Choice or Mimetism in the Decision to Migrate? A European Illustration

This paper examines the role of herd behavior (mimetism) and network effects as determinants of bilateral migration flows to thirteen of the EU-15 countries. Using an adapted gravity model controlling for economic activity, welfare progressivity, geospatial, and historic relationships, the results force us to question the ways in which we explain migration flows. Herd behavior influences positively the flows of migrants to Europe, whereas the existence of network complementarities in the receiving country does not consistently predict and may in some cases reduce the likelihood of immigrant inflows. Moreover, economic activity and particularly labor market conditions play a lesser role in migrants’ choice of location than was previously thought. The introduction of herd behavior as a determinant of European Migration in our empirical analysis changes the paradigm for understanding migration and suggests that prior definitions of social perceptions are inadequate. Cet article étudie le rôle des comportements mimétiques et des effets de réseaux dans les décisions de migration vers treize pays de l’Union européenne. En utilisant un modèle de gravité adapté à cette question et incluant des indicateurs mesurant l’activité économique, le progrès social, et les relations historiques, les résultats de cette étude précisent les méthodes traditionnelles d’évaluation des flux migratoires. Les comportements mimétiques influencent positivement les flux migratoires vers l’Europe, alors que les effets de réseaux dans le pays hôte ne prédisent pas de façon toujours satisfaisante les flux d’immigration. De plus, l’activité économique, et en particulier les conditions du marché du travail, jouent un rôle moindre que ceux mis en évidence dans des études précédentes. La prise en compte des comportements mimétiques en tant que déterminant des flux migratoires en Europe vient donc changer le paradigme pour l’étude des flux migratoires.migration, herd behavior, network effects, flux migratoires, comportements mimétiques, effets de réseaux

Toxicity and Cultural Entrenchment in Peer-Production Communities: Toward a Handbook on Intelligent System Design

Toxicity and abuse are common in online peer-production communities. The social structure of peer-production communities that aim to produce accurate and trustworthy information require some conflict and gate-keeping to spur content production and curation. However, conflict and gate-keeping often devolve into hierarchical power structures which punish newcomers and lock out marginalized groups through entrenched cultural norms. Community administrators often focus on content quality, rather than consideration for all user safety, to promote community growth and survival. Once toxic cultural norms dominate a peer-production community, it is very difficult for community administrators to stop these behaviors from undermining inclusive peer-production. We propose developing a "handbook of intelligent system design" that attempts to frame design protocols to better read user-community culture and accurately distinguish toxic negative interactions from beneficial conflict.Comment: 3 pages, 1 figure, The CHI 23 Workshop on Combating Toxicity, Harassment, and Abuse in Online Social Spaces, April 23--28, 2023, Hamburg, German

2021 Western Australian Crop Sowing Guide

This edition of the 2021 Crop Sowing Guide includes the major crops grown in WA - wheat, barley, canola, oat, lupins and pulses. The publication aims to provide information to support growers with decisions on the best choice of variety for each of the major crops for the upcoming season. The lupin and pulse sections also include an agronomy guide summary to support management decisions required for these high-valued crops. Market feedback for barley has been provided by GIWA to help with the decision on what to grow.https://researchlibrary.agric.wa.gov.au/bulletins/1275/thumbnail.jp

Cascadia Subduction Tremor muted by crustal faults

Deep, episodic slow slip on the Cascadia subduction megathrust of western North America is accompanied by low-frequency tremor in a zone of high fluid pressure between 30 and 40 km depth. Tremor density (tremor epicenters per square kilometer) varies along strike, and lower tremor density statistically correlates with upper plate faults that accommodate northward motion and rotation of forearc blocks. Upper plate earthquakes occur to 35 km depth beneath the faults. We suggest that the faults extend to the overpressured megathrust, where they provide fracture pathways for fluid escape into the upper plate. This locally reduces megathrust fluid pressure and tremor occurrence beneath the faults. Damping of tremor and related slow slip caused by fluid escape could affect fault properties of the megathrust, possibly influencing the behavior of great earthquakes

Aurora kinase A drives the evolution of resistance to third-generation EGFR inhibitors in lung cancer.

Although targeted therapies often elicit profound initial patient responses, these effects are transient due to residual disease leading to acquired resistance. How tumors transition between drug responsiveness, tolerance and resistance, especially in the absence of preexisting subclones, remains unclear. In epidermal growth factor receptor (EGFR)-mutant lung adenocarcinoma cells, we demonstrate that residual disease and acquired resistance in response to EGFR inhibitors requires Aurora kinase A (AURKA) activity. Nongenetic resistance through the activation of AURKA by its coactivator TPX2 emerges in response to chronic EGFR inhibition where it mitigates drug-induced apoptosis. Aurora kinase inhibitors suppress this adaptive survival program, increasing the magnitude and duration of EGFR inhibitor response in preclinical models. Treatment-induced activation of AURKA is associated with resistance to EGFR inhibitors in vitro, in vivo and in most individuals with EGFR-mutant lung adenocarcinoma. These findings delineate a molecular path whereby drug resistance emerges from drug-tolerant cells and unveils a synthetic lethal strategy for enhancing responses to EGFR inhibitors by suppressing AURKA-driven residual disease and acquired resistance

Prevalence of nuclear and mitochondrial DNA mutations related to adult mitochondrial disease.

