cometadata/datacite-rtg-text-other-reclassification-records huggingface dataset:
Single-Molecule FRET TACKLE Reveals Highly Dynamic Mismatched DNA−MutS Complexes
Creators: name: Weninger, Keith
name: Lanyi, Cherie
name: Erie, Dorothy A.
name: Sass, Lauryn E.
Publisher: name: The University of North Carolina at Chapel Hill University Libraries
Year: 2010

description: The first step in DNA mismatch repair (MMR) is the recognition of DNA mismatches or nucleotide insertions/deletions (IDLs) by MutS and MutS homologs. To investigate the conformational properties of MutS-mismatch complexes, we used single-molecule fluorescence resonance energy transfer (smFRET) to examine the dynamics of MutS-induced DNA bending at a GT-mismatch. The FRET measurements reveal that the MutS-GT-mismatch recognition complex is highly dynamic, undergoing conformational transitions between many states with different degrees of DNA bending. Due to the complexity of the data, we developed an analysis approach, called FRET TACKLE, in which we combine direct analysis of FRET transitions with examination of kinetic lifetimes to identify all of the conformational states and characterize the kinetics of the binding and conformational equilibria. The data reveal that MutS-GT complexes can reside in six different conformations, which have lifetimes that differ by as much as 20-fold and exhibit rates of interconversion that vary by two orders of magnitude. To gain further insight into the dynamic properties of GT-MutS complexes and to bolster the validity of our analysis, we complemented our experimental data with Monte Carlo simulations. Taken together, our results suggest that the dynamics of the MutS-mismatch complex could govern the efficiency of repair of different DNA mismatches. Finally, in addition to revealing these important biological implications of MutS-DNA interactions, this FRET TACKLE method will enable the analysis of the complex dynamics of other biological systems.
The Young and Bright Type Ia Supernova ASASSN-14lp: Discovery, Early-Time Observations, First-Light Time, Distance to NGC 4666, and Progenitor Constraints
Creators: name: Shappee, B. J.
name: Piro, A. L.
name: Holoien, T. W. -S.
name: Prieto, J. L.
name: Contreras, C.
name: Itagaki, K.
name: Burns, C. R.
name: Kochanek, C. S.
name: Stanek, K. Z.
name: Alper, E.
name: Basu, U.
name: Beacom, J. F.
name: Bersier, D.
name: Brimacombe, J.
name: Conseil, E.
name: Danilet, A. B.
name: Dong, Subo
name: Falco, E.
name: Grupe, D.
name: Hsiao, E. Y.
name: Kiyota, S.
name: Morrell, N.
name: Nicolas, J.
name: Phillips, M. M.
name: Pojmanski, G.
name: Simonian, G.
name: Stritzinger, M.
name: Szczygieł, D. M.
name: Thompson, T. A.
name: Thorstensen, J.
name: Wagner, M.
name: Woźniak, P. R.
Publisher: name: arXiv
Year: 2015
Subjects: subject: Cosmology and Nongalactic Astrophysics (astro-ph.CO)
subject: High Energy Astrophysical Phenomena (astro-ph.HE)
subject: FOS: Physical sciences

description: On 2014 Dec. 9.61, the All-Sky Automated Survey for SuperNovae (ASAS-SN or "Assassin") discovered ASASSN-14lp just $\sim2$ days after first light using a global array of 14-cm diameter telescopes. ASASSN-14lp went on to become a bright supernova ($V = 11.94$ mag), second only to SN 2014J for the year. We present prediscovery photometry (with a detection less than a day after first light) and ultraviolet through near-infrared photometric and spectroscopic data covering the rise and fall of ASASSN-14lp for more than 100 days. We find that ASASSN-14lp had a broad light curve ($Δm_{15}(B) = 0.80 \pm 0.05$), a $B$-band maximum at $2457015.82 \pm 0.03$, a rise time of $16.94^{+ 0.11 }_{- 0.10 }$ days, and moderate host--galaxy extinction ($E(B-V)_{\textrm{host}} = 0.33 \pm 0.06$). Using ASASSN-14lp we derive a distance modulus for NGC 4666 of $μ= 30.8 \pm 0.2$ corresponding to a distance of $14.7 \pm 1.5$ Mpc. However, adding ASASSN-14lp to the calibrating sample of Type Ia supernovae still requires an independent distance to the host galaxy. Finally, using our early-time photometric and spectroscopic observations, we rule out red giant secondaries and, assuming a favorable viewing angle and explosion time, any non-degenerate companion larger than $0.34 R_{\textrm{sun}}$.
description: 12 pages, 9 figures, 4 tables. Accepted to ApJ. Photometric data presented in this submission are included as an ancillary file. For a brief video explaining this paper, see https://www.youtube.com/watch?v=1bOV-Cqs-ag
(100656) Mary Kezia Baker
Creators: name: Professions, Victorian
Publisher: name: University of Oxford
Year: 2022
Subjects: subject: 220201 Business and Labour History
subject: FOS: Philosophy, ethics and religion
subject: History
subject: 140203 Economic History
subject: FOS: Economics and business

description: This three-year research project began in January 2014 and investigated whether, during the Victorian period, the professions formed a distinct self-sustaining social group with its own mores and values. The project looked at 16,000 individuals drawn from census data for Alnwick, Brighton, Bristol, Dundee, Greenock, Leeds, Merthyr Tydfil, Morpeth, and Winchester. The research project was funded by the UK Economic & Social Research Council and was based at the Universities of Oxford and Northumbria.
Volume Exclusion and Soft Interaction Effects on Protein Stability under Crowded Conditions
Creators: name: Miklos, Andrew C.
name: Pielak, Gary J.
name: Sharaf, Naima G.
name: Li, Conggang
Publisher: name: The University of North Carolina at Chapel Hill University Libraries
Year: 2010

