cometadata/datacite-rtg-text-other-reclassification-records huggingface dataset:
Mixtures of g-priors in Generalized Linear Models
Creators: name: Li, Yingbo
name: Clyde, Merlise A.
Publisher: name: arXiv
Year: 2015
Subjects: subject: Methodology (stat.ME)
subject: FOS: Computer and information sciences

description: Mixtures of Zellner's g-priors have been studied extensively in linear models and have been shown to have numerous desirable properties for Bayesian variable selection and model averaging. Several extensions of g-priors to Generalized Linear Models (GLMs) have been proposed in the literature; however, the choice of prior distribution of g and resulting properties for inference have received considerably less attention. In this paper, we unify mixtures of g-priors in GLMs by assigning the truncated Compound Confluent Hypergeometric (tCCH) distribution to 1/(1 + g), which encompasses as special cases several mixtures of g-priors in the literature, such as the hyper-g, Beta-prime, truncated Gamma, incomplete inverse-Gamma, benchmark, robust, hyper-g/n, and intrinsic priors. Through an integrated Laplace approximation, the posterior distribution of 1/(1 + g) is in turn a tCCH distribution, and approximate marginal likelihoods are thus available analytically, leading to "Compound Hypergeometric Information Criteria" for model selection. We discuss the local geometric properties of the g-prior in GLMs and show how the desiderata for model selection proposed by Bayarri et al, such as asymptotic model selection consistency, intrinsic consistency, and measurement invariance may be used to justify the prior and specific choices of the hyper parameters. We illustrate inference using these priors and contrast them to other approaches via simulation and real data examples. The methodology is implemented in the R package BAS and freely available on CRAN.
CASZ1 Promotes Vascular Assembly and Morphogenesis through the Direct Regulation of an EGFL7/RhoA-Mediated Pathway
Creators: name: Bautch, Victoria L.
name: Christine, Kathleen S.
name: Charpentier, Marta S.
name: Kushner, Erich J.
name: Conlon, Frank L.
name: Dorr, Kerry M.
name: Taylor, Joan M.
name: Amin, Nirav M.
Publisher: name: The University of North Carolina at Chapel Hill University Libraries
Year: 2013

description: The formation of the vascular system is essential for embryonic development and homeostasis. However, transcriptional control of this process is not fully understood. Here we report an evolutionarily conserved role for the transcription factor CASZ1 in blood vessel assembly and morphogenesis. In the absence of CASZ1, Xenopus embryos fail to develop a branched and lumenized vascular system, and CASZ1-depleted human endothelial cells display dramatic alterations in adhesion, morphology, and sprouting. Mechanistically, we show CASZ1 directly regulates Epidermal Growth Factor-Like Domain 7 (Egfl7). We further demonstrate that defects of CASZ1 or EGFL7-depleted cells are in part due to diminished RhoA expression and impaired focal adhesion localization. Moreover, these abnormal endothelial cell behaviors in CASZ1-depleted cells can be rescued by restoration of Egfl7. Collectively, these studies show CASZ1 is required to directly regulate a unique EGFL7/RhoA-mediated pathway to promote vertebrate vascular development.
Warning coloration, body size and the evolution of gregarious behavior in butterfly larvae
Creators: name: McLellan, Callum
name: Montgomery, Stephen
name: Cuthill, Innes
Publisher: name: Zenodo
Year: 2023
Subjects: comparative analysis
Phylogenetics
gregarious behavior
aposematism
defensive coloration
field study

description: Many species gain anti-predator benefits by combining gregarious behavior with warning coloration, yet there is debate over which trait evolves first, and which is the secondary adaptive enhancement. Body size can also influence how predators receive aposematic signals, and potentially constrain the evolution of gregarious behavior. To our knowledge, the causative links between the evolution of gregariousness, aposematism and larger body sizes have not been fully resolved. Here, using the most recently resolved butterfly phylogeny and an extensive new dataset of larval traits, we reveal the evolutionary interactions between important traits linked to larval gregariousness. We show that larval gregariousness has arisen many times across the butterflies, and aposematism is a likely prerequisite for gregariousness to evolve. We also find that body size may be an important factor for determining the coloration of solitary, but not gregarious larvae. Additionally, by exposing artificial 'larvae' to wild avian predation, we show that undefended, cryptic 'larvae' are heavily predated when aggregated but benefit from solitariness, whereas the reverse is true for aposematic prey. Our data reinforce the importance of aposematism for gregarious larval survival, whilst identifying new questions about the roles of body size and toxicity in the evolution of grouping behavior.
description: R StudioFunding provided by: Biotechnology and Biological Sciences Research Council
Crossref Funder Registry ID: http://dx.doi.org/10.13039/501100000268
Award Number:
description: A combination of two separate methods. Larval trait data collected from literature-mining. Field study data collected from field experiments (exposing artificial 'caterpillar' targets to wild avian predators).
title: Investigations of anti-adhesion and endothelial environment for plasmodium falciparum cytoadherence
Creators: name: Mustaffa, Khairul
Publisher: name: University of Liverpool Repository
Year: 2012

