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    [Research Article] Self-assembly of genetically encoded DNA-protein hybrid nanoscale shapes - We describe an approach to bottom-up fabrication that allows integration of the functional diversity of proteins into designed three-dimensional structural frameworks. A set of custom staple proteins based on transcription activator?like effector proteins folds a double-stranded DNA template into a user-defined shape. Each staple protein is designed to recognize and closely link two distinct double-helical DNA sequences at separate positions on t...
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    [Review] Vertically extensive and unstable magmatic systems: A unified view of igneous processes - Volcanoes are an expression of their underlying magmatic systems. Over the past three decades, the classical focus on upper crustal magma chambers has expanded to consider magmatic processes throughout the crust. A transcrustal perspective must balance slow (plate tectonic) rates of melt generation and segregation in the lower crust with new evidence for rapid melt accumulation in the upper crust before many volcanic eruptions. Reconciling these ...
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    [Research Article] Dynamics of cortical dendritic membrane potential and spikes in freely behaving rats - Neural activity in vivo is primarily measured using extracellular somatic spikes, which provide limited information about neural computation. Hence, it is necessary to record from neuronal dendrites, which can generate dendritic action potentials (DAPs) in vitro, which can profoundly influence neural computation and plasticity. We measured neocortical sub- and suprathreshold dendritic membrane potential (DMP) from putative distal-most dendrites u...
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    [Research Article] Transition from turbulent to coherent flows in confined three-dimensional active fluids - Transport of fluid through a pipe is essential for the operation of macroscale machines and microfluidic devices. Conventional fluids only flow in response to external pressure. We demonstrate that an active isotropic fluid, composed of microtubules and molecular motors, autonomously flows through meter-long three-dimensional channels. We establish control over the magnitude, velocity profile, and direction of the self-organized flows and correla...
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    [Research Article] Cryo-EM structures of the triheteromeric NMDA receptor and its allosteric modulation - N-methyl-d-aspartate receptors (NMDARs) are heterotetrameric ion channels assembled as diheteromeric or triheteromeric complexes. Here, we report structures of the triheteromeric GluN1/GluN2A/GluN2B receptor in the absence or presence of the GluN2B-specific allosteric modulator Ro 25-6981 (Ro), determined by cryogenic electron microscopy (cryo-EM). In the absence of Ro, the GluN2A and GluN2B amino-terminal domains (ATDs) adopt ?closed? and ?open?...
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    [Editorial] UK science, post-Brexit - Nine months since the British vote to exit the European Union (?Brexit?), the UK science community's initial dismay has given way to hard-boiled determination to limit the damage it will do to universities and research. On 29 March, Prime Minister Theresa May is expected to give formal notification of the UK's intention to withdraw under Article 50 of the Lisbon Treaty, the constitutional basis of the EU. This will set in motion a 2-year period o...
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    [In Brief] News at a glance - In science news around the world, the San people of Southern Africa release a code of ethics to guide researchers wanting to study their culture or genes, a series of films documenting nuclear tests from the 1945 to 1962 is released on YouTube, U.K. regulators grant the first license for mitochondrial replacement therapy, a researcher is accused of putting his name to a paper partially ghost-written by employees at chemical giant Monsanto, and mo...
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    [In Depth] Trump's 2018 budget proposal ?devalues? science - The 2018 budget proposal that President Donald Trump unveiled last week confirms two things that U.S. scientists have long suspected: The new president is no fan of research, and his administration has no overarching strategy for funding science. Deep proposed cuts to research at several agencies offer evidence that Trump doesn't see science?of any kind?as a spending priority. And along with neglect there's indifference. There's no telling how th...
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    [In Depth] Can flu shots help women get pregnant? - Two new clinical trials are testing whether flu vaccines increase the effectiveness of in vitro fertilization (IVF). The studies draw on new discoveries about the immune system's role in reproduction. Doctors used to think that the immune system had to shut down during pregnancy so that it wouldn't destroy the embryo. Now, researchers realize that the immune system remains active but learns to accept the embryo, developing what's known as toleran...
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    [In Depth] Ma, where did they put T. rex? - A new study gives the long-standing dinosaur family tree an overhaul. Based on analyses of hundreds of traits gleaned from existing studies and fossils, the study strikes down a fundamental split of dinosaurs into "bird-hipped" and "reptile-hipped"; it also shifts the charismatic theropods?the group that includes Tyrannosaurus rex and eventually gave rise to birds?to a new spot on the tree, closer to the bird-hipped dinos. The reorganization of t...
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    [In Depth] New Zealand temblor points to threat of compound quakes - A reassuring rule of thumb about earthquakes is breaking down. For decades, seismologists had assumed that individual faults?as well as isolated segments of longer faults?rupture independently of one another. That limits the maximum size of the potential earthquake that a fault zone can generate. But the magnitude-7.8 earthquake that struck New Zealand just after midnight on 14 November 2016?among the largest in the islands' modern history?has re...