description: Most proteins function in nature under crowded conditions, and crowding can change protein properties. Quantification of crowding effects, however, is difficult because solutions containing hundreds of grams per liter of macromolecules often interfere with observing the protein being studied. Models for macromolecular crowding tend to focus on the steric effects of crowders, neglecting potential chemical interactions between the crowder and the test protein. Here, we report the first systematic, quantitative, residue-level study of crowding effects on the equilibrium stability of a globular protein. We used a system comprising poly(vinylpyrrolidone)s (PVPs) of varying molecular weights as crowding agents and chymotrypsin inhibitor 2 (CI2) as a small globular test protein. Stability was quantified with NMR-detected amide 1H exchange. We analyze the data in terms of hard particle exclusion, confinement, and soft interactions. For all crowded conditions, nearly every observed residue experiences a stabilizing effect. The exceptions are residues where stabilities are unchanged. At a PVP concentration of 100 g/L, the data are consistent with theories of hard particle exclusion. At higher concentrations, the data are more consistent with confinement. The data show that the crowder also stabilizes the test protein by weakly binding its native state. We conclude that the role of native-state binding and other soft interactions need to be seriously considered when applying both theory and experiment to studies of macromolecular crowding.
Enzymatic Placement of 6- O -Sulfo Groups in Heparan Sulfate
Creators: name: Liu, Renpeng
name: Liu, Jian
Publisher: name: The University of North Carolina at Chapel Hill University Libraries
Year: 2011

description: Heparan sulfate is a highly sulfated polysaccharide that exhibits important physiological and pathological functions. The glucosamine residue of heparan sulfate can carry sulfo groups at the 2-N-, 3-O- and 6-O- positions, leading to diverse polysaccharide structures. 6-O-sulfation at the glucosamine residue contributes to a wide range of biological functions. Here, we report a method to control the positioning of 6-O-sulfo groups in oligosaccharides. This was achieved by synthesizing oligosaccharide backbones from a disaccharide building block utilizing glycosyltransferases followed by modifications using heparan sulfate N-sulfotransferase and 6-O-sulfotransferases. This method offers a viable approach preparing heparan sulfate oligosaccharides with precisely located 6-O-sulfo groups.
Glutathionylation at Cys-111 Induces Dissociation of Wild Type and FALS Mutant SOD1 Dimers
Creators: name: Dokholyan, Nikolay V.
name: Proctor, Elizabeth A.
name: Redler, Rachel L.
name: Wilcox, Kyle C.
name: Fee, Lanette
name: Caplow, Michael
Publisher: name: The University of North Carolina at Chapel Hill University Libraries
Year: 2011

description: Mutation of the ubiquitous cytosolic enzyme Cu/Zn superoxide dismutase (SOD1) is hypothesized to cause familial amyotrophic lateral sclerosis (FALS) through structural destabilization leading to misfolding and aggregation. Considering the late onset of symptoms as well as the phenotypic variability among patients with identical SOD1 mutations, it is clear that nongenetic factor(s) impact ALS etiology and disease progression. Here we examine the effect of Cys-111 glutathionylation, a physiologically prevalent post-translational oxidative modification, on the stabilities of wild type SOD1 and two phenotypically diverse FALS mutants, A4V and I112T. Glutathionylation results in profound destabilization of SOD1WT dimers, increasing the equilibrium dissociation constant Kd to ~10−20 μM, comparable to that of the aggressive A4V mutant. SOD1A4V is further destabilized by glutathionylation, experiencing an ~30-fold increase in Kd. Dissociation kinetics of glutathionylated SOD1WT and SOD1A4V are unchanged, as measured by surface plasmon resonance, indicating that glutathionylation destabilizes these variants by decreasing association rate. In contrast, SOD1I112T has a modestly increased dissociation rate but no change in Kd when glutathionylated. Using computational structural modeling, we show that the distinct effects of glutathionylation on different SOD1 variants correspond to changes in composition of the dimer interface. Our experimental and computational results show that Cys-111 glutathionylation induces structural rearrangements that modulate stability of both wild type and FALS mutant SOD1. The distinct sensitivities of SOD1 variants to glutathionylation, a modification that acts in part as a coping mechanism for oxidative stress, suggest a novel mode by which redox regulation and aggregation propensity interact in ALS.
(100650) Susannah Margaret Baker
Creators: name: Professions, Victorian
Publisher: name: University of Oxford
Year: 2022
Subjects: subject: 220201 Business and Labour History
subject: FOS: Philosophy, ethics and religion
subject: History
subject: 140203 Economic History
subject: FOS: Economics and business

description: This three-year research project began in January 2014 and investigated whether, during the Victorian period, the professions formed a distinct self-sustaining social group with its own mores and values. The project looked at 16,000 individuals drawn from census data for Alnwick, Brighton, Bristol, Dundee, Greenock, Leeds, Merthyr Tydfil, Morpeth, and Winchester. The research project was funded by the UK Economic & Social Research Council and was based at the Universities of Oxford and Northumbria.
Redesign of a WW Domain Peptide for Selective Recognition of Single-Stranded DNA
Creators: name: Park, Jessica H.
name: Stewart, Amanda L.
name: Waters, Marcey L.
Publisher: name: The University of North Carolina at Chapel Hill University Libraries
Year: 2011

