52 research outputs found

    Creating 3D Smear Frames for Animation

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    In the transition between 2D and 3D animation animators tried to be able to replicate all of the styles and techniques in 3D that they utilized in 2D. Motion blur eventually came to replace a popular 2D technique known as a smear frame. A smear frame is much more than a path of motion or a blur though, it has a style that cannot be replicated with such methods. I present a creative project with the intent on creating 3D smear frames in a self-made character rig. In order to achieve this I will be designing, modeling, texturing, rigging, animating, and rendering the character of Champ Champions

    α-Synuclein Suppression by Targeted Small Interfering RNA in the Primate Substantia Nigra

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    The protein α-synuclein is involved in the pathogenesis of Parkinson's disease and other neurodegenerative disorders. Its toxic potential appears to be enhanced by increased protein expression, providing a compelling rationale for therapeutic strategies aimed at reducing neuronal α-synuclein burden. Here, feasibility and safety of α-synuclein suppression were evaluated by treating monkeys with small interfering RNA (siRNA) directed against α-synuclein. The siRNA molecule was chemically modified to prevent degradation by exo- and endonucleases and directly infused into the left substantia nigra. Results compared levels of α-synuclein mRNA and protein in the infused (left) vs. untreated (right) hemisphere and revealed a significant 40–50% suppression of α-synuclein expression. These findings could not be attributable to non-specific effects of siRNA infusion since treatment of a separate set of animals with luciferase-targeting siRNA produced no changes in α-synuclein. Infusion with α-synuclein siRNA, while lowering α-synuclein expression, had no overt adverse consequences. In particular, it did not cause tissue inflammation and did not change (i) the number and phenotype of nigral dopaminergic neurons, and (ii) the concentrations of striatal dopamine and its metabolites. The data represent the first evidence of successful anti-α-synuclein intervention in the primate substantia nigra and support further development of RNA interference-based therapeutics

    Genome variation and population structure among 1142 mosquitoes of the African malaria vector species Anopheles gambiae and Anopheles coluzzii

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    Mosquito control remains a central pillar of efforts to reduce malaria burden in sub-Saharan Africa. However, insecticide resistance is entrenched in malaria vector populations, and countries with a high malaria burden face a daunting challenge to sustain malaria control with a limited set of surveillance and intervention tools. Here we report on the second phase of a project to build an open resource of high-quality data on genome variation among natural populations of the major African malaria vector species Anopheles gambiae and Anopheles coluzzii. We analyzed whole genomes of 1142 individual mosquitoes sampled from the wild in 13 African countries, as well as a further 234 individuals comprising parents and progeny of 11 laboratory crosses. The data resource includes high-confidence single-nucleotide polymorphism (SNP) calls at 57 million variable sites, genome-wide copy number variation (CNV) calls, and haplotypes phased at biallelic SNPs. We use these data to analyze genetic population structure and characterize genetic diversity within and between populations. We illustrate the utility of these data by investigating species differences in isolation by distance, genetic variation within proposed gene drive target sequences, and patterns of resistance to pyrethroid insecticides. This data resource provides a foundation for developing new operational systems for molecular surveillance and for accelerating research and development of new vector control tools. It also provides a unique resource for the study of population genomics and evolutionary biology in eukaryotic species with high levels of genetic diversity under strong anthropogenic evolutionary pressures

    Resistance to pirimiphos-methyl in West African Anopheles is spreading via duplication and introgression of the Ace1 locus

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    Vector population control using insecticides is a key element of current strategies to prevent malaria transmission in Africa. The introduction of effective insecticides, such as the organophosphate pirimiphos-methyl, is essential to overcome the recurrent emergence of resistance driven by the highly diverse Anopheles genomes. Here, we use a population genomic approach to investigate the basis of pirimiphos-methyl resistance in the major malaria vectors Anopheles gambiae and A. coluzzii. A combination of copy number variation and a single non-synonymous substitution in the acetylcholinesterase gene, Ace1, provides the key resistance diagnostic in an A. coluzzii population from Coˆte d’Ivoire that we used for sequence-based association mapping, with replication in other West African populations. The Ace1 substitution and duplications occur on a unique resistance haplotype that evolved in A. gambiae and introgressed into A. coluzzii, and is now common in West Africa primarily due to selection imposed by other organophosphate or carbamate insecticides. Our findings highlight the predictive value of this complex resistance haplotype for phenotypic resistance and clarify its evolutionary history, providing tools to for molecular surveillance of the current and future effectiveness of pirimiphos-methyl based interventions

