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This paper presents the results to date of the RepRap project – an ongoing project that has made and distributed freely a replicating rapid prototyper. We give the background reasoning that led to the invention of the machine, the selection of the processes that we and others have used to implement it, the designs of key parts of the machine and how these have evolved from their initial concepts and experiments, and estimates of the machine's reproductive success out in the world up to the time of writing (about 4500 machines in two and a half years).

We advance a holographic construction for the entanglement negativity of bipartite mixed state configurations of two disjoint intervals in \\[(1+1)\\] dimensional conformal field theories (\\[CFT_{1+1}\\]) through the \\[AdS_3/CFT_2\\] correspondence. Our construction constitutes the large central charge analysis of the entanglement negativity for mixed states under consideration and involves a specific algebraic sum of bulk space like geodesics anchored on appropriate intervals in the dual \\[CFT_{1+1}\\]. The construction is utilized to compute the holographic entanglement negativity for such mixed states in \\[CFT_{1+1}\\]s dual to bulk pure \\[AdS_3\\] geometries and BTZ black holes respectively. Our analysis exactly reproduces the universal features of corresponding replica technique results in the large central charge limit which serves as a consistency check.

Background Alpha‐synuclein (α‐Syn) oligomers and fibrils have been shown to augment the aggregation of TAR DNA‐binding Protein 43 (TDP‐43) monomers in vitro, supporting the idea that TDP‐43 proteinopathies such as ALS may be modulated by the presence of toxic forms of α‐Syn. Recently, parkinsonian features were reported in a study of European patients and Lewy bodies have been demonstrated pathologically in a similar series of patients. Based on these and other considerations, we sought to determine whether seed‐competent α‐Syn can be identified in spinal fluid of patients with ALS including familial, sporadic, and Guamanian forms of the disease. Methods Based on the finding that α‐Syn has been found to be a prion‐like protein, we have utilized a validated α‐Synuclein seed amplification assay to determine if seed‐competent α‐Syn could be detected in the spinal fluid of patients with ALS. Results Toxic species of α‐Syn were detected in CSF in 18 of 127 ALS patients, 5 of whom were from Guam. Two out of twenty six samples from patients with C9orf72 variant ALS had positive seed‐amplification assays (SAAs). No positive tests were noted in superoxide dismutase type 1 ALS subjects (n = 14). The SAA was negative in 31 control subjects. Conclusions Our findings suggest that a sub‐group of ALS occurs in which self‐replicating α‐Syn is detectable and likely contributes to its pathogenesis. This finding may have implications for the diagnosis and treatment of this disorder.

Virtual Reality (VR) has been increasingly referred to as the \"ultimate empathy machine\" since it allows users to experience any situation from any point of view. However, empirical evidence supporting the claim that VR is a more effective method of eliciting empathy than traditional perspective-taking is limited. Two experiments were conducted in order to compare the short and long-term effects of a traditional perspective-taking task and a VR perspective-taking task (Study 1), and to explore the role of technological immersion when it comes to different types of mediated perspective-taking tasks (Study 2). Results of Study 1 show that over the course of eight weeks participants in both conditions reported feeling empathetic and connected to the homeless at similar rates, however, participants who became homeless in VR had more positive, longer-lasting attitudes toward the homeless and signed a petition supporting the homeless at a significantly higher rate than participants who performed a traditional perspective-taking task. Study 2 compared three different types of perspective-taking tasks with different levels of immersion (traditional vs. desktop computer vs. VR) and a control condition (where participants received fact-driven information about the homeless). Results show that participants who performed any type of perspective-taking task reported feeling more empathetic and connected to the homeless than the participants who only received information. Replicating the results from Study 1, there was no difference in self-report measures for any of the perspective-taking conditions, however, a significantly higher number of participants in the VR condition signed a petition supporting affordable housing for the homeless compared to the traditional and less immersive conditions. We discuss the theoretical and practical implications of these findings.

mRNA vaccines have tremendous potential to fight against cancer and viral diseases due to superiorities in safety, efficacy and industrial production. In recent decades, we have witnessed the development of different kinds of mRNAs by sequence optimization to overcome the disadvantage of excessive mRNA immunogenicity, instability and inefficiency. Based on the immunological study, mRNA vaccines are coupled with immunologic adjuvant and various delivery strategies. Except for sequence optimization, the assistance of mRNA-delivering strategies is another method to stabilize mRNAs and improve their efficacy. The understanding of increasing the antigen reactiveness gains insight into mRNA-induced innate immunity and adaptive immunity without antibody-dependent enhancement activity. Therefore, to address the problem, scientists further exploited carrier-based mRNA vaccines (lipid-based delivery, polymer-based delivery, peptide-based delivery, virus-like replicon particle and cationic nanoemulsion), naked mRNA vaccines and dendritic cells-based mRNA vaccines. The article will discuss the molecular biology of mRNA vaccines and underlying anti-virus and anti-tumor mechanisms, with an introduction of their immunological phenomena, delivery strategies, their importance on Corona Virus Disease 2019 (COVID-19) and related clinical trials against cancer and viral diseases. Finally, we will discuss the challenge of mRNA vaccines against bacterial and parasitic diseases.

