bluuebunny/crossref_metadata_2025 huggingface dataset:
Two Stage Designs for Phase III Clinical Trials
Authors: Follmann Dean , Proschan Michael
Published: August 2020

Phase III platform trials are increasingly used to evaluate a sequence of treatments for a specific disease. Traditional approaches to structure such trials tend to focus on the sequential questions rather than the performance of the entire enterprise. We consider two-stage trials where an early evaluation is used to determine whether to continue with an individual study. To evaluate performance, we use the ratio of expected wins (RW), that is, the expected number of reported efficacious treatments using a two-stage approach compared to that using standard phase III trials. We approximate the test statistics during the course of a single trial using Brownian Motion and determine the optimal stage 1 time and type I error rate to maximize RW for fixed power. At times, a surrogate or intermediate endpoint may provide a quicker read on potential efficacy than use of the primary endpoint at stage 1. We generalize our approach to the surrogate endpoint setting and show improved performance, provided a good quality and powerful surrogate is available. We apply our methods to the design of a platform trial to evaluate treatments for COVID-19 disease.
SvFUL2, an A-class MADS-box transcription factor, is necessary for inflorescence determinacy in model panicoid cereal,Setaria viridis
Authors: Yang Jiani , Bertolini Edoardo , Braud Max , Preciado Jesus , Chepote Adriana , Jiang Hui , Eveland Andrea L.
Published: August 2020

Inflorescence architecture in cereal crops directly impacts yield potential through regulation of seed number and harvesting ability. Extensive architectural diversity found in inflorescences of grass species is due to spatial and temporal activity and determinacy of meristems, which control the number and arrangement of branches and flowers, and underlie plasticity. Timing of the floral transition is also intimately associated with inflorescence development and architecture, yet little is known about the intersecting pathways and how they are rewired during development. Here, we show that a single mutation in a gene encoding an AP1 A-class MADS-box transcription factor significantly delays flowering time and disrupts multiple levels of meristem determinacy in panicles of the C4model panicoid grass,Setaria viridis. Previous reports of A-class genes in cereals have revealed extensive functional redundancy, and in panicoid grasses, no associated inflorescence phenotypes have been described. InS. viridis, perturbation ofSvFul2, both through chemical mutagenesis and CRISPR/Cas9-based gene editing, converted a normally determinate inflorescence habit to an indeterminate one, and also repressed determinacy in axillary branch and floral meristems. Our analysis of gene networks connected to disruption ofSvFul2identified regulatory hubs at the intersect of floral transition and inflorescence determinacy, providing insights into the optimization of cereal crop architecture.
Passive muscle stretching reduces estimates of persistent inward current strength in soleus motor units
Authors: Trajano Gabriel S. , Taylor Janet L. , Orssatto Lucas B. R. , McNulty Craig R. , Blazevich Anthony J.
Published: August 2020

Prolonged (≥60 s) passive muscle stretching acutely reduces maximal force production at least partly through a suppression of efferent neural drive. The origin of this neural suppression has not been determined, however some evidence suggests that reductions in the amplitude of persistent inward currents (PICs) in the motoneurons may be important. The aim of the present study was to determine whether acute passive (static) muscle stretching affects PIC strength in gastrocnemius medialis (GM) and soleus (SOL) motor units. We calculated the difference in instantaneous discharge rates at recruitment and derecruitment (ΔF) for pairs of motor units in GM and SOL during triangular isometric plantar flexor contractions (20% maximum) both before and immediately after a 5-min control period and immediately after five 1-min passive plantar flexor stretches. After stretching there was a significant reduction in SOL ΔF (−25.6%; 95%CI = -45.1 to -9.1 %, p=0.002) but not GM ΔF. These data suggest passive muscle stretching can reduce the intrinsic excitability, via PICs, of SOL motor units. These findings (1) suggest that PIC strength might be reduced after passive stretching, (2) are consistent with previously-established post-stretch decreases in SOL but not GM EMG amplitudes during contraction, and (3) indicate that reductions in PIC strength could underpin the stretch-induced force loss.

SUMMARY STATEMENT

Motoneurons require an amplification mechanism to operate within the firing frequencies observed during normal motor behaviour. Here we present evidence that this amplification mechanism is reduced after passive muscle stretching.
Species-specific phototaxis of coral larvae causes variation in vertical positioning during dispersal
Authors: Mulla Aziz J , Lin Che-Hung , Takahashi Shunichi , Nozawa Yoko
Published: August 2020

