cometadata/datacite-rtg-text-other-reclassification-records huggingface dataset:
Overcoming Element Quality Dependence of Finite Elements with Adaptive Extended Stencil FEM (AES-FEM)
Creators: name: Conley, Rebecca
name: Delaney, Tristan J.
name: Jiao, Xiangmin
Publisher: name: arXiv
Year: 2015
Subjects: subject: Numerical Analysis (math.NA)
subject: FOS: Mathematics

description: The finite element methods (FEM) are important techniques in engineering for solving partial differential equations, but they depend heavily on element shape quality for stability and good performance. In this paper, we introduce the Adaptive Extended Stencil Finite Element Method (AES-FEM) as a means for overcoming this dependence on element shape quality. Our method replaces the traditional basis functions with a set of generalized Lagrange polynomial (GLP) basis functions, which we construct using local weighted least-squares approximations. The method preserves the theoretical framework of FEM, and allows imposing essential boundary conditions and integrating the stiffness matrix in the same way as the classical FEM. In addition, AES-FEM can use higher-degree polynomial basis functions than the classical FEM, while virtually preserving the sparsity pattern of the stiffness matrix. We describe the formulation and implementation of AES-FEM, and analyze its consistency and stability. We present numerical experiments in both 2D and 3D for the Poison equation and a time-independent convection-diffusion equation. The numerical results demonstrate that AES-FEM is more accurate than linear FEM, is also more efficient than linear FEM in terms of error versus runtime, and enables much better stability and faster convergence of iterative solvers than linear FEM over poor-quality meshes
Deletion of 3-Hydroxy-3-Methylglutaryl-Coenzyme A Reductase Promotes Expansion of the Resident Stem Cell Compartment
Creators: name: Doerfler, Alexandria
name: Han, Jun
name: Jarrett, Kelsey
name: Tang, Li
name: Jain, Antrix
name: Saltzman, Alexander
name: De Giorgi, Marco
name: Chuecos, Marcel
name: Hurley, Ayrea
name: Li, Ang
name: Morand, Pauline
name: Ayala, Claudia
name: Goodlett, David
name: Malovannaya, Anna
name: Martin, James
name: Vallim, Thomas
name: Shroyer, Noah
name: R. Lagor, William
Publisher: name: Health Research Alliance
Year: 2023
Subjects: Cell metabolism

description: BACKGROUND: The intestine occupies the critical interface between cholesterol absorption and excretion. Surprisingly little is known about the role of de novo cholesterol synthesis in this organ, and its relationship to whole body cholesterol homeostasis. Here, we investigate the physiological importance of this pathway through genetic deletion of the rate-limiting enzyme. METHODS: Mice lacking 3-hydroxy-3-methylglutaryl-coenzyme A reductase (Hmgcr) in intestinal villus and crypt epithelial cells were generated using a Villin-Cre transgene. Plasma lipids, intestinal morphology, mevalonate pathway metabolites, and gene expression were analyzed. RESULTS: Mice with intestine-specific loss of Hmgcr were markedly smaller at birth, but gain weight at a rate similar to wildtype littermates, and are viable and fertile into adulthood. Intestine lengths and weights were greater relative to body weight in both male and female Hmgcr intestinal knockout mice. Male intestinal knockout had decreased plasma cholesterol levels, whereas fasting triglycerides were lower in both sexes. Lipidomics revealed substantial reductions in numerous nonsterol isoprenoids and sterol intermediates within the epithelial layer, but cholesterol levels were preserved. Hmgcr intestinal knockout mice also showed robust activation of SREBP-2 (sterol-regulatory element binding protein-2) target genes in the epithelium, including the LDLR (low-density lipoprotein receptor). At the cellular level, loss of Hmgcr is compensated for quickly after birth through a dramatic expansion of the stem cell compartment, which persists into adulthood. CONCLUSIONS: Loss of Hmgcr in the intestine is compatible with life through compensatory increases in intestinal absorptive surface area, LDLR expression, and expansion of the resident stem cell compartment.
Lattice Monte Carlo Simulations of Polymer Melts
Creators: name: Hsu, Hsiao-Ping
Publisher: name: arXiv
Year: 2015
Subjects: subject: Soft Condensed Matter (cond-mat.soft)
subject: FOS: Physical sciences

description: We use Monte Carlo simulations to study polymer melts consisting of fully flexible and moderately stiff chains in the bond fluctuation model at a volume fraction $0.5$. In order to reduce the local density fluctuations, we test a pre-packing process for the preparation of the initial configurations of the polymer melts, before the excluded volume interaction is switched on completely. This process leads to a significantly faster decrease of the number of overlapping monomers on the lattice. This is useful for simulating very large systems, where the statistical properties of the model with a marginally incomplete elimination of excluded volume violations are the same as those of the model with strictly excluded volume. We find that the internal mean square end-to-end distance for moderately stiff chains in a melt can be very well described by a freely rotating chain model with a precise estimate of the bond-bond orientational correlation between two successive bond vectors in equilibrium. The plot of the probability distributions of the reduced end-to-end distance of chains of different stiffness also shows that the data collapse is excellent and described very well by the Gaussian distribution for ideal chains. However, while our results confirm the systematic deviations between Gaussian statistics for the chain structure factor $S_c(q)$ [minimum in the Kratky-plot] found by Wittmer et al.~\{EPL {\bf 77} 56003 (2007).\} for fully flexible chains in a melt, we show that for the available chain length these deviations are no longer visible, when the chain stiffness is included. The mean square bond length and the compressibility estimated from collective structure factors depend slightly on the stiffness of the chains.
description: 15 pages, 12 figures
LPA disruption with AAV-CRISPR potently lowers plasma apo(a) in transgenic mouse model: A proof-of-concept study
Creators: name: Doerfler, Alexandria
name: Park, So Hyun
name: Assini, Julia
name: Youssef, Amer
name: Saxena, Lavanya
name: Yaseen, Adam
name: De Giorgi, Marco
name: Chuecos, Marcel
name: Hurley, Ayrea
name: Li, Ang
name: M. Marcovina, Santica
name: Bao, Gang
name: B. Boffa, Michael
name: Koschinsky, Marlys L.
name: R. Lagor, William
Publisher: name: Health Research Alliance
Year: 2023
Subjects: Gene and molecular therapy