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    [In Depth] In search for unseen matter, physicists turn to dark sector - Scientists hunting unseen dark matter are looking deeper into the shadows. With searches for a favored dark matter candidate?weakly interacting massive particles (WIMPs)?coming up empty, physicists are now turning to the hypothetical "dark sector": an entire shadow realm of hidden particles. This week, physicists will meet at the University of Maryland in College Park for a workshop, sponsored by the U.S. Department of Energy (DOE), to mull ideas...
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    [In Depth] Tweak makes U.S. nukes more precise?and deadlier - A small fix made in the name of "stockpile stewardship" is turning U.S. submarine?launched missiles into more precise weapons. An improved mechanism installed in aging warhead now makes it possible to adjust the height at which they detonate, according to three experts writing in The Bulletin of the Atomic Scientists. This vastly increases the weapons' efficiency, the experts say, creating the impression that submarine-launched weapons could be u...
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    [Feature] Fishy business - Two Swedish fish researchers, with the aid of five colleagues elsewhere in the world, have alleged fraud in a study on the effects of microplastics on larval fish published in Science by two scientists at Uppsala University (UU) in June 2016. The study supposedly took place at the Ar Research Station in Gotland, but the whistleblowers say it never happened, based on eyewitness testimony and other evidence. A preliminary investigation by UU dismis...
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    [Perspective] Macrophage, a long-distance middleman - Macrophages were first identified in transparent starfish larvae (Astropecten pentacanthus) more than a century ago, so it is fitting that a new function for macrophages would again be discovered in transparent marine larvae, this time from zebra fish (Danio rerio). On page 1317 of this issue, Eom and Parichy (1) reveal a wholly unexpected tissue-specific function of macrophages?their cardinal role in long-distance communication between nonimmune...
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    [Perspective] Powering up perovskite photoresponse - The most notable scientific milestone in photovoltaics in the past several years is the emergence of solar cells based on hybrid organic-inorganic perovskite materials. While conventional silicon and thin-film solar cells have seen steady improvements in their power-conversion efficiencies (PCEs) spanning several decades, hybrid perovskite solar cells have already reached a certified 22.1% PCE (1), matching conventional solar cell technologies in...
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    [Perspective] Bringing proteins into the fold - Molecular engineers have become increasingly adept at repurposing life's building blocks to make custom self-assembled shapes. Because a single drop of solution contains billions of such shapes, DNA origami smiley faces (1), RNA stars (2), and designer protein polyhedra (3) may vastly outnumber most other human-made objects on Earth. These shapes lack immediate practical utility, but they transmit a powerful message: Researchers are beginning to ...
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    [Perspective] From chaos to order in active fluids - There are few sights more spectacular than the swarming of a school of fish or a flock of birds that suddenly gives way to a directional motion. Arguably, our admiration is rooted in the surprise that individual organisms, capable of self-propulsion on their own, organize to move en masse in a coherent fashion. Coherent motion is common in a large class of biological and synthetic materials that are often referred to as active matter. Such materi...
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    [Perspective] Using fire to promote biodiversity - Fire profoundly influences people, climate, and ecosystems (1). The impacts of this interaction are likely to grow, with climate models forecasting widespread increases in fire frequency and intensity because of rising global temperatures (2). However, the relationship between fire and biodiversity is complex (3, 4). Many plants and animals require fire for their survival, yet even in fire-prone ecosystems, some species and communities are highly...
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    [Perspective] Genes, environment, and ?bad luck? - It is a human trait to search for explanations for catastrophic events and rule out mere ?chance? or ?bad luck.? When it comes to human cancer, the issue of natural causes versus bad luck was raised by Tomasetti and Vogelstein about 2 years ago (1). Their study, which was widely misinterpreted as saying that most cancers are due neither to genetic inheritance nor environmental factors but simply bad luck, sparked controversy. To date, a few hundr...
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    [Retrospective] Hans Rosling (1948?2017) - Like a lot of Hans Rosling's admirers, we discovered his work via his famous 2006 TED talk, ?The Best Stats You've Ever Seen.? It was a mind-blowing speech (with more than 11 million views to date) with innovative graphics, good jokes, and a profound message: The world is getting better, and even some of the poorest countries are making progress. Hans was a showman, but he didn't sacrifice an ounce of complexity. He was?and this is a term of hono...
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    [Policy Forum] A roadmap for rapid decarbonization - Although the Paris Agreement's goals (1) are aligned with science (2) and can, in principle, be technically and economically achieved (3), alarming inconsistencies remain between science-based targets and national commitments. Despite progress during the 2016 Marrakech climate negotiations, long-term goals can be trumped by political short-termism. Following the Agreement, which became international law earlier than expected, several countries pu...
