cometadata/datacite-rtg-text-other-reclassification-records huggingface dataset:
Anillin localization suggests distinct mechanisms of division plane specification in mouse oogenic meiosis I and II
Creators: name: Maddox, Amy Shaub
name: Fadero, Tanner
Publisher: name: The University of North Carolina at Chapel Hill University Libraries
Year: 2015

description: Anillin is a conserved cytokinetic ring protein implicated in actomyosin cytoskeletal organization and cytoskeletal-membrane linkage. Here we explored anillin localization in the highly asymmetric divisions of the mouse oocyte that lead to the extrusion of two polar bodies. The purposes of polar body extrusion are to reduce the chromosome complement within the egg to haploid, and to retain the majority of the egg cytoplasm for embryonic development. Anillin's proposed roles in cytokinetic ring organization suggest that it plays important roles in achieving this asymmetric division. We report that during meiotic maturation, anillin mRNA is expressed and protein levels steadily rise. In meiosis I, anillin localizes to a cortical cap overlying metaphase I spindles, and a broad ring over anaphase spindles that are perpendicular to the cortex. Anillin is excluded from the cortex of the prospective first polar body, and highly enriched in the cytokinetic ring that severs the polar body from the oocyte. In meiosis II, anillin is enriched in a cortical stripe precisely coincident with and overlying the meiotic spindle midzone. These results suggest a model in which this cortical structure contributes to spindle re-alignment in meiosis II. Thus, localization of anillin as a conserved cytokinetic ring marker illustrates that the geometry of the cytokinetic ring is distinct between the two oogenic meiotic cytokineses in mammals.
Capsa: A Unified Framework for Quantifying Risk in Deep Neural Networks
Creators: name: Lolla, Sadhana
name: Elistratov, Iaroslav
name: Perez, Alejandro
name: Ahmadi, Elaheh
name: Rus, Daniela
name: Amini, Alexander
Publisher: name: arXiv
Year: 2023
Subjects: subject: Machine Learning (cs.LG)
subject: Artificial Intelligence (cs.AI)
subject: FOS: Computer and information sciences

description: The modern pervasiveness of large-scale deep neural networks (NNs) is driven by their extraordinary performance on complex problems but is also plagued by their sudden, unexpected, and often catastrophic failures, particularly on challenging scenarios. Existing algorithms that provide risk-awareness to NNs are complex and ad-hoc. Specifically, these methods require significant engineering changes, are often developed only for particular settings, and are not easily composable. Here we present capsa, a framework for extending models with risk-awareness. Capsa provides a methodology for quantifying multiple forms of risk and composing different algorithms together to quantify different risk metrics in parallel. We validate capsa by implementing state-of-the-art uncertainty estimation algorithms within the capsa framework and benchmarking them on complex perception datasets. We demonstrate capsa's ability to easily compose aleatoric uncertainty, epistemic uncertainty, and bias estimation together in a single procedure, and show how this approach provides a comprehensive awareness of NN risk.
description: Neural Information Processing Systems (NeurIPS) 2022. Workshop on Machine Learning for Autonomous Driving (ML4AD)
title: Learning from Machine Learning
title: AND/AND and other forms of algorithmic ambiguity
titleType: Subtitle
Creators: name: Rein, Lisa
Publisher: name: The Dynamic Archive
Year: 2022
Subjects: Digital Media
Performance
Media Theory

description: At the core of the digital, as the etymology suggests, lies the process of dividing everything into clearly distinguishable units. Every process and every being has to be classifiable to survive the digital paradigm, even though analogue matter is not per se made to be compartmentalized and digitally readable. Image analysis software, colloquially referred to as "image recognition" (even though, strictly speaking the software does not recognize anything), is deeply rooted in this digital motivation to calculate, measure and categorize.
title: The molecular basis of thiol odorant sensitivity in the mammalian olfactory system
Creators: name: Helen. Spice, Rachel
Publisher: name: University of Liverpool Repository
Year: 2023

description: This thesis is an investigation into the potential mechanisms that could explain the olfactory sensitivity to thiol compounds ~ought to be conserved across mammalian species. Proteomics techniques were employed as unbiased tools to search for highly conserved proteins in olfactory cilia theoretically capable of strong interactions with thiol odorants. Comparisons of the protein profiles and directed protein labelling studies of olfactory cilia from three mammalian species - the house mouse (Mus musculus), the rat (Rattus norvegicus) and the sheep (Ovis aries) - and respiratory cilia preparations from the rat enabled the identification of cytoskeletal proteins and olfactory receptors as potential targets for sulphydryl-mediated thiol odorant interactions. It is therefore predicted that olfactory detection of thiol odorants utilises a traditional olfactory receptor conserved across mammalian. species, the observed thiol sensitivity potentially a byproduct of a strong interaction between odorant and receptor. This study also represents the first broad ranging study of the protein complement of mammalian olfactory cilia derived from the three model species. The characterisation of olfactory and respiratory cilia proteomes from multiple mammalian species has highlighted a novel family of putative pheromone binding proteins uniquely associated with mouse olfactory cilia preparations. It has also provided further evidence for the ongoing investigations of the functions of odorant-binding proteins and annexins.
Adeno-associated virus-mediated gene transfer of the heart/muscle adenine nucleotide translocator (ANT) in mouse
Creators: name: Coskun, P E
name: Samulski, R J
name: Flierl, A
name: Wallace, D C
name: Chen, Y
Publisher: name: The University of North Carolina at Chapel Hill University Libraries
Year: 2005