description: A unique feature of mature Plasmodium falciparum (P. falciparum) parasitized RBC (pRBC) is that they bind to surface molecules of microvasculature endothelium via the parasite-derived surface protein PfEMP1. This ligand is associated with the cytoadherence pathology seen in severe malaria (SM) and recently our group has shown that even when treated with effective anti-malarial drug, pRBC are still able to cytoadhere, therefore, there is a need to find an adjunct treatment (in addition to antimalarial drugs) that can inhibit and reverse the adhesion process. Previous reports have suggested that sulphated glycoconjugates are highly effective at disrupting P. falciparum pRBC rosettes. Here, we investigate that effect by using sulphated polysaccharides and modified heparin for their effect to interrupt pRBC sequestration. We found that not all sulphated compounds or modified heparins were able to interrupt the sequestration process. Consideration of the inhibitory compounds generated some 18rules 19 fore exhibition of inhibitory properties: Sulphate position either at 6-O, or/and 2-O sulphate and N-sulphate is necessary for each compound. In addition, the multivalent effect and drug exhibit low anticoagulant activity also determined an active response to inhibit and de-sequestered P. falciparum pRBC on protein and endothelial cells. Here, we provide evidence that polysaccharides that possess a different level of sulphate, conformational structure and sulphate position act differently. This study also addressed the importance of pH host environment and extracellular matrix (glycocalyx) on the surface of endothelial cells on mediating pRBC binding. It found that pRBC bind significantly higher at pH 7-7.2 to CD36 and ICAM-1. Meanwhile, glycocalyx might interact as an instantaneous binder before pRBC reached ICAM-1 or CD36, unfortunately we cannot prove this due to methods and antibody chosen. The work reported in this thesis opens up new possibilities for therapeutic strategies targeting binding interaction of pRBC to host cells.
Triacylglycerol Synthesis Enzymes Mediate Lipid Droplet Growth by Relocalizing from the ER to Lipid Droplets
Creators: name: Haas, Joel T.
name: Wilfling, Florian
name: Christiano, Romain
name: Cheng, Ji-Xin
name: Wang, Huajin
name: Buhman, Kimberly K.
name: Gould, Travis J.
name: Liu, Xinran
name: Coleman, Rosalind A.
name: Krahmer, Natalie
name: Walther, Tobias C.
name: Fröhlich, Florian
name: Bewersdorf, Joerg
name: Graham, Morven
name: Farese, Robert V.
name: Uchida, Aki
Publisher: name: The University of North Carolina at Chapel Hill University Libraries
Year: 2013

description: Lipid droplets (LDs) store metabolic energy and membrane lipid precursors. With excess metabolic energy, cells synthesize triacylglycerol (TG) and form LDs that grow dramatically. It is unclear how TG synthesis relates to LD formation and growth. Here, we identify two LD subpopulations: smaller LDs of relatively constant size, and LDs that grow larger. The latter population contains isoenzymes for each step of TG synthesis. Glycerol-3-phosphate acyltransferase 4 (GPAT4), which catalyzes the first and rate-limiting step, relocalizes from the endoplasmic reticulum (ER) to a subset of forming LDs, where it becomes stably associated. ER-to-LD targeting of GPAT4 and other LD-localized TG synthesis isozymes is required for LD growth. Key features of GPAT4 ER-to-LD targeting and function in LD growth are conserved between Drosophila and mammalian cells. Our results explain how TG synthesis is coupled with LD growth and identify two distinct LD subpopulations based on their capacity for localized TG synthesis.
Decoy Receptor CXCR7 Modulates Adrenomedullin-Mediated Cardiac and Lymphatic Vascular Development
Creators: name: Hoopes, Samantha L.
name: Karpinich, Natalie O.
name: Caron, Kathleen M.
name: Kushner, Erich J.
name: Klein, Klara R.
name: Espenschied, Scott T.
name: Bautch, Victoria L.
name: Dunworth, William P.
name: Willcockson, Helen H.
Publisher: name: The University of North Carolina at Chapel Hill University Libraries
Year: 2014

description: Atypical 7-transmembrane receptors, often called decoy receptors, act promiscuously as molecular sinks to regulate ligand bioavailability and consequently temper the signaling of canonical G protein-coupled receptor (GPCR) pathways. Loss of mammalian CXCR7, the most recently described decoy receptor, results in postnatal lethality due to aberrant cardiac development and myocyte hyperplasia. Here, we provide the molecular underpinning for this proliferative phenotype by demonstrating that the dosage and signaling of adrenomedullin (Adm = gene, AM = protein)—a mitogenic peptide-hormone required for normal cardiovascular development—is tightly controlled by CXCR7. To this end, Cxcr7−/− mice exhibit gain-of-function cardiac and lymphatic vascular phenotypes which can be reversed upon genetic depletion of adrenomedullin ligand. In addition to identifying a biological ligand accountable for the phenotypes of Cxcr7−/− mice, these results reveal a previously underappreciated role for decoy receptors as molecular rheostats in controlling the timing and extent of GPCR-mediated cardiac and vascular development.
Maximal correlation between flavor entanglement and oscillation damping due to localization effects
Creators: name: Bittencourt, Victor A. S. V.
name: Villas-Boas, Celso J.
name: Bernardini, Alex E.
Publisher: name: arXiv
Year: 2014
Subjects: subject: High Energy Physics - Phenomenology (hep-ph)
subject: High Energy Physics - Theory (hep-th)
subject: Quantum Physics (quant-ph)
subject: FOS: Physical sciences