Controlling vertical positioning is a key factor limiting the distance coral larvae can travel, as oceanic currents are faster closer to surface. Currently, the vertical position of coral larvae is assumed to be determined by buoyant, lipid-rich gametes. However, here we show that some, but not all, coral species can control vertical positioning by phototaxis. We first examined the effect of light on the vertical positioning of larvae from five different coral species in the laboratory. We found that larvae from P. verrucosa, but not from other coral species, show phototaxis towards light and accumulate near the surface. This behavior was consistent at any age and at any time during the day. In field experiments, using P. verrucosa larvae at three different depths (1, 7 and 15 m), the accumulation of larvae in the top half of transparent chambers was observed at all depths. However, such behavior failed to occur in dark chambers. We conclude that larvae from P. verrucosa, but not all coral species, accumulate close to the seawater surface as a result of actively swimming towards sunlight. This finding provides a new hypothesis that phototactic behavior is a key factor in regulating vertical positioning for the dispersal of coral larvae.
Pheromone receptor of the globally invasive quarantine pest of the palm tree, the red palm weevil (Rhynchophorus ferrugineus)
Authors: Antony Binu , Johny Jibin , Montagné Nicolas , Jacquin-Joly Emmanuelle , Capoduro Rémi , Cali Khasim , Persaud Krishna , Al-Saleh Mohammed Ali , Pain Arnab
Published: August 2020

Palm trees are of immense economic, sociocultural, touristic and patrimonial significance all over the world, and date palm-related knowledge, traditions and practices are now included in UNESCO’s list of the Intangible Cultural Heritage of Humanity. Of all the pests that infest these trees, the red palm weevil (RPW),Rhynchophorus ferrugineus(Olivier) is its primary enemy. The RPW is a category-1 quarantine insect pest that causes enormous economic losses in the cultivation of palm trees worldwide. The RPW synchronizes mass gathering on the palm tree for feeding and mating, regulated by a male-produced pheromone composed of two methyl-branched compounds, (4RS,5RS)-4-methylnonan-5-ol (ferrugineol) and 4(RS)-methylnonan-5-one (ferrugineone). Despite the importance of odorant detection in long-range orientation towards palm trees, palm colonization and mating, nothing regarding the molecular mechanisms of pheromone detection in this species is known. In this study, we report the identification and characterization of the first RPW pheromone receptor,RferOR1. Using gene silencing and functional expression inDrosophilaolfactory receptor neurons, we demonstrate thatRferOR1is tuned to both ferrugineol and ferrugineone and binds five other structurally related molecules. We reveal the lifetime expression ofRferOR1, which correlates with adult mating success irrespective of age, a factor that could explain the wide distribution and spread of this pest. As palm weevils are challenging to control based on conventional methods, elucidation of the mechanisms of pheromone detection opens new routes for mating disruption and the early detection of this pestviathe development of pheromone receptor-based biosensors.
Top predators govern multitrophic diversity effects in tritrophic food webs
Authors: Ceulemans Ruben , Guill Christian , Gaedke Ursula
Published: August 2020

It is well known that functional diversity strongly affects ecosystem functioning. However, even in rather simple model communities consisting of only two or, at best, three trophic levels, the relationship between multitrophic functional diversity and ecosystem functioning appears difficult to generalize, due to its high contextuality. In this study, we considered several differently structured tritrophic food webs, in which the amount of functional diversity was varied independently on each trophic level. To achieve generalizable results, largely independent of parametrization, we examined the outcomes of 128, 000 parameter combinations sampled from ecologically plausible intervals, with each tested for 200 randomly sampled initial conditions. Analysis of our data was done by training a Random Forest model. This method enables the identification of complex patterns in the data through partial dependence graphs, and the comparison of the relative influence of model parameters, including the degree of diversity, on food web properties. We found that bottom-up and top-down effects cascade simultaneously throughout the food web, intimately linking the effects of functional diversity of any trophic level to the amount of diversity of other trophic levels, which may explain the difficulty in unifying results from previous studies. Strikingly, only with high diversity throughout the whole food web, different interactions synergize to ensure efficient exploitation of the available nutrients and efficient biomass transfer, ultimately leading to a high biomass and production on the top level. The temporal variation of biomass showed a more complex pattern with increasing multitrophic diversity: while the system initially became less variable, eventually the temporal variation rose again due to the increasingly complex dynamical patterns. Importantly, top predator diversity and food web parameters affecting the top trophic level were of highest importance to determine the biomass and temporal variability of any trophic level. Overall, our study reveals that the mechanisms by which diversity influences ecosystem functioning are affected by every part of the food web, hampering the extrapolation of insights from simple monotrophic or bitrophic systems to complex natural food webs.
RFPlasmid: Predicting plasmid sequences from short read assembly data using machine learning
Authors: van Bloois Linda van der Graaf , Wagenaar Jaap A. , Zomer Aldert L.
Published: August 2020

Antimicrobial resistance (AMR) genes in bacteria are often carried on plasmids and these plasmids can transfer AMR genes between bacteria. For molecular epidemiology purposes and risk assessment, it is important to know if the genes are located on highly transferable plasmids or in the more stable chromosomes. However, draft whole genome sequences are fragmented, making it difficult to discriminate plasmid and chromosomal contigs. Current methods that predict plasmid sequences from draft genome sequences rely on single features, like k-mer composition, circularity of the DNA molecule, copy number or sequence identity to plasmid replication genes, all of which have their drawbacks, especially when faced with large single copy plasmids, which often carry resistance genes. With our newly developed prediction tool RFPlasmid, we use a combination of multiple features, including k-mer composition and databases with plasmid and chromosomal marker proteins, to predict if the likely source of a contig is plasmid or chromosomal. The tool RFPlasmid supports models for 17 different bacterial species, includingCampylobacter,E. coli, andSalmonella, and has a species agnostic model for metagenomic assemblies or unsupported organisms. RFPlasmid is available both as standalone tool and via web interface.
Muscle Metabolic Energy Costs While Modifying Propulsive Force Generation During Walking
Authors: Pimentel Richard E. , Pieper Noah L. , Clark William H. , Franz Jason R.
Published: August 2020