description: Lipoprotein(a) (Lp(a)) represents a unique subclass of circulating lipoprotein particles and consists of an apolipoprotein( a) (apo(a)) molecule covalently bound to apolipoprotein B-100. The metabolism of Lp(a) particles is distinct from that of low-density lipoprotein (LDL) cholesterol, and currently approved lipid-lowering drugs do not provide substantial reductions in Lp(a), a causal risk factor for cardiovascular disease. Somatic genome editing has the potential to be a one-time therapy for individuals with extremely high Lp(a). We generated an LPA transgenic mouse model expressing apo(a) of physiologically relevant size. Adeno-associated virus (AAV) vector delivery of CRISPR-Cas9 was used to disrupt the LPA transgene in the liver. AAV-CRISPR nearly completely eliminated apo(a) from the circulation within a week. We performed genome-wide off-target assays to determine the specificity of CRISPR-Cas9 editing within the context of the human genome. Interestingly, we identified intrachromosomal rearrangements within the LPA cDNA in the transgenic mice as well as in the LPA gene in HEK293T cells, due to the repetitive sequences within LPA itself and neighboring pseudogenes. This proof-of-concept study establishes the feasibility of using CRISPR-Cas9 to disrupt LPA in vivo, and highlights the importance of examining the diverse consequences of CRISPR cutting within repetitive loci and in the genome globally.
Engraftment of a Galactose Receptor Footprint onto Adeno-associated Viral Capsids Improves Transduction Efficiency
Creators: name: Asokan, Aravind
name: Shen, Shen
name: Horowitz, Eric D.
name: Agbandje-McKenna, Mavis
name: Troupes, Andrew N.
name: Pulicherla, Nagesh
name: Samulski, Richard J.
name: Brown, Sarah M.
Publisher: name: The University of North Carolina at Chapel Hill University Libraries
Year: 2013

description: New viral strains can be evolved to recognize different host glycans through mutagenesis and experimental adaptation. However, such mutants generally harbor amino acid changes that affect viral binding to a single class of carbohydrate receptors. We describe the rational design and synthesis of novel, chimeric adeno-associated virus (AAV) strains that exploit an orthogonal glycan receptor for transduction. A dual glycan-binding AAV strain was first engineered as proof of concept by grafting a galactose (Gal)-binding footprint from AAV serotype 9 onto the heparan sulfate-binding AAV serotype 2. The resulting chimera, AAV2G9, continues to bind heparin affinity columns but interchangeably exploits Gal and heparan sulfate receptors for infection, as evidenced by competitive inhibition assays with lectins, glycans, and parental AAV strains. Although remaining hepatotropic like AAV2, the AAV2G9 chimera mediates rapid onset and higher transgene expression in mice. Similarly, engraftment of the Gal footprint onto the laboratory-derived strain AAV2i8 yielded an enhanced AAV2i8G9 chimera. This new strain remains liver-detargeted like AAV2i8 while selectively transducing muscle tissues at high efficiency, comparable with AAV9. The AAV2i8G9 chimera is a promising vector candidate for targeted gene therapy of cardiac and musculoskeletal diseases. In addition to demonstrating the modularity of glycan receptor footprints on viral capsids, our approach provides design strategies to expand the AAV vector toolkit.
Applications of inorganic-organic hybrid architectures based on polyoxometalates in catalyzed and photocatalyzed chemical transformations
Creators: name: Heravi, Majid Mommahed
name: Lotfian, Nahid
name: Mirzaei, Masoud
name: Heidari, Bahareh
Publisher: name: figshare
Year: 2020
Subjects: subject: 30302 Nanochemistry and Supramolecular Chemistry
subject: FOS: Chemical sciences
subject: 30502 Natural Products Chemistry
subject: 30205 Non-metal Chemistry
subject: Nuclear Chemistry
subject: 30303 Optical Properties of Materials
subject: 30503 Organic Chemical Synthesis
subject: Organic Chemistry

description: The scope of this article is to reveal the fruitful combination of POM species with metal coordination complexes, leading to the construction of several efficient multifunctional catalysts. In this review, we try to underscore various catalytic and photocatalytic reactions catalyzed by POM‐based inorganic‐organic hybrid. Notably, it has been well established that depending on the type of the reaction, the activity and selectivity of these hybrid catalyst can be drastically improved by the rational and correct choice of the organic metal complex and POM anion providing a marriage of convenience.
(3925) Jean Connell
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.
Extracellular Signal-regulated Kinase (ERK) Phosphorylates Histone Deacetylase 6 (HDAC6) at Serine 1035 to Stimulate Cell Migration
Creators: name: Wu, Jheng Yu
name: Bepler, Gerold
name: Nicosia, Santo V.
name: Der, Channing J.
name: Xiang, Shengyan
name: Hu, Chen
name: Zhang, Xiaohong
name: Wang, Chuangui
name: Williams, Kendra A.
name: Fang, Bin
name: Cox, Adrienne D.
name: Koomen, John
name: Haura, Eric
name: Matthias, Patrick
name: Zhang, Shengping
name: Zhang, Mu
name: Bai, Wenlong
name: Ryan, Meagan
Publisher: name: The University of North Carolina at Chapel Hill University Libraries
Year: 2013