Many multicellular systems problems can only be understood by studying how cells move, grow, divide, interact, and die. Tissue-scale dynamics emerge from systems of many interacting cells as they respond to and influence their microenvironment. The ideal \"virtual laboratory\" for such multicellular systems simulates both the biochemical microenvironment (the \"stage\") and many mechanically and biochemically interacting cells (the \"players\" upon the stage). PhysiCell-physics-based multicellular simulator-is an open source agent-based simulator that provides both the stage and the players for studying many interacting cells in dynamic tissue microenvironments. It builds upon a multi-substrate biotransport solver to link cell phenotype to multiple diffusing substrates and signaling factors. It includes biologically-driven sub-models for cell cycling, apoptosis, necrosis, solid and fluid volume changes, mechanics, and motility \"out of the box.\" The C++ code has minimal dependencies, making it simple to maintain and deploy across platforms. PhysiCell has been parallelized with OpenMP, and its performance scales linearly with the number of cells. Simulations up to 105-106 cells are feasible on quad-core desktop workstations; larger simulations are attainable on single HPC compute nodes. We demonstrate PhysiCell by simulating the impact of necrotic core biomechanics, 3-D geometry, and stochasticity on the dynamics of hanging drop tumor spheroids and ductal carcinoma in situ (DCIS) of the breast. We demonstrate stochastic motility, chemical and contact-based interaction of multiple cell types, and the extensibility of PhysiCell with examples in synthetic multicellular systems (a \"cellular cargo delivery\" system, with application to anti-cancer treatments), cancer heterogeneity, and cancer immunology. PhysiCell is a powerful multicellular systems simulator that will be continually improved with new capabilities and performance improvements. It also represents a significant independent code base for replicating results from other simulation platforms. The PhysiCell source code, examples, documentation, and support are available under the BSD license at http://PhysiCell.MathCancer.org and http://PhysiCell.sf.net.

[Display omitted] Rotavirus disease is a leading global cause of mortality and morbidity in children under 5years of age. The effectiveness of the two globally used oral rotavirus vaccines quickly became apparent when introduced into both developed and developing countries, with significant reductions in rotavirus-associated mortality and hospitalizations. However, the effectiveness and impact of the vaccines is reduced in developing country settings, where the burden and mortality is highest. New rotavirus vaccines, including live oral rotavirus candidates and non-replicating approaches continue to be developed, with the major aim to improve the global supply of rotavirus vaccines and for local implementation, and to improve vaccine effectiveness in developing settings. This review provides an overview of the new rotavirus vaccines in development by developing country manufacturers and provides a rationale why newer candidates continue to be explored. It describes the new live oral rotavirus vaccine candidates as well as the non-replicating rotavirus vaccines that are furthest along in development.

Recent advances in molecular approaches and DNA sequencing have greatly progressed the field of ecology and allowed for the study of complex communities in unprecedented detail. Next generation sequencing (NGS) can reveal powerful insights into the diversity, composition, and dynamics of cryptic organisms, but results may be sensitive to a number of technical factors, including molecular practices used to generate amplicons, sequencing technology, and data processing. Despite the popularity of some techniques over others, explicit tests of the relative benefits they convey in molecular ecology studies remain scarce. Here we tested the effects of PCR replication, sequencing depth, and sequencing platform on ecological inference drawn from environmental samples of soil fungi. We sequenced replicates of three soil samples taken from pine biomes in North America represented by pools of either one, two, four, eight, or sixteen PCR replicates with both 454 pyrosequencing and Illumina MiSeq. Increasing the number of pooled PCR replicates had no detectable effect on measures of α- and β-diversity. Pseudo-β-diversity - which we define as dissimilarity between re-sequenced replicates of the same sample - decreased markedly with increasing sampling depth. The total richness recovered with Illumina was significantly higher than with 454, but measures of α- and β-diversity between a larger set of fungal samples sequenced on both platforms were highly correlated. Our results suggest that molecular ecology studies will benefit more from investing in robust sequencing technologies than from replicating PCRs. This study also demonstrates the potential for continuous integration of older datasets with newer technology.

In memory of Dr. Dennis John McFarland, who passed away recently, our objective is to continue his efforts to compare psychometric networks and latent variable models statistically. We do so by providing a commentary on his latest work, which he encouraged us to write, shortly before his death. We first discuss the statistical procedure McFarland used, which involved structural equation modeling (SEM) in standard SEM software. Next, we evaluate the penta-factor model of intelligence. We conclude that (1) standard SEM software is not suitable for the comparison of psychometric networks with latent variable models, and (2) the penta-factor model of intelligence is only of limited value, as it is nonidentified. We conclude with a reanalysis of the Wechlser Adult Intelligence Scale data McFarland discussed and illustrate how network and latent variable models can be compared using the recently developed R package Psychonetrics. Of substantive theoretical interest, the results support a network interpretation of general intelligence. A novel empirical finding is that networks of intelligence replicate over standardization samples.

[This corrects the article DOI: 10.1371/journal.pone.0166491.].