description: Localization effects and quantum decoherence driven by the mass-eigenstate wave packet propagation are shown to support a statistical correlation between quantum entanglement and damped oscillations in the scenario of three-flavor quantum mixing for neutrinos. Once the mass-eigenstates that support flavor oscillations are identified as three-{\em qubit} modes, a decoherence scale can be extracted from correlation quantifiers, namely the entanglement of formation and the logarithmic negativity. Such a decoherence scale is compared with the coherence length of damped oscillations. Damping signatures exhibited by flavor transition probabilities as an effective averaging of the oscillating terms are then explained as owing to loss of entanglement between mass modes involved in the relativistic propagation.
description: 13 pages, 03 figures
title: The tumorigenicity-promoting activity of C-FABP in prostate cancer cells depends on its fatty acid-binding ability
Creators: name: Malki, Mohammed Imad
Publisher: name: University of Liverpool Repository
Year: 2012

description: Cutaneous fatty acid-binding protein (C-FABP) or FABP5, is a FABP family member that can bind to long chain fatty acids with high affinity. C-FABP was identified by our research group as a gene involved in malignant progression of prostate cancer and able to promote the growth of primary tumours and induce metastasis when transfected into rat benign Rama 37 model cells. It was demonstrated that C-FABP was a prognostic marker for patient outcome and a target of tumour-suppression for prostate cancer. As an initial step to understanding the complex molecular mechanisms involved in the cancer promoting activity of C-FABP, this study investigated the possible relationship between tumorigenicity-promoting activity of C-FABP and its fatty acid-binding capability. After single and double mutations were generated in the fatty acid binding motif of the C-FABP cDNA, wild type and mutant C-FABP cDNAs were excised from the mammalian vector pIRES2-EGFP and inserted into pBluescript cloning vector to generate a complimentary restriction sites at both ends of the cDNAs. The C-FABP cDNAs were excised from the pBluescript vector with KpnI and PstI and inserted into pQEs expression vector to form three constructs that express the wild type and two mutant C-FABPs (C-FABP-WT, C-FABP-R109A and C-FABP-R109/129A), respectively. SDS-PAGE and sequence analysis confirmed the correct insertion of C-FABPs into expression vector pQE. The pure recombinant proteins were subsequently produced and purified. The importance of fatty acid-binding activity to the cancer promoting function was assessed by comparing the cancer promoting abilities exerted by C-FABPs with different fatty acid-binding capabilities. To test whether the recombinant proteins produced were biological active, the fatty acid binding ability of wild type and mutant C-FABPs were tested. When fatty acid binding ability of the wild type C-FABP is set at 1, the average fatty acid binding ability the C-FABP-R109A and C-FABP-R109/129A were significantly reduced to 0.32% and 0.09%, respectively (Student t-test, P0.5). The most significant change occurred in C-FABP-WT stimulated cells that produced more than a 6.7-fold (85%) increase in the number of colonies formed in soft agar when compared to controls (Student t-test, P
Synthesis and characterization of nano crystallite carboxamide-based iron(III) complexes: SOD mimetic activity, antibacterial and anticancer activity and molecular docking study
Creators: name: Al-Harbi, Sami A.
Publisher: name: Taylor & Francis
Year: 2023
Subjects: subject: Biochemistry
subject: Microbiology
subject: FOS: Biological sciences
subject: Biotechnology
subject: Environmental Sciences not elsewhere classified
subject: Chemical Sciences not elsewhere classified
subject: Cancer
subject: Hematology

description: Three carboxamide-based ligands and their iron(III) complexes were prepared and structurally characterized. Analytical, thermal and mass spectra measurements showed a 1:1 stoichiometric (M:L) of the synthesized iron(III) complexes. The distorted octahedral geometry of the present iron(III) complexes was assigned based on the results of spectroscopy and magnetometry. Processing of X-ray diffraction data for powder samples by the software Expo 2014 confirmed the octahedral geometry of the three iron(III) complexes. Electrochemical properties of the present iron(III) complexes were studied by cyclic voltammetric measurements. The present iron(III) complexes exhibit SOD like activity with IC50 values of 16.45, 15.24 and 9.70 μM. The drive forces (−λ or ΔG°) controlling these biocatalytic reactions were determined and correlated with catalytic activity. The proposed catalytic mechanistic implications for the conversion of O2•− to H2O2 and H2O were discussed. The antimicrobial activity has been studied in vitro against G(+) and G(−) pathogenic bacteria. The in vitro anticancer activity of the carboxamide-based ligands and their iron(III) complexes against human Hepatocellular carcinoma (HepG-2) cell lines was examined. The obtained results demonstrated the potent anticancer activity of iron(III) complexes with increased safety on normal cells compared to cisplatin. Molecular docking calculations confirmed the experimental findings of the antibacterial and anticancer activities of both free ligands and their iron(III) chelates. Communicated by Ramaswamy H. Sarma
Differential Regulation of Microtubule Severing by APC Underlies Distinct Patterns of Projection Neuron and Interneuron Migration
Creators: name: Yan, Jessica
name: Rubenstein, John L.R.
name: Salas, Eduardo
name: Snider, William D.
name: Ghukasyan, Vladimir
name: Stanco, Amelia
name: Oon, Eesim
name: Wilkins, Gary
name: Monckton, Chase
name: Blair, Joshua
name: Perez, Abby
name: Oh, Adrianna
name: Eom, Tae-Yeon
name: Deslauriers, Danielle
name: Anton, E.S.
name: Guo, Jiami
Publisher: name: The University of North Carolina at Chapel Hill University Libraries
Year: 2014