description: Mitochondrial myopathy, associated with muscle weakness and progressive external ophthalmoplegia, is caused by mutations in mitochondria oxidative phosphorylation genes including the heart–muscle isoform of the mitochondrial adenine nucleotide translocator (ANT1). To develop therapies for mitochondrial disease, we have prepared a recombinant adeno-associated viral vector (rAAV) carrying the mouse Ant1 cDNA. This vector has been used to transduce muscle cells and muscle from Ant1 mutant mice, which manifest mitochondrial myopathy. AAV-ANT1 transduction resulted in long-term, stable expression of the Ant1 transgene in muscle precursor cells as well as differentiated muscle fibers. The transgene ANT1 protein was targeted to the mitochondrion, was inserted into the mitochondrial inner membrane, formed a functional ADP/ATP carrier, increased the mitochondrial export of ATP and reversed the histopathological changes associated with the mitochondrial myopathy. Thus, AAV transduction has the potential of providing symptomatic relief for the ophthalmoplegia and ptosis resulting from paralysis of the extraocular eye muscles cause by mutations in the Ant1 gene.
Comparison of N-by-1 Rectangular Patch Antenna Design at 2.4 GHz and 5 GHz
Creators: name: Damaraju, Sri Sai Satyanarayana
Publisher: name: figshare
Year: 2019
Subjects: subject: 100501 Antennas and Propagation
subject: FOS: Electrical engineering, electronic engineering, information engineering

description: In the present era, advancement in communication systems requires the development of minimal weight, low profile antennas and low cost which can maintain high performance over a wide spectrum of frequencies. Microstrip patch antenna has provided the needs of the modern era with various designs. The objective of this paper is to design and simulate a 2x1, 4x1 and 8x1 Rectangular patch array antenna at 2.4 GHz and 5 GHz then compare the performance analysis using Antenna Magus software. This is being tested for better gain and high directivity for applications such as wireless systems and satellite communications.
Adeno-associated virus-mediated expression and constitutive secretion of NPY or NPY13-36 suppresses seizure activity in vivo
Creators: name: McCown, T J
name: Foti, S
name: Samulski, R J
name: Haberman, R P
Publisher: name: The University of North Carolina at Chapel Hill University Libraries
Year: 2007

description: Neuropeptide Y (NPY) is a 36-amino-acid peptide that attenuates seizure activity following direct infusion or adeno-associated virus (AAV)-mediated expression in the central nervous system. However, NPY activates all NPY receptor subtypes, potentially causing unwanted side effects. NPY13-36 is a C-terminal peptide fragment of NPY that primarily activates the NPY Y2 receptor, thought to mediate the antiseizure activity. Therefore, we investigated if recombinant adeno-associated virus-mediated expression and constitutive secretion of NPY or NPY13-36 could alter limbic seizure sensitivity. Rats received bilateral piriform cortex infusions of AAV vectors that express and constitutively secrete full-length NPY (AAV-FIB-NPY) or NPY13-36 (AAV-FIB-NPY13-36). Control rats received no infusion, as we have previously shown that vectors expressing and secreting reporter genes like GFP (AAV-FIB-EGFP), as well as vectors expressing peptides that lack secretion sequences (AAV-GAL) have no effect on seizures. One week later, all animals received kainic acid (10 mg kg−1, intraperitoneally), and the latencies to wet dog shakes and limbic seizure behaviors were determined. Although both control and vector-treated rats developed wet dog shake behaviors with similar latencies, the latencies to class III and class IV limbic seizures were significantly prolonged in both NPY- and NPY13-36-treated groups. Thus, AAV-mediated expression and constitutive secretion of NPY and NPY13-36 is effective in attenuating limbic seizures, and provides a platform for delivering therapeutic peptide fragments with increased receptor selectivity.
Bioluminescent virion shells: new tools for quantitation of AAV vector dynamics in cells and live animals
Creators: name: Samulski, R J
name: Li, C
name: Johnson, J S
name: Asokan, A
Publisher: name: The University of North Carolina at Chapel Hill University Libraries
Year: 2008

description: Current technologies for visualizing infectious pathways of viruses rely on fluorescent labeling of capsid proteins by chemical conjugation or genetic manipulation. For non-invasive in vivo imaging of such agents in mammalian tissue, we engineered bioluminescent Gaussia luciferase-tagged Adeno-Associated Viral (gLuc/AAV) vectors. The enzyme was incorporated into recombinant AAV serotype 1, 2, and 8 capsids by fusion to the N-terminus of the VP2 capsid subunit to yield bioluminescent virion shells. The gLuc/AAV vectors were utilized to quantify kinetics of cell surface binding by AAV2 capsids in vitro. Bioluminescent virion shells displayed an exponential decrease in luminescent signal following cellular uptake in vitro. A similar trend was observed following intramuscular injection in vivo, although the rate of decline in bioluminescent signal varied markedly between AAV serotypes. While gLuc/AAV1 and gLuc/AAV8 vectors displayed rapid decrease in bioluminescent signal to background levels within 30 min, the signal from gLuc/AAV2 vectors persisted for over 2 hrs. Bioluminescent virion shells might be particularly useful in quantifying dynamics of viral vector uptake in cells and peripheral tissues in live animals.
Azimuthal harmonics of color fields in a high energy nucleus
Creators: name: Lappi, T.
Publisher: name: arXiv
Year: 2015
Subjects: subject: High Energy Physics - Phenomenology (hep-ph)
subject: Nuclear Theory (nucl-th)
subject: FOS: Physical sciences

