cometadata/datacite-rtg-text-other-reclassification-records huggingface dataset:
Assessing adaptation of the cancer kinome in response to targeted therapies
Creators: name: Johnson, Gary L.
name: Zawistowski, Jon S.
name: Graves, Lee M.
Publisher: name: The University of North Carolina at Chapel Hill University Libraries
Year: 2014

description: Cancer cells are dependent on protein kinase signalling networks to drive proliferation and to promote survival, and, accordingly, kinases continue to represent a major target class for development of anti-cancer therapeutics. Kinase inhibitors nevertheless have yielded only limited success with many different malignancies due to the inability of single agents to sustain a durable clinical response. Cancer cell kinomes are highly resilient and able to bypass targeted kinase inhibition, leading to tumour resistance. A novel platform has been developed to analyse the activity of the expressed kinome using MIBs (multiplexed inhibitor beads), which consist of Sepharose beads with covalently immobilized inhibitors that preferentially bind activated kinases. Coupling MIB capture with MS (MIB-MS) allows simultaneous determination of the activity of over 75% of the expressed kinome, facilitating high-throughput assessment of adaptive kinase responses resulting from deregulated feedback and feedforward regulatory mechanisms. The adaptive response frequently involves transcriptional up-regulation of specific kinases that allow bypass of the targeted kinase. Understanding how the kinome reprogrammes to targeted kinase inhibition will allow novel therapeutic strategies to be developed for durable clinical responses.
Associations of Comorbid Conditions and Transitions Across States of Knee Osteoarthritis in a Community-Based Cohort
Creators: name: Arbeeva, L.S.
name: Golightly, Y.M.
name: Nelson, A.E.
name: Jordan, J.M.
name: Murphy, L.B.
name: Cleveland, R.J.
name: Alvarez, C.
name: Callahan, L.F.
name: Renner, J.B.
name: Schwartz, T.A.
Publisher: name: John Wiley and Sons Inc
Year: 2021

description: Objective: To examine relationships between knee osteoarthritis (KOA) and obesity, diabetes mellitus (DM), and cardiovascular disease (CVD). Methods: Associations of time-dependent obesity, DM, and CVD with KOA transition states over approximately 18 years were examined among 4093 participants from a community-based cohort. Transition states were 1) no knee symptoms and no radiographic KOA (rKOA; Kellgren-Lawrence grade ≥2 in at least one knee), 2) asymptomatic rKOA, 3) knee symptoms only, 4) symptomatic rKOA (sxKOA; rKOA and symptoms in same knee). Markov multistate models estimated adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) for associations between comorbid conditions and transitions across states, adjusting for baseline age, sex, race, education, enrollment cohort, birth year, and time-dependent knee injury history. Results: At baseline, 40% of participants had obesity, 13% had DM, and 22% had CVD (mean age = 61 years; 34% Black; 37% male). Compared with those without obesity, those with obesity had a higher hazard of worsening from no rKOA/no symptoms to asymptomatic rKOA (aHR = 1.7; 95% CI = 1.3-2.2) and from knee symptoms to sxKOA (aHR = 1.7; 95% CI = 1.3-2.3), as well as a lower hazard of symptom resolution from sxKOA to asymptomatic rKOA (aHR = 0.5 [95% = CI 0.4-0.7]). Compared with those without CVD, those with CVD had a higher hazard of worsening from no rKOA/symptoms to knee symptoms (aHR = 1.5; 95% CI = 1.1-2.1). DM was not associated with transitions of rKOA. Conclusion: Prevention of obesity and CVD may limit the development or worsening of rKOA and symptoms.
Charge Renormalization and Charge Oscillation in Asymmetric Primitive Model
Creators: name: Ding, Mingnan
name: Liang, Yihao
name: Lu, Bing-Sui
name: Xing, Xiangjun
Publisher: name: arXiv
Year: 2015
Subjects: subject: Soft Condensed Matter (cond-mat.soft)
subject: Statistical Mechanics (cond-mat.stat-mech)
subject: Chemical Physics (physics.chem-ph)
subject: FOS: Physical sciences

description: The Debye charging method is generalized to study the linear response properties of the asymmetric primitive model for electrolytes. Analytic results are obtained for the effective charge distributions of constituent ions inside the electrolyte, from which all static linear response properties of system follow. It is found that, as the ion density increases, both the screening length and the dielectric constant receive substantial renormalization due to ionic correlations. Furthermore, the valence of larger ion is substantially renormalized upwards by ionic correlations, whilst that of smaller ions remains approximately the same. For sufficiently high density, the system exhibit charge oscillations. The threshold ion density for charge oscillation is much lower than the corresponding value for symmetric electrolytes. Our results agree well with large scale Monte Carlo simulations.
description: 26 pages, 10 pdf figures
Racial/Ethnic, Socioeconomic, and Geographic Disparities in the Epidemiology of Knee and Hip Osteoarthritis
Creators: name: Cleveland, R.J.
name: Callahan, L.F.
name: Golightly, Y.
name: Allen, K.D.
Publisher: name: W.B. Saunders
Year: 2021