description: Coordinated migration of distinct classes of neurons to appropriate positions leads to the formation of functional neuronal circuitry in the cerebral cortex. Two major classes of cortical neurons, interneurons and projection neurons, utilize distinctly different modes (radial vs. tangential) and routes of migration to arrive at their final positions in the cerebral cortex. Here, we show that adenomatous polyposis coli (APC) modulates microtubule (MT) severing in interneurons to facilitate tangential mode of interneuron migration, but not the glial-guided, radial migration of projection neurons. APC regulates the stability and activity of the MT severing protein p60-katanin in interneurons to promote the rapid remodeling of neuronal processes necessary for interneuron migration. These findings reveal how severing and restructuring of MTs facilitate distinct modes of neuronal migration necessary for laminar organization of neurons in the developing cerebral cortex.
title: An investigation of GRP78 expression and inhibition in squamous cell carcinoma of the head and neck
Creators: name: Aslam, Mohammed Afeef
Publisher: name: University of Liverpool Repository
Year: 2012

description: GRP78 is a known cyto-protective gene which is induced in microenvironments typical of tumours with low glucose and hypoxia. Furthermore up-regulation of GRP78 has been linked to chemo- and radioresistance as well as poor survival outcome. This study is the first to confirm that GRP78 is up-regulated in tumours of the oropharynx, larynx and hypopharynx compared with matched histologically normal tissue (p(Χ2)
BLF-SSH Polarons coupled to Acoustic Phonons in the Adiabatic limit
Creators: name: Chandler, Carl J.
name: Marsiglio, F.
Publisher: name: arXiv
Year: 2014
Subjects: subject: Strongly Correlated Electrons (cond-mat.str-el)
subject: FOS: Physical sciences

description: We survey polaron formation in the BLF-SSH model using acoustic phonons in the adiabatic limit. Multiple different numerical optimization routines and strong coupling analytical calculations are used to find a robust ground state energy for a wide range of coupling strengths. The electronic configuration and accompanying ionic distortions of the polaron were determined, as well as a non-zero critical coupling strength for polaron formation in two and three dimensions.
description: 9 pages, 6 figures
Flux growth utilizing the reaction between flux and crucible
Creators: name: Yan, J. -Q.
Publisher: name: arXiv
Year: 2015
Subjects: subject: Materials Science (cond-mat.mtrl-sci)
subject: Strongly Correlated Electrons (cond-mat.str-el)
subject: Superconductivity (cond-mat.supr-con)
subject: FOS: Physical sciences

description: Flux growth involves dissolving the components of the target compound in an appropriate flux at high temperatures and then crystallizing under supersaturation controlled by cooling or evaporating the flux. A refractory crucible is generally used to contain the high temperature melt. The reaction between the melt and crucible materials can modify the composition of the melt, which typically results in growth failure, or contaminates the crystals. Thus one principle in designing a flux growth is to select suitable flux and crucible materials thus to avoid any reaction between them. In this paper, we review two cases of flux growth in which the reaction between flux and Al$_2$O$_3$ crucible tunes the oxygen content in the melt and helps the crystallization of desired compositions. For the case of La$_5$Pb$_3$O, Al$_2$O$_3$ crucible oxidizes La to form a passivating La$_2$O$_3$ layer which not only prevents further oxidization of La in the melt but also provides [O] to the melt. For the case of La$_{0.4}$Na$_{0.6}$Fe$_2$As$_2$, it is believed that the Al$_2$O$_3$ crucible reacts with NaAsO$_2$ and the reaction consumes oxygen in the melt thus maintaining an oxygen-free environment.
description: 5 pages, 4 figures, to appear in Journal of Crystal Growth
Supervised screening of Tecovirimat-like compounds as potential inhibitors for the monkeypox virus E8L protein
Creators: name: Mehmood, Aamir
name: Nawab, Sadia
name: Jia, Guihua
name: Kaushik, Aman Chandra
name: Wei, Dong-Qing
Publisher: name: Taylor & Francis
Year: 2023
Subjects: subject: Biochemistry
subject: Pharmacology
subject: Biotechnology
subject: Chemical Sciences not elsewhere classified
subject: Biological Sciences not elsewhere classified
subject: Information Systems not elsewhere classified
subject: Infectious Diseases
subject: FOS: Health sciences
subject: Virology
subject: Computational Biology

description: Monkeypox virus (MPXV) is a budding public health threat worldwide, and there lacks a personalized drug availability to treat MPXV infections. Tecovirimat, an antiviral drug against pox viruses, is recently confirmed to be effective against the MPXV in vitro using nanomolar concentrations. Therefore, the current study considers Tecovirimat as a reference compound for a machine learning-based guided screening to scan bioactive compounds from the DrugBank with similar chemical features or moieties as the Tecovirimat to inhibit the MPXV E8L surface binding protein. We used AlphaFold2 to model the E8L’s 3D structure, followed by the conformational activity investigation of shortlisted drugs through computational structural biology approaches, including molecular docking and molecular dynamics simulations. As a result, we have shortlisted five drugs named ABX-1431, Alflutinib, Avacopan, Caspitant, and Darapalib that effectively engage the MPXV surface binding protein. Furthermore, the affinity of the proposed drugs is relatively higher than the Tecovirimat by having higher docking scores, establishing more hydrogen and hydrophobic bonds, engaging key residues in the target’s structure, and exhibiting stable molecular dynamics. Communicated by Ramaswamy H. Sarma
Enabled Negatively Regulates Diaphanous-Driven Actin Dynamics In Vitro and In Vivo
Creators: name: Tsygankov, Denis
name: Wood, Will
name: Peifer, Mark
name: Kovar, David R.
name: Nowotarski, Stephanie H.
name: Sees, Jennifer A.
name: Elston, Timothy C.
name: Lakhani, Vinal
name: Evans, Iwan
name: Winkelman, Jonathan D.
name: Bilancia, Colleen G.
name: Comber, Kate
Publisher: name: The University of North Carolina at Chapel Hill University Libraries
Year: 2014