description: Recent experimental results have revealed a surprisingly rich structure of multiparticle azimuthal correlations in high energy proton-nucleus collisions. Final state collective effects can be responsible for many of the observed effects, but it has recently been argued that a part of these correlations are present already in the wavefunctions of the colliding particles. We evaluate the momentum space 2-particle cumulant azimuthal anisotropy coefficients v_n{2}, n=2,3,4 from fundamental representation Wilson line distributions describing the high energy nucleus. These would correspond to the flow coefficients in very forward proton nucleus scattering. We find significant differences beteen Wilson lines from the MV model and from JIMWLK evolution. The magnitude and transverse momentum dependence of the v_n{2} values suggest that the fluctuations present in the initial fields are a significant contribution to the observed anisotropies.
description: 6 pages, 3 figures, ReVTEX V2: added references and labels on figures
A muscle-targeting peptide displayed on AAV2 improves muscle tropism on systemic delivery
Creators: name: Qiao, C
name: Cao, Z
name: Yu, C-Y
name: Yuan, Z
name: Li, J
name: Wang, B
name: Xiao, X
Publisher: name: The University of North Carolina at Chapel Hill University Libraries
Year: 2009

description: Adeno-associated virus (AAV) has become a leading gene transfer vector for striated muscles. However, the AAV vectors also exhibit broad tropisms after systemic delivery. In an attempt to improve muscle tropism, we inserted a 7-amino-acid (ASSLNIA) muscle-targeting peptide (MTP) in the capsids of AAV2 at residue 587 or 588, generating AAV587MTP and AAV588MTP. In vitro studies showed that both viruses diminished their infectivity on non-muscle cell lines as well as on un-differentiated myoblasts, however, preserved or enhanced their infectivity on differentiated myotubes. AAV587MTP, but not AAV588MTP, also abolished its heparin-binding capacity and infected myotubes in a heparin-independent manner. Furthermore, in vivo studies by intravenous vector administration in mice showed that AAV587MTP enhanced its tropism to various muscles and particularly to the heart (24.3 fold of unmodified AAV2), whereas reduced its tropism to the non-muscle tissues such as the liver, lungs and spleen, etc. This alteration of tissue tropism is not simply due to the loss of heparin-binding, since a mutant AAV2 (AAVHBSMut) containing heparin-binding site mutations lost infectivity on both non-muscle and muscle cells. Furthermore, free MTP peptide, but not the scrambled control peptide, competitively inhibited AAV587MTP infection on myotubes. These results suggest that AAV2 could be re-targeted to the striated muscles by a muscle-targeting peptide inserted after residue 587 of the capsids. This proof of principle study showed first evidence of peptide-directed muscle targeting upon systemic administration of AAV vectors.
A small regulatory element from chromosome 19 enhances liver-specific gene expression
Creators: name: Asokan, A
name: Hirsch, M
name: Li, C
name: Samulski, R J
name: Wu, Z
name: Carter, P
name: Zhou, X
Publisher: name: The University of North Carolina at Chapel Hill University Libraries
Year: 2009

description: Tissue-specific promoters for gene therapy are typically too big for adeno-associated virus (AAV) vectors; thus, the exploration of small effective non-viral regulatory elements is of particular interest. Wild-type AAV can specifically integrate into a region on human chromosome 19 termed AAVS1. Earlier work has determined that a 347 bp fragment (Chr19) of AAVS1 has promoter and transcriptional enhancer activities. In this study, we further characterized this genetic regulation and investigated its application to AAV gene therapy in vitro and in vivo. The Chr19 347 bp fragment was dissected into three regulatory elements in human embryonic kidney cells: (i) TATA-independent promoter activity distributed throughout the fragment regardless of orientation, (ii) an orientation-dependent insulator function near the 5′ end and (iii) a 107 bp enhancer region near the 3′ end. The small enhancer region, coupled to the mini-CMV promoter, was used to drive the expression of several reporters following transduction by AAV2. In vivo data demonstrated enhanced transgene expression from the Chr19-mini-CMV promoter cassette after tail vein injection primarily in the liver at levels comparable to the chicken β-actin promoter and higher than the liver-specific TTR promoter (>2-fold). However, we did not observe this increase after muscle injection, suggesting tissue-specific enhancement. All of the results support identification of a small DNA fragment (347 bp) from AAV Chr19 integration site capable of providing efficient and enhanced liver-specific transcription when used in recombinant AAV vectors.
Strong Variability of Overlapping Iron Broad Absorption Lines in Five Radio-selected Quasars
Creators: name: Zhang, Shaohua
name: Zhou, Hongyan
name: Wang, Tinggui
name: Wang, Huiyuan
name: Shi, Xiheng
name: Liu, Bo
name: Liu, Wenjuan
name: Li, Zhenzhen
name: Wang, Shufen
Publisher: name: arXiv
Year: 2015
Subjects: subject: Astrophysics of Galaxies (astro-ph.GA)
subject: Cosmology and Nongalactic Astrophysics (astro-ph.CO)
subject: FOS: Physical sciences

