 1987;368(2):1297-1304
Simulation der internen Struktur von Zellen mittels Delaunay-Triangulation
No full textThe goal of this project is to develop a framework for a cell that takes in consideration its internal structure, using an agent-based approach. In this framework, a cell was simulated as many sub-particles interacting to each other. This sub-particles can, in principle, represent any internal structure from the cell (organelles, etc). In the model discussed here, two types of sub-particles were used: membrane sub-particles and cytosolic elements. A kinetic and dynamic Delaunay triangulation was used in order to define the neighborhood relations between the sub-particles. However, it was soon noted that the relations defined by the Delaunay triangulation were not suitable to define the interactions between membrane sub-particles. The cell membrane is a lipid bilayer, and does not present any long range interactions between their sub-particles. This means that the membrane particles should not be able to interact in a long range. Instead, their interactions should be confined to the two-dimensional surface supposedly formed by the membrane. A method to select, from the original three-dimensional triangulations, connections restricted to the two-dimensional surface formed by the cell membrane was then developed. The algorithm uses as starting point the three-dimensional Delaunay triangulation involving both internal and membrane sub-particles. From this triangulation, only the subset of connections between membrane sub-particles was considered. Since the cell is full of internal particles, the collection of the membrane particles' connections will resemble the surface to be obtained, even though it will still have many connections that do not belong to the restricted triangulation on the surface. This "thick surface" was called a quasi-surface. The following step was to refine the quasi-surface, cutting out some of the connections so that the ones left made a proper surface triangulation with the membrane points. For that, the quasi-surface was separated in clusters. Clusters are defined as areas on the quasi-surface that are not yet properly triangulated on a two-dimensional surface. Each of the clusters was then re-triangulated independently, using re-triangulation methods also developed during this work. The interactions between cytosolic elements was given by a Lennard-Jones potential, as well as the interactions between cytosolic elements and membrane particles. Between only membrane particles, the interactions were given by an elastic interaction. For each particle, the equation of motion was written. The algorithm chosen to solve the equations of motion was the Verlet algorithm. Since the cytosol can be approximated as a gel, it is reasonable to suppose that the sub-cellular particles are moving in an overdamped environment. Therefore, an overdamped approximation was used for all interactions. Additionally, an adaptive algorithm was used in order to define the size of the time step used in each interaction. After the method to re-triangulate the membrane points was implemented, the time needed to re-triangulate a single cluster was studied, followed by an analysis on how the time needed to re-triangulate each point in a cluster varied with the cluster size. The frequency of appearance for each cluster size was also compared, as this information is necessary to guarantee that the total time needed by to re-triangulate a cell is convergent. At last, the total time spent re-triangulating a surface was plotted, as well as a scaling for the total re-triangulation time with the variation. Even though there is still a lot to be done, the work presented here is an important step on the way to the main goal of this project: to create an agent-based framework that not only allows the simulation of any sub-cellular structure of interest but also provides meaningful interaction relations to particles belonging to the cell membrane.Das Ziel dieser Arbeit ist die Entwicklung eines Modells für eine Zelle, welches die Eigenschaften der internen Struktur berücksichtigen kann. Hierzu wird ein Agenten-basierter Ansatz verwendet, in dem die Zelle durch eine Vielzahl miteinan- der wechselwirkender Teilchen simuliert wird. Prinzipiell können diese Teilchen jede interne Struktur der Zelle repräsentieren. In dem hier besprochenen Modell werden zwei Arten verwendet: Membranteilchen und zytosolische Elemente. Das entwickelte Modell eignet sich damit sowohl zur Simulation von einzelnen Zellen als auch zur Beschreibung multi-zellulären Systemen. Eine kinetische und dynamische Delaunay-Triangulation wurde zur Definition der Nachbarschaftsbeziehungen zwischen den Teilchen verwendet. Allerdings eignen sich die Eigenschaften der Delaunay-Triangulation nicht, die Wechselwirkungen zwischen Membranteilchen zu beschreiben. Zur Lösung dieses Problems wurde eine Methode entwickelt, die aus der ur- sprünglich dreidimensionalen Triangulation nur diejenigen Verbindungen auswählt, die die Oberfläche der Zelle, also die Membran, bilden. Das Problem der Rekonstruktion einer auf eine zwei-dimensionale gekrümmte Fläche eingeschränkten Punktmenge ist sehr komplex und nicht vollständig gelöst. Der hier vorgestellte Algorithmus ist stark an die spezifische Anwendung innerhalb dieser Arbeit angepasst, aber nicht vollständig fehlerfrei. Die entwickelte Methode hat zwei Schwachpunkte, an denen es zu Fehlern kommen kann: die Bestimmung und Auswahl der Ränder der Cluster und zu strikte Einschränkungen bei der Retriangulation für Cluster mit vielen internen Punkten. Obwohl noch einige Erweiterungen möglich sind, ist die Autorin überzeugt, dass die hier vorgestellte Arbeit einen wichtigen Schritt auf dem Weg zu einem Agenten- basierten Modell ist, welches nicht nur die Simulation von sub-zellulären Struktu- ren erlaubt sondern auch sinnvolle Wechselwirkungen zwischen Membranteilchen berücksichtigt
A novel mutation of WFS1 gene in a Japanese man of Wolfram syndrome with positive diabetes-related antibodies
No full textWolfram syndrome is a rare, autosomal recessive disorder characterized by early-onset diabetes mellitus, optic atrophy and neurological and endocrinological abnormalities. A 47-year-old Japanese man with frequent severe hypoglycemic episodes was diagnosed as Wolfram syndrome based on clinical features and laboratory data. He had positive glutamic acid decarboxylase (GAD) and insulinoma-associated antigen-2 (IA-2) antibodies, both uncommon in this syndrome. Genetic analysis revealed that WFS1 gene of the patient has a homozygous 5 base pairs (AAGGC) insertion at position 1279 in exon 8, causing a frameshift at codon 371 leading to premature termination at codon 443
project-aero/transient-indicators: Files associated with 2020-01-13 manuscript draft. Author correction.
No full textThe author of the Wolfram Notebook has been corrected to be S. M. O'Regan
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