description: A β-sheet mini-protein based on the FBP11 WW1 domain sequence has been redesigned for the molecular recognition of ssDNA. A previous report showed that a β-hairpin peptide dimer, (WKWK)2, binds ssDNA with low micromolar affinity but with little selectivity over duplex DNA. This report extends those studies to a three-stranded β-sheet mini-protein designed to mimic the OB-fold. The new peptide binds ssDNA with low micromolar affinity and shows about 10-fold selectivity for ssDNA over duplex DNA. The redesigned peptide no longer binds its native ligand, the polyproline helix, confirming that the peptide has been redesigned for the function of binding ssDNA. Structural studies provide evidence that this peptide consists of a well structured β-hairpin made of Strands 2&3 with a less structured first strand that provides affinity for ssDNA but does not improve the stability of the full peptide. These studies provide insight into protein-DNA interactions as well as a novel example of protein-redesign.
Substitution of the Human αC Region with the Analogous Chicken Domain Generates a Fibrinogen with Severely Impaired Lateral Aggregation: Fibrin Monomers Assemble into Protofibrils but Protofibrils Do Not Assemble into Fibers
Creators: name: Ping, Lifang
name: Lord, Susan T.
name: Huang, Lihong
name: Gorkun, Oleg V.
name: Profumo, Aldo
name: Cardinali, Barbara
Publisher: name: The University of North Carolina at Chapel Hill University Libraries
Year: 2011

description: Fibrin polymerization occurs in two steps: the assembly of fibrin monomers into protofibrils and the lateral aggregation of protofibrils into fibers. Here we describe a novel fibrinogen that apparently impairs only lateral aggregation. This variant is a hybrid, where the human αC region has been replaced with the homologous chicken region. Several experiments indicate this hybrid human-chicken (HC) fibrinogen has an overall structure similar to normal. Thrombin-catalyzed fibrinopeptide release from HC fibrinogen was normal. Plasmin digests of HC fibrinogen produced fragments that were similar to normal D and E; further, as with normal fibrinogen, the knob ‘A’ peptide, GPRP, reversed the plasmin cleavage associated with addition of EDTA. Dynamic light scattering and turbidity studies with HC fibrinogen showed polymerization was not normal. Whereas early small increases in hydrodynamic radius and absorbance paralleled the increases seen during the assembly of normal protofibrils, HC fibrinogen showed no dramatic increase in scattering as observed with normal lateral aggregation. To determine whether HC and normal fibrinogen could form a copolymer, we examined mixtures of these. Polymerization of normal fibrinogen was markedly changed by HC fibrinogen, as expected for mixed polymers. When the mixture contained 0.45 μM normal and 0.15 M HC fibrinogen, the initiation of lateral aggregation was delayed and the final fiber size was reduced relative to normal fibrinogen at 0.45 μM. Considered altogether our data suggest that HC fibrin monomers can assemble into protofibrils or protofibril-like structures but these either cannot assemble into fibers or assemble into very thin fibers.
title: „Erinnert euch …!“ (Lk 24,6)
title: Zur Rolle der Frauen und Bedeutung des Sich-Erinnerns in der lukanischen Ostererzählung
titleType: Subtitle
Creators: name: Huber, Konrad
Publisher: name: University of Vienna. Faculty of Catholic Theology
Year: 2023
Subjects: Neutestamentliche Bibelwissenschaft
New Testament studies
ÖFOS 2012 -- GEISTESWISSENSCHAFTEN (6) -- Philosophie, Ethik, Religion (603) -- Theologie (6032) -- Neutestamentliche Bibelwissenschaft (603214)
ÖFOS 2012 -- HUMANITIES (6) -- Philosophy, Ethics, Religion (603) -- Theology (6032) -- New Testament studies (603214)
Remembering;
Women
Easter
Gospel of Luke
Luke 24
Narrative Analysis

description: Vor dem Hintergrund der besonderen Aufmerksamkeit, die Frauen insgesamt bei Lukas erfahren, wirft das Faktum, dass in Lk 24 keine expliziten Erscheinungen des Auferstandenen vor Frauen erzählt werden, Fragen nach der Rolle der Frauen und nach der Intention ihrer Darstellung bei Lukas auf. In drei Schritten sucht der Beitrag nach der versteckten Präsenz von Frauen in Lk 24, nach der Charakterisierung und spezifischen Funktion der in Lk 24,1–12 im Rahmen der Vermittlung der Auferstehungsbotschaft ausdrücklich genannten Frauen sowie nach der Bedeutung der neuerlichen Schilderung dieser Ereignisse in Lk 24,22–24 und thematisiert, damit verbunden, den auf drei unterschiedlichen Ebenen der Erzählung eingeschriebenen Aspekt der Erinnerung. Sich im Akt des Erinnerns der Auferstehungsbotschaft zu vergewissern, erweist sich als vorrangige Aufgabe der als Jüngerinnen uneingeschränkt positiv gezeichneten Frauen. Das gilt es vollumfänglich in Erinnerung zu halten, gegebenenfalls auch gegen eine lukanische Darstellung, die die Frauen latent in den Hintergrund rückt.
(100651) Alice Emma Baker
Creators: name: Professions, Victorian
Publisher: name: University of Oxford
Year: 2022
Subjects: subject: 220201 Business and Labour History
subject: FOS: Philosophy, ethics and religion
subject: History
subject: 140203 Economic History
subject: FOS: Economics and business

description: This three-year research project began in January 2014 and investigated whether, during the Victorian period, the professions formed a distinct self-sustaining social group with its own mores and values. The project looked at 16,000 individuals drawn from census data for Alnwick, Brighton, Bristol, Dundee, Greenock, Leeds, Merthyr Tydfil, Morpeth, and Winchester. The research project was funded by the UK Economic & Social Research Council and was based at the Universities of Oxford and Northumbria.
New candidates for extremely metal-poor emission-line galaxies in the SDSS/BOSS DR10
Creators: name: Guseva, N. G.
name: Izotov, Y. I.
name: Fricke, K. J.
name: Henkel, C.
Publisher: name: arXiv
Year: 2015
Subjects: subject: Astrophysics of Galaxies (astro-ph.GA)
subject: FOS: Physical sciences