description: It is estimated that 32.5 million US adults have clinical osteoarthritis (OA), with the most common sites being knee and hip. OA is associated with substantial individual and societal costs. Race/ethnicity, socioeconomic status (SES), and geographic variations in the prevalence of knee and hip OA are well established around the world. In addition, clinical outcomes associated with hip and knee OA differ according to race/ethnicity, SES, and geography. This variation is likely multifactorial and may also reflect country-specific differences in health care systems. The interplay between different factors, such as geography, SES, and race/ethnicity, is difficult to study.
Second order analysis of control-affine problems with scalar state constraint
Creators: name: Aronna, M. Soledad
name: Bonnans, Frédéric
name: Goh, Bean San
Publisher: name: arXiv
Year: 2014
Subjects: subject: Optimization and Control (math.OC)
subject: Numerical Analysis (math.NA)
subject: FOS: Mathematics
subject: 49K15, 49K27

description: In this article we establish new second order necessary and sufficient optimality conditions for a class of control-affine problems with a scalar control and a scalar state constraint. These optimality conditions extend to the constrained state framework the Goh transform, which is the classical tool for obtaining an extension of the Legendre condition.
description: To appear in Mathematical Programming - Series A
Foot Osteoarthritis Frequency and Associated Factors in a Community-Based Cross-Sectional Study of White and African American Adults
Creators: name: Jordan, J.M.
name: Nelson, A.E.
name: Renner, J.B.
name: Hillstrom, H.J.
name: Flowers, P.
name: Hannan, M.T.
name: Golightly, Y.M.
Publisher: name: John Wiley and Sons Inc
Year: 2021

description: Objective: Few studies have explored foot osteoarthritis (OA) in the general population. The purpose of this study was to determine the frequency of foot OA and identify associated factors in a cross-sectional analysis of a large community-based cohort. Methods: Data were from the 2013–2015 study visit of the Johnston County OA Project. Radiographic OA of the foot was defined using the La Trobe radiographic atlas (≥2 osteophytes or joint space narrowing in at least 1 of 5 joints). Symptomatic OA of the foot was defined as foot radiographic OA with pain, aching, or stiffness in the same foot. At the foot-level, separate logistic regression models with generalized estimating equations to account for intraperson correlations were performed to examine associations of foot radiographic OA or symptomatic OA with age, body mass index (BMI), sex, race, educational attainment, and previous foot injury. Results: Of 864 participants with available data (mean age 71 years, mean BMI 30 kg/m2, 68% women, 33% African American, 13% <12 years of schooling), 22% had foot radiographic OA, 20% had foot symptoms, and 5% had foot symptomatic OA. Radiographic, but not symptomatic, foot OA was more common in African American than White participants. Participants with obesity, compared to normal weight, had >2 times the odds of radiographic OA and >5 times the odds of symptomatic OA in adjusted models. Conclusion: Foot radiographic OA and foot symptoms were common in the sample, but both conditions simultaneously (i.e., symptomatic OA) occurred infrequently. Notably, obesity was linked with foot symptomatic OA, perhaps implicating metabolic or mechanical influences.
Lifting matroid divisors on tropical curves
Creators: name: Cartwright, Dustin
Publisher: name: arXiv
Year: 2015
Subjects: subject: Algebraic Geometry (math.AG)
subject: FOS: Mathematics
subject: 14T05, 05B35

description: Tropical geometry gives a bound on the ranks of divisors on curves in terms of the combinatorics of the dual graph of a degeneration. We show that for a family of examples, curves realizing this bound might only exist over certain characteristics or over certain fields of definition. Our examples also apply to the theory of metrized complexes and weighted graphs. These examples arise by relating the lifting problem to matroid realizability. We also give a proof of Mnëv universality with explicit bounds on the size of the matroid, which may be of independent interest.
description: 27 pages, 7 figures, final submitted version: several proofs clarified and various minor changes
Mutations in the Procaspase-3 Dimer Interface Affect the Activity of the Zymogen †
Creators: name: Clark, A. Clay
name: Feeney, Brett
name: Tripathy, Ashutosh
name: Pop, Cristina
Publisher: name: The University of North Carolina at Chapel Hill University Libraries
Year: 2003

description: The interface of the procaspase-3 dimer plays a critical role in zymogen maturation. We show that replacement of valine 266, the residue at the center of the procaspase-3 dimer interface, with glutamate resulted in an increase in enzyme activity of ~60-fold, representing a pseudoactivation of the procaspase. In contrast, substitution of V266 with histidine abolished the activity of the procaspase-3 as well as that of the mature caspase. While the mutations do not affect the dimeric properties of the procaspase, we show that the V266E mutation may affect the formation of a loop bundle that is important for stabilizing the active site. In contrast, the V266H mutation affects the positioning of loop L3, the loop that forms the bulk of the substrate binding pocket. In some cases, the amino acids affected by the mutations are >20 Å from the interface. Overall, the results demonstrate that the integrity of the dimer interface is important for maintaining the proper active site conformation.
Reduction by symmetries in singular quantum-mechanical problems: general scheme and application to Aharonov-Bohm model
Creators: name: Smirnov, A. G.
Publisher: name: arXiv
Year: 2014
Subjects: subject: Mathematical Physics (math-ph)
subject: FOS: Physical sciences

