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Search Results: 1 - 10 of 53049 matches for " David Speicher "
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Detection of human herpesvirus 8 by quantitative polymerase chain reaction: development and standardisation of methods
Speicher David J,Johnson Newell W
BMC Infectious Diseases , 2012, DOI: 10.1186/1471-2334-12-210
Abstract: Background Human herpesvirus 8 (HHV-8), the aetiological agent of Kaposi’s sarcoma (KS), multicentric Castleman’s disease (MCD), and primary effusion lymphoma (PEL) is rare in Australia, but endemic in Sub-Saharan Africa, parts of South-east Asia and Oceania. While the treatment of external KS lesions can be monitored by clinical observation, the internal lesions of KS, MCD and PEL require extensive and expensive internal imaging, or autopsy. In patients with MCD and PEL, if HHV-8 viraemia is not reduced quickly, ~50% die within 24 months. HHV-8 qPCR is a valuable tool for monitoring HHV-8 viraemia, but is not available in many parts of the world, including those with high prevalence of KS and HHV-8. Methods A new molecular facility with stringent three-phase workflow was established, adhering to NPAAC and CLSI guidelines. Three fully validated quantitative assays were developed: two for detection and quantification of HHV-8; one for GAPDH, necessary for normalisation of viral loads in tissue and peripheral blood. Results The HHV-8 ORF73 and ORF26 qPCR assays were 100% specific. All qPCR assays, displayed a broad dynamic range (102 to 1010 copies/μL TE Buffer) with a limit of detection of 4.85x103, 5.61x102, and 2.59x102 copies/μL TE Buffer and a limit of quantification of 4.85x103, 3.01x102, and 1.38x102 copies/μL TE Buffer for HHV-8 ORF73, HHV-8 ORF26, and GAPDH respectively. The assays were tested on a panel of 35 KS biopsies from Queensland. All were HHV-8 qPCR positive with average viral load of 2.96x105 HHV-8 copies/μL DNA extract (range: 4.37x103 to 1.47x106 copies/μL DNA extract): When normalised these equate to an average viral load of 2.44x104 HHV-8 copies/103 cells (range: 2.20x102 to 7.38x105 HHV-8 copies/103 cells). Conclusions These are the first fully optimised, validated and MIQE compliant HHV-8 qPCR assays established in Australia. They worked well for qualitative detection of HHV-8 in archival tissue, and are well-suited for quantitative detection in whole blood. They are now available for research, for clinical diagnosis of HHV-8 infection, and for monitoring treatment efficacy.
On the rate of convergence and Berry-Esseen type theorems for a multivariate free central limit theorem
Roland Speicher
Mathematics , 2007,
Abstract: We address the question of a Berry Esseen type theorem for the speed of convergence in a multivariate free central limit theorem. For this, we estimate the difference between the operator-valued Cauchy transforms of the normalized partial sums in an operator-valued free central limit theorem and the Cauchy transform of the limiting operator-valued semicircular element.
Free probability and random matrices
Roland Speicher
Mathematics , 2014,
Abstract: The concept of freeness was introduced by Voiculescu in the context of operator algebras. Later it was observed that it is also relevant for large random matrices. We will show how the combination of various free probability results with a linearization trick allows to address successfully the problem of determining the asymptotic eigenvalue distribution of general selfadjoint polynomials in independent random matrices.
Free Probability Theory
Roland Speicher
Mathematics , 2009,
Abstract: Free probability theory was created by Dan Voiculescu around 1985, motivated by his efforts to understand special classes of von Neumann algebras. His discovery in 1991 that also random matrices satisfy asymptotically the freeness relation transformed the theory dramatically. Not only did this yield spectacular results about the structure of operator algebras, but it also brought new concepts and tools into the realm of random matrix theory. In the following we will give, mostly from the random matrix point of view, a survey on some of the basic ideas and results of free probability theory.
Polynomials in Asymptotically Free Random Matrices
Roland Speicher
Mathematics , 2015, DOI: 10.5506/APhysPolB.46.1611
Abstract: Recent work of Belinschi, Mai and Speicher resulted in a general algorithm to calculate the distribution of any selfadjoint polynomial in free variables. Since many classes of independent random matrices become asymptotically free if the size of the matrices goes to infinity, this algorithm allows then also the calculation of the asymptotic eigenvalue distribution of polynomials in such independent random matrices. We will recall the main ideas of this approach and then also present its extension to the case of the Brown measure of non-selfadjoint polynomials.
Free Calculus
Roland Speicher
Mathematics , 2001,
Abstract: I give a survey about my work on combinatorial and probabilistic aspects of free probability theory. In particular, I present the combinatorial description of freeness in terms of free cumulants and I give some ideas of the main results of my joint work with Philippe Biane on a stochastic integration theory for free Brownian motion.