description: We present a spectroscopic study of eight extremely low-metallicity candidate emission-line galaxies with oxygen abundances possibly below 12 +log O/H = 7.35. These galaxies were selected from Data Release 10 of the Sloan Digital Sky Survey/Baryon Oscillation Spectroscopic Survey (SDSS/BOSS DR10). We will call these extremely metal-deficient galaxies XMD galaxies. The electron temperature-sensitive emission line [O~{\sc iii}] $λ$4363 is detected in three galaxies and marginally detected in two galaxies, allowing for abundance determination by a "direct" method. Because of large uncertainties in the [O {\sc iii}]$λ$4363Å line fluxes, we also calculated oxygen abundance in these galaxies together with the remaining three galaxies using a strong-line semi-empirical method. This method gives oxygen abundances higher than 7.35 for three galaxies with detected [O {\sc iii}]$λ$4363Å line and lower than 7.35 for the remaining five objects of the sample. The newly-discovered galaxies represent excellent targets for follow-up spectroscopic observations with the largest telescopes to improve the oxygen abundance determination and to increase the number of these very rare low-metallicity objects. The extreme location of the most massive and luminous XMD galaxies and XMD candidates in the stellar mass-metallicity diagram implies that these galaxies may be genuine young objects. With stellar masses of up to $\sim$ 10$^7$ - 10$^8$$M_{\odot}$, the galaxies are not chemically enriched and strongly deviate to lower metallicity as compared to the relation obtained for a large sample of low-redshift, star-forming galaxies.
description: 10 pages, 5 figures, 4 tables, accepted in Astronomy and Astrophysics
Scaled boundary isogeometric analysis with C1 coupling for Kirchhoff plate theory
Creators: name: Arf, Jeremias
name: Reichle, Mathias
name: Klinkel, Sven
name: Simeon, Bernd
Publisher: name: arXiv
Year: 2023
Subjects: subject: Numerical Analysis (math.NA)
subject: FOS: Mathematics

description: Although isogeometric analysis exploits smooth B-spline and NURBS basis functions for the definition of discrete function spaces as well as for the geometry representation, the global smoothness in so-called multipatch parametrizations is an issue. Especially, if strong C1 regularity is required, the introduction of function spaces with good convergence properties is not straightforward. However, in 2D there is the special class of analysis-suitable G1 (AS-G1) parametrizations that are suitable for patch coupling. In this contribution we show that the concept of scaled boundary isogeometric analysis fits to the AS-G1 idea and the former is appropriate to define C1-smooth basis functions. The proposed method is applied to Kirchhoff plates and its capability is demonstrated utilizing several numerical examples. Its applicability to non-trivial and trimmed shapes is demonstrated.
title: Deep visual generation for automotive design upgrading and market optimising
Creators: name: Huang, Jingming
Publisher: name: University of Glasgow
Year: 2023

description: The rising levels of homogeneity of modern cars in terms of price and functions has made exterior styling increasingly vital for market success. Recently, researchers have attempted to apply deep learning, especially deep generative models, to automotive exterior design, which has enabled machines to deliver diverse novel designs from large-scale data. In this thesis, we argue that recent advancements in deep learning techniques, particularly in deep generation, can be utilised to facilitate different aspects of automotive exterior design, including design generation, evaluation, and market profit predicting. We conducted three independent studies, each providing tailored solutions to specific automotive design scenarios. These include: a study focused on adapting the latest deep generative model to achieve regional modifications in existing designs, and evaluating these adjustments in terms of design aesthetic and prospective profit changes; another study dedicated to developing a predictive model to assess the modernity of existing designs regarding the future fashion trends; and a final study aiming to incorporate the distinctive shape characteristics of a cheetah into the side view designs of cars. This thesis has four main contributions. First, the developed DVM-CAR dataset is the first large-scale automotive dataset containing designs and marketing data over 10 years. It can be used for different types of research needs from multiple disciplines. Second, given the inherent constraints in automotive design, such as the need to maintain “family face”, and the fact that unconstrained design generation can be seen as a special form of regional modification, our research distinctively focuses on the regional modifications to existing designs, a departure from existing studies. Third, our studies are the first works that integrate the design modules with market profit optimisation. This reforms the traditional product design optimisation frameworks by replacing the abridged design profiles with graphical designs. Finally, the proposed data-driven measures offer effective approaches for automotive aesthetic evaluation and market forecasting, including approaches that can make assessments from a dynamic perspective by examining the evolving fashion trends.
SAMUTER La viña y el vino en la comarca de la Plana Utiel - Requena
Creators: name: Tamarit, Francisco Higón
Publisher: name: Zenodo
Year: 2023
Subjects: SAMUTER, Sistema agroalimentario, Requena - Utiel