    Synopsis of the pelidnotine scarabs (Coleoptera, Scarabaeidae, Rutelinae, Rutelini) and annotated catalog of the species and subspecies

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    The pelidnotine scarabs (Scarabaeidae: Rutelinae: Rutelini) are a speciose, paraphyletic assemblage of beetles that includes spectacular metallic species (“jewel scarabs”) as well as species that are ecologically important as herbivores, pollinators, and bioindicators. These beetles suffer from a complicated nomenclatural history, due primarily to 20th century taxonomic and nomenclatural errors. We review the taxonomic history of the pelidnotine scarabs, present a provisional key to genera with overviews of all genera, and synthesize a catalog of all taxa with synonyms, distributional data, type specimen information, and 107 images of exemplar species. As a result of our research, the pelidnotine leaf chafers (a paraphyletic group) include 27 (26 extant and 1 extinct) genera and 420 valid species and subspecies (419 extant and 1 extinct). Our research makes biodiversity research on this group tractable and accessible, thus setting the stage for future studies that address evolutionary and ecological trends. Based on our research, 1 new species is described, 1 new generic synonym and 12 new species synonyms are proposed, 11 new lectotypes and 1 new neotype are designated, many new or revised nomenclatural combinations, and many unavailable names are presented. The following taxonomic changes are made: New generic synonym: The genus Heteropelidnota Ohaus, 1912 is a new junior synonym of Pelidnota MacLeay, 1819. New species synonyms: Plusiotis adelaida pavonacea Casey, 1915 is a syn. n. of Chrysina adelaida (Hope, 1841); Odontognathus gounellei Ohaus, 1908 is a revised synonym of Pelidnota ebenina (Blanchard, 1842); Pelidnota francoisgenieri Moore & Jameson, 2013 is a syn. n. of Pelidnota punctata (Linnaeus, 1758); Pelidnota genieri Soula, 2009 is a syn. n. of Pelidnota punctata (Linnaeus, 1758); Pelidnota lutea (Olivier, 1758) is a revised synonym of Pelidnota punctata (Linnaeus, 1758); Pelidnota (Pelidnota) texensis Casey, 1915 is a revised synonym of Pelidnota punctata (Linnaeus, 1758); Pelidnota (Strigidia) zikani (Ohaus, 1922) is a revised synonym of Pelidnota tibialis tibialis Burmeister, 1844; Pelidnota ludovici Ohaus, 1905 is a syn. n. of Pelidnota burmeisteri tricolor Nonfried, 1894; Rutela fulvipennis Germar, 1824 is syn. n. of Pelidnota cuprea (Germar, 1824); Pelidnota pulchella blanda Burmeister, 1844 is a syn. n. of Pelidnota pulchella pulchella (Kirby, 1819); Pelidnota pulchella scapularis Burmeister, 1844 is a syn. n. of Pelidnota pulchella pulchella (Kirby, 1819); Pelidnota xanthogramma Perty, 1830 is a syn. n. of Pelidnota pulchella pulchella (Kirby, 1819). New or revised statuses: Pelidnota fabricelavalettei Soula, 2009, revised status, is considered a species; Pelidnota rioensis Soula, 2009, stat. n., is considered a species; Pelidnota semiaurata semiaurata Burmeister, 1844, stat. rev., is considered a subspecies. New or comb. rev. and revised status: Plusiotis guaymi Curoe, 2001 is formally transferred to the genus Chrysina (C. guaymi (Curoe, 2001), comb. n.); Plusiotis transvolcanica Morón & Nogueira, 2016 is transferred to the genus Chrysina (C. transvolcanica (Morón & Nogueira, 2016), comb. n.). Heteropelidnota kuhnti Ohaus, 1912 is transferred to the genus Pelidnota (P. kuhnti (Ohaus, 1912), comb. n.); Odontognathus riedeli Ohaus, 1905 is considered a subspecies of Pelidnota rubripennis Burmeister, 1844 (Pelidnota rubripennis riedeli (Ohaus, 1905), revised status and comb. rev.); Pelidnota (Strigidia) acutipennis (F. Bates, 1904) is transferred to the genus Sorocha (Sorocha acutipennis (F. Bates, 1904), comb. rev.); Pelidnota (Odontognathus) nadiae Martínez, 1978 is transferred