description: We develop a general technique for finding self-adjoint extensions of a symmetric operator that respect a given set of its symmetries. Problems of this type naturally arise when considering two- and three-dimensional Schrödinger operators with singular potentials. The approach is based on constructing a unitary transformation diagonalizing the symmetries and reducing the initial operator to the direct integral of a suitable family of partial operators. We prove that symmetry preserving self-adjoint extensions of the initial operator are in a one-to-one correspondence with measurable families of self-adjoint extensions of partial operators obtained by reduction. The general scheme is applied to the three-dimensional Aharonov-Bohm Hamiltonian describing the electron in the magnetic field of an infinitely thin solenoid. We construct all self-adjoint extensions of this Hamiltonian, invariant under translations along the solenoid and rotations around it, and explicitly find their eigenfunction expansions.
description: Final version
Scaling and complexity of stress fluctuations associated with smooth and jerky flow in a FeCoNiTiAl high-entropy alloy
Creators: name: Lebyodkin, Mikhail
name: Brechtl, Jamieson
name: Lebedkina, Tatiana
name: Wen, Kangkang
name: Liaw, Peter K.
name: Shen, Tongde
Publisher: name: arXiv
Year: 2023
Subjects: subject: Materials Science (cond-mat.mtrl-sci)
subject: Data Analysis, Statistics and Probability (physics.data-an)
subject: FOS: Physical sciences

description: Recent observations of jerky flow in high-entropy alloys (HEA) revealed a high role of self-organization of dislocations in their plasticity. The present work reports first results of investigation of stress fluctuations during plastic deformation of a FeCoNiTiAl alloy, examined in a wide temperature range covering both smooth and jerky flow. These fluctuations, which accompany the overall deformation behavior representing an essentially slower stress evolution controlled by the work hardening, were processed using complementary approaches comprising the Fourier spectral analysis, the refined composite multiscale entropy, and multifractal formalisms. The joint analysis at distinct scales testified that even a macroscopically smooth plastic flow is accompanied with nonrandom fluctuations, disclosing self-organized dynamics of dislocations. Qualitative changes in such a fine-scale "noise" were found with varying temperature. The observed diversity is significant for understanding the relationships between different scales of plasticity of HEAs and crystal materials in general.
description: 13 pages main body, 6 figures, 2 appendices, 65 citations (22 pages overall)
Affinity, Kinetic, and Structural Study of the Interaction of 3- O -Sulfotransferase Isoform 1 with Heparan Sulfate †
Creators: name: Zhang, Fuming
name: Liu, Jian
name: Linhardt, Robert J.
name: Xu, Ding
name: Kemp, Melissa
name: Muñoz, Eva
Publisher: name: The University of North Carolina at Chapel Hill University Libraries
Year: 2006

description: The 3-O-sulfonation of glucosamine residues in heparan sulfate (HS) by 3-O-sulfotransferase (3-OST) is a key substitution that is present in HS sequences of biological importance, in particular HS anticoagulant activity. Six different isoforms of 3-OST have been identified that exhibit different substrate specificity. In this paper the affinity and kinetics of the interaction between 3-O-sulfotransferase isoform 1 (3-OST-1) and HS have been examined using surface plasmon resonance (SPR). 3-OST-1 binds with micomolar affinity to HS (KD= 2.79 µM), and this interaction is apparently independent of the presence of the coenzyme, 3′-phosphoadenosine 5′-phosphosulfate (PAPS). A conformational change in the complex has also been detected, supporting data from previous studies. Selected 3-OST-1 mutants have provided valuable information of amino acid residues that participate in 3-OST-1 interaction with HS substrate and its catalytic activity. The results from this study contribute to understanding the substrate specificity among the 3-OST isoforms and in the mechanism of 3-OST-1-catalyzed biosynthesis of anticoagulant HS.
Analysis of Autophosphorylating Kinase Activities of Arabidopsis and Human Cryptochromes †
Creators: name: Özgür, Sezgin
name: Sancar, Aziz
Publisher: name: The University of North Carolina at Chapel Hill University Libraries
Year: 2006

description: Cryptochromes are FAD-based blue-light photoreceptors that regulate growth and development in plants and the circadian clock in animals. Arabidopsis thaliana and humans possess two cryptochromes. Recently, it was found that Arabidopsis cryptochrome 1 (AtCry1) binds ATP and exhibits autokinase activity that is simulated by blue light. Similarly, it was reported that human cryptochrome 1 (HsCry1) exhibited autophosphorylation activity under blue light. To test the generality of light stimulated kinase function of cryptochromes, we purified AtCry1, AtCry2, HsCry1 and HsCry2 and probed them for kinase activity under a variety of conditions. We find that AtCry1, which contains near stoichiometric amount of FAD and human HsCry1 and HsCry2, which contain only trace amounts of FAD have autokinase activity but AtCry2, which also contains stoichiometric amounts of FAD does not. Finally, we find that the kinase activity of AtCry1 is not significantly affected by light or the redox status of the flavin cofactor.
Dynamic Coupling and Allosteric Behavior in a Nonallosteric Protein †
Creators: name: Edgell, Marshall H.
name: Lee, Andrew L.
name: Clarkson, Michael W.
name: Gilmore, Steven A.
Publisher: name: The University of North Carolina at Chapel Hill University Libraries
Year: 2006