OBJECTIVE: The prevalence of mitochondrial disease has proven difficult to establish, predominantly as a result of clinical and genetic heterogeneity. The phenotypic spectrum of mitochondrial disease has expanded significantly since the original reports that associated classic clinical syndromes with mitochondrial DNA (mtDNA) rearrangements and point mutations. The revolution in genetic technologies has allowed interrogation of the nuclear genome in a manner that has dramatically improved the diagnosis of mitochondrial disorders. We comprehensively assessed the prevalence of all forms of adult mitochondrial disease to include pathogenic mutations in both nuclear and mtDNA. METHODS: Adults with suspected mitochondrial disease in the North East of England were referred to a single neurology center from 1990 to 2014. For the midyear period of 2011, we evaluated the minimum prevalence of symptomatic nuclear DNA mutations and symptomatic and asymptomatic mtDNA mutations causing mitochondrial diseases. RESULTS: The minimum prevalence rate for mtDNA mutations was 1 in 5,000 (20 per 100,000), comparable with our previously published prevalence rates. In this population, nuclear mutations were responsible for clinically overt adult mitochondrial disease in 2.9 per 100,000 adults. INTERPRETATION: Combined, our data confirm that the total prevalence of adult mitochondrial disease, including pathogenic mutations of both the mitochondrial and nuclear genomes (≈1 in 4,300), is among the commonest adult forms of inherited neurological disorders. These figures hold important implications for the evaluation of interventions, provision of evidence-based health policies, and planning of future services

Twenty-eight divergent polysaccharide loci specifying within- and amongst-strain capsule diversity in three strains of Bacteroides fragilis

Comparison of the complete genome sequence of Bacteroides fragilis 638R, originally isolated in the USA, was made with two previously sequenced strains isolated in the UK (NCTC 9343) and Japan (YCH46). The presence of 10 loci containing genes associated with polysaccharide (PS) biosynthesis, each including a putative Wzx flippase and Wzy polymerase, was confirmed in all three strains, despite a lack of cross-reactivity between NCTC 9343 and 638R surface PS-specific antibodies by immunolabelling and microscopy. Genomic comparisons revealed an exceptional level of PS biosynthesis locus diversity. Of the 10 divergent PS-associated loci apparent in each strain, none is similar between NCTC 9343 and 638R. YCH46 shares one locus with NCTC 9343, confirmed by mAb labelling, and a second different locus with 638R, making a total of 28 divergent PS biosynthesis loci amongst the three strains. The lack of expression of the phase-variable large capsule (LC) in strain 638R, observed in NCTC 9343, is likely to be due to a point mutation that generates a stop codon within a putative initiating glycosyltransferase, necessary for the expression of the LC in NCTC 9343. Other major sequence differences were observed to arise from different numbers and variety of inserted extra-chromosomal elements, in particular prophages. Extensive horizontal gene transfer has occurred within these strains, despite the presence of a significant number of divergent DNA restriction and modification systems that act to prevent acquisition of foreign DNA. The level of amongst-strain diversity in PS biosynthesis loci is unprecedented

A comprehensive platform for highly multiplexed mammalian functional genetic screens

<p>Abstract</p> <p>Background</p> <p>Genome-wide screening in human and mouse cells using RNA interference and open reading frame over-expression libraries is rapidly becoming a viable experimental approach for many research labs. There are a variety of gene expression modulation libraries commercially available, however, detailed and validated protocols as well as the reagents necessary for deconvolving genome-scale gene screens using these libraries are lacking. As a solution, we designed a comprehensive platform for highly multiplexed functional genetic screens in human, mouse and yeast cells using popular, commercially available gene modulation libraries. The Gene Modulation Array Platform (GMAP) is a single microarray-based detection solution for deconvolution of loss and gain-of-function pooled screens.</p> <p>Results</p> <p>Experiments with specially constructed lentiviral-based plasmid pools containing ~78,000 shRNAs demonstrated that the GMAP is capable of deconvolving genome-wide shRNA "dropout" screens. Further experiments with a larger, ~90,000 shRNA pool demonstrate that equivalent results are obtained from plasmid pools and from genomic DNA derived from lentivirus infected cells. Parallel testing of large shRNA pools using GMAP and next-generation sequencing methods revealed that the two methods provide valid and complementary approaches to deconvolution of genome-wide shRNA screens. Additional experiments demonstrated that GMAP is equivalent to similar microarray-based products when used for deconvolution of open reading frame over-expression screens.</p> <p>Conclusion</p> <p>Herein, we demonstrate four major applications for the GMAP resource, including deconvolution of pooled RNAi screens in cells with at least 90,000 distinct shRNAs. We also provide detailed methodologies for pooled shRNA screen readout using GMAP and compare next-generation sequencing to GMAP (i.e. microarray) based deconvolution methods.</p

Defective Presynaptic Choline Transport Underlies Hereditary Motor Neuropathy

The neuromuscular junction (NMJ) is a specialized synapse with a complex molecular architecture that provides for reliable transmission between the nerve terminal and muscle fiber. Using linkage analysis and whole-exome sequencing of DNA samples from subjects with distal hereditary motor neuropathy type VII, we identified a mutation in SLC5A7, which encodes the presynaptic choline transporter (CHT), a critical determinant of synaptic acetylcholine synthesis and release at the NMJ. This dominantly segregating SLC5A7 mutation truncates the encoded product just beyond the final transmembrane domain, eliminating cytosolic-C-terminus sequences known to regulate surface transporter trafficking. Choline-transport assays in both transfected cells and monocytes from affected individuals revealed significant reductions in hemicholinium-3-sensitive choline uptake, a finding consistent with a dominant-negative mode of action. The discovery of CHT dysfunction underlying motor neuropathy identifies a biological basis for this group of conditions and widens the spectrum of disorders that derive from impaired NMJ transmission. Our findings compel consideration of mutations in SLC5A7 or its functional partners in relation to unexplained motor neuronopathies