We pose that an age-related increase in the metabolic cost of walking arises in part from a redistribution of joint power where muscles spanning the hip compensate for insufficient ankle push-off and smaller peak propulsive forces (FP). Young adults elicit a similar redistribution when walking with smaller FPvia biofeedback. We used targeted FPbiofeedback and musculoskeletal models to estimate the metabolic costs of operating lower limb muscles in young adults walking across a range of FP. Our simulations support the theory of distal-to-proximal redistribution of joint power as a determinant of increased metabolic cost in older adults during walking.
Purification of recombinant SARS-CoV-2 spike, its receptor binding domain, and CR3022 mAb for serological assay
Authors: Tee Kang Lan , Jackson Philip J. , Scarrott Joseph M. , Jaffe Stephen R. P. , Johnson Abayomi O. , Johari Yusuf , Pohle Thilo H. , Mozzanino Theo , Price Joseph , Grinham James , Brown Adam , Nicklin Martin J. , James David C. , Dickman Mark J. , Wong Tuck Seng
Published: August 2020

Serology testing for COVID-19 is highly attractive because of the relatively short diagnosis time and the ability to test for an active immune response against the SARS-CoV-2. In many types of serology tests, the sensitivity and the specificity are directly influenced by the quality of the antigens manufactured. Protein purification of these recombinantly expressed viral antigens [e.g., spike and its receptor binding domain (RBD)] is an important step in the manufacturing process. Simple and high-capacity protein purification schemes for spike, RBD, and CR3022 mAb, recombinantly expressed in CHO and HEK293 cells, are reported in this article. The schemes consist of an affinity chromatography step and a desalting step. Purified proteins were validated in ELISA-based serological tests. Interestingly, extracellular matrix proteins [most notably heparan sulfate proteoglycan (HSPG)] were co-purified from spike-expressing CHO culture with a long cultivation time. HSPG-spike interaction could play a functional role in the pathology and the pathogenesis of SARS-CoV-2 and other coronaviruses.
Characterisation ofMedicago truncatulaCLE34 and CLE35 in nodulation control
Authors: Mens Celine , Hastwell April H. , Su Huanan , Gresshoff Peter M. , Mathesius Ulrike , Ferguson Brett J.
Published: August 2020

Legume plants form a symbiosis with N2-fixing soil rhizobia, resulting in new root organs called nodules that enable N2-fixation. Nodulation is a costly process that is tightly regulated by the host through Autoregulation of Nodulation (AON) and nitrate-dependent regulation of nodulation. Both pathways require legume-specific CLAVATA/ESR-related (CLE) peptides. Nitrogen-induced nodulation-suppressing CLE peptides have not previously been characterised inMedicago truncatula, with only rhizobia-induced MtCLE12 and MtCLE13 identified. Here, we report on novel peptides MtCLE34 and MtCLE35 in nodulation control pathways. The nodulation-suppressing CLE peptides of five legume species were classified into three clades based on sequence homology and phylogeny. This approached identified MtCLE34 and MtCLE35 and four new CLE peptide orthologues ofPisum sativum. Whereas MtCLE12 and MtCLE13 are induced by rhizobia, MtCLE34 and MtCLE35 respond to both rhizobia and nitrate. MtCLE34 was identified as a pseudogene lacking a functional CLE-domain. Overexpression ofMtCLE12, MtCLE13andMtCLE35inhibits nodulation. Together, our findings indicate that MtCLE12 and MtCLE13 have a distinct role in AON, while MtCLE35 regulates nodule numbers in a rhizobia- and nitrate-dependent manner. MtCLE34 likely had a similar role to MtCLE35 but its function was lost due to a nonsense mutation resulting in the loss of the mature peptide.
Single-cell cytometry via multiplexed fluorescence prediction by label-free reflectance microscopy
Authors: Cheng Shiyi , Fu Sipei , Kim Yumi Mun , Song Weiye , Li Yunzhe , Xue Yujia , Yi Ji , Tian Lei
Published: August 2020

Traditional imaging cytometry uses fluorescence markers to identify specific structures, but is limited in throughput by the labeling process. Here we develop a label-free technique that alleviates the physical staining and provides highly multiplexed readouts via a deep learning-augmented digital labeling method. We leverage the rich structural information and superior sensitivity in reflectance microscopy and show that digital labeling predicts highly accurate subcellular features after training on immunofluorescence images. We demonstrate up to 3× improvement in the prediction accuracy over the state-of-the-art. Beyond fluorescence prediction, we demonstrate that single-cell level structural phenotypes of cell cycles are correctly reproduced by the digital multiplexed images, including Golgi twins, Golgi haze during mitosis and DNA synthesis. We further show that the multiplexed readouts enable accurate multi-parametric single-cell profiling across a large cell population. Our method can dramatically improve the throughput for imaging cytometry toward applications for phenotyping, pathology, and high-content screening.
A spark of 3D revisualization: new method for re-exploring segmented data
Authors: Hu Yuzhi , Limaye A. , Lu Jing
Published: August 2020