to the genus Sorocha (Sorocha nadiae (Martínez, 1978), comb. rev.); Pelidnota (Ganonota) plicipennis Ohaus, 1934 is transferred to the genus Sorocha (Sorocha plicipennis (Ohaus, 1934), comb. rev.); Pelidnota similis Ohaus, 1908 is transferred to the genus Sorocha (Sorocha similis (Ohaus, 1908), comb. rev.); Pelidnota (Ganonota) yungana Ohaus, 1934 is transferred to Sorocha (Sorocha yungana (Ohaus, 1934), comb. rev.); Pelidnota malyi Soula, 2010: 58, revised status; Xenopelidnota anomala porioni Chalumeau, 1985, revised subspecies status. To stabilize the classification of the group, a neotype is designated for the following species: Pelidnota thiliezi Soula, 2009. Lectotypes are designated for the following names (given in their original combinations): Pelidnota brevicollis Casey, 1915, Pelidnota brevis Casey, 1915, Pelidnota debiliceps Casey, 1915, Pelidnota hudsonica Casey, 1915, Pelidnota oblonga Casey, 1915, Pelidnota pallidipes Casey, 1915, Pelidnota ponderella Casey, 1915, Pelidnota strenua Casey, 1915, Pelidnota tarsalis Casey, 1915, Pelidnota texensis Casey, 1915, and Scarabaeus punctatus Linnaeus, 1758. The following published infrasubspecific names are unavailable per ICZN Article 45.6.1: Pelidnota (Odontognathus) cuprea var. coerulea Ohaus, 1913; Pelidnota (Odontognathus) cuprea var. rufoviolacea Ohaus, 1913; Pelidnota (Odontognathus) cuprea var. nigrocoerulea Ohaus, 1913; Pelidnota pulchella var. fulvopunctata Ohaus, 1913; Pelidnota pulchella var. sellata Ohaus, 1913; Pelidnota pulchella var. reducta Ohaus, 1913; Pelidnota unicolor var. infuscata Ohaus, 1913. The following published species name is unavailable per ICZN Article 11.5: Neopatatra synonyma Moore & Jameson, 2013. The following published species name is unavailable per application of ICZN Article 16.1: Parhoplognathus rubripennis Soula, 2008. Synopsis of the pelidnotine scarabs (Coleoptera, Scarabaeidae, Rutelinae, Rutelini) 3 The following published species name is unavailable per application of ICZN Article 16.4.1: Strigidia testaceovirens argentinica Soula, 2006, Pelidnota (Strigidia) testaceovirens argentinica (Soula, 2006), and Pelidnota testaceovirens argentinica (Soula, 2006). The following published species names are unavailable per application of ICZN Article 16.4.2: Homonyx digennaroi Soula, 2010; Homonyx lecourti Soula, 2010; Homonyx mulliei Soula, 2010; Homonyx simoensi Soula, 2010; Homonyx wagneri Soula, 2010; Homonyx zovii Demez & Soula, 2011; Pelidnota arnaudi Soula, 2009; Pelidnota brusteli Soula, 2010; Pelidnota chalcothorax septentrionalis Soula, 2009; Pelidnota degallieri Soula, 2010; Pelidnota lavalettei Soula, 2008; Pelidnota lavalettei Soula, 2009; Pelidnota dieteri Soula, 2011; Strigidia gracilis decaensi Soula, 2008, Pelidnota (Strigidia) gracilis decaensi (Soula, 2008), and Pelidnota gracilis decaensi (Soula, 2008); Pelidnota halleri Demez & Soula, 2011; Pelidnota injantepalominoi Demez & Soula, 2011; Pelidnota kucerai Soula, 2009; Pelidnota malyi Soula, 2010: 36-37; Pelidnota mezai Soula, 2009; Pelidnota polita darienensis Soula, 2009; Pelidnota polita orozcoi Soula, 2009; Pelidnota polita pittieri Soula, 2009; Pelidnota punctulata decolombia Soula, 2009; Pelidnota punctulata venezolana Soula, 2009; Pelidnota raingeardi Soula, 2009; Pelidnota schneideri Soula, 2010; Pelidnota simoensi Soula, 2009; Pelidnota unicolor subandina Soula, 2009; Sorocha carloti Demez & Soula, 2011; Sorocha castroi Soula, 2008; Sorocha fravali Soula, 2011; Sorocha jeanmaurettei Demez & Soula, 2011; Sorocha yelamosi Soula, 2011; Xenopelidnota bolivari Soula, 2009; Xenopelidnota pittieri pittieri Soula, 2009. Due to unavailability of the name Pseudogeniates cordobaensis Soula 2009, we describe the species as intentionally new (Pseudogeniates cordobaensis Moore, Jameson, Garner, Audibert, Smith, and Seidel, sp. n.)