description: Long-range intraprotein interactions give rise to many important protein behaviors. Understanding how energy is transduced through protein structures to either transmit a signal or elicit conformational changes is therefore a current challenge in structural biology. In an effort to understand such linkages, multiple V→A mutations were made in the small globular protein eglin c. The physical responses, as mapped by NMR spin relaxation, residual dipolar couplings (RDCs), and scalar couplings, illustrate that the interior of this non-allosteric protein forms a dynamic network and that local perturbations are transmitted as dynamic and structural changes to distal sites as far as 16 Å away. Two basic types of propagation responses were observed: contiguous pathways of enhanced (attenuated) dynamics with no change in structure; and dispersed (non-contiguous) changes in methyl rotation rates that appear to result from subtle deformation of backbone structure. In addition, energy transmission is found to be unidirectional. In one mutant, an allosteric conformational change of a side chain is seen in the context of a pathway of propagated changes in ps-ns dynamics. The observation of so many long-range interactions in a small, rigid system lends experimental weight to the idea that all well-folded proteins inherently possess allosteric features [Gunasekaran et al. (2004) Proteins 57, 433−443], and that dynamics are a rich source of information for mapping and gaining mechanistic insight into communication pathways in individual proteins.
Identification of the N-Linked Glycosylation Sites of Vitamin K-Dependent Carboxylase and Effect of Glycosylation on Carboxylase Function †
Creators: name: Straight, David L.
name: Zheng, Mei-Yan
name: Tie, Jian-Ke
name: Stafford, Darrel W.
name: Pope, R. Marshall
Publisher: name: The University of North Carolina at Chapel Hill University Libraries
Year: 2006

description: The vitamin K-dependent carboxylase is an integral membrane protein which is required for the post-translational modification of a variety of vitamin K-dependent proteins. Previous studies have suggested carboxylase is a glycoprotein with N-linked glycosylation sites. In the present study, we identified the N-glycosylation sites of carboxylase by mass spectrometric peptide mapping analyses combined with site-directed mutagenesis. Our mass spectrometric results show that the N-linked glycosylation in carboxylase occurs at positions N459, N550, N605, and N627. Eliminating these glycosylation sites by changing asparagine to glutamine caused the mutant carboxylase to migrate faster in SDS-PAGE gel analyses, adding further evidence that these sites are glycosylated. In addition, the mutation studies identified N525, a site not recoverable by mass spectroscopy analysis, as a glycosylation site. Furthermore, the potential glycosylation site at N570 is glycosylated only if all the five natural glycosylation sites are simultaneously mutated. Removal of the oligosaccharides by glycosidase from wild-type carboxylase or by eliminating the functional glycosylation sites by site-directed mutagenesis did not affect either the carboxylation or epoxidation activity when the small pentapeptide FLEEL was used as substrate, suggesting that N-linked glycosylation is not required for the enzymatic function of carboxylase. In contrast, when site N570 and the five natural glycosylation sites were mutated simultaneously, the resulting carboxylase protein was degraded. Our results suggest that N-linked glycosylation is not essential for carboxylase enzymatic activity but it is important for protein folding and stability.
Foot Osteoarthritis: Addressing an Overlooked Global Public Health Problem
Creators: name: Golightly, Y.M.
name: Gates, L.S.
Publisher: name: John Wiley and Sons Inc
Year: 2021

description: Foot pain affects at least one in three adults over the age of 45 (1), and one in six adults ≥50 years old with foot pain also have radiographic evidence of foot osteoarthritis (OA) (2). Unfortunately, our knowledge of foot OA and its burden substantially lags behind that of other joint sites (i.e., knee, hip, and hand). Given the link of foot pain and disorders with disability and reduced quality of life (3), a greater understanding is needed of foot OA and its pathogenesis and risk factors, especially since it is likely a serious disease with a significant public health burden.
Two time distribution in Brownian directed percolation
Creators: name: Johansson, Kurt
Publisher: name: arXiv
Year: 2015
Subjects: subject: Mathematical Physics (math-ph)
subject: Probability (math.PR)
subject: FOS: Physical sciences
subject: FOS: Mathematics
subject: 60K35, 60B20, 82B43, 60K37

description: In the zero temperature Brownian semi-discrete directed polymer we study the joint distribution of two last-passage times at positions ordered in the time-like direction. This is the situation when we have the slow de-correlation phenomenon. We compute the limiting joint distribution function in a scaling limit. This limiting distribution is given by an expansion in determinants which is not a Fredholm expansion. A somewhat similar looking formula was derived non-rigorously in a related model by Dotsenko.
description: 40 pages. In the second version some errors have been corrected and some extra material has been added
Insight into the prospective evaluation of third-order interelectronic corrections on Li-like ions
Creators: name: Soguel, R. N.
name: Fritzsche, S.
Publisher: name: arXiv
Year: 2023
Subjects: subject: Atomic Physics (physics.atom-ph)
subject: FOS: Physical sciences

description: Relying on the redefined vacuum state approach, and based on one-particle three-loop Feynman diagrams, partial third-order interelectronic corrections to the valence electron energy shift are investigated in Li-like ions. The idea is to begin with simple one-particle gauge-invariant subsets composed of Feynman diagrams and to keep track of them in the many-electron frame, which is a strong asset of the formalism. An independent derivation is undertaken with the help of perturbation theory to cross-check the expressions. This two-method scheme helps to resolve how the different terms are distributed among three- and four-electron contributions. Furthermore, it provides a tool to overcome the difficulties related to the derivation of reducible terms, which are tricky to deal with. These two independent derivations and the comparison of the resulting expressions are fully consistent, except for two expressions. In these cases, the discrepancy can be traced back to a different topology of the poles.
Inflammatory, Structural, and Pain Biochemical Biomarkers May Reflect Radiographic Disc Space Narrowing: The Johnston County Osteoarthritis Project
Creators: name: Goode, A.P.
name: Jimenez, M.
name: Cleveland, R.J.
name: Chen, J.
name: Huebner, J.L.
name: Kraus, V.B.
name: Jordan, J.M.
name: DeFrate, L.E.
name: Gracely, R.
name: George, S.Z.
name: Schwartz, T.A.
name: Golightly, Y.M.
Publisher: name: John Wiley and Sons Inc.
Year: 2020