3D scientific visualization is a popular non-destructive investigation tool, however current imaging processing and 3D visualization software has compatibility barriers which make replicability and reproducibility in research difficult. To solve this, we developed a new revisualization method and demonstrated four case studies using three mainstream image processing and 3D visualization software. Our method offers interchangeability amongst current image processing and 3D visualization software.
Subgenomic satellite particle generation in recombinant AAV vectors results from DNA lesion/breakage and non-homologous end joining
Authors: Zhang Junping , Guo Ping , Yu Xiangping , Pouchnik Derek , Firrman Jenni , Wei Hongying , Sang Nianli , Herzog Roland , Diao Yong , Xiao Weidong
Published: August 2020

Recombinant AAV (rAAV) vectors have been developed for therapeutic treatment of genetic diseases. Nevertheless, current rAAV vectors administered to patients often contain non-vector related DNA contaminants. Here, we present a thorough molecular analysis of the configuration of non-standard AAV genomes generated during rAAV production. In addition to the sub-vector genomic size particles containing incomplete AAV genomes, our results found that rAAV preparations were contaminated with multiple categories of subgenomic particles with either snapback genomes or vector genomes with deletions in the mid regions. Through CRISPR and restriction enzyme-based in vivo and in vitro modeling, we identified that the main mechanism leading to the formation of non-canonical genome particles occurred through nonhomologous end joining of fragmented vector genomes caused by genome lesions or DNA breaks that were generated by the host cell/environment. The results of this study advance our understanding of AAV vectors and provide new clues on improving vector efficiency and safety profile for use in human gene therapy.
Oxidoreductases generate hydrogen peroxide that drives iron-dependent lipid peroxidation during ferroptosis
Authors: Yan Bo , Ai Youwei , Zhang Ze , Sun Qi , Ma Yan , Zhang Zhiyuan , Wang Xiaodong
Published: August 2020

The inhibition of antioxidant systems of glutathione peroxidase 4 (GPX4) or ferroptosis suppressor protein 1 (FSP1) causes iron-dependent peroxidation of polyunsaturated phospholipids that leads to cell death, a process known as ferroptosis. The mechanisms underlying iron-dependent lipid peroxidation are under active debate. Here, we report that two endoplasmic reticulum-residing oxidoreductases, NADPH-cytochrome P450 reductase (POR) and NADH-cytochrome b5 reductase (CYB5R1), are responsible for the iron-dependent peroxidation of polyunsaturated phospholipids and membrane disruption that executes ferroptosis. Genetic ablation of POR and CYB5R1 or mutations that eliminate POR’s electron transfer activity blocked ferroptosis.In vitroenzymatic assays established that POR and CYB5R1 catalyze hydrogen peroxide production by transferring electrons from NADPH/NADH to oxygen, which is then used to carry out iron-dependent lipid peroxidation via a Fenton reaction. The lipid peroxidation reaction catalyzed by POR and CYB5R1 additively disrupts polyunsaturated phospholipid-containing liposomes. Finally, POR knockdown confers significant protective effects during concanavalin A-induced, ferroptosis-associated acute liver injuryin vivo.Our study thus indicates that POR and CYB5R1 are the enzymes of the “oxidant” system that operates to contravene the antioxidant GPX4/FSP1 systems; the balance between these two systems determines cell commitment to ferroptosis.
Working and Reference Memory tasks trigger opposed long-term synaptic changes in the rat dentate gyrus
Authors: Missaire Mégane , Fraize Nicolas , Comte Jean-Christophe , Truchet Bruno , Parmentier Régis , Salin Paul-Antoine , Malleret Gaël
Published: August 2020

Long-term storage of information into memory is supposed to rely on long-term synaptic plasticity processes. Detection of such synaptic changes after training in long-term or reference memory (RM) tasks has yet been scarce, variable and only studied on a short time scale. On the other hand, short-term or working memory (WM) is largely known to depend on persistent neuronal activity or short-term plasticity processes. However, processing information into WM could also involve long-term synaptic changes that could be responsible for the erasure/forgetting of items previously stored in WM playing the role of proactive interference. In order to study long-term synaptic changes associated with RM or WM, we trained chronically implanted rats in three different radial maze tasks: a classical RM task and two WM tasks involving different levels of proactive interference. Synaptic responses at the perforant path to dentate gyrus synapse were recorded on a long-time scale (24h) in freely-moving rats after training in one of these three tasks. We found that consolidation of long-term information leads to a delayed synaptic potentiation, occurring 9 hours after RM training and predicting good behavioral performance on the following day. In contrast, optimal information processing into WM triggers a synaptic depression immediately observed after training and lasting 3 hours, that could act as a mechanism for interference erasure/forgetting.
A sensory integration account for time perception
Authors: Toso Alessandro , Fassihi Arash , Paz Luciano , Pulecchi Francesca , Diamond Mathew E.
Published: August 2020