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    [Book Review] Rain check - Make It Rain, Kristine Harper's detailed history of weather control in the United States, includes colorful details of cloud-seeding experiments, but the book is not so much about attempts to control the weather as it is about the political battles waged over the harnessing of the atmosphere: the control of weather control itself. Rather than revealing a history of what we might today call evidence-led policy, the book is a rogue's gallery of pol...
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    [Letter] Patent pools for CRISPR technology - Author: Lawrence Horn...
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    [Letter] Patent pools for CRISPR technology?Response - Authors: Jorge L. Contreras, Jacob S. Sherkow...
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    [Letter] Specimen collection crucial to taxonomy - Authors: Eliécer E. Gutiérrez, Ronald H. Pine...
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    [This Week in Science] Identifying the hosts of quasar absorbers - Author: Keith T. Smith...
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    [This Week in Science] Cell projections set up pigment pattern - Author: Beverly A. Purnell...
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    [This Week in Science] Nanograined metals avoid going soft - Author: Brent Grocholski...
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    [This Week in Science] Metal-oxide synergy - Author: Phil Szuromi...
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    [This Week in Science] Using ?you? to generalize from me to others - Author: Gilbert Chin...
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    [This Week in Science] Estimating transmission chains for dengue - Author: Caroline Ash...
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    [This Week in Science] Helping T cells feel at home in the liver - Author: Angela Colmone...
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    [This Week in Science] Why pain and stress lead to depression - Author: Leslie K. Ferrarelli...
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    [This Week in Science] Cancer and the unavoidable R factor - Author: Paula A. Kiberstis...
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    [This Week in Science] Making magma chambers from mush - Author: Brent Grocholski...
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    [This Week in Science] Dendrites are more active than expected - Author: Peter Stern...
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    [This Week in Science] Added complexity in an asymmetric receptor - Author: Valda Vinson...
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    [This Week in Science] Protein-folded DNA nanostructures - Author: Phil Szuromi...
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    [This Week in Science] Go with the changing flow - Author: Marc S. Lavine...
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    [This Week in Science] How perovskites have the edge - Author: Phil Szuromi...
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    [This Week in Science] Chromatin state dictates drug response - Author: Paula A. Kiberstis...
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    [This Week in Science] Lysosomal cholesterol activates mTORC1 - Author: L. Bryan Ray...
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    [This Week in Science] NAD+ binding modulates protein interactions - Author: L. Bryan Ray...
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    [This Week in Science] Tugging on Notch receptor tunes signaling - Author: L. Bryan Ray...
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    [This Week in Science] Fire management, made to measure - Author: Julia Fahrenkamp-Uppenbrink...
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    [This Week in Science] Influenz-ing IFN responses in dendritic cells - Author: Lindsey Pujanandez...
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    [This Week in Science] It's easier to see green - Author: Shahid Naeem...
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    [Editors' Choice] A new angle on streams - Author: H. Jesse Smith...
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    [Editors' Choice] Turning toys into tools - Author: Megan Eldred...
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    [Editors' Choice] Stronger pancreas through starvation - Author: L. Bryan Ray...
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    [Editors' Choice] The evolution of edited RNA transcripts - Author: Laura M. Zahn...
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    [Editors' Choice] Recovering galaxy images from noisy data - Author: Keith T. Smith...
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    [Editors' Choice] Notch1 promotes cancer spread - Author: Priscilla N. Kelly...
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    [Editors' Choice] Dirac cones in a boron monolayer - Author: Jelena Stajic...
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    [Report] [C ii] 158-?m emission from the host galaxies of damped Lyman-alpha systems - Gas surrounding high-redshift galaxies has been studied through observations of absorption line systems toward background quasars for decades. However, it has proven difficult to identify and characterize the galaxies associated with these absorbers due to the intrinsic faintness of the galaxies compared with the quasars at optical wavelengths. Using the Atacama Large Millimeter/Submillimeter Array, we report on detections of [C ii] 158-?m line a...
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    [Report] Extremely efficient internal exciton dissociation through edge states in layered 2D perovskites - Understanding and controlling charge and energy flow in state-of-the-art semiconductor quantum wells has enabled high-efficiency optoelectronic devices. Two-dimensional (2D) Ruddlesden-Popper perovskites are solution-processed quantum wells wherein the band gap can be tuned by varying the perovskite-layer thickness, which modulates the effective electron-hole confinement. We report that, counterintuitive to classical quantum-confined systems wher...
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    [Report] Grain boundary stability governs hardening and softening in extremely fine nanograined metals - Conventional metals become harder with decreasing grain sizes, following the classical Hall-Petch relationship. However, this relationship fails and softening occurs at some grain sizes in the nanometer regime for some alloys. In this study, we discovered that plastic deformation mechanism of extremely fine nanograined metals and their hardness are adjustable through tailoring grain boundary (GB) stability. The electrodeposited nanograined nickel...