description: The purpose of this work is to determine the relationship between biomarkers of inflammation, structure, and pain with radiographic disc space narrowing (DSN) in community-based participants. A total of 74 participants (37 cases and 37 controls) enrolled in the Johnston County Osteoarthritis Project during 2006–2010 were selected. The cases had at least mild radiographic DSN and low back pain (LBP). The controls had neither radiographic evidence of DSN nor LBP. The measured analytes from human serum included N-cadherin, Keratin-19, Lumican, CXCL6, RANTES, IL-17, IL-6, BDNF, OPG, and NPY. A standard dolorimeter measured pressure-pain threshold. The coefficients of variation were used to evaluate inter- and intra-assay reliability. Participants with similar biomarker profiles were grouped together using cluster analysis. The binomial regression models were used to estimate risk ratios (RR) and 95% confidence intervals (CI) in propensity score-matched models. Significant associations were found between radiographic DSN and OPG (RR = 3.90; 95% CI: 1.83, 8.31), IL-6 (RR = 2.54; 95% CI: 1.92, 3.36), and NPY (RR = 2.06 95% CI: 1.62, 2.63). Relative to a cluster with low levels of biomarkers, a cluster representing elevated levels of OPG, RANTES, Lumican, Keratin-19, and NPY (RR = 3.04; 95% CI: 1.22, 7.54) and a cluster representing elevated levels of NPY (RR = 2.91; 95% CI: 1.15, 7.39) were significantly associated with radiographic DSN. Clinical Significance: These findings suggest that individual and combinations of biochemical biomarkers may reflect radiographic DSN. This is just one step toward understanding the relationships between biochemical biomarkers and DSN that may lead to improved intervention delivery.
Cosmic Reionization On Computers III. The Clumping Factor
Creators: name: Kaurov, Alexander A.
name: Gnedin, Nickolay Y.
Publisher: name: arXiv
Year: 2014
Subjects: subject: Cosmology and Nongalactic Astrophysics (astro-ph.CO)
subject: FOS: Physical sciences

description: We use fully self-consistent numerical simulations of cosmic reionization, completed under the Cosmic Reionization On Computers (CROC) project, to explore how well the recombinations in the ionized IGM can be quantified by the effective "clumping factor." The density distribution in the simulations (and, presumably, in a real universe) is highly inhomogeneous and more-or-less smoothly varying in space. However, even in highly complex and dynamic environments the concept of the IGM remains reasonably well-defined; the largest ambiguity comes from the unvirialized regions around galaxies that are over-ionized by the local enhancement in the radiation field ("proximity zones"). That ambiguity precludes computing the IGM clumping factor to better than about 20\%. We also discuss a "local clumping factor," defined over a particular spatial scale, and quantify its scatter on a given scale and its variation as a function of scale.
description: 9 pages, 10 figure, submitted to ApJ
MMP-20 Is Predominately a Tooth-Specific Enzyme with a Deep Catalytic Pocket that Hydrolyzes Type V Collagen †
Creators: name: Cantley, Lewis C.
name: Komisarof, Justin A.
name: Yamakoshi, Yasuo
name: Lee, Daniel H.
name: Bartlett, John D.
name: Klingenhoff, Andreas
name: Turk, Benjamin E.
name: Wright, J. Timothy
name: Simmer, James P.
name: Reichenberger, Ernst
Publisher: name: The University of North Carolina at Chapel Hill University Libraries
Year: 2006

description: Matrix metalloproteinase-20 (MMP-20, enamelysin) has a highly restricted pattern of expression. In healthy tissues, MMP-20 is observed in the enamel organ and pulp organ of developing teeth and is present only as an activated enzyme. To identify other tissues that may express MMP-20, we performed a systematic mouse tissue expression screen. Among the non-tooth tissues assayed, MMP-20 transcripts were only identified in minute quantities within the large intestine. The murine Mmp20 promoter was cloned, sequenced and assessed for potential tooth-specific regulatory elements. In silico analysis identified four promoter modules that were common to Mmp20 and at least two of three co-regulated predominantly tooth-specific genes that encode ameloblastin, amelogenin, and enamelin. We asked if the highly restricted MMP-20 expression pattern was associated with a broad substrate specificity that might preclude its expression in other tissues. An iterative mixture-based random doedecamer peptide library screen with Edman sequencing of MMP-20 cleavage products revealed that, among MMPs previously screened, MMP-20 had unique substrate preferences. These preferences indicate that MMP-20 has a deep and wide catalytic pocket that can accommodate substrates with large aromatic residues in the P1′ position. Based on matrices derived from the peptide library data, we identified and then confirmed that Type V collagen is an MMP-20 substrate. Since Type V collagen is not present in dental enamel but is an otherwise widely distributed collagen, and since only active MMP-20 has been observed in teeth, our data suggests that control of MMP-20 activity is primarily regulated by transcriptional means.
Oliver Twist on the Victorian page and stage
Creators: name: Gilmour, Michael
Publisher: name: Figshare
Year: 2019
Subjects: subject: 199999 Studies in the Creative Arts and Writing not elsewhere classified
subject: FOS: Arts (arts, history of arts, performing arts, music)