description: La viña y el vino en la comarca de la Planta Utiel-Requena forma parte del proyecto SAMUTER (Sistemas Agroalimentarios Multifuncionales y Territorializados) (https://samuter.paisajeterritoriouam.es/). El análisis del Sistema Agroalimentario Multifuncional y Territorializado de la industria vitivinícola en este territorio parte de la interacción del sector primario (agricultura) y una categoría concreta de industria agroalimentaria, como es la industria del vino. The vineyard and wine in the Utiel-Requena region is part of the SAMUTER project (Multifunctional and Territorialised Agri-food Systems) (https://samuter.paisajeterritoriouam.es/). The analysis of the Multifunctional and Territorialised Agri-food System of the wine industry in this territory is based on the interaction between the primary sector (agriculture) and a specific category of agri-food industry, the wine industry.
A crosstalk and non-uniformity correction method for the Compact Space-borne Compton Polarimeter POLAR
Creators: name: Xiao, Hualin
name: Hajdas, Wojtek
name: Wu, Bobing
name: Produit, Nicolas
name: Bao, Tianwei
name: Batsch, Tadeusz
name: Britvich, Ilia
name: Cadoux, Franck
name: Chai, Junying
name: Dong, Yongwei
name: Gauvin, Neal
name: Kong, Minnan
name: Kong, Siwei
name: Rybka, Dominik K.
name: Leluc, Catherine
name: Li, Lu
name: Liu, Jiangtao
name: Liu, Xin
name: Marcinkowski, Radoslaw
name: Paniccia, Mercedes
name: Pohl, Martin
name: Rapin, Divic
name: Rutczynska, Aleksandra
name: Shi, Haoli
name: Song, Liming
name: Sun, Jianchao
name: Szabelski, Jacek
name: Wang, Ruijie
name: Wen, Xing
name: Xu, Hanhui
name: Zhang, Laiyu
name: Zhang, Li
name: Zhang, Shuangnan
name: Zhang, Xiaofeng
name: Zhang, Yongjie
name: Zwolinska, Ania
Publisher: name: arXiv
Year: 2015
Subjects: subject: Instrumentation and Detectors (physics.ins-det)
subject: Nuclear Experiment (nucl-ex)
subject: FOS: Physical sciences

description: In spite of extensive observations and numerous theoretical studies in the past decades several key questions related with Gamma-Ray Bursts (GRB) emission mechanisms are still to be answered. Precise detection of the GRB polarization carried out by dedicated instruments can provide new data and be an ultimate tool to unveil their real nature. A novel space-borne Compton polarimeter POLAR onboard the Chinese space station TG2 is designed to measure linear polarization of gamma-rays arriving from GRB prompt emissions. POLAR uses plastics scintillator bars (PS) as gamma-ray detectors and multi-anode photomultipliers (MAPMTs) for readout of the scintillation light. Inherent properties of such detection systems are crosstalk and non-uniformity. The crosstalk smears recorded energy over multiple channels making both non-uniformity corrections and energy calibration more difficult. Rigorous extraction of polarization observable requires to take such effects properly into account. We studied influence of the crosstalk on energy depositions during laboratory measurements with X-ray beams. A relation between genuine and recorded energy was deduced using an introduced model of data analysis. It postulates that both the crosstalk and non-uniformities can be described with a single matrix obtained in calibrations with mono-energetic X- and gamma-rays. Necessary corrections are introduced using matrix based equations allowing for proper evaluation of the measured GRB spectra. Validity of the method was established during dedicated experimental tests. The same approach can be also applied in space utilizing POLAR internal calibration sources. The introduced model is general and with some adjustments well suitable for data analysis from other MAPMT-based instruments.
A Highly Conserved Interaction Involving the Middle Residue of the SXN Active-Site Motif Is Crucial for Function of Class B Penicillin-Binding Proteins: Mutational and Computational Analysis of PBP 2 from N. gonorrhoeae
Creators: name: Fedarovich, Alena
name: Nicholas, Robert A.
name: Tomberg, Joshua
name: Davies, Christopher
name: Temple, Brenda
Publisher: name: The University of North Carolina at Chapel Hill University Libraries
Year: 2012

description: Insertion of an aspartate residue at position 345a in penicillin-binding protein 2 (PBP 2), which lowers the rate of penicillin acylation by ~6-fold, is commonly observed in penicillin-resistant strains of Neisseria gonorrhoeae. Here, we show that insertions of other amino acids also lower the penicillin acylation rate of PBP 2, but none supported growth of N. gonorrhoeae, indicating loss of essential transpeptidase activity. The Asp345a mutation likely acts by altering the interaction between its adjacent residue, Asp346, in the β2a-β2d hairpin loop and Ser363, the middle residue of the SXN active site motif. Because the adjacent aspartate creates ambiguity in the position of the insertion, we also examined if insertions at position 346a could confer decreased susceptibility to penicillin. However, only aspartate insertions were identified, indicating that only an Asp-Asp couple can confer resistance and retain transpeptidase function. The importance of the Asp346-Ser363 interaction was assessed by mutation of each residue to Ala. Although both mutants lowered the acylation rate of penicillin G by 5-fold, neither could support growth of N. gonorrhoeae, again indicating loss of transpeptidase function. Interaction between a residue in the equivalent of the β2a-β2d hairpin loop and the middle residue of the SXN motif is observed in crystal structures of other Class B PBPs and its importance is also supported by multi-sequence alignments. Overall, these results suggest that this conserved interaction can be manipulated (e.g. by insertion) to lower the acylation rate by β-lactam antibiotics and increase resistance, but only if essential transpeptidase activity is preserved.
A Simple Method for Correction of Circular Dichroism Spectra Obtained from Membrane-Containing Samples
Creators: name: Chakraborty, Hirak
name: Lentz, Barry R.
Publisher: name: The University of North Carolina at Chapel Hill University Libraries
Year: 2012