The connection between stimulus perception and time perception remains unknown. The present study combines human and rat psychophysics with sensory cortical neuronal firing to construct a computational model for the percept of elapsed time embedded within sense of touch. When subjects judged the duration of a vibration applied to the fingertip (human) or whiskers (rat), increasing stimulus mean speed led to increasing perceived duration. Symmetrically, increasing vibration duration led to increasing perceived intensity. We modeled spike trains from vibrissal somatosensory cortex as input to dual leaky integrators – an intensity integrator with short time constant and a duration integrator with long time constant – generating neurometric functions that replicated the actual psychophysical functions of rats. Returning to human psychophysics, we then confirmed specific predictions of the dual leaky integrator model. This study offers a framework, based on sensory coding and subsequent accumulation of sensory drive, to account for how a feeling of the passage of time accompanies the tactile sensory experience.
A constitutively monomeric UVR8 photoreceptor allele confers enhanced UV-B photomorphogenesis
Authors: Podolec Roman , Lau Kelvin , Wagnon Timothée B. , Hothorn Michael , Ulm Roman
Published: August 2020

The plant UV-B photoreceptor UVR8 plays an important role in UV-B acclimation and survival. UV-B absorption by homodimeric UVR8 induces its monomerization and interaction with the E3 ubiquitin ligase COP1, leading ultimately to gene expression changes. UVR8 is inactivated through redimerization, facilitated by RUP1 and RUP2. Here, we describe a novel semi-dominant, hyperactive allele, namelyuvr8-17D, that harbors a glycine-101 to serine mutation. UVR8G101S-overexpression led to weak constitutive photomorphogenesis and extreme UV-B responsiveness. UVR8G101Swas observed to be predominantly monomericin vivoand, once activated by UV-B, was not efficiently inactivated. Analysis of a UVR8G101Scrystal structure revealed the distortion of a loop region normally involved in stabilization of the UVR8 homodimer. Plants expressing a UVR8 variant combining G101S with the previously described W285A mutation exhibited robust constitutive photomorphogenesis. This work provides further insight into UVR8 activation and inactivation mechanisms, and describes a genetic tool for the manipulation of photomorphogenic responses.
A Systemic and Molecular Study of Subcellular Localization of SARS-CoV-2 Proteins
Authors: Zhang Jing , Cruz-cosme Ruth , Zhuang Meng-Wei , Liu Dongxiao , Liu Yuan , Teng Shaolei , Wang Pei-Hui , Tang Qiyi
Published: August 2020

Coronavirus possesses the largest RNA genome among all the RNA viruses. Its genome encodes about 29 proteins. Most of the viral proteins are non-structural proteins (NSP) except envelop (E), membrane (M), nucleocapsid (N) and Spike (S) proteins that constitute the viral nucleocapsid, envelop and surface. We have recently cloned all the 29 SARS-CoV-2 genes into vectors for their expressions in mammalian cells except NSP11 that has only 14 amino acids (aa). We are able to express all the 28 cloned SARS-CoV-2 genes in human cells to characterize their subcellular distributions. The proteins of SARS-CoV-2 are mostly cytoplasmic but some are both cytoplasmic and nuclear. Those punctate staining proteins were further investigated by immunofluorescent assay (IFA) using specific antibodies or by co-transfection with an organelle marker-expressing plasmid. As a result, we found that NSP15, ORF6, M and ORF7a are related to Golgi apparatus, and that ORF7b, ORF8 and ORF10 colocalize with endoplasmic reticulum (ER). Interestingly, ORF3a distributes in cell membrane, early endosome, endosome, late endosome and lysosome, which suggests that ORF3a might help the infected virus to usurp endosome and lysosome for viral use. Furthermore, we revealed that NSP13 colocalized with SC35, a protein standing for splicing compartments in the nucleus. Our studies for the first time visualized the subcellular locations of SARS-CoV-2 proteins and might provide novel insights into the viral proteins’ biological functions.
Detecting selection with a genetic cross
Authors: Fraser Hunter B.
Published: August 2020

Distinguishing which traits have evolved under natural selection, as opposed to neutral evolution, is a major goal of evolutionary biology. Several tests have been proposed to accomplish this, but these either rely on false assumptions or suffer from low power. Here, I introduce a new approach to detecting lineage-specific selection that makes minimal assumptions and only requires phenotypic data from ∼10 individuals. The test compares the phenotypic difference between two populations to what would be expected by chance under neutral evolution, which can be estimated from the phenotypic distribution of an F2cross between those populations. Simulations show that the test is robust to parameters such as the number of loci affecting the trait, the distribution of locus effect sizes, heritability, dominance, and epistasis. Comparing its performance to the QTL sign test—an existing test of selection that requires both genotype and phenotype data—the new test achieves comparable power with 50- to 100-fold fewer individuals (and no genotype data). Applying the test to empirical data spanning over a century shows strong directional selection in many crops, as well as on naturally selected traits such as head shape in HawaiianDrosophilaand skin color in humans. Applied to gene expression data, the test reveals that the strength of stabilizing selection acting on mRNA levels in a species is strongly associated with that species’ effective population size. In sum, this test is applicable to phenotypic data from almost any genetic cross, allowing selection to be detected more easily and powerfully than previously possible.