description: This thesis examines the various theatrical Oliver Twists that appeared on the nineteenth-century page and stage; it pays particular attention to archival sources and the people who brought favourite (and some more unfamiliar) moments to a theatregoing public in London. While interested in Dickens’s aesthetic and professional connections to the popular stage, this thesis is not primarily interested in Dickens’s stage work or indeed his plays; instead, I seek to show that Oliver Twist took on a varied theatrical life outside of the limits of the novel. In doing so, I aim to highlight lesser known figures of the nineteenth-century popular cultural landscape – by moving attention away from Dickens, these forgotten figures can be brought more fully into critical discussion, and their work more fully appreciated and explored. We are, in the twenty-first century, astutely aware of the continued proliferation of adaptations bearing the name Oliver Twist or some variant. the most famous of which is situated at the intersection of the stage and page, theatre and television. Though one could point to David Lean’s classic film (1948) as one towering example of an Oliver Twist made for the screen, Lionel Bart’s sensationally successful (and itself continually adapted) Oliver! is surely the most embedded within popular cultural consciousness. In the edited collection Dickens and Modernity (2012), both Josh Marsh and Carrie Sickmann have contended that Oliver! surely ‘marked a genuine ‘revolution’ in theatre history… and spur to the Dickens adaptation industry’; they go on to relate how Oliver! has contributed to an ongoing process of adaptation, whereby the story of the orphan boy has been transported to new times and new places.
Compatibility of Larmor's formula with radiation reaction for a radiating charge
Creators: name: Singal, Ashok K.
Publisher: name: arXiv
Year: 2014
Subjects: subject: Classical Physics (physics.class-ph)
subject: FOS: Physical sciences

description: It is shown that the well-known disparity in classical electrodynamics between the power losses calculated from the radiation reaction and that from Larmor's formula, is succinctly understood when a proper distinction is made between quantities expressed in terms of a "real time" and those expressed in terms of a retarded time. It is explicitly shown that an accelerated charge, taken to be a sphere of vanishingly small radius $r_{\rm o} $, experiences at any time a self-force proportional to the acceleration it had at a time $r_{\rm o} /c$ earlier, while the rate of work done on the charge is obtained by a scalar product of the self-force with the instantaneous (present) value of its velocity. Now if the retarded value of acceleration is expressed in terms of the present values of acceleration, then we get the rate of work done according to the radiation reaction equation, however if we instead express the present value of velocity in terms of its time-retarded value, then we get back the familiar Larmor's radiation formula. From this simple relation between the two we show that they differ because Larmor's formula, in contrast with the radiation reaction, is written not in terms of the real-time values of quantities specifying the charge motion but is instead expressed in terms of the time-retarded values. Moreover, it is explicitly shown that the difference in the two formulas for radiative power loss exactly matches the difference in the temporal rate of the change of energy in the self-fields between the retarded and real times. From this it becomes obvious that the ad hoc introduction of an acceleration-dependent energy term, usually referred to in the prevalent literature as Schott-term, in order to make the two formulas comply with each other, is redundant.
description: 22 pages, I figure, Foundations of Physics 2015. arXiv admin note: text overlap with arXiv:1410.7699
Unactivated PKR Exists in an Open Conformation Capable of Binding Nucleotides †
Creators: name: Cole, James L.
name: Tessmer, Ingrid
name: Erie, Dorothy A.
name: Craig, Ranyelle
name: Lemaire, Peter A.
Publisher: name: The University of North Carolina at Chapel Hill University Libraries
Year: 2006

description: The dsRNA-activated protein kinase, PKR, plays a pivotal role in the cellular antiviral response. PKR contains an N-terminal dsRNA binding domain (dsRBD) and a C-terminal kinase domain. An autoinhibition model has been proposed in which latent PKR exists in a closed conformation where the substrate binding cleft of the kinase is blocked by the dsRBD. Binding to dsRNA activates the enzyme by inducing an open conformation and enhancing dimerization. We have tested this model by characterizing the affinity and kinetics of nucleotide substrate binding to PKR. The fluorescent nucleotide mant-AMPPNP binds to unactivated PKR with Kd ~ 30 μM and the affinity is not strongly affected by autophosphorylation or binding to dsRNA. Biphasic binding kinetics are observed where the fast phase depends on nucleotide concentration but the slow phase is ligand-independent. The kinetic data fit to a two-step model of ligand binding followed by a slow conformation change. The kinetics are also not strongly affected by phosphorylation state or dsRNA binding. Thus, the equilibrium and kinetic data indicate that substrate accessibility of the kinase is not modulated by PKR activation state as predicted by the autoinhibition model. In atomic force microscopy images, monomers of the latent protein are resolved with three separate regions linked by flexible, bridge-like structures. Resolution of the individual domains in the images supports a model in which unactivated PKR exists in an open conformation where the kinase domain is accessible and capable of binding substrate.
Infection Curve Flattening via Targeted Interventions and Self-Isolation
Creators: name: Doostmohammadian, Mohammadreza
name: Zarrabi, Houman
name: Doustmohammadian, Azam
name: Rabiee, Hamid R.
Publisher: name: arXiv
Year: 2023
Subjects: subject: Social and Information Networks (cs.SI)
subject: Systems and Control (eess.SY)
subject: Physics and Society (physics.soc-ph)
subject: FOS: Computer and information sciences
subject: FOS: Electrical engineering, electronic engineering, information engineering
subject: FOS: Physical sciences