description: Actin regulators facilitate cell migration by controlling cell protrusion architecture and dynamics. As the behavior of individual actin regulators becomes clear, we must address why cells require multiple regulators with similar functions and how they cooperate to create diverse protrusions. We characterized Diaphanous (Dia) and Enabled (Ena) as a model, using complementary approaches: cell culture, biophysical analysis, and Drosophila morphogenesis. We found that Dia and Ena have distinct biochemical properties that contribute to the different protrusion morphologies each induces. Dia is a more processive, faster elongator, paralleling the long, stable filopodia it induces in vivo, while Ena promotes filopodia with more dynamic changes in number, length, and lifetime. Acting together, Ena and Dia induce protrusions distinct from those induced by either alone, with Ena reducing Dia-driven protrusion length and number. Consistent with this, EnaEVH1 binds Dia directly and inhibits DiaFH1FH2-mediated nucleation in vitro. Finally, Ena rescues hemocyte migration defects caused by activated Dia.
Investigation of photoluminescence and DNA binding properties of benzimidazole compounds containing benzophenone group
Creators: name: Bal, Mustafa
name: Köse, Ayşegül
name: Güngör, Seyit Ali
Publisher: name: Taylor & Francis
Year: 2023
Subjects: Biophysics
Biochemistry
Space Science
Physical Sciences not elsewhere classified
Pharmacology
Chemical Sciences not elsewhere classified
Biological Sciences not elsewhere classified

description: The synthesis of benzimidazole compounds containing benzophenone group in accordance with the literature and the investigation of DNA binding properties of these compounds by using UV-vis and photoluminescence spectroscopy methods constitute the basis of this research. The structures of the compounds were determined by methods such as FT-IR, 1H, 13C NMR, UV-vis, Photoluminescence spectroscopy, and X-ray crystallography. By using methods such as UV-vis, Photoluminescence spectroscopy, and viscosity tests, information were collected about the binding types, binding mode, and binding energies of the compounds with DNA. In addition, the binding interactions of the compounds with DNA were investigated using the molecular docking technique. Using this information, calibration equations, correlation coefficients (r2), and DNA binding constants (Kb) were calculated for their compounds. The binding constants (Kb) calculated for substances A, B, and C were found to be 3.0 × 104, 7.0 × 104, and 3.0 × 104 M−1, respectively. UV-vis, EB competitive binding, and viscosity tests showed that the compounds tended to bind to the DNA structure via the groove binding mode. At the end of molecular docking studies, it was determined that compound B showed the best DNA binding activity in in vitro studies. Compared with the studies in the literature, it is thought that the synthesized compounds can take place in cancer drug research as DNA binding agents. Communicated by Ramaswamy H. Sarma
Some Special Features of a Rotating-Moving D$p$-Brane
Creators: name: Safarzadeh-Maleki, Farzin
Publisher: name: arXiv
Year: 2015
Subjects: subject: High Energy Physics - Theory (hep-th)
subject: FOS: Physical sciences

description: Using the boundary string field theory (BSFT) techniques we study the boundary state and partition function for a dynamical (rotating-moving) D$p$-brane coupled to the electromagnetic and tachyonic background fields in superstring theory. By making use of the created partition function, the super BSFT action with a tachyonic field and Dirac-Born-Infeld type action will be constructed. By analyzing the obtained action interesting features will be revealed.
Hs3st3-Modified Heparan Sulfate Controls KIT+ Progenitor Expansion by Regulating 3-O-Sulfotransferases
Creators: name: Xu, Yongmei
name: Shworak, Nicholas W.
name: Hoffman, Matthew P.
name: Lombaert, Isabelle M.A.
name: Cowherd, Samuel N.
name: Liu, Jian
name: Patel, Vaishali N.
Publisher: name: The University of North Carolina at Chapel Hill University Libraries
Year: 2014