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    [Report] Active sites for CO2 hydrogenation to methanol on Cu/ZnO catalysts - The active sites over commercial copper/zinc oxide/aluminum oxide (Cu/ZnO/Al2O3) catalysts for carbon dioxide (CO2) hydrogenation to methanol, the Zn-Cu bimetallic sites or ZnO-Cu interfacial sites, have recently been the subject of intense debate. We report a direct comparison between the activity of ZnCu and ZnO/Cu model catalysts for methanol synthesis. By combining x-ray photoemission spectroscopy, density functional theory, and kinetic Monte...
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    [Report] How ?you? makes meaning - ?You? is one of the most common words in the English language. Although it typically refers to the person addressed (?How are you??), ?you? is also used to make timeless statements about people in general (?You win some, you lose some.?). Here, we demonstrate that this ubiquitous but understudied linguistic device, known as ?generic-you,? has important implications for how people derive meaning from experience. Across six experiments, we found th...
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    [Report] Dengue diversity across spatial and temporal scales: Local structure and the effect of host population size - A fundamental mystery for dengue and other infectious pathogens is how observed patterns of cases relate to actual chains of individual transmission events. These pathways are intimately tied to the mechanisms by which strains interact and compete across spatial scales. Phylogeographic methods have been used to characterize pathogen dispersal at global and regional scales but have yielded few insights into the local spatiotemporal structure of en...
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    [Report] Lysosomal cholesterol activates mTORC1 via an SLC38A9?Niemann-Pick C1 signaling complex - The mechanistic target of rapamycin complex 1 (mTORC1) protein kinase is a master growth regulator that becomes activated at the lysosome in response to nutrient cues. Here, we identify cholesterol, an essential building block for cellular growth, as a nutrient input that drives mTORC1 recruitment and activation at the lysosomal surface. The lysosomal transmembrane protein, SLC38A9, is required for mTORC1 activation by cholesterol through conserv...
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    [Report] A conserved NAD+ binding pocket that regulates protein-protein interactions during aging - DNA repair is essential for life, yet its efficiency declines with age for reasons that are unclear. Numerous proteins possess Nudix homology domains (NHDs) that have no known function. We show that NHDs are NAD+ (oxidized form of nicotinamide adenine dinucleotide) binding domains that regulate protein-protein interactions. The binding of NAD+ to the NHD domain of DBC1 (deleted in breast cancer 1) prevents it from inhibiting PARP1 [poly(adenosine...
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    [Report] A macrophage relay for long-distance signaling during postembryonic tissue remodeling - Macrophages have diverse functions in immunity as well as in development and homeostasis. We identified a function for these cells in long-distance communication during postembryonic tissue remodeling. Ablation of macrophages in zebrafish prevented melanophores from coalescing into adult pigment stripes. Melanophore organization depends on signals provided by cells of the yellow xanthophore lineage via airinemes, long filamentous projections with...
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    [Report] Notch-Jagged complex structure implicates a catch bond in tuning ligand sensitivity - Notch receptor activation initiates cell fate decisions and is distinctive in its reliance on mechanical force and protein glycosylation. The 2.5-angstrom-resolution crystal structure of the extracellular interacting region of Notch1 complexed with an engineered, high-affinity variant of Jagged1 (Jag1) reveals a binding interface that extends ~120 angstroms along five consecutive domains of each protein. O-Linked fucose modifications on Notch1 ep...
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    [Report] PI3K pathway regulates ER-dependent transcription in breast cancer through the epigenetic regulator KMT2D - Activating mutations in PIK3CA, the gene encoding phosphoinositide-(3)-kinase ? (PI3K?), are frequently found in estrogen receptor (ER)?positive breast cancer. PI3K? inhibitors, now in late-stage clinical development, elicit a robust compensatory increase in ER-dependent transcription that limits therapeutic efficacy. We investigated the chromatin-based mechanisms leading to the activation of ER upon PI3K? inhibition. We found that PI3K? inhibiti...
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    [Report] Stem cell divisions, somatic mutations, cancer etiology, and cancer prevention - Cancers are caused by mutations that may be inherited, induced by environmental factors, or result from DNA replication errors (R). We studied the relationship between the number of normal stem cell divisions and the risk of 17 cancer types in 69 countries throughout the world. The data revealed a strong correlation (median = 0.80) between cancer incidence and normal stem cell divisions in all countries, regardless of their environment. The major...
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    [New Products] New Products - A weekly roundup of information on newly offered instrumentation, apparatus, and laboratory materials of potential interest to researchers. ...
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    [Working Life] Learning from rejections - Author: Andy Tay...
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