description: Understanding the impact of network clustering and small-world properties on epidemic spread can be crucial in developing effective strategies for managing and controlling infectious diseases. Particularly in this work, we study the impact of these network features on targeted intervention (e.g., self-isolation and quarantine). The targeted individuals for self-isolation are based on centrality measures and node influence metrics. Compared to our previous works on scale-free networks, small-world networks are considered in this paper. Small-world networks resemble real-world social and human networks. In this type of network, most nodes are not directly connected but can be reached through a few intermediaries (known as the small-worldness property). Real social networks, such as friendship networks, also exhibit this small-worldness property, where most people are connected through a relatively small number of intermediaries. We particularly study the epidemic curve flattening by centrality-based interventions/isolation over small-world networks. Our results show that high clustering while having low small-worldness (higher shortest path characteristics) implies flatter infection curves. In reality, a flatter infection curve implies that the number of new cases of a disease is spread out over a longer period of time, rather than a sharp and sudden increase in cases (a peak in epidemic). In turn, this reduces the strain on healthcare resources and helps to relieve the healthcare services.
Individuality and universality in the growth-division laws of single E. coli cells
Creators: name: Kennard, Andrew S.
name: Osella, Matteo
name: Javer, Avelino
name: Grilli, Jacopo
name: Nghe, Philippe
name: Tans, Sander
name: Cicuta, Pietro
name: Lagomarsino, Marco Cosentino
Publisher: name: arXiv
Year: 2014
Subjects: subject: Cell Behavior (q-bio.CB)
subject: FOS: Biological sciences

description: The mean size of exponentially dividing E. coli cells cultured in different nutrient conditions is known to depend on the mean growth rate only. However, the joint fluctuations relating cell size, doubling time and individual growth rate are only starting to be characterized. Recent studies in bacteria (i) revealed the near constancy of the size extension in a single cell cycle (adder mechanism), and (ii) reported a universal trend where the spread in both size and doubling times is a linear function of the population means of these variables. Here, we combine experiments and theory and use scaling concepts to elucidate the constraints posed by the second observation on the division control mechanism and on the joint fluctuations of sizes and doubling times. We found that scaling relations based on the means both collapse size and doubling-time distributions across different conditions, and explain how the shape of their joint fluctuations deviates from the means. Our data on these joint fluctuations highlight the importance of cell individuality: single cells do not follow the dependence observed for the means between size and either growth rate or inverse doubling time. Our calculations show that these results emerge from a broad class of division control mechanisms (including the adder mechanism as a particular case) requiring a certain scaling form of the so-called "division hazard rate function", which defines the probability rate of dividing as a function of measurable parameters. This gives a rationale for the universal body-size distributions observed in microbial ecosystems across many microbial species, presumably dividing with multiple mechanisms. Additionally, our experiments show a crossover between fast and slow growth in the relation between individual-cell growth rate and division time, which can be understood in terms of different regimes of genome replication control.
description: 39 pages, 7 main figures, 17 supplementary figures
The Bergman projection on fat Hartogs triangles: L^p boundedness
Creators: name: Edholm, L. D.
name: McNeal, J. D.
Publisher: name: arXiv
Year: 2015
Subjects: subject: Complex Variables (math.CV)
subject: FOS: Mathematics
subject: 32W05, 32A25

description: A class of pseudoconvex domains in $\mathbb{C}^{n}$ generalizing the Hartogs triangle is considered. The $L^p$ boundedness of the Bergman projection associated to these domains is established, for a restricted range of $p$ depending on the "fatness" of domains. This range of $p$ is shown to be sharp.
Scaling Limit for the Kernel of the Spectral Projector and Remainder Estimates in the Pointwise Weyl Law
Creators: name: Canzani, Yaiza
name: Hanin, Boris
Publisher: name: arXiv
Year: 2014
Subjects: subject: Spectral Theory (math.SP)
subject: Analysis of PDEs (math.AP)
subject: Differential Geometry (math.DG)
subject: FOS: Mathematics

description: Let (M, g) be a compact smooth Riemannian manifold. We obtain new off-diagonal estimates as λ tend to infinity for the remainder in the pointwise Weyl Law for the kernel of the spectral projector of the Laplacian onto functions with frequency at most λ. A corollary is that, when rescaled around a non self-focal point, the kernel of the spectral projector onto the frequency interval (λ, λ+ 1] has a universal scaling limit as λ goes to infinity (depending only on the dimension of M). Our results also imply that if M has no conjugate points, then immersions of M into Euclidean space by an orthonormal basis of eigenfunctions with frequencies in (λ, λ+ 1] are embeddings for all λ sufficiently large.
description: Published version. Modified parametrix construction in Section 3. References added and typos corrected
Accurate Coarse Residual for Two-Level Asynchronous Domain Decomposition Methods
Creators: name: Gbikpi-Benissan, Guillaume
name: Magoulès, Frédéric
Publisher: name: arXiv
Year: 2023
Subjects: subject: Numerical Analysis (math.NA)
subject: Distributed, Parallel, and Cluster Computing (cs.DC)
subject: FOS: Mathematics
subject: FOS: Computer and information sciences

description: Recently, asynchronous coarse-space correction has been achieved within both the overlapping Schwarz and the primal Schur frameworks. Both additive and multiplicative corrections have been discussed. In this paper, we address some implementation drawbacks of the proposed additive correction scheme. In the existing approach, each coarse solution is applied only once, leaving most of the iterations of the solver without coarse-space information while building the right-hand side of the coarse problem. Moreover, one-sided routines of the Message Passing Interface (MPI) standard were considered, which introduced the need for a sleep statement in the iterations loop of the coarse solver. This implies a tuning of the sleep period, which is a non-discrete quantity. In this paper, we improve the accuracy of the coarse right-hand side, which allowed for more frequent corrections. In addition, we highlight a two-sided implementation which better suits the asynchronous coarse-space correction scheme. Numerical experiments show a significant performance gain with such increased incorporation of the coarse space.
G(l,k,d)-modules via groupoids
Creators: name: Mazorchuk, Volodymyr
name: Stroppel, Catharina
Publisher: name: arXiv
Year: 2014
Subjects: subject: Representation Theory (math.RT)
subject: Combinatorics (math.CO)
subject: Group Theory (math.GR)
subject: FOS: Mathematics