description: CD spectroscopy is an important technique in structural biology for examining folding and conformational changes of proteins in solution. However, the use of CD spectroscopy in a membrane-medium (and also in a non-homogeneous medium) is limited by i) high light scattering and ii) differential scattering of incident left and right circularly polarized light, especially at lower wavelengths (<200 nm). We report a novel methodology to estimate the distortion of circular dichroism (CD) spectra caused by light scattering for membrane-bound peptides and proteins. The method is applied to three proteins with very different secondary structures to illustrate the limits of its capabilities when calibrated with a simple soluble peptide ([Ac]ANLKALEAQKQKEQRQAAEELANAK[OH]: std. peptide) with a balanced secondary structure. The method with this calibration standard was quite successful in estimating α-helix but more limited when it comes to proteins with very high β-sheet of β-turn content.
Catalysis by a De Novo Zinc-Mediated Protein Interface: Implications for Natural Enzyme Evolution and Rational Enzyme Engineering
Creators: name: Der, Bryan S.
name: Edwards, David R.
name: Kuhlman, Brian
Publisher: name: The University of North Carolina at Chapel Hill University Libraries
Year: 2012

description: Here we show that a recent computationally designed zinc-mediated protein interface is serendipitously capable of catalyzing carboxyester and phosphoester hydrolysis. Although the original motivation was to design a de novo zinc-mediated protein-protein interaction (called MID1-zinc), we observed in the homodimer crystal structure a small cleft and open zinc coordination site. We investigated if the cleft and zinc site at the designed interface were sufficient to form a primitive active site that can perform hydrolysis. MID1-zinc hydrolyzes 4-nitrophenyl acetate (4NPA) with a rate acceleration of 105 and a kcat/KM of 630 M−1s−1, and 4-nitrophenyl phosphate (4NPP) with a rate acceleration of 104 and a kcat/KM of 14 M−1s−1. These rate accelerations by an unoptimized active site highlight the catalytic power of zinc and suggests that the clefts formed by protein-protein interactions are well-suited for creating enzyme active sites. This discovery has implications for protein evolution and engineering: from an evolutionary perspective, 3-coordinated zinc at a homodimer interface cleft represents a simple evolutionary path to nascent enzymatic activity; from a protein engineering perspective, future efforts in de novo design of enzyme active sites may benefit from exploring clefts at protein interfaces for active site placement.
Energetic and Structural Basis for Activation of the Epithelial Sodium Channel by Matriptase
Creators: name: Gentzsch, Martina
name: Dang, Hong
name: García-Caballero, Agustin
name: Dokholyan, Nikolay V.
name: Stutts, M. Jackson
name: Kota, Pradeep
Publisher: name: The University of North Carolina at Chapel Hill University Libraries
Year: 2012

description: Limited proteolysis, accomplished by endopeptidases, is a ubiquitous phenomenon underlying the regulation and activation of many enzymes, receptors and other proteins synthesized as inactive precursors. Serine proteases are one of the largest and conserved families of endopeptidases involved in diverse cellular activities including wound healing, blood coagulation and immune responses. Heteromeric α,β,γ-epithelial sodium channels (ENaC) associated with diseases like cystic fibrosis and Liddle’s syndrome, are irreversibly stimulated by membrane-anchored proteases (MAPs) and furin-like convertases. Matriptase/Channel activating protease-3 (CAP3) is one of the several MAPs that potently activate ENaC. Despite identification of protease cleavage sites, the basis for enhanced susceptibility of α- and γ-ENaC to proteases remains elusive. Here, we elucidate the energetic and structural bases for activation of ENaC by CAP3. We find a region near the γ-ENaC furin site that is previously unidentified as a critical cleavage site for CAP3-mediated stimulation. We also report that CAP3 mediates cleavage of ENaC at basic residues downstream of the furin site. Our results indicate that surface proteases alone are sufficient to fully activate uncleaved ENaC, and explain how ENaC in epithelia expressing surface-active proteases can appear refractory to soluble proteases. Our results support a model in which proteases prime ENaC for activation by cleaving at the furin site, and cleavage at downstream sites is accomplished by membrane surface proteases or extracellular soluble proteases. Based on our results, we propose a dynamics-driven “anglerfish” mechanism that explains less stringent sequence requirements for substrate recognition and cleavage by matriptase compared to furin.
Boundary terms and conserved charges in higher-derivative gauged supergravity
Creators: name: Cassani, Davide
name: Ruipérez, Alejandro
name: Turetta, Enrico
Publisher: name: arXiv
Year: 2023
Subjects: subject: High Energy Physics - Theory (hep-th)
subject: General Relativity and Quantum Cosmology (gr-qc)
subject: FOS: Physical sciences

description: We address some issues in higher-derivative gauged supergravity with Chern-Simons terms, focusing on the five-dimensional case. We discuss the variational problem with Dirichlet boundary conditions as well as holographic renormalization in asymptotically locally AdS spacetimes, and derive the corresponding boundary terms. We then employ Wald's formalism in order to define conserved charges associated to local symmetries (diffeomorphisms and U(1) gauge transformations), taking into account the effect of generic gauge Chern-Simons terms. We prove that the first law of black hole mechanics and the quantum statistical relation hold in this setup. Chern-Simons terms also lead us to distinguish between Noether charges and Page (or Komar) charges which satisfy the Gauss law. We make use of the latter to compute corrections to the angular momentum and electric charge of the supersymmetric black hole in AdS$_5$ from its corrected near-horizon geometry. This also allows us to derive the microcanonical form of the entropy as a function of the conserved charges relying entirely on the near-horizon geometry. Finally, we comment on four-derivative gauged supergravity in four dimensions, showing that field redefinitions permit to simplify the action at linear order in the corrections, so that the equations of motion are those of the two-derivative theory.
description: 39 pages
(100653) Arthur Richard Baker
Creators: name: Professions, Victorian
Publisher: name: University of Oxford
Year: 2022
Subjects: subject: 220201 Business and Labour History
subject: FOS: Philosophy, ethics and religion
subject: History
subject: 140203 Economic History
subject: FOS: Economics and business