Significance Statement

Natural selection is the force that underlies the spectacular adaptations of all organisms to their environments. However, not all traits are under selection; a key question is which traits have been shaped by selection, as opposed to the random drift of neutral traits. Here, I develop a test of selection on quantitative traits that can be applied to almost any genetic cross between divergent populations or species. The test is robust to a wide range of potential confounders, and has greater power to detect selection than existing tests. Applied to empirical data, the test reveals widespread selection in both domesticated and wild species, allowing selection to be detected more easily and powerfully than previously possible.
Purification of Recombinant Adeno-Associated Viruses (rAAVs) by Cesium Chloride Gradient Sedimentation
Authors: Su Qin , Sena-Esteves Miguel , Gao Guangping
Published: August 2020

Centrifugation to equilibrium in cesium chloride gradients has been used for more than 40 yr to purify viruses. The application of high G-forces for a long period of time to a solution of CsCl generates a density gradient that allows separation of empty, partially packaged, and fully packaged viral particles from cellular debris, proteins, and nucleic acids in the crude viral lysate on the basis of their buoyant densities. This protocol describes the use of CsCl gradients to purify AAV vectors from crude viral lysates.
Binding Antibodies to Attached Cells or Tissues in Preparation for Staining
Authors: Rodig Scott J.
Published: August 2020

Cells for staining are usually prepared from one of three sources: adherent cells, suspension cells, or whole tissues. Antibodies generally are applied directly to the area of the cells or tissues that is being studied. The antibodies can be labeled directly or they can be detected by using a labeled secondary reagent that will bind specifically to the primary antibody. Detection reagents for cell staining can be labeled with fluorochromes, enzymes, gold, or iodine.
Separating and integrating non-financial and financial measures: a case study of a sporting organization playing the value-in-kind (VIK) game
Authors: Burfitt Brian Anthony , Baxter Jane , Mouritsen Jan
Published: August 2020

Purpose

The purpose of this study is to characterise types of practices – or “routings” as they are denoted in this paper – that have been developed to incorporate non-financial inscriptions, representing value-in-kind (VIK) sponsorship resources, into accounting systems.

Design/methodology/approach

This study adopts field-based research, utilising Latour's (1999) concept of “circulating reference”, to illustrate how VIK (non-cash) resources were managed in an Australian sporting organization.

Findings

This paper contributes to our understanding of: first, how accounting infrastructure is constituted and stabilised by a network of multiple and overlapping accounting practices; second, how VIK resources are allocated and managed via local practices; and third, the importance of “budget relief” as a method of valuation in accounting practice.

Research limitations/implications

Our paper has implications for understanding how financial and non-financial accounting inscriptions are related in practice, requiring both integration and separation within networks of multiple and overlapping routings of accounting practices.

Originality/value

Our work highlights previously unexplored accounting practices, which assist in the process of utilizing VIK resources in the context of a sporting organization.
The inverted U-shaped relationship between crowdfunding success and reward options and the moderating effect of price differentiation
Authors: Cai Zhigang , Zhang Pengzhu , Han Xiao
Published: August 2020

Purpose

The paper is to explore crowdfunding success determinants from the reward menu design aspect, distinguishing from extant studies focusing on characteristics of project creators or crowdfunding projects and funding dynamics. Both the number of reward options and price differentiation of rewards are considered.

Design/methodology/approach

The authors use the quadratic model to identify a curvilinear relationship between the number of reward options and crowdfunding success, by running regressions on data collected from one of the most influential reward-based crowdfunding platforms in China. In addition, they explore the moderating effect of price differentiation on the curvilinear relationship.

Findings

The authors find an inverted U-shape relationship between the number of reward options and the optimal number of options is around 10. In addition, they find that the curvilinear relationship is moderated by reward price differentiation.

Practical implications

This paper has managerial implications for crowdfunding project creators and platform managers. To achieve better crowdfunding outcomes, a proper number of reward options with diversified reward prices should be provided.

Originality/value

The paper contributes to the literatures in antecedents of crowdfunding success from reward menu design aspect based on theories in investment and purchasing decision making. It is different from existing studies focusing on the characteristics of project creators and crowdfunding projects or funding dynamics. It also parallels retirement contribution plan design studies by exploring the reward menu design in the crowdfunding context.
Involys: a Moroccan SME playing with African giants
Authors: Minialai Caroline , El Mabrouki Mohamed Nabil , Chamchati Oumaima
Published: August 2020

Supplementary materials

Teaching notes are available for educators only.

Learning outcomes

Objective 1 analyse the internationalization process of Involys and compare it with the traditional theoretical analyses; Objective 2 analyse and learn from past successes and failures in Africa, building up a meaningful strategic analysis with a specific focus on: understanding the advantages and disadvantages of size (small and medium-sized enterprise (SME) suppliers/State Institutions customers); understanding the importance of institutional barriers and opportunities in this specific context; understanding and measuring the distances issues and the way they affect the company’s development Objective 3 learn to be creative and concrete in proposing feasible solutions to the Board of Involys.