description: We present the variability study of broad absorption lines (BALs) in a uniformly radio-selected sample of 28 BAL quasars using the archival data from the FIRST Bright Quasar Survey (FBQS) and the Sloan Digital Sky Survey (SDSS), as well as those obtained by ourselves, covering time scales $\sim 1-10$ years in the quasar's rest-frame. To our surprise, 5 quasars showing strong variations are all belong to a special subclass of overlapping iron low ionization BAL (OFeLoBAL) quasars, however, other 4 non-overlapping FeLoBALs (non-OFeLoBALs) are invariable except one case with weak optical depth change. Meanwhile, we also find 6 typical variations of high-ionization and low-ionization BALs in this BAL quasar sample. Photoionization models suggest that OFeLoBALs are formed in a relative dense ($n_e>10^6$ cm$^{-3}$) outflows at a distance from the subparsec to the dozens of parsecs from the continuum source. They differ from those of non-OFeLoBALs, which are likely produced by low-density gas, locating at a distance of hundreds to thousands parsecs. Thus, OFeLoBALs and non-OFeLoBALs, i.e., FeLoBALs with/without strong BAL variations, perhaps represent the bimodality of Fe II absorption, the former is located in the active galactic nucleus environment rather than the host galaxy. We suggest that high density and small distance are the necessary conditions that cause OFeLoBALs. As suggested in the literature, strong BAL variability is possibly due to variability of the covering factor of BAL regions caused by clouds transiting across the line of sight rather than ionization variations.
description: 19 pages, 5 figures, ApJ accepted
LGViT: Dynamic Early Exiting for Accelerating Vision Transformer
Creators: name: Xu, Guanyu
name: Hao, Jiawei
name: Shen, Li
name: Hu, Han
name: Luo, Yong
name: Lin, Hui
name: Shen, Jialie
Publisher: name: arXiv
Year: 2023
Subjects: subject: Computer Vision and Pattern Recognition (cs.CV)
subject: Artificial Intelligence (cs.AI)
subject: FOS: Computer and information sciences

description: Recently, the efficient deployment and acceleration of powerful vision transformers (ViTs) on resource-limited edge devices for providing multimedia services have become attractive tasks. Although early exiting is a feasible solution for accelerating inference, most works focus on convolutional neural networks (CNNs) and transformer models in natural language processing (NLP).Moreover, the direct application of early exiting methods to ViTs may result in substantial performance degradation. To tackle this challenge, we systematically investigate the efficacy of early exiting in ViTs and point out that the insufficient feature representations in shallow internal classifiers and the limited ability to capture target semantic information in deep internal classifiers restrict the performance of these methods. We then propose an early exiting framework for general ViTs termed LGViT, which incorporates heterogeneous exiting heads, namely, local perception head and global aggregation head, to achieve an efficiency-accuracy trade-off. In particular, we develop a novel two-stage training scheme, including end-to-end training and self-distillation with the backbone frozen to generate early exiting ViTs, which facilitates the fusion of global and local information extracted by the two types of heads. We conduct extensive experiments using three popular ViT backbones on three vision datasets. Results demonstrate that our LGViT can achieve competitive performance with approximately 1.8 $\times$ speed-up.
description: ACM MM 2023
Analysis of neuronal proliferation, migration and differentiation in the postnatal brain using equine infectious anemia virus-based lentiviral vectors
Creators: name: Therit, B
name: Ghashghaei, H T
name: Liang, H
name: Patel, M
name: Olsen, J C
name: Anton, E S
name: Jacquet, B V
name: Salinas-Mondragon, R
name: Iyengar, M
name: Lai, C
Publisher: name: The University of North Carolina at Chapel Hill University Libraries
Year: 2009

description: Ongoing neurogenesis in discrete sectors of the adult central nervous system depends on the mitotic activity of an elusive population of adult stem cells. The existence of adult neural stem cells provides an alternative approach to transplantation of embryonic stem cells in cell-based therapies. Owing to the limited intrinsic fate of adult stem cells and inhibitory nature of the adult brain for neurogenesis, accommodation for circuit replacement in the brain will require genetic and epigenetic manipulation. Here, we show that a replication-incompetent Equine Infectious Anemia Virus (EIAV) is highly suitable for stable and persistent gene transfer to adult neural stem cells. The transduced regions were free of long-lasting neuroimmune responses to EIAV. Transduction in the subventricular zone was specific to the stem cell niche, but spared the progeny of adult neural stem cells that includes transit amplifying progenitors (TAPs) and migrating neuroblasts. With time, EIAV-transduced stem cells passed on the transgene to TAPs and migrating neuroblasts, which ultimately differentiated into neurons in the olfactory bulbs. We show that EIAV is highly suitable for discovery and assessment of mechanisms that regulate proliferation, migration and differentiation in the postnatal brain.
High redshift galaxies in the ALHAMBRA survey: I. selection method and number counts based on redshift PDFs
Creators: name: Viironen, K.
name: Marín-Franch, A.
name: López-Sanjuan, C.
name: Varela, J.
name: Chaves-Montero, J.
name: Cristóbal-Hornillos, D.
name: Molino, A.
name: Fernández-Soto, A.
name: Vilella-Rojo, G.
name: Ascaso, B.
name: Cenarro, A. J.
name: Cerviño, M.
name: Cepa, J.
name: Ederoclite, A.
name: Márquez, I.
name: Masegosa, J.
name: Moles, M.
name: Oteo, I.
name: Pović, M.
name: Aguerri, J. A. L.
name: Alfaro, E.
name: Aparicio-Villegas, T.
name: Benítez, N.
name: Broadhurst, T.
name: Cabrera-Caño, J.
name: Castander, J. F.
name: Del Olmo, A.
name: Delgado, R. M. González
name: Husillos, C.
name: Infante, L.
name: Martínez, V. J.
name: Perea, J.
name: Prada, F.
name: Quintana, J. M.
Publisher: name: arXiv
Year: 2015
Subjects: subject: Astrophysics of Galaxies (astro-ph.GA)
subject: FOS: Physical sciences

