MEMS 411: Mini Test Frame

A lightweight, cheap, and portable compression test frame designed for testing students\u27 structural designs for the Machine Elements class. Measures load and displacement applied on the specimen to determine the specimen with the highest strength

Real-space imaging of several molecular layers of C60_{60} in the rotational glass phase

C$_{60}$ is a model system to study molecule–surface interactions and phase transitions due to its high symmetry and strong covalent π bonding within the molecule versus weak van-der-Waals coupling between neighboring molecules. In the solid, at room temperature, the molecule rotates and behaves as a sphere. However, the pentagonal and hexagonal atomic arrangement imposes deviations from the spherical symmetry that become important at low temperatures. The orientation of the C$_{60}$ can be viewed to represent classic spins. For geometrical reasons the preferred orientation of neighboring C$_{60}$ cannot be satisfied for all of the neighboring molecules, making C$_{60}$ a model for disordered spin systems with frustration. We study several molecular layers of C$_{60}$ islands on highly oriented pyrolytic graphite using scanning tunneling microscopy at liquid nitrogen temperatures. By imaging several layers we obtain a limited access to the three-dimensional rotational structure of the molecules in an island. We find one rotationally disordered layer between two partially rotationally ordered layers with hexagonal patterns. This exotic pattern shows an example of the local distribution of order and disorder in geometrically frustrated systems. Scanning tunneling spectroscopy data confirms the weak interactions of neighboring molecules

Real-space imaging of several molecular layers of C60 in the rotational glass phase

C60 is a model system to study molecule–surface interactions and phase transitions due to its high symmetry and strong covalent π bonding within the molecule versus weak van-der-Waals coupling between neighboring molecules. In the solid, at room temperature, the molecule rotates and behaves as a sphere. However, the pentagonal and hexagonal atomic arrangement imposes deviations from the spherical symmetry that become important at low temperatures. The orientation of the C60 can be viewed to represent classic spins. For geometrical reasons the preferred orientation of neighboring C60 cannot be satisfied for all of the neighboring molecules, making C60 a model for disordered spin systems with frustration. We study several molecular layers of C60 islands on highly oriented pyrolytic graphite using scanning tunneling microscopy at liquid nitrogen temperatures. By imaging several layers we obtain a limited access to the three-dimensional rotational structure of the molecules in an island. We find one rotationally disordered layer between two partially rotationally ordered layers with hexagonal patterns. This exotic pattern shows an example of the local distribution of order and disorder in geometrically frustrated systems. Scanning tunneling spectroscopy data confirms the weak interactions of neighboring molecules

A cell atlas of human thymic development defines T cell repertoire formation.

The thymus provides a nurturing environment for the differentiation and selection of T cells, a process orchestrated by their interaction with multiple thymic cell types. We used single-cell RNA sequencing to create a cell census of the human thymus across the life span and to reconstruct T cell differentiation trajectories and T cell receptor (TCR) recombination kinetics. Using this approach, we identified and located in situ CD8αα+ T cell populations, thymic fibroblast subtypes, and activated dendritic cell states. In addition, we reveal a bias in TCR recombination and selection, which is attributed to genomic position and the kinetics of lineage commitment. Taken together, our data provide a comprehensive atlas of the human thymus across the life span with new insights into human T cell development

The effect on HIV transmission and cost-effectiveness of programmes for female sex workers in East, Central, and Southern Africa:a modelling study

BACKGROUND: HIV prevalence and incidence has declined in East, Central, and Southern Africa (ECSA), but remains high among female sex workers (FSWs). Sex worker programmes have the potential to considerably increase access to HIV testing, prevention, and treatment. We aimed to quantify these improvements by modelling the potential effect of sex worker programmes at two different intensities on HIV incidence and key health outcomes, and assessed the programmes' potential cost-effectiveness in order to help inform HIV policy decisions. METHODS: Using a model previously used to review policy decisions in ECSA, we assumed a low-intensity sex worker programme had run from 2010 until 2023; this resulted in care disadvantages among FSWs being reduced, and also increased testing, condom use, and willingness to take pre-exposure prophylaxis (PrEP). After 2023, three policy options were considered: discontinuation, continuation, and a scale-up of the programme to high-intensity, which would have a broader reach, and higher influences on condom use, antiretroviral therapy (ART) adherence, testing, and PrEP use. Outputs of the key outcomes (the percentage of FSWs who were diagnosed with HIV, on ART, and virally suppressed; the percentage of FSWs with zero condomless partners, and HIV incidence) were compared in 2030. The maximum cost for a sex worker programme to be cost-effective was calculated over a 50-year time period and in the context of 10 million adults. The cost-effectiveness analysis was conducted from a health-care perspective; costs and disability-adjusted life-years were both discounted to present US$values at 3$500 per disability-adjusted life-year averted, $34 million per year can be spent for a high-intensity programme to be cost-effective. INTERPRETATION: A sex worker programme, even with low-level interventions, has a positive effect on key outputs for FSWs. A high-intensity programme has a considerably higher effect; HIV incidence among FSW and in the general population can be substantially reduced, and should be considered for implementation by policy makers. FUNDING: Wellcome Trust

Decoding human fetal liver haematopoiesis.