description: Histone deacetylase 6 (HDAC6) is well known for its ability to promote cell migration through deacetylation of its cytoplasmic substrates such as α-tubulin. However, how HDAC6 itself is regulated to control cell motility remains elusive. Previous studies have shown that one third of extracellular signal-regulated kinase (ERK) is associated with the microtubule cytoskeleton in cells. Yet, no connection between HDAC6 and ERK has been discovered. Here, for the first time, we reveal that ERK binds to and phosphorylates HDAC6 to promote cell migration via deacetylation of α-tubulin. We have identified two novel ERK-mediated phosphorylation sites: threonine 1031 and serine 1035 in HDAC6. Both sites were phosphorylated by ERK1 in vitro, whereas Ser-1035 was phosphorylated in response to the activation of EGFR-Ras-Raf-MEK-ERK signaling pathway in vivo. HDAC6-null mouse embryonic fibroblasts rescued by the nonphosphorylation mimicking mutant displayed significantly reduced cell migration compared with those rescued by the wild type. Consistently, the nonphosphorylation mimicking mutant exerted lower tubulin deacetylase activity in vivo compared with the wild type. These data indicate that ERK/HDAC6-mediated cell motility is through deacetylation of α-tubulin. Overall, our results suggest that HDAC6-mediated cell migration could be governed by EGFR-Ras-Raf-MEK-ERK signaling.
Curvature Perturbation and Domain Wall Formation with Pseudo Scaling Scalar Dynamics
Creators: name: Ema, Yohei
name: Nakayama, Kazunori
name: Takimoto, Masahiro
Publisher: name: arXiv
Year: 2015
Subjects: subject: General Relativity and Quantum Cosmology (gr-qc)
subject: Cosmology and Nongalactic Astrophysics (astro-ph.CO)
subject: High Energy Physics - Phenomenology (hep-ph)
subject: FOS: Physical sciences

description: Cosmological dynamics of scalar field with a monomial potential $ϕ^{n}$ with a general background equation of state is revisited. It is known that if $n$ is smaller than a critical value, the scalar field exhibits a coherent oscillation and if $n$ is larger it obeys a scaling solution without oscillation. We study in detail the case where $n$ is equal to the critical value, and find a peculiar scalar dynamics which is neither oscillating nor scaling solution, and we call it a pseudo scaling solution. We also discuss cosmological implications of a pseudo scaling scalar dynamics, such as the curvature perturbation and the domain wall problem.
description: 22 pages, 2 figures; version published on JCAP
Formation of Arabidopsis Cryptochrome 2 Photobodies in Mammalian Nuclei: APPLICATION AS AN OPTOGENETIC DNA DAMAGE CHECKPOINT SWITCH
Creators: name: Ozturk, Nuri
name: Chiou, Yi Ying
name: Hassan, Bachar H.
name: Ye, Rui
name: Sancar, Aziz
name: Ozkan-Dagliyan, Irem
Publisher: name: The University of North Carolina at Chapel Hill University Libraries
Year: 2013

description: Nuclear bodies are discrete suborganelle structures that perform specialized functions in eukaryotic cells. In plant cells, light can induce de novo formation of nuclear bodies called photobodies (PBs) composed of the photosensory pigments, phytochrome (PHY) or cryptochrome (CRY). The mechanisms of formation, the exact compositions, and the functions of plant PBs are not known. Here, we have expressed Arabidopsis CRY2 (AtCRY2) in mammalian cells and analyzed its fate after blue light exposure to understand the requirements for PB formation, the functions of PBs, and their potential use in cell biology. We found that light efficiently induces AtCRY2-PB formation in mammalian cells, indicating that, other than AtCRY2, no plant-specific proteins or nucleic acids are required for AtCRY2-PB formation. Irradiation of AtCRY2 led to its degradation; however, degradation was not dependent upon photobody formation. Furthermore, we found that AtCRY2 photobody formation is associated with light-stimulated interaction with mammalian COP1 E3 ligase. Finally, we demonstrate that by fusing AtCRY2 to the TopBP1 DNA damage checkpoint protein, light-induced AtCRY2 PBs can be used to activate DNA damage signaling pathway in the absence of DNA damage.
Full Implementation of the Genetic Code by Tryptophanyl-tRNA Synthetase Requires Intermodular Coupling
Creators: name: Carter Jr., Charles W.
name: Li, Li
Publisher: name: The University of North Carolina at Chapel Hill University Libraries
Year: 2013