description: Context. Most observational results on the high redshift restframe UV-bright galaxies are based on samples pinpointed using the so called dropout technique or Ly-alpha selection. However, the availability of multifilter data allows now replacing the dropout selections by direct methods based on photometric redshifts. In this paper we present the methodology to select and study the population of high redshift galaxies in the ALHAMBRA survey data. Aims. Our aim is to develop a less biased methodology than the traditional dropout technique to study the high redshift galaxies in ALHAMBRA and other multifilter data. Thanks to the wide area ALHAMBRA covers, we especially aim at contributing in the study of the brightest, less frequent, high redshift galaxies. Methods. The methodology is based on redshift probability distribution functions (zPDFs). It is shown how a clean galaxy sample can be obtained by selecting the galaxies with high integrated probability of being within a given redshift interval. However, reaching both a complete and clean sample with this method is challenging. Hence, a method to derive statistical properties by summing the zPDFs of all the galaxies in the redshift bin of interest is introduced. Results. Using this methodology we derive the galaxy rest frame UV number counts in five redshift bins centred at z=2.5, 3.0, 3.5, 4.0, and 4.5, being complete up to the limiting magnitude at m_UV(AB)=24. With the wide field ALHAMBRA data we especially contribute in the study of the brightest ends of these counts, sampling well the surface densities down to m_UV(AB)=21-22. Conclusions. We show that using the zPDFs it is easy to select a clean sample of high redshift galaxies. We also show that statistical analysis of the properties of galaxies is better done using a probabilistic approach, which takes into account both the incompleteness and contamination in a natural way.
description: 16 pages, 11 figures; Accepted for A&A; language corrected
Delivering multiple gene products in the brain from a single adeno-associated virus vector
Creators: name: Samulski, R J
name: Foti, S B
name: McCown, T J
Publisher: name: The University of North Carolina at Chapel Hill University Libraries
Year: 2009

description: For certain gene therapy applications, the simultaneous delivery of multiple genes would allow for novel therapies. In the case of adeno-associated virus (AAV) vectors, the limited packaging capacity greatly restricts current methods of carrying multiple transgene cassettes. To address this issue, a recombinant AAV (rAAV) vector was designed such that a furin proteolytic cleavage site (RKRRKR) was placed between the coding sequences of two genes (green fluorescent protein (GFP) and galanin), to allow cleavage of the chimeric protein into two fragments. In addition, these constructs contained the fibronectin secretory signal sequence that causes the gene products to be constitutively secreted from transduced cells. In vitro studies show that after transfection of HEK293 cells, the appropriate cleavage and constitutive secretion occurred regardless of the order of the genes in the transgene cassette. In vivo, infusion of rAAV vectors into the piriform cortex resulted in both GFP expression and significant galanin attenuation of kainic acid-induced seizure activity. Thus, the present results establish the utility of a proteolytic approach for the expression and secretion of multiple gene products from a single AAV vector transgene cassette.
Commuting Probability of Finite Groups (Extended)
Creators: name: Sen, Snehinh
Publisher: name: arXiv
Year: 2023
Subjects: subject: Group Theory (math.GR)
subject: FOS: Mathematics
subject: Primary: 20D60, Secondary: 20-02, 20E45

description: The target of this article is to discuss the concept of \textit{commuting probability} of finite groups which, in short, is a probabilistic measure of how abelian our group is. We shall compute the value of commuting probability for many special classes of non-abelian groups and also establish some local and global bounds. We will conclude with a few topics for further reading.
description: 18 pages, expository, extended version of an article which appeared in Resonance, Indian Academy of Science
CoxKnockoff: Controlled Feature Selection for the Cox Model Using Knockoffs
Creators: name: Li, Daoji
name: Yu, Jinzhao
name: Zhao, Hui
Publisher: name: arXiv
Year: 2023
Subjects: subject: Methodology (stat.ME)
subject: FOS: Computer and information sciences

description: Although there is a huge literature on feature selection for the Cox model, none of the existing approaches can control the false discovery rate (FDR) unless the sample size tends to infinity. In addition, there is no formal power analysis of the knockoffs framework for survival data in the literature. To address those issues, in this paper, we propose a novel controlled feature selection approach using knockoffs for the Cox model. We establish that the proposed method enjoys the FDR control in finite samples regardless of the number of covariates. Moreover, under mild regularity conditions, we also show that the power of our method is asymptotically one as sample size tends to infinity. To the best of our knowledge, this is the first formal theoretical result on the power for the knockoffs procedure in the survival setting. Simulation studies confirm that our method has appealing finite-sample performance with desired FDR control and high power. We further demonstrate the performance of our method through a real data example.
description: 22 pages including the Supporting Information
Mannitol-facilitated CNS entry of rAAV2 vector significantly delayed the neurological disease progression in MPS IIIB mice
Creators: name: Fu, H
name: Gulaid, K
name: Muenzer, J
name: DiRosario, J
name: McCarty, D M
Publisher: name: The University of North Carolina at Chapel Hill University Libraries
Year: 2009