description: The exquisite control of growth factor function by heparan sulfate (HS) is dictated by the tremendous structural heterogeneity of sulfated modifications. It is not known how specific HS structures control growth factor-dependent progenitor expansion during organogenesis. We isolated KIT+ progenitors from fetal salivary glands during a stage of rapid progenitor expansion and profiled HS biosynthetic enzyme expression. Enzymes generating a specific type of 3-O-sulfated-HS (3-O-HS) are enriched, and FGF10/FGFR2b signaling directly regulates their expression. Bioengineered 3-O-HS binds FGFR2b and stabilizes FGF10/FGFR2b complexes in a receptor- and growth factor-specific manner. Rapid autocrine feedback increases 3-O-HS, KIT and progenitor expansion. Knockdown of multiple Hs3st isoforms limits fetal progenitor expansion, but is rescued with bioengineered 3-O-HS, which also increases adult progenitor expansion. Rapidly altering a specific 3-O-sulfated epitope provides a cellular mechanism to modulate the response to FGFR2b signaling and control progenitor expansion. 3-O-HS may expand KIT+ progenitors in vitro for regenerative therapy.
Submodular relaxation for inference in Markov random fields
Creators: name: Osokin, Anton
name: Vetrov, Dmitry
Publisher: name: arXiv
Year: 2015
Subjects: subject: Computer Vision and Pattern Recognition (cs.CV)
subject: Optimization and Control (math.OC)
subject: Machine Learning (stat.ML)
subject: FOS: Computer and information sciences
subject: FOS: Mathematics

description: In this paper we address the problem of finding the most probable state of a discrete Markov random field (MRF), also known as the MRF energy minimization problem. The task is known to be NP-hard in general and its practical importance motivates numerous approximate algorithms. We propose a submodular relaxation approach (SMR) based on a Lagrangian relaxation of the initial problem. Unlike the dual decomposition approach of Komodakis et al., 2011 SMR does not decompose the graph structure of the initial problem but constructs a submodular energy that is minimized within the Lagrangian relaxation. Our approach is applicable to both pairwise and high-order MRFs and allows to take into account global potentials of certain types. We study theoretical properties of the proposed approach and evaluate it experimentally.
description: This paper is accepted for publication in IEEE Transactions on Pattern Analysis and Machine Intelligence
title: Outcomes in clinical trials in children with asthma
Creators: name: Sinha, Ian
Publisher: name: University of Liverpool Repository
Year: 2011

description: The selection of outcomes is a critically important decision when designing randomised controlled trials (RCTs). Informed clinical decisions can only be based on the results of RCTs that have measured outcomes of importance to both clinicians and patients. It can be difficult to know which outcomes should be measured in RCTs. Some groups advocate core outcome sets, which are a minimum set of outcomes that should be measured, and reported, in all clinical trials in a given condition. These increase the likelihood that important outcomes are measured, reduce nonuniformity between studies, and reduce the risk of outcome reporting bias. We systematically reviewed studies that determined which outcomes to measure in clinical trials in children, and found that such work had been conducted in only few conditions, and the quality of existing work was variable. Few studies used structured consensus techniques to reach agreement about which outcomes to measure in trials, and parents were seldom involved. No studies included children. One condition in which there were no robust recommendations about which outcomes to measurein RCTs was childhood asthma, which is a condition of considerable global importance. We subsequently aimed to assess whether the absence of a core outcome set for RCTs of children with asthma meant that certain outcome domains were measured less frequently than others, and whether there was nonuniformity between studies in terms of outcomes selected. We conducted a systematic review of RCTs of children with asthma, published between January 1988 and December 2007, and found that the included studies focussed on short-term disease activity, but quality of life, functional status, and long-term outcomes were infrequently measured. Certain outcomes were measured and reported in various ways. We recommended that a core outcome set should be developed for childhood asthma, using structured consensus techniques, such as the Delphi process. In order to aid the development of such a core set, we first systematically reviewed studies that used the Delphi process to determine which outcomes to measure in clinical trials. We observed variations in the methodology used, identified potential sources of bias, and provided recommendations about how such studies could be conducted and reported. In order to develop a core outcome set for childhood asthma, we used a Delphi process to ascertain the views of 46 clinicians, and around 100 parents and young people, about which outcomes are most important and relevant from their perspective, when making shared decisions about regular therapies which control asthma. The most important outcomes were symptoms, exacerbations, and quality of life. Although consensus still needs to be reached amongst other groups of individuals involved in clinical trials, we conclude that these outcomes should be measured, and reported, in all RCTs that aim to evaluate the effectiveness of regular therapies for children and young people with asthma.
Mesenchymal Chemotaxis Requires Selective Inactivation of Myosin II at the Leading Edge via a Noncanonical PLCγ/PKCα Pathway
Creators: name: Rahman, Anisur
name: Bear, James E.
name: King, Samantha J.
name: Lebedeva, Irina P.
name: Rotty, Jeremy D.
name: Johnson, Heath E.
name: Haugh, Jason M.
name: Asokan, Sreeja B.
Publisher: name: The University of North Carolina at Chapel Hill University Libraries
Year: 2014

description: Chemotaxis, migration towards soluble chemical cues, is critical for processes such as wound healing and immune surveillance, and is exhibited by various cell types from rapidly-migrating leukocytes to slow-moving mesenchymal cells. To interrogate the mechanisms involved in mesenchymal chemotaxis, we observed cell migration in microfluidic chambers that generate stable gradients of the chemoattractant PDGF. Surprisingly, we found that pathways implicated in amoeboid chemotaxis, such as PI3K and mTOR signaling, are dispensable for chemotaxis to PDGF. Instead, we find that local inactivation of Myosin IIA, through a non-canonical Ser1/2 phosphorylation of the regulatory light chain, is essential. This site is phosphorylated by PKCα, which is activated by an intracellular gradient of diacylglycerol generated by PLCγ. Using a combination of TIRF imaging and gradients of activators/inhibitors in the microfluidic chambers, we demonstrate that this signaling pathway and subsequent inhibition of Myosin II activity at the leading edge is required for mesenchymal chemotaxis.
Novel indenopyrrol-4-one derivatives as potent BRDT inhibitors: synthesis, molecular docking, drug-likeness, ADMET, and DFT studies
Creators: name: Gheidari, Davood
name: Mehrdad, Morteza
name: Bayat, Mohammad
Publisher: name: Taylor & Francis
Year: 2023
Subjects: Biochemistry
Space Science
Pharmacology
Chemical Sciences not elsewhere classified
Biological Sciences not elsewhere classified