description: Tryptophanyl-tRNA Synthetase (TrpRS) Urzyme (fragments A and C), a 130-residue construct containing only secondary structures positioning the HIGH and KMSKS active site signatures and the specificity helix, accelerates tRNATrp aminoacylation with ∼10-fold specificity toward tryptophan, relative to structurally related tyrosine. We proposed that including the 76-residue connecting peptide 1 insertion (Fragment B) might enhance tryptophan affinity and hence amino acid specificity, because that subdomain constrains the orientation of the specificity helix. We test that hypothesis by characterizing two new constructs: the catalytic domain (fragments A–C) and the Urzyme supplemented with the anticodon-binding domain (fragments A, C, and D). The three constructs, together with the full-length enzyme (fragments A–D), comprise a factorial experiment from which we deduce individual and combined contributions of the two modules to the steady-state kinetics parameters for tryptophan-dependent 32PPi exchange, specificity for tryptophan versus tyrosine, and aminoacylation of tRNATrp. Factorial design directly measures the energetic coupling between the two more recent modules in the contemporary enzyme and demonstrates its functionality. Combining the TrpRS Urzyme individually in cis with each module affords an analysis of long term evolution of amino acid specificity and tRNA aminoacylation, both essential for expanding the genetic code. Either module significantly enhances tryptophan activation but unexpectedly eliminates amino acid specificity for tryptophan, relative to tyrosine, and significantly reduces tRNA aminoacylation. Exclusive dependence of both enhanced functionalities of full-length TrpRS on interdomain coupling energies between the two new modules argues that independent recruitment of connecting peptide 1 and the anticodon-binding domain during evolutionary development of Urzymes would have entailed significant losses of fitness.
Impact of penicillin G on the trophic diversity (Moens & Vincx, 1997) of marine nematode community: results from microcosm experiments
Creators: name: NASRI, Ahmed
name: BOUFAHJA, Fehmi
name: HEDFI, Amor
name: MAHMOUDI, Ezzeddine
name: AÏSSA, Patricia
name: ESSID, Naceur
Publisher: name: Station Biologique de Roscoff (SBR)
Year: 2015

description: Marine nematodes from Bizerte lagoon sediments (Tunisia, Northern Mediterranean) were treated with the penicillin G in microcosm experiment for 30 days. Sediment was treated with five concentrations of this antibiotic (D1: 3 mg.L-1, D2: 30 mg.L-1, D3: 300 mg.L-1, D4: 600 mg.L-1, D5: 700 mg.L-1). Differences in univariate indices for trophic structure of nematode assemblages occurred between control and treatments. Results from multivariate analyses of trophic group abundance demonstrated that the responses of nematode were dependent on the concentrations used for the sediment treatment. Microvores (M), Deposit feeders (DF) and Ciliate consumers (CF), most abundant in control microcosm, were very much affected and their abundance decreased significantly in response to antibiotic contamination. Suckers of epistrates (EF) seems unaffected by the treatment but abundance of optional Predators (FP) and exclusive Predators (Pr) showed significant increase in dominance compared to the control.
Glycerol-3-phosphate Acyltransferase (GPAT)-1, but Not GPAT4, Incorporates Newly Synthesized Fatty Acids into Triacylglycerol and Diminishes Fatty Acid Oxidation
Creators: name: Ilkayeva, Olga R.
name: Wendel, Angela A.
name: Muoio, Deborah M.
name: Coleman, Rosalind A.
name: Cooper, Daniel E.
Publisher: name: The University of North Carolina at Chapel Hill University Libraries
Year: 2013

description: Four glycerol-3-phosphate acyltransferase (GPAT) isoforms, each encoded by a separate gene, catalyze the initial step in glycerolipid synthesis; in liver, the major isoforms are GPAT1 and GPAT4. To determine whether each of these hepatic isoforms performs a unique function in the metabolism of fatty acid, we measured the incorporation of de novo synthesized fatty acid or exogenous fatty acid into complex lipids in primary mouse hepatocytes from control, Gpat1−/−, and Gpat4−/− mice. Although hepatocytes from each genotype incorporated a similar amount of exogenous fatty acid into triacylglycerol (TAG), only control and Gpat4−/− hepatocytes were able to incorporate de novo synthesized fatty acid into TAG. When compared with controls, Gpat1−/− hepatocytes oxidized twice as much exogenous fatty acid. To confirm these findings and to assess hepatic β-oxidation metabolites, we measured acylcarnitines in liver from mice after a 24-h fast and after a 24-h fast followed by 48 h of refeeding with a high sucrose diet to promote lipogenesis. Confirming the in vitro findings, the hepatic content of long-chain acylcarnitine in fasted Gpat1−/− mice was 3-fold higher than in controls. When compared with control and Gpat4−/− mice, after the fasting-refeeding protocol, Gpat1−/− hepatic TAG was depleted, and long-chain acylcarnitine content was 3.5-fold higher. Taken together, these data demonstrate that GPAT1, but not GPAT4, is required to incorporate de novo synthesized fatty acids into TAG and to divert them away from oxidation.
New near-infrared period-luminosity-metallicity relations for RR Lyrae stars and the outlook for Gaia
Creators: name: Muraveva, Tatiana
name: Palmer, Max
name: Clementini, Gisella
name: Luri, Xavier
name: Cioni, Maria-Rosa L
name: Moretti, Maria Ida
name: Marconi, Marcella
name: Ripepi, Vincenzo
name: Rubele, Stefano
Publisher: name: arXiv
Year: 2015
Subjects: subject: Solar and Stellar Astrophysics (astro-ph.SR)
subject: FOS: Physical sciences