    Evaluating the Effects of SARS-CoV-2 Spike Mutation D614G on Transmissibility and Pathogenicity.

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    Global dispersal and increasing frequency of the SARS-CoV-2 spike protein variant D614G are suggestive of a selective advantage but may also be due to a random founder effect. We investigate the hypothesis for positive selection of spike D614G in the United Kingdom using more than 25,000 whole genome SARS-CoV-2 sequences. Despite the availability of a large dataset, well represented by both spike 614 variants, not all approaches showed a conclusive signal of positive selection. Population genetic analysis indicates that 614G increases in frequency relative to 614D in a manner consistent with a selective advantage. We do not find any indication that patients infected with the spike 614G variant have higher COVID-19 mortality or clinical severity, but 614G is associated with higher viral load and younger age of patients. Significant differences in growth and size of 614G phylogenetic clusters indicate a need for continued study of this variant

    Effectiveness of nail bed repair in children with or without replacing the fingernail : NINJA multicentre randomized clinical trial

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    Background Surgery for nail bed injuries in children is common. One of the key surgical decisions is whether to replace the nail plate following nail bed repair. The aim of this RCT was to assess the clinical effectiveness and cost-effectiveness of nail bed repair with fingernail replacement/substitution compared with repair without fingernail replacement. Methods A two-arm 1 : 1 parallel-group open multicentre superiority RCT was performed across 20 secondary-care hospitals in the UK. The co-primary outcomes were surgical-site infection at around 7 days after surgery and cosmetic appearance summary score at a minimum of 4 months. Results Some 451 children presenting with a suspected nail bed injury were recruited between July 2018 and July 2019; 224 were allocated to the nail-discarded arm, and 227 to the nail-replaced arm. There was no difference in the number of surgical-site infections at around 7 days between the two interventions or in cosmetic appearance. The mean total healthcare cost over the 4 months after surgery was €84 (95 per cent c.i. 34 to 140) lower for the nail-discarded arm than the nail-replaced arm (P < 0.001). Conclusion After nail bed repair, discarding the fingernail was associated with similar rates of infection and cosmesis ratings as replacement of the finger nail, but was cost saving

    Exponential growth, high prevalence of SARS-CoV-2, and vaccine effectiveness associated with the Delta variant