description: This three-year research project began in January 2014 and investigated whether, during the Victorian period, the professions formed a distinct self-sustaining social group with its own mores and values. The project looked at 16,000 individuals drawn from census data for Alnwick, Brighton, Bristol, Dundee, Greenock, Leeds, Merthyr Tydfil, Morpeth, and Winchester. The research project was funded by the UK Economic & Social Research Council and was based at the Universities of Oxford and Northumbria.
Towards conformal cosmology
Creators: name: Libanov, M.
name: Rubakov, V.
name: Rubtsov, G.
Publisher: name: arXiv
Year: 2015
Subjects: subject: High Energy Physics - Theory (hep-th)
subject: Cosmology and Nongalactic Astrophysics (astro-ph.CO)
subject: General Relativity and Quantum Cosmology (gr-qc)
subject: High Energy Physics - Phenomenology (hep-ph)
subject: FOS: Physical sciences

description: Approximate de Sitter symmetry of inflating Universe is responsible for the approximate flatness of the power spectrum of scalar perturbations. However, this is not the only option. Another symmetry which can explain nearly scale-invariant power spectrum is conformal invariance. We give a short review of models based on conformal symmetry which lead to the scale-invariant spectrum of the scalar perturbations. We discuss also potentially observable features of these models.
description: Mini-review, prepared for JETP Letters; 11 pages, 3 figures
Entamoeba histolytica Rho1 Regulates Actin Polymerization through a Divergent, Diaphanous-Related Formin
Creators: name: Bosch, Dustin E.
name: Siderovski, David P.
name: Yang, Bing
Publisher: name: The University of North Carolina at Chapel Hill University Libraries
Year: 2012

description: Entamoeba histolytica requires a dynamic actin cytoskeleton for intestinal and systemic pathogenicity. Diaphanous-related formins represent an important family of actin regulators that are activated by Rho GTPases. The E. histolytica genome encodes a large family of Rho GTPases and three diaphanous-related formins, of which EhFormin1 is known to regulate mitosis and cytokinesis in trophozoites. We demonstrate that EhFormin1 modulates actin polymerization through its formin homology 2 (FH2) domain. Despite a highly divergent diaphanous autoinhibitory domain, EhFormin1 is autoinhibited by an N- and C-terminal intramolecular interaction, but activated upon binding of EhRho1 to the N-terminal domain tandem. A crystal structure of the EhRho1·GTPγS/EhFormin1 complex illustrates an EhFormin1 conformation that diverges from mammalian mDia1 and lacks a secondary interaction with a Rho insert helix. The structural model also highlights residues required for specific recognition of the EhRho1 GTPase and suggests that the molecular mechanisms of EhFormin1 autoinhibition and activation differ from mammalian homologs.
The free boundary Euler equations with large surface tension
Creators: name: Disconzi, Marcelo M.
name: Ebin, David G.
Publisher: name: arXiv
Year: 2015
Subjects: subject: Analysis of PDEs (math.AP)
subject: FOS: Mathematics

description: We study the free boundary Euler equations with surface tension in three spatial dimensions, showing that the equations are well-posed if the coefficient of surface tension is positive. Then we prove that under natural assumptions, the solutions of the free boundary motion converge to solutions of the Euler equations in a domain with fixed boundary when the coefficient of surface tension tends to infinity.
description: to appear in Journal of Differential Equations
Aeroelastic Demonstrator and Methodology for Experimental Investigation of Propeller Aerodynamic Derivatives
Creators: name:  JIRI CECRDLE
Publisher: name: Proceedings of the Aerospace Europe Conference - EUCASS - CEAS - 2023
Year: 2023
Subjects: WHIRL FLUTTER
AERODYNAMIC DERIVATIVE
W-STING DEMONSTRATOR

description: Whirl flutter is a specific type of flutter instability, for which the experimental validation of analytical results is required. To determine propeller aerodynamic forces on a vibrating propeller, aerodynamic derivatives are used. Described demonstrator represents a sting-mounted nacelle with a motor and propeller It includes engine pitch and yaw degrees-of-freedom. For the measurement, a single degreeof-freedom model is used and blocking of either pitch or yaw movement is provided. Pitching moment and vertical force due to the pitch angle and pitching moment and vertical force due to the yaw angle derivatives are investigated. Measured quantities include pitch and yaw angles and pivot moments.
SAMUTER Citricultura en la Ribera del Júcar
Creators: name: Campos, Emilio Barba
Publisher: name: Zenodo
Year: 2023
Subjects: SAMUTER, Sistema Agroalimentario, Júcar