What is Usability? A Characterization based on ISO 9241-11 and ISO/IEC 25010
Maximilian Speicher
Computer Science , 2015,
Abstract: According to Brooke* "Usability does not exist in any absolute sense; it can only be defined with reference to particular contexts." That is, one cannot speak of usability without specifying what that particular usability is characterized by. Driven by the feedback of a reviewer at an international conference, I explore in which way one can precisely specify the kind of usability they are investigating in a given setting. Finally, I come up with a formalism that defines usability as a quintuple comprising the elements level of usability metrics, product, users, goals and context of use. Providing concrete values for these elements then constitutes the investigated type of usability. The use of this formalism is demonstrated in two case studies. * J. Brooke. SUS: A "quick and dirty" usability scale. In P. W. Jordan, B. Thomas, B. A. Weerdmeester, and A. L. McClelland, editors, Usability Evaluation in Industry. Taylor and Francis, 1996.
Timeless Links Replication Termination to Mitotic Kinase Activation
Jayaraju Dheekollu,Andreas Wiedmer,James Hayden,David Speicher,Anthony L. Gotter,Tim Yen,Paul M. Lieberman
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0019596
Abstract: The mechanisms that coordinate the termination of DNA replication with progression through mitosis are not completely understood. The human Timeless protein (Tim) associates with S phase replication checkpoint proteins Claspin and Tipin, and plays an important role in maintaining replication fork stability at physical barriers, like centromeres, telomeres and ribosomal DNA repeats, as well as at termination sites. We show here that human Tim can be isolated in a complex with mitotic entry kinases CDK1, Auroras A and B, and Polo-like kinase (Plk1). Plk1 bound Tim directly and colocalized with Tim at a subset of mitotic structures in M phase. Tim depletion caused multiple mitotic defects, including the loss of sister-chromatid cohesion, loss of mitotic spindle architecture, and a failure to exit mitosis. Tim depletion caused a delay in mitotic kinase activity in vivo and in vitro, as well as a reduction in global histone H3 S10 phosphorylation during G2/M phase. Tim was also required for the recruitment of Plk1 to centromeric DNA and formation of catenated DNA structures at human centromere alpha satellite repeats. Taken together, these findings suggest that Tim coordinates mitotic kinase activation with termination of DNA replication.
IL8 and Cathepsin B as Melanoma Serum Biomarkers
Hongtao Zhang,Ting Fu,Suzanne McGettigan,Suresh Kumar,Shujing Liu,David Speicher,Lynn Schuchter,Xiaowei Xu
International Journal of Molecular Sciences , 2011, DOI: 10.3390/ijms12031505
Abstract: Melanoma accounts for only a small portion of skin cancer but it is associated with high mortality. Melanoma serum biomarkers that may aid early diagnosis or guide therapy are needed clinically. However, studies of serum biomarkers have often been hampered by the serum interference that causes false readouts in immunological tests. Here we show that, after using a special buffer to eliminate the serum interference, IL-8 and cathepsin B levels were significantly elevated in melanoma patients ( p < 0.05). More?importantly, the combination of IL-8 and cathepsin B were also studied as a prognosis?marker for melanoma mortality. Our study provides a novel approach to examine serum?biomarkers.
The Physiological Molecular Shape of Spectrin: A Compact Supercoil Resembling a Chinese Finger Trap
Jeffrey W. Brown?,Esther Bullitt?,Sira Sriswasdi?,Sandra Harper?,David W. Speicher,C. James McKnight
PLOS Computational Biology , 2015, DOI: 10.1371/journal.pcbi.1004302
Abstract: The primary, secondary, and tertiary structures of spectrin are reasonably well defined, but the structural basis for the known dramatic molecular shape change, whereby the molecular length can increase three-fold, is not understood. In this study, we combine previously reported biochemical and high-resolution crystallographic data with structural mass spectroscopy and electron microscopic data to derive a detailed, experimentally-supported quaternary structure of the spectrin heterotetramer. In addition to explaining spectrin’s physiological resting length of ~55-65 nm, our model provides a mechanism by which spectrin is able to undergo a seamless three-fold extension while remaining a linear filament, an experimentally observed property. According to the proposed model, spectrin’s quaternary structure and mechanism of extension is similar to a Chinese Finger Trap: at shorter molecular lengths spectrin is a hollow cylinder that extends by increasing the pitch of each spectrin repeat, which decreases the internal diameter. We validated our model with electron microscopy, which demonstrated that, as predicted, spectrin is hollow at its biological resting length of ~55-65 nm. The model is further supported by zero-length chemical crosslink data indicative of an approximately 90 degree bend between adjacent spectrin repeats. The domain-domain interactions in our model are entirely consistent with those present in the prototypical linear antiparallel heterotetramer as well as recently reported inter-strand chemical crosslinks. The model is consistent with all known physical properties of spectrin, and upon full extension our Chinese Finger Trap Model reduces to the ~180-200 nm molecular model currently in common use.
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