description: In this note we describe a seemingly new approach to the complex representation theory of the wreath product $G\wr S_d$ where $G$ is a finite abelian group. The approach is motivated by an appropriate version of Schur-Weyl duality. We construct a combinatorially defined groupoid in which all endomorphism algebras are direct products of symmetric groups and prove that the groupoid algebra is isomorphic to the group algebra of $G\wr S_d$. This directly implies a classification of simple modules. As an application, we get a Gelfand model for $G\wr S_d$ from the classical involutive Gelfand model for the symmetric group. We describe the Schur-Weyl duality which motivates our approach and relate it to various Schur-Weyl dualities in the literature. Finally, we discuss an extension of these methods to all complex reflection groups of type $G(\ell,k,d)$.
description: To appear in J. Alg. Combin
The association between walking speed from short- and standard-distance tests with the risk of all-cause mortality among adults with radiographic knee osteoarthritis: data from three large United States cohort studies
Creators: name: Callahan, L.F.
name: Lewis, C.E.
name: LaValley, M.
name: White, D.K.
name: Frey-Law, L.A.
name: Nevitt, M.
name: Zhang, Y.
name: Cleveland, R.J.
name: Master, H.
name: Thoma, L.M.
name: Christiansen, M.B.
name: Golightly, Y.M.
name: Voinier, D.
name: Neogi, T.
name: Jakiela, J.T.
name: Nelson, A.E.
Publisher: name: W.B. Saunders Ltd
Year: 2020

description: Objective: Adults with radiographic knee OA (rKOA) are at increased risk of mortality and walking difficulty may modify this relation. Little is known about specific aspects of walking difficulty that increase mortality risk. We investigated the association of walking speed (objective measure of walking difficulty) with mortality and examined the threshold that best discriminated this risk in adults with rKOA. Methods: Participants with rKOA from the Johnston County Osteoarthritis Project (JoCoOA, longitudinal population-based cohort), Osteoarthritis Initiative and Multicenter Osteoarthritis Study (OAI and MOST, cohorts of individuals with or at high risk of knee OA) were included. Baseline speed was measured via 2.4-meter (m) walk test (short-distance) in JoCoOA and 20-m walk test (standard-distance) in OAI and MOST. To examine the association of walking speed with mortality risk over 9 years, hazard ratios (HR) and 95% confidence intervals (CI) were calculated from Cox regression models adjusted for potential confounders. A Maximal Likelihood Ratio Chi-square Approach was utilized to identify an optimal threshold of walking speed predictive of mortality. Results: Deaths after 9 years of follow-up occurred in 23.3% (290/1244) of JoCoOA and 5.9% (249/4215) of OAI + MOST. Walking 0.2 m/s slower during short- and standard-distance walk tests was associated with 23% (aHR [95%CI]; 1.23 [1.10, 1.39]) and 25% (1.25 [1.09, 1.43]) higher mortality risk, respectively. Walking <0.5 m/s on short-distance and <1.2 m/s standard-distance walk tests, best discriminated those with and without mortality risk. Conclusion: Slower walking speed measured via short- and standard-distance walk tests was associated with increased mortality risk in adults with rKOA.
Direct Evidence for Specific Interactions of the Fibrinogen αC-Domains with the Central E Region and with Each Other †
Creators: name: Litvinov, Rustem I.
name: Weisel, John W.
name: Medved, Leonid
name: Gorkun, Oleg V.
name: Yakovlev, Sergiy
name: Tsurupa, Galina
Publisher: name: The University of North Carolina at Chapel Hill University Libraries
Year: 2007

description: The carboxyl-terminal regions of the fibrinogen Aα chains (αC regions) form compact αC-domains tethered to the bulk of the molecule with flexible αC-connectors. It was hypothesized that in fibrinogen two αC-domains interact intramolecularly with each other and with the central E region preferentially through its N-termini of Bβ chains, and that removal of fibrinopeptides A and B upon fibrin assembly results in dissociation of the αC regions and their switch to intermolecular interactions. To test this hypothesis, we studied the interactions of the recombinant αC region (Aα221-610 fragment) and its sub-fragments, αC-connector (Aα221-391) and αC-domain (Aα392-610), between each other and with the recombinant (Bβ1-66)2 and (β15-66)2 fragments and NDSK corresponding to the fibrin(ogen) central E region, using laser tweezers-based force spectroscopy. TheαC-domain, but not the αC-connector, bound to NDSK, which contains fibrinopeptides A and B, and less frequently to desA-NDSK and (Bβ1-66)2 containing only fibrinopeptides B; it was poorly reactive with desAB-NDSK and (β15-66)2 both lacking fibrinopeptides B. The interactions of the αC-domains with each other and with the αC-connector were also observed, although they were weaker and heterogeneous in strength. These results provide the first direct evidence for the interaction between the αC-domains and the central E region through fibrinopeptides B, in agreement with the above hypothesis, and indicate that fibrinopeptides A are also involved. They also confirm the hypothesized homomeric interactions between the αC-domains and display their interaction with the αC-connectors, which may contribute to covalent cross-linking of α polymers in fibrin.