description: La Citricultura en la Ribera del Júcar forma parte del proyecto SAMUTER (Sistemas Agroalimentarios Multifuncionales y Territorializados) (https://samuter.paisajeterritoriouam.es/). El SAMUTER de la citricultura analiza la situación actual del sistema de cultivo de cítricos, fundamentalmente el naranjo, en la Comunidad Valenciana, tomando como ejemplo un sector territorial de la comarca de la Ribera Alta del Júcar, con centro neurálgico en el municipio de Carcaixent. Este municipio es conocido como “la cuna de la naranja”. La delimitación territorial de este Samuter citrícola, incluye siete municipios de esta comarca; el criterio diferenciador es el significado y la importancia que en ellos tiene el cultivo del naranjo: L’Alcudia, Alginet, Algemesí, Alzira, Carcaixent, Carlet y Guadassuar. Se analizan los diferentes aspectos relacionados con la producción y comercialización, así como las implicaciones socioculturales y los elementos patrimoniales relacionados con este cultivo. Citriculture in Ribera del Júcar is part of the SAMUTER project (Multifunctional and Territorialised Agri-Food Systems) (https://samuter.paisajeterritoriouam.es/). The SAMUTER citriculture project analyses the current situation of the citrus cultivation system, mainly orange trees, in the Valencian Community, taking as an example a territorial sector of the Ribera Alta del Júcar region, with its nerve centre in the municipality of Carcaixent. This municipality is known as "the cradle of the orange". The territorial delimitation of this citrus-growing Samuter includes seven municipalities in this region; the differentiating criterion is the significance and importance of orange growing in them: L'Alcudia, Alginet, Algemesí, Alzira, Carcaixent, Carlet and Guadassuar. The different aspects related to production and marketing are analysed, as well as the socio-cultural implications and heritage elements related to this crop.
Fluorescent Phosphatidylinositol 4,5-Bisphosphate Derivatives with Modified 6-Hydroxy Group as Novel Substrates for Phospholipase C
Creators: name: Harden, T. Kendall
name: Zhang, Qisheng
name: Barrett, Matthew
name: Sondek, John
name: Wang, Xiaoyang
Publisher: name: The University of North Carolina at Chapel Hill University Libraries
Year: 2012

description: The capacity to monitor spatiotemporal activity of phospholipase C (PLC) isozymes with a PLC-selective sensor would dramatically enhance understanding of the physiological function and disease relevance of these signaling proteins. Previous structural and biochemical studies defined critical roles for several of the functional groups of the endogenous substrate of PLC isozymes, phosphatidylinositol 4,5-bisphosphate (PIP2), indicating that these sites cannot be readily modified without compromising interactions with the lipase active site. However, the role of the 6-hydroxy group of PIP2 for interaction and hydrolysis by PLC has not been explored, possibly due to challenges in synthesizing 6-hydroxy derivatives. Here, we describe an efficient route for the synthesis of novel, fluorescent PIP2 derivatives modified at the 6-hydroxy group. Two of these derivatives were used in assays of PLC activity in which the fluorescent PIP2 substrates were separated from their diacylglycerol products and reaction rates quantified by fluorescence. Both PIP2 analogues effectively function as substrates of PLC-δ1, and the KM and Vmax values obtained with one of these are similar to those observed with native PIP2 substrate. These results indicate that the 6-hydroxy group can be modified to develop functional substrates for PLC isozymes, thereby serving as the foundation for further development of PLC-selective sensors.
From Mechanical Force to RhoA Activation
Creators: name: Lessey, Elizabeth C.
name: Burridge, Keith
name: Guilluy, Christophe
Publisher: name: The University of North Carolina at Chapel Hill University Libraries
Year: 2012

description: Throughout their lives all cells constantly experience and respond to various mechanical forces. These frequently originate externally but can also arise internally as a result of the contractile actin cytoskeleton. Mechanical forces trigger multiple signaling pathways. Several converge and result in the activation of the GTPase RhoA. In this review we focus on the pathways by which mechanical force leads to RhoA regulation, especially when force is transmitted via cell adhesion molecules that mediate either cell-matrix or cell-cell interactions. We discuss both the upstream signaling events that lead to activation of RhoA, as well as the downstream consequences of this pathway. These include not only cytoskeletal reorganization and, in a positive feedback loop, increased myosin-generated contraction, but also profound effects on gene expression and differentiation.
null Kurzschlüsse von IGBT und Diode im Active-Neutral-Point-Clamped-Dreipunktumrichter
Creators: name: Hammes, David
Publisher: name: Universität Rostock
Year: 2021
Subjects: subject: 600 Technology (Applied sciences)
subject: 620 Engineering & allied operations
subject: 621.3 Electrical Engineering, Electronics

description: Die Arbeit beschäftigt sich mit den auftretenden Halbleiterkurzschlüssen im Active-Neutral-Point-Clamped-Dreipunktumrichter. Sie haben den Nachteil, dass nach einem Durchbruch eines Halbleiters die Gefahr besteht, dass weitere Bauelemente zerstört werden und Folgeschäden entstehen. Daher hat die Arbeit die Aufgabe, alle möglichen Schaltkombinationen im Umrichter zur Erzeugung der drei Phasenausgangsspannungen zu untersuchen, welcher Durchbruch eines Halbleiters dabei eintreten kann, und welche Kurzschlüsse sich daraus schlussendlich ergeben werden.
Parameterless stopping criteria for recursive density matrix expansions
Creators: name: Kruchinina, Anastasia
name: Rudberg, Elias
name: Rubensson, Emanuel H.
Publisher: name: arXiv
Year: 2015
Subjects: subject: Computational Physics (physics.comp-ph)
subject: Materials Science (cond-mat.mtrl-sci)
subject: Numerical Analysis (math.NA)
subject: Chemical Physics (physics.chem-ph)
subject: FOS: Physical sciences
subject: FOS: Mathematics
subject: 65F15, 65F60, 81-08

description: Parameterless stopping criteria for recursive polynomial expansions to construct the density matrix in electronic structure calculations are proposed. Based on convergence order estimation the new stopping criteria automatically and accurately detect when the calculation is dominated by numerical errors and continued iteration does not improve the result. Difficulties in selecting a stopping tolerance and appropriately balancing it in relation to parameters controlling the numerical accuracy are avoided. Thus, our parameterless stopping criteria stands in contrast to the standard approach to stop as soon as some error measure goes below a user-defined parameter or tolerance. We demonstrate that the stopping criteria work well both in dense and sparse matrix calculations and in large-scale self-consistent field calculations with the quantum chemistry program Ergo (www.ergoscf.org).