Case overview/synopsis

Involys is a medium-sized Moroccan company designing and implementing enterprise resource planning (ERP) systems. It was co-founded in the 1980s by its present chief executive officer (CEO), quite a charismatic individual. As its listing on the Casablanca Stock Exchange, the company has set its main goal to develop its business on the African markets. This is a significant shift in commercial strategy for a company who has built its past success on working with Northern countries. Involys tries with its ERP system to accompany state-level reforms. The case study takes place in 2017, Involys has just lost a significant project in Cameroun, despite significant pre-sale investments, and is trying to build on its success in Gabon to accelerate and improve its competitive position in Africa. The case focusses on the internationalization process of a firm involved in long terms contracts and dealing mainly with institutions such as states or state departments. The issues of sizes, institutional barriers and distance should be specifically addressed in a south-south context.

Complexity academic level

Master’s degree executive training programs.

Subject code

CSS 5: International business.
Do schools and alcohol mix? Australian parents' perspectives
Authors: Gilligan Conor , Shaw Therese , Beatty Shelley , Thomas Laura , Lombardi Karen Louise , Johnston Robyn Susanne
Published: August 2020

Purpose

Alcohol use by adults at school events and alcohol promotion through school fundraising activities is common, but little is known about secondary school parents' attitudes towards these practices. Parental attitudes may influence principals' decision-making on this topic, particularly in jurisdictions where education department guidance is limited. This study explored parents' attitudes towards the consumption or promotion of alcohol in schools or at school events.

Design/methodology/approach

Parents (n = 298) from five non-government secondary schools in Western Australia completed an online survey and provided responses relating to the promotion and availability of alcohol through their child's school.

Findings

This sample of parents were evenly divided in support of alcohol consumption or support of schools as alcohol-free zones. Parents reporting higher alcohol consumption were more supportive of alcohol promotion and use through schools, and those with higher education supported use of alcohol for school fundraising. Almost 20% of parents were neutral on several measures indicating they could be swayed by social pressure. Engaging parents is an ongoing challenge for school principals and alcohol may play a part in engagement activities. The results from this small, exploratory study suggest even engaged parents may have very differing views on alcohol use in schools.

Practical implications

Education departments are encouraged to explore these issues carefully and introduce changes incrementally to assist decision-making and minimise potential parent disengagement.

Originality/value

This paper addresses a knowledge gap about parents' attitudes towards alcohol in secondary schools. These findings can support those involved in the development of school alcohol policies.
Vehicle aerodynamic simulation analysis and research on bumpy road
Authors: Xin Zheng , Su Donghai
Published: August 2020

Purpose

In order to certify the testing of vehicle Cd on the real road can be replaced by the much simplified steady-state simulation process inside wind tunnel.

Design/methodology/approach

The paper opted innovative methods to verify the feasibility of using aerodynamic wind tunnel test for vehicle development purpose, including establishing the typical sinusoidal mapping function for road shapes during vehicle driving process to simplify the complexity of the road and choosing three different kinds of road spectrum amplitudes to establish the vehicle motion model, which can accurately predict the vehicle motion characteristics in the road driving process. The new approach simulates the vehicle aerodynamics on the road by taking into account the pitch angle changes during vehicle motion.

Findings

By comparing the transient drag coefficient on road with the steady-state simulated value in the conventional aerodynamic wind tunnel. This paper provides empirical insights about the flow field analysis around the vehicle on road that can verify the feasibility of using aerodynamic wind tunnel test for vehicle development purpose.

Research limitations/implications

Because of establishing the typical sinusoidal mapping function for road shapes, the study results may lack generalizability. Therefore, researchers are encouraged to test the proposed propositions further.

Practical implications

This paper includes implications for the flow field analysis around the vehicle on road that can verify the feasibility of using aerodynamic wind tunnel test for vehicle development purpose.

Originality/value

This paper fulfills an identified need to use aerodynamic wind tunnel test for vehicle development purpose.
Optimum reliability acceptance sampling plan using Type-I generalized hybrid censoring scheme for products under warranty
Authors: Chakrabarty Jimut Bahan , Chowdhury Shovan , Roy Soumya
Published: August 2020

Purpose

The purpose of this paper is to design an optimal reliability acceptance sampling plan (RASP) using the Type-I generalized hybrid censoring scheme (GHCS) for non-repairable products sold under the general rebate warranty. A cost function approach is proposed for products having Weibull distributed lifetimes incorporating relevant costs.

Design/methodology/approach

For Weibull distributed product lifetimes, acceptance criterion introduced by Lieberman and Resnikoff (1955) is derived for Type-I GHCS. A cost function is formulated using expected warranty cost and other relevant cost components incorporating the acceptance criterion. The cost function is optimized following a constrained optimization approach to arrive at the optimum RASP. The constraint ensures that the producer's and the consumer's risks are maintained at agreed-upon levels.

