SUMMARY Hair follicles (HFs) undergo cyclic bouts of degeneration, rest, and regeneration. During rest (telogen), the hair germ (HG) appears as a small cell cluster between the slow-cycling bulge and dermal papilla (DP). Here we show that HG cells are derived from bulge stem cells (SCs) but become responsive quicker to DP-promoting signals. In vitro, HG cells also proliferate sooner but display shorter-lived potential than bulge cells. Molecularly, they more closely resemble activated bulge rather than transit-amplifying (matrix) cells. Transcriptional profiling reveals precocious activity of both HG and DP in late telogen, accompanied by Wnt signaling in HG and elevated FGFs and BMP inhibitors in DP. FGFs and BMP inhibitors participate with Wnts in exerting selective and potent stimuli to the HG both in vivo and in vitro. Our findings suggest a model where HG cells fuel initial steps in hair regeneration, while the bulge is the engine maintaining the process.

Highlights d AI system that can diagnose COVID-19 pneumonia using CT scans d Prediction of progression to critical illness d Potential to improve performance of junior radiologists to the senior level d Can assist evaluation of drug treatment effects with CT quantification

Since its inception, the blockchain technology has shown promising application prospects. From the initial cryptocurrency to the current smart contract, blockchain has been applied to many fields. Although there are some studies on the security and privacy issues of blockchain, there lacks a systematic examination on the security of blockchain systems. In this paper, we conduct a systematic study on the security threats to blockchain and survey the corresponding real attacks by examining popular blockchain systems. We also review the security enhancement solutions for blockchain, which could be used in the development of various blockchain systems, and suggest some future directions to stir research efforts into this area.

Immune checkpoint blockade, exemplified by antibodies targeting the PD-1 receptor, can induce durable tumor regressions in some patients. To enhance the efficacy of existing immunotherapies, we screened for small molecules capable of increasing the activity of T cells suppressed by PD-1. Here, we show that short-term exposure to small-molecule inhibitors of cyclin-dependent kinases 4 and 6 (CDK4/6) significantly enhances T-cell activation, contributing to antitumor effects , due in part to the derepression of NFAT family proteins and their target genes, critical regulators of T-cell function. Although CDK4/6 inhibitors decrease T-cell proliferation, they increase tumor infiltration and activation of effector T cells. Moreover, CDK4/6 inhibition augments the response to PD-1 blockade in a novel organotypic tumor spheroid culture system and in multiple murine syngeneic models, thereby providing a rationale for combining CDK4/6 inhibitors and immunotherapies. Our results define previously unrecognized immunomodulatory functions of CDK4/6 and suggest that combining CDK4/6 inhibitors with immune checkpoint blockade may increase treatment efficacy in patients. Furthermore, our study highlights the critical importance of identifying complementary strategies to improve the efficacy of immunotherapy for patients with cancer. .

Topological insulators are an emerging class of materials that host highly robust in-gap surface or interface states while maintaining an insulating bulk. Most advances in this field have focused on topological insulators and related topological crystalline insulators in two dimensions and three dimensions, but more recent theoretical work has predicted the existence of one-dimensional symmetry-protected topological phases in graphene nanoribbons (GNRs). The topological phase of these laterally confined, semiconducting strips of graphene is determined by their width, edge shape and terminating crystallographic unit cell and is characterized by a [Formula: see text] invariant (that is, an index of either 0 or 1, indicating two topological classes-similar to quasi-one-dimensional solitonic systems). Interfaces between topologically distinct GNRs characterized by different values of [Formula: see text] are predicted to support half-filled, in-gap localized electronic states that could, in principle, be used as a tool for material engineering. Here we present the rational design and experimental realization of a topologically engineered GNR superlattice that hosts a one-dimensional array of such states, thus generating otherwise inaccessible electronic structures. This strategy also enables new end states to be engineered directly into the termini of the one-dimensional GNR superlattice. Atomically precise topological GNR superlattices were synthesized from molecular precursors on a gold surface, Au(111), under ultrahigh-vacuum conditions and characterized by low-temperature scanning tunnelling microscopy and spectroscopy. Our experimental results and first-principles calculations reveal that the frontier band structure (the bands bracketing filled and empty states) of these GNR superlattices is defined purely by the coupling between adjacent topological interface states. This manifestation of non-trivial one-dimensional topological phases presents a route to band engineering in one-dimensional materials based on precise control of their electronic topology, and is a promising platform for studies of one-dimensional quantum spin physics.

DNA replication origins are fundamental to chromosome organization and duplication, but understanding of these elements is limited because only a small fraction of these sites have been identified in eukaryotic genomes. Origin Recognition Complex (ORC) and minichromosome maintenance (MCM) proteins form prereplicative complexes at origins of replication. Using these proteins as molecular landmarks for origins, we identified ORC- and MCM-bound sites throughout the yeast genome. Four hundred twenty-nine sites in the yeast genome were predicted to contain replication origins, and approximately 80% of the loci identified on chromosome X demonstrated origin function. A substantial fraction of the predicted origins are associated with repetitive DNA sequences, including subtelomeric elements (X and Y') and transposable element-associated sequences (long terminal repeats). These findings identify the global set of yeast replication origins and open avenues of investigation into the role(s) ORC and MCM proteins play in chromosomal architecture and dynamics.

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We propose a di erential equation model for gene expression and provide two methods to construct the model from a set of temporal data. We model both transcription and translation by kinetic equations with feedback loops from translation products to transcription. Degradation of proteins and mRNAs is also incorporated. We study two methods to construct the model from experimental data: Minimum Weight Solutions to Linear Equations (MWSLE), which determines the regulation by solving under-determined linear equations, and Fourier Transform for Stable Systems (FTSS), which re nes the model with cell cycle constraints. The results suggest that a minor set of temporal data may be su cient t o c o nstruct the model at the genome level. We also give a comprehensive discussion of other extended models: the RNA Model, the Protein Model, and the Time Delay Model.