description: We present results of the analysis of 70 RR Lyrae stars located in the bar of the Large Magellanic Cloud (LMC). Combining spectroscopically determined metallicity of these stars from the literature with precise periods from the OGLE III catalogue and multi-epoch $K_{\rm s}$ photometry from the VISTA survey of the Magellanic Clouds system (VMC), we derive a new near-infrared period-luminosity-metallicity (${\rm PL_{K_{\rm s}}Z}$) relation for RR Lyrae variables. In order to fit the relation we use a fitting method developed specifically for this study. The zero-point of the relation is estimated in two different ways: by assuming the value of the distance to the LMC and by using Hubble Space Telescope (HST) parallaxes of five RR Lyrae stars in the Milky Way (MW). The difference in distance moduli derived by applying these two approaches is $\sim0.2$ mag. To investigate this point further we derive the ${\rm PL_{K_{\rm s}}Z}$ relation based on 23 MW RR Lyrae stars which had been analysed in Baade-Wesselink studies. We compared the derived ${\rm PL_{K_{\rm s}}Z}$ relations for RR Lyrae stars in the MW and LMC. Slopes and zero-points are different, but still consistent within the errors. The shallow slope of the metallicity term is confirmed by both LMC and MW variables. The astrometric space mission Gaia is expected to provide a huge contribution to the determination of the RR Lyrae ${\rm PL_{K_{\rm s}}Z}$ relation, however, calculating an absolute magnitude from the trigonometric parallax of each star and fitting a ${\rm PL_{K_{\rm s}}Z}$ relation directly to period and absolute magnitude leads to biased results. We present a tool to achieve an unbiased solution by modelling the data and inferring the slope and zero-point of the relation via statistical methods.
description: 38 pages, 5 figures. The paper is accepted for publication in the Astrophysical Journal
Additive equations in dense variables via truncated restriction estimates
Creators: name: Henriot, Kevin
Publisher: name: arXiv
Year: 2015
Subjects: subject: Combinatorics (math.CO)
subject: Number Theory (math.NT)
subject: FOS: Mathematics
subject: 11B30, 11P55

description: We study translation-invariant additive equations of the form $\sum_{i=1}^s λ_i \mathbf{P}(\mathbf{n}_i) = 0$ in variables $\mathbf{n}_i \in \mathbb{Z}^d$, where the $λ_i$ are nonzero integers summing to zero, and $\mathbf{P}$ is a system of homogeneous polynomials such that the above equation is invariant by translation. We investigate the solvability of this equation in subsets of density $(\log N)^{-c(\mathbf{P},\mathbfλ)}$ of a large box $[N]^d$, via the energy increment method. We obtain positive results in roughly the number of variables currently needed to derive a count of the solutions in the complete box $[N]^d$, for the curve $\mathbf{P} = (x,\dots,x^k)$ and the multidimensional systems of large degree studied by Parsell, Prendiville and Wooley, using only a weak form of restriction estimates. We also obtain results for the $(d+1)$-dimensional parabola $\mathbf{P}=(x_1,\dots,x_d,x_1^2+\dotsb+x_d^2)$ that rely on the recent Strichartz estimates of Bourgain and Demeter.
description: 41 pages
(3926) Elizabeth [Lily] Ann Watt Dollar
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.
AAV-CRISPR gene editing is negated by pre-existing immunity to Cas9
Creators: name: Li, Ang
name: Tanner, Mark R.
name: Lee, Ciaran M.
name: Hurley, Ayrea
name: De Giorgi, Marco
name: Jarrett, Kelsey
name: Davis, Timothy
name: Doerfler, Alexandria
name: Bao, Gang
name: Beeton, Christine
name: R. Lagor, William
Publisher: name: Health Research Alliance
Year: 2023
Subjects: Gene and molecular therapy

description: Adeno-associated viral (AAV) vectors are a leading candidate for the delivery of CRISPR-Cas9 for therapeutic genome editing in vivo. However, AAV-based delivery involves persistent expression of the Cas9 nuclease, a bacterial protein. Recent studies indicate a high prevalence of neutralizing antibodies and T cells specific to the commonly used Cas9 orthologs from Streptococcus pyogenes (SpCas9) and Staphylococcus aureus (SaCas9) in humans. We tested in a mouse model whether pre-existing immunity to SaCas9 would pose a barrier to liver genome editing with AAV packaging CRISPR-Cas9. Although efficient genome editing occurred in mouse liver with pre-existing SaCas9 immunity, this was accompanied by an increased proportion of CD8+ T cells in the liver. This cytotoxic T cell response was characterized by hepatocyte apoptosis, loss of recombinant AAV genomes, and complete elimination of genome-edited cells, and was followed by compensatory liver regeneration. Our results raise important efficacy and safety concerns for CRISPR-Cas9-based in vivo genome editing in the liver.
Mental health impact of the COVID-19 pandemic on patients with neurodegenerative diseases and perceived family caregiver burden in Lima, Peru
Creators: name: Sanchez D.C.
name: Diaz M.M.
name: Bailey M.
name: Garcia B.
name: Aguilar X.R.
Publisher: name: John Wiley and Sons Ltd
Year: 2024