Findings

Optimal solution using the above approach is obtained for Type-I GHCS. As a special case of Type-I GHCS, the proposed approach is also used to arrive at the optimal design for Type-I hybrid censoring scheme as shown in Chakrabarty et al. (2019). Observations regarding the change in optimal design and computational times between the two censoring schemes are noted. An extensive simulation study is performed to validate the model for finite sample sizes and the results obtained are found to be in strong agreement. In order to analyze the sensitivity of the optimal solution due to misspecification of parameter values and cost components, a well-designed sensitivity analysis is carried out using a real-life failure data set from Lawless (2003). Interesting observations are made regarding the change in optimal cost due to change in parameter values, the impact of warranty cost in optimal design and change in optimal design due to change in lot sizes.

Originality/value

The research presents an approach for designing optimal RASPs using Type-I generalized hybrid censoring. The study formulates optimum life test sampling plans by minimizing the average aggregate costs involved, which makes it valuable in dealing with real-life problems pertaining to product quality management.
Obstacles and opportunities for networked practice: a social network analysis of an inter-organizational STEM ecosystem
Authors: Liou Yi-Hwa , Daly Alan J.
Published: August 2020

Purpose

This study responds to major administrative and policy priorities to support science, technology, engineering and mathematics (STEM) education by investigating a multi-sector ecosystem of regional organizations that support a STEM pipeline for education and careers.

Design/methodology/approach

We use social network analysis to investigate an entire region within a geographic region of California which included 316 organizations that represent different stakeholder groups, including educational institutions (school districts, schools and higher education), government, private companies, museums, libraries and multiple community-based organizations. This STEM ecosystem reflects a systems-level analysis of a region from a unique social network perspective.

Findings

Results indicate that organizations have a surface-level access to STEM-related information, but the deeper and more intense relationship which involves strategic collaboration is limited. Further, interactions around information and collaboration between organizations were purportedly in part to be about education, rarely included PK-12 schools and district as central actors in the ecosystem. In addition, while institutions of higher education occupy a central position in connecting and bridging organizations within the ecosystem, higher education's connectivity to the PK-12 education sector is relatively limited in terms of building research and practice partnerships.

Originality/value

This research has implications for how regional-level complex systems are analyzed, led and catalyzed and further reflects the need to intentionally attend to the growth of STEM networks.
Validity and reliability: the Iranian version of Lawton IADL in elderly community dwellers
Authors: Mirzadeh Fatemeh Sadat , Alizadeh-Khoei Mahtab , Sharifi Farshad , Aminaloroaya Reyhaneh , Hormozi Sakar , Fakhrzadeh Hossein
Published: August 2020

Purpose

Normal aging changes, acute and chronic illness, and the long stay in the hospital made the decline in elderly physical and mental abilities in non-instrumental and Instrumental Activities Daily Livings (IADL). This paper aims to determine the validity and reliability of Lawton IADL in the Iranian elderly community relevancy to physical, mental and cognitive measurements.

Design/methodology/approach

A cross-sectional study with 422 participants, age 60 years old and over selected by face-to-face interviewing from the geriatric clinic, Tehran medical university from January to June 2019.

Findings

Of 422 participants referring to outpatient clinics the majority were male (62.8%); with an average of 66.9 ± 5.95 years old. Reliability was significantly high (Cronbach’s alpha = 0.96, p < 0.001). There was a significant relationship between IADL with Short-Form Health Survey36-Mental Component Score (SF36-MCS), with p < 0.01. Reliability was significantly high (Cronbach’s alpha = 0.96, p < 0.001). In the factor analysis with eigenvalues more than one, two components were found; that the first factor named as observational daily activities, whereas the second factor named “advanced daily activities”.

Research limitations/implications

The limitation of this study was the low number of similar studies to compare the results and the stronger discussion.

Originality/value

Determining IADL's dependency in the community elderly is important to maintain their self-care manages. More studies are needed to manifest the relationship between mental health and IADL's independence. Therefore, validation in different settings is important in planning for the geriatrics team.
Alcohol and public mental health for older people: 20 years of UK policy change
Authors: Rao Rahul Tony
Published: August 2020

Purpose

The purpose of this paper is to detail developments in UK alcohol policy for older people over the past 20 years, based on evidence for a growing public health problem with alcohol misuse in older people.

Design/methodology/approach

A literature search was carried out using health and social care databases, including grey literature.

Findings

There has been considerable progress in areas such as screening and brief intervention, low-risk drinking and service provision for integrated care in older people with dual diagnosis.

Research limitations/implications

There remains a dearth of research and policy for older people with alcohol misuse and dual diagnosis prior to 2011. Although there remains limited empirical evidence for public health interventions to improve health outcomes from alcohol-related harm, improvements in population health from implementation of recent policy changes and intervention programmes remains to be seen.

Practical implications

This review has implications for best practice in the provision of integrated care to reduce harm and improve health and social outcomes in older people with alcohol misuse and dual diagnosis.

Originality/value

This review draws together a large area of research and policy on alcohol misuse in older people that has the potential to improve public mental health for older people who are at risk of alcohol-related harm.