description: The presence of the blood-brain barrier (BBB) presents the most critical challenge in therapeutic development for mucopolysaccharidosis (MPS) IIIB, a lysosomal storage disease with severe neurological manifestation, because of alpha-N-acetylglucosaminidase (NaGlu) deficiency. Earlier, we showed a global central nervous system (CNS) transduction in mice by mannitol-facilitated entry of intravenous (IV)-delivered recombinant adeno-associated viral serotype 2 (rAAV2) vector. In this study, we optimized the approach and showed that the maximal transduction in the CNS occurred when the rAAV2 vector was IV injected at 8 min after mannitol administration, and was approximately 10-fold more efficient than IV delivery of the vector at 5 or 10 min after mannitol infusion. Using this optimal (8 min) regimen, a single IV infusion of rAAV2-CMV-hNaGlu vector is therapeutically beneficial for treating the CNS disease of MPS IIIB in adult mice, with significantly extended survival, improved behavioral performance, and reduction of brain lysosomal storage pathology. The therapeutic benefit correlated with maximal delivery to the CNS, but not peripheral tissues. This milestone data shows the first effective gene delivery across the BBB to treat CNS disease. The critical timing of vector delivery and mannitol infusion highlights the important contribution of this pretreatment to successful intervention, and the long history of safe use of mannitol in patients bodes well for its application in CNS gene therapy.
Systemic delivery of AAV8 in utero results in gene expression in diaphragm and limb muscle: treatment implications for muscle disorders
Creators: name: Xiao, X
name: Li, J
name: Koppanati, B M
name: Clemens, P R
Publisher: name: The University of North Carolina at Chapel Hill University Libraries
Year: 2009

description: One of the major challenges in the treatment of primary muscle disorders, which often affect many muscle groups, is achieving efficient, widespread transgene expression in muscle. In utero gene transfer can potentially address this problem by accomplishing gene delivery when the tissue mass is small and the immune system is immature. Previous studies with systemic in utero adeno-associated viral (AAV) vector serotype 1 gene delivery to embryonic day 16 (E-16) pups resulted in high levels of transduction in diaphragm and intercostal muscles, but no detectable transgene expression in limb muscles. Recently newer AAV serotypes such as AAV8 have demonstrated widespread and high transgene expression in skeletal muscles and diaphragm by systemic delivery in adult and neonatal mice. We tested AAV8 vector gene delivery by intraperitoneal administration in E-16 mice in utero. Using an AAV8 vector carrying a lacZ reporter gene, we observed high level transduction of diaphragm and intercostal muscles and more moderate transduction of multiple limb muscles and heart. Our current studies demonstrate the potential of AAV8 to achieve widespread muscle transduction in utero and suggest its therapeutic potential for primary muscle disorders.
Non-thermal emission from standing relativistic shocks: an application to red giant winds interacting with AGN jets
Creators: name: Bosch-Ramon, V.
Publisher: name: arXiv
Year: 2015
Subjects: subject: High Energy Astrophysical Phenomena (astro-ph.HE)
subject: FOS: Physical sciences

description: Galactic and extragalactic relativistic jets have rich environments that are full of moving objects, such as stars and dense clumps. These objects can enter into the jets and generate shocks and non-thermal emission. We characterize the emitting properties of the downstream region of a standing shock formed due to the interaction of a relativistic jet with an obstacle. We focus on the case of red giants interacting with an extragalactic jet. We perform relativistic axisymmetric hydrodynamical simulations of a relativistic jet meeting an obstacle of very large inertia. The results are interpreted in the framework of a red giant whose dense and slow wind interacts with the jet of an active galactic nucleus. Assuming that particles are accelerated in the standing shock generated in the jet as it impacts the red giant wind, we compute the non-thermal particle distribution, the Doppler boosting enhancement, and the non-thermal luminosity in gamma rays. The available non-thermal energy from jet-obstacle interactions is potentially enhanced by a factor of $\sim 100$ when accounting for the whole surface of the shock induced by the obstacle, instead of just the obstacle section. The observer gamma-ray luminosity, including the flow velocity and Doppler boosting effects, can be ~300(g/10)^2 times higher than when the emitting flow is assumed at rest and only the obstacle section is considered, where g is the jet Lorentz factor. For a whole population of red giants inside the jet of an AGN, the predicted persistent gamma-ray luminosities may be potentially detectable for a jet pointing to the observer. Obstacles interacting with relativistic outflows, for instance clouds and populations of stars for extragalactic jets, or stellar wind inhomogeneities in microquasar jets and in winds of pulsars in binaries, should be taken into account when investigating the non-thermal emission from these sources.
description: 7 pages, 6 figures, version after proofs to appear in Astronomy & Astrophysics
Improvement of the mdx mouse dystrophic phenotype by systemic in utero AAV8 delivery of a minidystrophin gene
Creators: name: Watchko, J F
name: Zheng, H
name: Reay, D P
name: Clemens, P R
name: Koppanati, B M
name: Daood, M
name: Xiao, X
name: Wang, B
name: Li, J
Publisher: name: The University of North Carolina at Chapel Hill University Libraries
Year: 2010