description: Background: Neurodegenerative diseases lead to difficulties with functional activities. In Peru, most caregivers are family members. Little is known about the COVID-19 pandemic's effect on caregivers in Peru. Methods: This was a cross-sectional, prospective study of family caregivers of dependent patients with dementia or Parkinson's Disease in Lima, Peru. A caregiver burden and mental health questionnaire was administered to the caregiver. Results: We enrolled 48 caregivers (65% females, mean ± SD age 49.0 ± 12.3 years); 70% of patients had dementia. Nearly 40% of caregivers reported having full-time jobs, and 82% felt overwhelmed with almost 75% dedicating more time to caregiving during the pandemic. Caregivers perceived patients felt lonelier (52%), had an increase in hallucinations (50%), or forgetfulness (71%) compared to pre-pandemic. Conclusions: Our study highlights that perceived caregiver burden and patient behavioral symptoms may have been exacerbated during the pandemic. In countries such as Peru, more caregiving resources and interventions are needed.
On the occurrence of sea lamprey Petromyzon marinus (Agnatha: Petromyzonidae) in Tunisian waters (central Mediterranean Sea)
Creators: name: RAFRAFI-NOUIRA, Sihem
name: EL KAMEL-MOUTALIBI, Olfa
name: BOUMAÏZA, Moncef
name: REYNAUD, Christian
name: CAPAPÉ, Christian
Publisher: name: Station Biologique de Roscoff (SBR)
Year: 2015

description: A specimen of sea lamprey Petromyzon marinus Linnaeus, 1758 was found for the third time off Ras Jebel, in the Gulf of Tunis, northern Tunisia. The specimen is described with morphometric measurements, while the species occurrence in the area and the Mediterranean Sea is discussed and commented. Additionally, sea lamprey remains an occasional visitor in the Tunisian waters and, consequently, the occurrence of a breeding population seems unlikely.
Leucine Facilitates Insulin Signaling through a Gα i Protein-dependent Signaling Pathway in Hepatocytes
Creators: name: Yao, Ping
name: Sun, Xiufa
name: Li, Xiang
name: Mei, Shuang
name: Liu, Zhenqi
name: Cao, Wenhong
name: Wang, Xiaolei
name: Yang, Xuefeng
name: Hao, Liping
name: Liu, Liegang
name: Ma, Yan
name: Gu, Haihua
name: Liu, Rui
Publisher: name: The University of North Carolina at Chapel Hill University Libraries
Year: 2013

description: In this study, we addressed the direct effect of leucine on insulin signaling. In investigating the associated mechanisms, we found that leucine itself does not activate the classical Akt- or ERK1/2 MAP kinase-dependent signaling pathways but can facilitate the insulin-induced phosphorylations of Akt473 and ERK1/2 in a time- and dose-dependent manner in cultured hepatocytes. The leucine-facilitated insulin-induced phosphorylation of Akt at residue 473 was not affected by knocking down the key component of mTORC1 or -2 complexes but was blocked by inhibition of c-Src (PP2), PI3K (LY294002), Gαi protein (pertussis toxin or siRNA against Gαi1 gene, or β-arrestin 2 (siRNA)). Similarly, the leucine-facilitated insulin activation of ERK1/2 was also blunted by pertussis toxin. We further show that leucine facilitated the insulin-mediated suppression of glucose production and expression of key gluconeogenic genes in a Gαi1 protein-dependent manner in cultured primary hepatocytes. Together, these results show that leucine can directly facilitate insulin signaling through a Gαi protein-dependent intracellular signaling pathway. This is the first evidence showing that macronutrients like amino acid leucine can facilitate insulin signaling through G proteins directly.
Many Ways to Loop DNA
Creators: name: Griffith, Jack D.
Publisher: name: The University of North Carolina at Chapel Hill University Libraries
Year: 2013

description: In the 1960s, I developed methods for directly visualizing DNA and DNA-protein complexes using an electron microscope. This made it possible to examine the shape of DNA and to visualize proteins as they fold and loop DNA. Early applications included the first visualization of true nucleosomes and linkers and the demonstration that repeating tracts of adenines can cause a curvature in DNA. The binding of DNA repair proteins, including p53 and BRCA2, has been visualized at three- and four-way junctions in DNA. The trombone model of DNA replication was directly verified, and the looping of DNA at telomeres was discovered.
(3927) Margaret E Robinson
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.
Policymakers' Views on a Model of Science Education of the Society of Acceleration and Uncertainty – the FEDORA Concept - Deliverable 5.5
Creators: name: Erduran, Sibel
name: Chan, Jessica
Publisher: name: Zenodo
Year: 2023
Subjects: Attitudes
Science education
Futures thinking
Delphi methodology

description: Research activities of WP5 bear two action goals. The first action goal (T5.1-5.3), led by UOXF, is to produce policy briefs for FEDORA. While WP5 utilised information and materials from the other work packages (WPs) to inform its specific focuses, it also reciprocated other WPs by providing feedback insofar as it guides how other WPs can engage with policymakers. WP5 used Delphi methodology (Murray & Hammons, 1995) in its cycle of multiple tasks (T5.1-T5.3). These tasks aimed at assessing policymakers’ views of and attitudes towards future-oriented science education. The assessment then became the basis for building an initial consensus. The second action goal of WP5 is to align MoRRI (Monitoring the evolution and benefits of Responsible Research and Innovation) indicators on science literacy and science education (SLSE) with the results produced by other WPs. This deliverable focuses on the first action goal of consensus building. Figure 1 illustrates the specific tasks for the policy brief action goal for FEDORA. Tasks 5.1 and 5.2 have been explained and reported in deliverables 5.1 – 5.4. This deliverable, D5.5, will give details on Task 5.3 – consensus building through the final-round of the Delphi survey.
Two universal physical principles shape the power-law statistics of real-world networks
Creators: name: Lorimer, Tom
name: Gomez, Florian
name: Stoop, Ruedi
Publisher: name: arXiv
Year: 2015
Subjects: subject: Physics and Society (physics.soc-ph)
subject: Statistical Mechanics (cond-mat.stat-mech)
subject: FOS: Physical sciences