description: We synthesized new, structurally distinct series of indeno[1,2-b]pyrrol-4(1H)-ones. Effective derivatives were found by in silico screening, and our studies revealed that compound 5h exhibited good binding energies for inhibition of BRDT. In addition, DFT studies were carried out by means of the B3LYP/6-3lG basis set in the gas phase to investigate the conformation of protein-ligand interactions. The results of the investigation suggest that these compounds could be considered novel BRDT inhibitors. The pharmacokinetic and drug-like properties of the new indenopyrrol-4(1H)-one derivatives exhibited that these compounds could be represented as potential candidates for further development into anticancer-like agents. Additionally, based on the optimised structures, the optimum geometry for each of the selected molecules was developed. Then, the estimated and the experimentally determined IR vibrational frequencies for each compound were compared. The results of this comparison showed that the theoretical and experimental data were in excellent agreement, which could support the reliability of the experimental analytical data and the applicability of the mathematical model. Communicated by Ramaswamy H. Sarma
Signature and concordance of positive knots
Creators: name: Baader, Sebastian
name: Dehornoy, Pierre
name: Liechti, Livio
Publisher: name: arXiv
Year: 2015
Subjects: subject: Geometric Topology (math.GT)
subject: FOS: Mathematics
subject: 57M27

description: We derive a linear estimate of the signature of positive knots, in terms of their genus. As an application, we show that every knot concordance class contains at most finitely many positive knots.
description: 10 pages, 7 figures
title: Rational maps represented by both rabbit and aeroplane matings
Creators: name: Exall, Freddie
Publisher: name: University of Liverpool Repository
Year: 2011

description: Understanding parameter spaces of rational maps is an active area of complex dynamics. There is a region of a particular parameter space of rational maps which contains all possible matings with the rabbit polynomial in a well understood manner. In an effort to further understand which hyperbolic components of the parameter space correspond to matings with the aeroplane we relate the family of matings with the aeroplane to the family of matings with the rabbit. We present an algorithm, described in chapter 3, which calculates the mating with the rabbit which is Thurston equivalent to a given post-critically finite mating with the aeroplane. Chapter 4 gives a result describing which matings with the rabbit are Thurston equivalent to some mating with the aeroplane. Chapter 5 studies the algorithm in more detail, giving results bounding the number of steps required for the algorithm to produce a result.
title: Online and offline rock music networks: a case study on Liverpool, 2007-2009
Creators: name: Barna, Roza Emilia
Publisher: name: University of Liverpool Repository
Year: 2012

description: This thesis explores the relationship between the online and offline presence and activity of contemporary indie rock bands in Liverpool. It addresses two main questions: firstly, how should the relationship of music, place, and social groups be described and understood in the age of the Internet; and secondly, what can research on local music making suggest about the relationship between online and offline worlds. These questions are addressed through ethnographic research conducted between 2007-2009. The research involved qualitative analysis of online content, discourse, and connections related to Liverpool indie bands and music events, as well as first-hand observation of offline events and interviews with musicians. On the basis of this, the thesis proposes two main arguments: Firstly, online presentation and interaction surrounding bands and events are closely connected to offline events, places, and personal relationships. Local music ‘scenes’ must therefore be understood as both online and offline, and their temporal and spatial (self-)positioning in online space can only be understood with reference to offline places and temporal dynamics. Secondly, the ‘network’ is a useful concept for describing and analysing the relationship of online and offline worlds. It is conceptualised in the thesis as the dynamic set of active, enacted, and negotiated connections among those participating in music making. This conceptualisation enables the description of the social world of participants in music making within a particular local environment, which at the same time branches out globally through the active collective online presence of these participants. The analysis of a band’s network structures enables the identification of both its individual characteristics and collective-oriented ties along such lines as genre and style, career stage and success, and aims and strategies. The network complements the notion of the ‘scene,’ which is defined by an expressed and represented coherence with regard to the aspects of genre aesthetics and ethics; locality; discursive participation and identification; and personal relationships. Moreover, the analysis shows that online technology has provided new means for music networks to function as cultural resource and form part of identities related to music making and place.
title: Quantitative functional magnetic resonance imaging in cerebral small vessel disease
Creators: name: Lumley, Guy
Publisher: name: University of Liverpool Repository
Year: 2012