Definitive haematopoiesis in the fetal liver supports self-renewal and differentiation of haematopoietic stem cells and multipotent progenitors (HSC/MPPs) but remains poorly defined in humans. Here, using single-cell transcriptome profiling of approximately 140,000 liver and 74,000 skin, kidney and yolk sac cells, we identify the repertoire of human blood and immune cells during development. We infer differentiation trajectories from HSC/MPPs and evaluate the influence of the tissue microenvironment on blood and immune cell development. We reveal physiological erythropoiesis in fetal skin and the presence of mast cells, natural killer and innate lymphoid cell precursors in the yolk sac. We demonstrate a shift in the haemopoietic composition of fetal liver during gestation away from being predominantly erythroid, accompanied by a parallel change in differentiation potential of HSC/MPPs, which we functionally validate. Our integrated map of fetal liver haematopoiesis provides a blueprint for the study of paediatric blood and immune disorders, and a reference for harnessing the therapeutic potential of HSC/MPPs.We acknowledge funding from the Wellcome Human Cell Atlas Strategic Science Support (WT211276/Z/18/Z); M.H. is funded by Wellcome (WT107931/Z/15/Z), The Lister Institute for Preventive Medicine and NIHR and Newcastle-Biomedical Research Centre; S.A.T. is funded by Wellcome (WT206194), ERC Consolidator and EU MRG-Grammar awards and; S.B. is funded by Wellcome (WT110104/Z/15/Z) and St. Baldrick’s Foundation; E.L. is funded by a Wellcome Sir Henry Dale and Royal Society Fellowships, European Haematology Association, Wellcome and MRC to the Wellcome-MRC Cambridge Stem Cell Institute and BBSRC

GC-Rich Sequence Elements Recruit PRC2 in Mammalian ES Cells

Polycomb proteins are epigenetic regulators that localize to developmental loci in the early embryo where they mediate lineage-specific gene repression. In Drosophila, these repressors are recruited to sequence elements by DNA binding proteins associated with Polycomb repressive complex 2 (PRC2). However, the sequences that recruit PRC2 in mammalian cells have remained obscure. To address this, we integrated a series of engineered bacterial artificial chromosomes into embryonic stem (ES) cells and examined their chromatin. We found that a 44 kb region corresponding to the Zfpm2 locus initiates de novo recruitment of PRC2. We then pinpointed a CpG island within this locus as both necessary and sufficient for PRC2 recruitment. Based on this causal demonstration and prior genomic analyses, we hypothesized that large GC-rich elements depleted of activating transcription factor motifs mediate PRC2 recruitment in mammals. We validated this model in two ways. First, we showed that a constitutively active CpG island is able to recruit PRC2 after excision of a cluster of activating motifs. Second, we showed that two 1 kb sequence intervals from the Escherichia coli genome with GC-contents comparable to a mammalian CpG island are both capable of recruiting PRC2 when integrated into the ES cell genome. Our findings demonstrate a causal role for GC-rich sequences in PRC2 recruitment and implicate a specific subset of CpG islands depleted of activating motifs as instrumental for the initial localization of this key regulator in mammalian genomes.Burroughs Wellcome FundCharles E. Culpeper FoundationMassachusetts General HospitalBroad Institute of MIT and Harvar

Tracking the international spread of SARS-CoV-2 lineages B.1.1.7 and B.1.351/501Y-V2

Publisher Copyright: © 2021 O'Toole Á et al.Late in 2020, two genetically-distinct clusters of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with mutations of biological concern were reported, one in the United Kingdom and one in South Africa. Using a combination of data from routine surveillance, genomic sequencing and international travel we track the international dispersal of lineages B.1.1.7 and B.1.351 (variant 501Y-V2). We account for potential biases in genomic surveillance efforts by including passenger volumes from location of where the lineage was first reported, London and South Africa respectively. Using the software tool grinch (global report investigating novel coronavirus haplotypes), we track the international spread of lineages of concern with automated daily reports, Further, we have built a custom tracking website (cov-lineages.org/global_report.html) which hosts this daily report and will continue to include novel SARS-CoV-2 lineages of concern as they are detected.Peer reviewe