description: The study of complex networks has pursued an understanding of macroscopic behavior by focusing on power-laws in microscopic observables. Here, we uncover two universal fundamental physical principles that are at the basis of complex networks generation. These principles together predict the generic emergence of deviations from ideal power laws, which were previously discussed away by reference to the thermodynamic limit. Our approach proposes a paradigm shift in the physics of complex networks, toward the use of power-law deviations to infer meso-scale structure from macroscopic observations.
description: 14 pages, 7 figures
COMPARATIVE DESCRIPTION OF RUNCIA-AURATA N-SP AND RUNCIA-CORONATA (QUATREFAGES, 1844) (GASTROPODA, OPISTOBRANCHIA)
Creators: name: Garcia, J. C.
name: Lopez, C. M.
name: Luque, A. A.
name: Cervera, J. L.
Publisher: name: Station Biologique de Roscoff (SBR)
Year: 1986

Abstract
(3920) Matilda McCaskie
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.
Energetic, spatial and momentum character of a buried interface: the two-dimensional electron gas between two metal oxides
Creators: name: Nemšák, S.
name: Conti, G.
name: Gray, A. X.
name: Pálsson, G. K.
name: Conlon, C.
name: Eiteneer, D.
name: Keqi, A.
name: Rattanachata, A.
name: Saw, A. Y.
name: Bostwick, A.
name: Moreschini, L.
name: Strocov, V.
name: Kobayashi, M.
name: Stolte, W.
name: Ueda, S.
name: Kobayashi, K.
name: Gloskovskii, A.
name: Drube, W.
name: Jackson, C.
name: Moetakef, P.
name: Janotti, A.
name: Bjaalie, L.
name: Himmetoglu, B.
name: Van de Walle, C. G.
name: Borek, S.
name: Minár, J.
name: Braun, J.
name: Ebert, H.
name: Plucinski, L.
name: Kortright, J. B.
name: de Groot, F. M. F.
name: Schneider, C. M.
name: Balents, L.
name: Stemmer, S.
name: Fadley, C. S.
Publisher: name: arXiv
Year: 2015
Subjects: subject: Materials Science (cond-mat.mtrl-sci)
subject: Other Condensed Matter (cond-mat.other)
subject: Strongly Correlated Electrons (cond-mat.str-el)
subject: FOS: Physical sciences

description: The interfaces between two condensed phases often exhibit emergent physical properties that can lead to new physics and novel device applications, and are the subject of intense study in many disciplines. We here apply novel experimental and theoretical techniques to the characterization of one such interesting interface system: the two-dimensional electron gas (2DEG) formed in multilayers consisting of SrTiO$_3$ (STO) and GdTiO$_3$ (GTO). This system has been the subject of multiple studies recently and shown to exhibit very high carrier charge densities and ferromagnetic effects, among other intriguing properties. We have studied a 2DEG-forming multilayer of the form [6 unit cells STO/3 unit cells of GTO]$_{20}$ using a unique array of photoemission techniques including soft and hard x-ray excitation, soft x-ray angle-resolved photoemission, core-level spectroscopy, resonant excitation, and standing-wave effects, as well as theoretical calculations of the electronic structure at several levels and of the actual photoemission process. Standing-wave measurements below and above a strong resonance have been introduced as a powerful method for studying the 2DEG depth distribution. We have thus characterized the spatial and momentum properties of this 2DEG with unprecedented detail, determining via depth-distribution measurements that it is spread throughout the 6 u.c. layer of STO, and measuring the momentum dispersion of its states. The experimental results are supported in several ways by theory, leading to a much more complete picture of the nature of this 2DEG, and suggesting that oxygen vacancies are not the origin of it. Similar multi-technique photoemission studies of such states at buried interfaces, combined with comparable theory, will be a very fruitful future approach for exploring and modifying the fascinating world of buried-interface physics and chemistry.
description: 34 pages, 10 figures
Applications of Dainshefsky's Dienes in the Asymmetric synthesis of Aza-Diels-Alder Reaction
Creators: name: Heravi, Majid Mommahed
name: Kal-Koshvandi, Afsaneh Taheri
Publisher: name: figshare
Year: 2020
Subjects: subject: 30302 Nanochemistry and Supramolecular Chemistry
subject: FOS: Chemical sciences
subject: 30502 Natural Products Chemistry
subject: 30205 Non-metal Chemistry
subject: 30504 Organic Green Chemistry
subject: 30599 Organic Chemistry not elsewhere classified
subject: Organic Chemistry
subject: 30503 Organic Chemical Synthesis
subject: 30303 Optical Properties of Materials
subject: Nuclear Chemistry