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    SARS-CoV-2 infections were rising during early summer 2021 in many countries associated with the Delta variant. We assessed RT-PCR swab-positivity in the REal-time Assessment of Community Transmission-1 (REACT-1) study in England. We observed sustained exponential growth with average doubling time (June-July 2021) of 25 days driven by complete replacement of Alpha variant by Delta, and by high prevalence at younger less-vaccinated ages. Unvaccinated people were three times more likely than double-vaccinated people to test positive. However, after adjusting for age and other variables, vaccine effectiveness for double-vaccinated people was estimated at between ~50% and ~60% during this period in England. Increased social mixing in the presence of Delta had the potential to generate sustained growth in infections, even at high levels of vaccination

    Efficacy and safety of baricitinib or ravulizumab in adult patients with severe COVID-19 (TACTIC-R): a randomised, parallel-arm, open-label, phase 4 trial

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    Background From early in the COVID-19 pandemic, evidence suggested a role for cytokine dysregulation and complement activation in severe disease. In the TACTIC-R trial, we evaluated the efficacy and safety of baricitinib, an inhibitor of Janus kinase 1 (JAK1) and JAK2, and ravulizumab, a monoclonal inhibitor of complement C5 activation, as an adjunct to standard of care for the treatment of adult patients hospitalised with COVID-19. Methods TACTIC-R was a phase 4, randomised, parallel-arm, open-label platform trial that was undertaken in the UK with urgent public health designation to assess the potential of repurposing immunosuppressants for the treatment of severe COVID-19, stratified by a risk score. Adult participants (aged ≥18 years) were enrolled from 22 hospitals across the UK. Patients with a risk score indicating a 40% risk of admission to an intensive care unit or death were randomly assigned 1:1:1 to standard of care alone, standard of care with baricitinib, or standard of care with ravulizumab. The composite primary outcome was the time from randomisation to incidence (up to and including day 14) of the first event of death, invasive mechanical ventilation, extracorporeal membrane oxygenation, cardiovascular organ support, or renal failure. The primary interim analysis was triggered when 125 patient datasets were available up to day 14 in each study group and we included in the analysis all participants who were randomly assigned. The trial was registered on ClinicalTrials.gov (NCT04390464). Findings Between May 8, 2020, and May 7, 2021, 417 participants were recruited and randomly assigned to standard of care alone (145 patients), baricitinib (137 patients), or ravulizumab (135 patients). Only 54 (39%) of 137 patients in the baricitinib group received the maximum 14-day course, whereas 132 (98%) of 135 patients in the ravulizumab group received the intended dose. The trial was stopped after the primary interim analysis on grounds of futility. The estimated hazard ratio (HR) for reaching the composite primary endpoint was 1·11 (95% CI 0·62–1·99) for patients on baricitinib compared with standard of care alone, and 1·53 (0·88–2·67) for ravulizumab compared with standard of care alone. 45 serious adverse events (21 deaths) were reported in the standard-of-care group, 57 (24 deaths) in the baricitinib group, and 60 (18 deaths) in the ravulizumab group. Interpretation Neither baricitinib nor ravulizumab, as administered in this study, was effective in reducing disease severity in patients selected for severe COVID-19. Safety was similar between treatments and standard of care. The short period of dosing with baricitinib might explain the discrepancy between our findings and those of other trials. The therapeutic potential of targeting complement C5 activation product C5a, rather than the cleavage of C5, warrants further evaluation

    Evaluating the Effects of SARS-CoV-2 Spike Mutation D614G on Transmissibility and Pathogenicity

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    Global dispersal and increasing frequency of the SARS-CoV-2 spike protein variant D614G are suggestive of a selective advantage but may also be due to a random founder effect. We investigate the hypothesis for positive selection of spike D614G in the United Kingdom using more than 25,000 whole genome SARS-CoV-2 sequences. Despite the availability of a large dataset, well represented by both spike 614 variants, not all approaches showed a conclusive signal of positive selection. Population genetic analysis indicates that 614G increases in frequency relative to 614D in a manner consistent with a selective advantage. We do not find any indication that patients infected with the spike 614G variant have higher COVID-19 mortality or clinical severity, but 614G is associated with higher viral load and younger age of patients. Significant differences in growth and size of 614G phylogenetic clusters indicate a need for continued study of this variant
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