description: Duchenne muscular dystrophy (DMD) is a devastating primary muscle disease with pathological changes in skeletal muscle that are ongoing at birth. Progressive deterioration in striated muscle function in affected individuals ultimately results in early death due to cardio-pulmonary failure. Since affected individuals can be identified prior to birth by prenatal genetic testing for DMD, gene replacement treatment could be started in utero. This approach offers the possibility of preventing pathological changes in muscle that begin early in life. To test in utero gene transfer utilizing the AAV8 vector in the mdx mouse model of DMD, a minidystrophin gene driven by the human cytomegalovirus promoter was delivered systemically by intraperitoneal injection to the fetus at embryonic day 16. Treated mdx mice studied at 9 weeks after birth demonstrated widespread expression of recombinant dystrophin in skeletal muscle, restoration of the dystrophin associated glycoprotein complex in dystrophin-expressing muscle fibers, improved muscle pathology, and functional benefit to the transduced diaphragm compared to untreated littermate controls. These results support the potential of the AAV8 vector to efficiently cross the blood vessel barrier to achieve systemic gene transfer to skeletal muscle in utero in a mouse model of muscular dystrophy, to significantly improve the dystrophic phenotype and to ameliorate the processes that lead to exhaustion of skeletal muscle regenerative capacity.
Self-complementary AAV mediates gene targeting and enhances endonuclease delivery for double-strand break repair
Creators: name: Samulski, R J
name: Green, L
name: Hirsch, M L
name: Porteus, M H
Publisher: name: The University of North Carolina at Chapel Hill University Libraries
Year: 2010

description: Adeno-associated virus (AAV) mediates gene targeting in humans by providing exogenous DNA for allelic replacement through homologous recombination. In comparison to other methods of DNA delivery or alternative DNA substrates, AAV gene targeting is reported to be very efficient, perhaps due to its single-stranded DNA genome, the inverted terminal repeats (ITRs), and/or the consequence of induced cellular signals on infection or uncoating. These viral attributes were investigated in the presence and absence of an I-Sce endonuclease-induced double-strand break (DSB) within a chromosomal defective reporter in human embryonic kidney cells. Gene correction was evaluated using self-complementary (sc) AAV, which forms a duplexed DNA molecule and results in earlier and robust transgene expression compared with conventional single-strand (ss) AAV genomes. An scAAV repair substrate was modestly enhanced for reporter correction showing no dependency on ssAAV genomes for this process. The AAV ITR sequences were also investigated in a plasmid repair context. No correction was noted in the absence of a DSB, however, a modest inhibitory effect correlated with the increasing presence of ITR sequences. Similarly, signaling cascades stimulated upon recombinant AAV transduction had no effect on plasmid-mediated DSB repair. Noteworthy, was the 20-fold additional enhancement in reporter correction using scAAV vectors, over ss versions, to deliver both the repair substrate and the endonuclease. In this case, homologous recombination repaired the defective reporter in 4% of cells without any selection. This report provides novel insights regarding the recombination substrates used by AAV vectors in promoting homologous recombination and points to the initial steps in vector optimization that could facilitate their use in gene correction of genetic disorders.
Self-deflecting plasmonic lattice solitons and sur-face modes in chirped plasmonic arrays
Creators: name: Li, Chunyan
name: Cui, Ran
name: Ye, Fangwei
name: Kartashov, Yaroslav V.
name: Torner, Lluis
name: Chen, Xianfeng
Publisher: name: arXiv
Year: 2015
Subjects: subject: Optics (physics.optics)
subject: FOS: Physical sciences

description: We show that chirped metal-dielectric waveguide arrays with focusing cubic nonlinearity can support plasmonic lattice solitons that undergo self-deflection in the transverse plane. Such lattice solitons are deeply-subwavelength self-sustained excitations, although they cover several periods of the array. Upon propagation,the excitations accelerate in the transverse plane and follow trajectories curved in the direction in which the separation between neighboring metallic layers decreases, a phenomenon that yields considerable deflection angles. The deflection angle can be controlled by varying the array chirp. We also reveal the existence of surface modes at the boundary of truncated plasmonic chirped arraythat form even in the absence of nonlinearity.
description: 5 pages, 6 figures, to appear in Optics Letters
Liver-specific microRNA-122 target sequences incorporated in AAV vectors efficiently inhibits transgene expression in the liver
Creators: name: Qiao, C
name: Mayer, C
name: Li, J
name: Zheng, H
name: Yuan, Z
name: Xiao, X
name: Li, J
name: He, B
Publisher: name: The University of North Carolina at Chapel Hill University Libraries
Year: 2011

description: Vectors based on adeno-associated virus (AAV) are effective in gene delivery in vivo. Tissue-specific gene expression is often needed to minimize ectopic expression in unintended cells and undesirable consequences. Here we investigated if incorporation of target sequences of tissue-specific microRNA (miRNA) into AAV vectors could inhibit ectopic expression in tissues such as the liver and hematopoietic cells. First we inserted liver-specific miR-122 target sequences (miR-122T) into the 3′ untranslated region (UTR) of a number of AAV vectors. After intravenous delivery in mice, we found that 5 copies of the 20mer miR-122T reduced liver expression of luciferase by 50-fold and β-galactosidase (LacZ) by 70-fold. Five copies of miR-122T also reduced mRNA levels of a secretable protein (myostatin propeptide) from the AAV vector plasmid by 23–fold in the liver. However, gene expression in other tissues including the heart was not inhibited. Similarly, we inserted 4 copies of miR-142-3pT or miR-142-5pT, both hematopoietic lineage-specific, into the 3′ UTR of the AAV-luciferase vector. We wished to see if they could prolong transgene expression by inhibiting expression in antigen-presenting cells. However, in vivo luciferase gene expression in major tissues declined with time regardless of the miR-142 target sequences used. Quantitative analysis of the vector DNA in various tissues revealed that the decline of transgene expression in vivo was mainly due to promoter shut-off other than loss of AAV-transduced cells by immune destruction. Moreover, transgene expression was not detected in circulating mononuclear cells after delivering AAV9 vector with or without miR142T. These results demonstrate that live-specific miR-122 target sequence in AAV vectors was highly efficient in reducing liver expression, whereas hematopoietic miR-142 target sequences were ineffective in preventing decline of AAV vector gene expression in non-hematopoietic tissues resulted from promoter shut-off.
Laminar Flame Speed Modeling of Hydrogen, Methanol and Ammonia Using Machine Learning of Machine Learning
Creators: Shahpouri, Saeid
Norouzi, Armin
Hayduk, Christopher
Fandakov, Alexander
Rezaei, Reza
Koch, Charles Robert
Shahbakhti, Mahdi
Publisher: name: University of Alberta Library
Year: 2022