description: Introduction: Cerebral small vessel disease (cSVD) is an important, but relatively poorly understood cause of both lacunar strokes and vascular dementia. Structural magnetic resonance imaging (MRI) markers of cSVD, including lacunes, white matter lesions (WML) and microbleeds, have been shown not to correlate consistently with clinical severity, as gauged by cognitive decline, and might offer little more than endpoint markers of disease. However, alternative developing MR techniques, including functional MRI (fMRI) using the blood-oxygen-level-dependent (BOLD) signal, offer a promising approach to charting disease severity. Aims: The primary aim is to determine whether ‘n’, a measure of neurovascular coupling (NVC) which underpins interpretation of the BOLD signal, differs between patients with cSVD and healthy matched controls. If ‘n’ does differ, a secondary aim is to determine whether ‘n’ correlates with tests of cognitive function. Methods: Eleven patients with cSVD and sixteen age-, education- and gender-matched healthy controls were recruited. Participants underwent a battery of cognitive tests focused upon executive functions and a series of MRI scans. These included structural scans, arterial spin labelling (ASL) to measure cerebral blood flow and BOLD signal. Oxygen calibrated fMRI was used with a modified Stroop Interference Task. Results: The cSVD group performed worse on the digit symbol substitution test (DSST) (p = 0.00005) than the control group. There was a significantly different BOLD response in 11 regions between patient and control groups, which were aggregated into frontal, parietal, motor, insular and total regions. ‘n’ was reduced across total regions (p = 0.02) in the patient group. ‘M’ was increased in the patient group and correlated inversely with ‘n’. DSST did not correlate with ‘n’ in patients. Conclusion: The results suggest an uncoupling of the neurovascular response in patients with cSVD, possibly associated with an increase in the oxygen extraction fraction. A larger sample size would be needed to investigate whether altered neurovascular coupling might highlight at-risk subjects who have not yet had a stroke.
title: Investigating the role of Toll-like receptors in juvenile onset systemic lupus erythematosus
Creators: name: Thorbinson, Colin
Publisher: name: University of Liverpool Repository
Year: 2011

description: Background: Juvenile-onset Systemic Lupus Erythematosus (JSLE) is a chronic debilitating multi-system autoimmune condition characterised by auto-antibody production directed against nuclear antigens. It is associated with a more severe onset and more aggressive clinical course than in adults, with poor prognostic factors presenting earlier in childhood. It has been proposed that dysregulated neutrophil apoptosis may be a source of autoantigen in JSLE. Toll-like receptors (TLRs) are essential in the function of the innate immune system recognising pathogenic material. Upon stimulation they initiate a non-specific immune response leading to the production of an antigen-specific immune defence and autoantibody production. TLRs have been implicated in the development of autoimmunity. TLRs 3, 7, 8 and 9 are capable of recognising nucleic autoantigens typical of SLE and their expression has been shown to positively correlate with anti-dsDNA titres and disease activity in adult-onset SLE. To date there have been no studies examining the role of TLRs in JSLE. Aim: To assess whether apoptotic neutrophils in JSLE are providing a source of nuclear autoantigen which are being detected through TLRs 3, 7, 8 and 9 resulting in an inflammatory response through activation of an adaptive autoimmune response. Methods: Peripheral Blood Mononuclear Cells (PBMCs) and B cells were isolated from JSLE patients, Juvenile Idiopathic Arthritis (JIA) (inflammatory controls) and non-inflammatory controls. TLR 3, 7-9 mRNA and protein expression was measured using quantitative PCR (qPCR) and flow cytometry respectively. PBMCs were incubated with TLR agonists, activation was measured by IFN-a protein and mRNA expression, by ELISA and qPCR respectively. Neutrophils were isolated from healthy controls and incubated with JSLE serum to induce apoptosis. Apoptotic neutrophils were incubated with PBMCs at varying concentrations for 6 hours. After which IFN-a mRNA expression was measured by qPCR. PBMCs were treated with a MyD88 inhibitor to block TLRs 7-9 or left untreated. MyD88 treated and untreated PBMCs were incubated with TLR9 agonist or apoptotic neutrophils for 6 hours. TLR activation was measured using IFN-a mRNA expression by qPCR. Results: JSLE patients have a significantly increased PBMC TLR 3, 8 and 9 protein and mRNA expression compared to controls (p
The Architecture of CCAN Proteins Creates a Structural Integrity to Resist Spindle Forces and Achieve Proper Intrakinetochore Stretch
Creators: name: Wan, Xiaohu
name: Badger, Benjamin L.
name: DeLuca, Jennifer G.
name: Salmon, Edward D.
name: Suzuki, Aussie
Publisher: name: The University of North Carolina at Chapel Hill University Libraries
Year: 2014

description: Constitutive Centromere Associated Network (CCAN) proteins, particularly CENP-C, CENP-T and the CENP-H/-I complex, mechanically link CENP-A-containing centromeric chromatin within the inner kinetochore to outer kinetochore proteins, like the Ndc80 complex, that bind kinetochore microtubules. Accuracy of chromosome segregation depends critically upon Aurora B phosphorylation of Ndc80/Hec1. To determine how CCAN protein architecture mechanically constrains intrakinetochore stretch between CENP-A and Ndc80/Hec1 for proper Ndc80/Hec1 phosphorylation, we used super-resolution fluorescence microscopy and selective protein depletion. We found that at bi-oriented chromosomes in late prometaphase cells, CENP-T is stretched ~16 nm to the inner end of Ndc80/Hec1, much less than expected for full-length CENP-T. Depletion of various CCAN linker proteins induced hyper-intrakinetochore stretch (an additional 20-60 nm) with corresponding significant decreases in Aurora B phosphorylation of Ndc80/Hec1. Thus, proper intrakinetochore stretch is required for normal kinetochore function and depends critically on all the CCAN mechanical linkers to the Ndc80 complex.