description: Asymmetric hetero-Diels-Alder (AHDA) reactions provide a multitude of opportunities for the highly efficient, regio- and stereoselective construction of various heterocycles in enantiomerically pure form. The asymmetric aza-Diels-Alder (A-aza-DA) reaction using diversely hetero-dienophiles and hetero-dienes have been increasingly developed as a valuable method for the synthesis of functionalized nitrogen ring systems. The purpose of this review is to give a detailed discussion of the A-aza-DA reaction particularly, the stereoselective reactions of imines as dienophiles with Dainshefsky dienes to obtain optically pure aza-Diels-Alder products. The development of stereoselective variants of the reaction make use of imines as the dienophile and Dainshefsky dienes is at the forefront of these studies. This review updates the A-aza-DA reactions covering the literature from 1972 till date.
Novel Yeast-based Strategy Unveils Antagonist Binding Regions on the Nuclear Xenobiotic Receptor PXR
Creators: name: Ekins, Sean
name: Bloch, Nicolin
name: Mani, Sridhar
name: Kalpana, Ganjam
name: Negassa, Abdissa
name: Redinbo, Matthew R.
name: Chaudhry, Anik
name: Mukherjee, Paromita
name: Li, Hao
name: Venkatesh, Madhukumar
Publisher: name: The University of North Carolina at Chapel Hill University Libraries
Year: 2013

description: The pregnane X receptor (PXR) is a master regulator of xenobiotic metabolism, and its activity is critical toward understanding the pathophysiology of several diseases, including inflammation, cancer, and steatosis. Previous studies have demonstrated that ketoconazole binds to ligand-activated PXR and antagonizes receptor control of gene expression. Structure-function as well as computational docking analysis suggested a putative binding region containing critical charge clamp residues Gln-272, and Phe-264 on the AF-2 surface of PXR. To define the antagonist binding surface(s) of PXR, we developed a novel assay to identify key amino acid residues on PXR based on a yeast two-hybrid screen that examined mutant forms of PXR. This screen identified multiple “gain-of-function” mutants that were “resistant” to the PXR antagonist effects of ketoconazole. We then compared our screen results identifying key PXR residues to those predicted by computational methods. Of 15 potential or putative binding residues based on docking, we identified three residues in the yeast screen that were then systematically verified to functionally interact with ketoconazole using mammalian assays. Among the residues confirmed by our study was Ser-208, which is on the opposite side of the protein from the AF-2 region critical for receptor regulation. The identification of new locations for antagonist binding on the surface or buried in PXR indicates novel aspects to the mechanism of receptor antagonism. These results significantly expand our understanding of antagonist binding sites on the surface of PXR and suggest new avenues to regulate this receptor for clinical applications.
Reproductive biology and fecundity of the black scorpion fish Scorpaena porcus (Linnaeus, 1758) at the Algerian coast
Creators: name: MOKRANE, Zakia
name: ZEROUALI-KHODJA, Fatiha
Publisher: name: Station Biologique de Roscoff (SBR)
Year: 2015

description: This study provides elements on indices and the cycle of reproduction of the species Scorpaena porcus. The size of sampled specimens varied between 10.3 and 39.5 cm, with weight ranging between 25.1 and 656.7 g. The sex-ratio determined based on a sample of 343 individuals, was in favour of females (59.42%). The size at the beginning of the maturity was around 17.8 cm for females and 18.8 cm for males. The monthly evolution of the sexual maturity indicated that the spawning period occurs in summer, confirmed by the evolution of both the gonado-somatic index (GSI) and hepato- somatic index (HSI), as well as the oviparous reproduction mode of the species. The histological structure of the testicles was generally semi cystic. While the ovaries are characterized by the presence of stroma in the central cavity during the prematurity and gelatinous matrix at the maturity; the evolution of vitellogenesis started from the central cavity toward the peripheral cavity, surrounded by a thin membrane. The absolute fecundity of this species varied between 22600 and 93400 eggs, depending on the size, total weight and ovaries weight, whilst its relative fecundity varied from 97 to 258 eggs per gram of body mass for specimens weighting from 87.7 to 456 g. Females ranging from 18 to 24 cm in size, had a significant contribution in the reproduction of this species.
Joint computational and experimental investigations on the synthesis and properties of hantzsch-type compounds: An overview
Creators: name: Heravi, Majid Mommahed
name: Tayebeh Hosseinnejad
name: Pachin, Marzieh Omrani
Publisher: name: figshare
Year: 2020
Subjects: subject: 30302 Nanochemistry and Supramolecular Chemistry
subject: FOS: Chemical sciences
subject: 30502 Natural Products Chemistry
subject: 30205 Non-metal Chemistry
subject: Nuclear Chemistry
subject: 30303 Optical Properties of Materials
subject: 30503 Organic Chemical Synthesis
subject: Organic Chemistry

description: In this review, we try to highlight the significance, mechanism propositions, computational and experimental assessments of Hantzsch dihydropyridine (DHPs) which readily oxidized to the corresponding pyridines as one of the most important aromatic heterocycles. We also try to give an overview to its ability in transfer hydrogenation, acting as hydride donors from computational and experimental points of view. Our survey is also extended to computational assessments on the structural and biological properties of Hantzsch DHPs.
(3922) John Love
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.
The degree of mobility of Einstein metrics
Creators: name: Matveev, Vladimir S.
name: Rosemann, Stefan
Publisher: name: arXiv
Year: 2015
Subjects: subject: Differential Geometry (math.DG)
subject: FOS: Mathematics
subject: 53-02 (Primary), 53B10, 53B30, 53B50 (Secondary)

description: Two pseudo-Riemannian metrics are called projectively equivalent if their unparametrized geodesics coincide. The degree of mobility of a metric is the dimension of the space of metrics that are projectively equivalent to it. We give a complete list of possible values for the degree of mobility of Riemannian and Lorentzian Einstein metrics on simply connected manifolds, and describe all possible dimensions of the space of essential projective vector fields.
description: 22 pages, 1 figure