Conference Abstract. Part of the Proceedings of the Canadian Society for Mechanical Engineering International Congress 2022.
Peptide affinity reagents for AAV capsid recognition and purification
Creators: name: Pulicherla, N
name: Asokan, A
Publisher: name: The University of North Carolina at Chapel Hill University Libraries
Year: 2011

description: We report the discovery of AAV capsid-binding peptides identified through phage panning. The heptapeptide motif GYVSRHP selectively recognized AAV serotype 8 capsids and blocked transduction in vitro. Recombinant AAV8 vectors were purified directly from crude cell lysate and supernatant through sequential application of peptide affinity and anion exchange chromatography. Peptide affinity reagents may serve as useful alternatives to monoclonal antibodies in AAV capsid recognition, and offer readily scalable solutions for purification of clinical grade AAV vectors.
The influence of epileptic neuropathology and prior peripheral immunity on CNS transduction by rAAV2 and rAAV5
Creators: name: Samulski, R J
name: Blake, B L
name: Weinberg, M S
name: McCown, T J
Publisher: name: The University of North Carolina at Chapel Hill University Libraries
Year: 2011

description: Adeno-associated virus (AAV) provides a promising platform for clinical treatment of neurological disorders owing to its established efficacy and lack of apparent pathogenicity. To use viral vectors in treating neurological disease, however, transduction must occur under neuropathological conditions. Previous studies in rodents have shown that AAV5 more efficiently transduces cells in the hippocampus and piriform cortex than AAV2. Using the kainic acid (KA) model of temporal lobe epilepsy and AAV2 and 5 carrying a hybrid chicken β-actin promoter driving green fluorescent protein (GFP), we found that limbic seizure activity caused substantial neuropathology and resulted in a significant reduction in subsequent AAV5 transduction. Nonetheless, this reduced transduction still was greater than AAV2 transduction in control rats. Although KA seizures compromise blood–brain barrier function, potentially increasing exposure of target tissue to circulating neutralizing antibodies, we observed no interaction between KA seizure-induced damage and immunization status on AAV transduction. Finally, while we confirmed the near total neuronal-specific transgene expression for both serotypes in control rats, AAV5–GFP expression was increasingly localized to astrocytes in seizure-damaged areas. Thus, the pathological milieu of the injured brain can reduce transduction efficacy and alter viral tropism- both relevant concerns when considering viral vector gene therapy for neurological disorders.
Efficient transduction of vascular smooth muscle cells with a translational AAV2.5 vector: a new perspective for in-stent restenosis gene therapy
Creators: name: Keuylian, Z
name: McPhee, S W J
name: Karakikes, I
name: Merlet, E
name: Lipskaia, L
name: Hadri, L
name: Samulski, R J
name: Blaise, R
name: Atassi, F
name: Chen, J
name: Marchand, A
name: Mougenot, N
name: Limon, I
name: Lompré, A-M
name: Hajjar, R J
Publisher: name: The University of North Carolina at Chapel Hill University Libraries
Year: 2013

description: Coronary artery disease represents the leading cause of mortality in the developed world. Percutaneous coronary intervention (PCI) involving stent placement remains disadvantaged by restenosis or thrombosis. Vascular gene-therapy-based methods may be approached, but lack a vascular gene delivery vector.We report a safe and efficient long-term transduction of rat carotid vessels after balloon-injury intervention with a translational optimized AAV2.5 vector. Compared to other known AAV serotypes, AAV2.5 demonstrated the highest transduction efficiency of human coronary artery vascular smooth muscle cells (VSMC) in vitro. Local delivery of AAV2.5-driven transgenes in injured carotid arteries resulted in transduction as soon as day 2 after surgery and persisted for at least 30 days. In contrast to adenovirus 5 vector, inflammation was not detected in AAV2.5-transduced vessels. The functional effects of AAV2.5-mediated gene transfer on neointimal thickening were assessed using the sarco/endoplasmic reticulum Ca2+ ATPase (SERCA2a) human gene, known to inhibit VSMC proliferation. At 30 days, human SERCA2a mRNA was detected in transduced arteries. Morphometric analysis revealed a significant decrease of neointimal hyperplasia in AAV2.5-SERCA2a transduced arteries: 28.36±11.30 (n=8) vs 77.96±24.60 (n=10) μm2, in AAV2.5-GFP-infected, p<0.05.In conclusion, AAV2.5 vector can be considered as a promising safe and effective vector for vascular gene therapy.