The preparation, crystal structures, and electric and magnetic properties of (BETS)2MX4 molecular conductors (BETS = bis(ethylenedithio)tetraselenafulvalene; M = Mn2+, Fe3+, Co2+, Ni2+, Cu2+; X = Cl, Br, CN) are reported. Resistivity measurements down to 2 K reveal the coexistence of the BETS π conduction electrons and the localized magnetic moments of the anions in the κ-(BETS)2FeCl4 and κ-(BETS)4(CoCl4)(C2H3Cl3) salts. Another FeCl4 phase, λ-(BETS)2FeCl4, undergoes a sharp metal-insulator (MI) transition around 8 K. At the same temperature, a magnetic transition of the FeCl4-anions takes place cooperatively. A superconducting transition is observed at 4.6 K in λ-(BETS)2(FeCl4)0.5(GaCl4)0.5, where half of the anion sites are occupied by magnetic ions. The crystals prepared from 1,1,2-trichloroethane solutions with the NiCl42- and MnCl42- anions exhibit the behavior of a semimetal down to ≈100 K. The (BETS)4(Cu2Cl6) salt remains metallic down to 4.2 K. ESR studies show that the Fe3+ ions in κ- and λ-(BETS)2FeCl4 are in a high-spin state. The temperature dependencies of the spin susceptibilities of κ- and λ-(BETS)2FeCl4 indicate antiferromagnetic interactions between the Fe3+ ions. The crystal structure analyses of κ- and λ-(BETS)2FeCl4 have been carried out at 298 and 10 K. Closer BETS···FeCl4 contacts in λ-(BETS)2FeCl4 are observed, which is consistent with the larger Weiss temperature of this compound.
Cardiothoracic surgeons are faced with the dilemma that many clinical questions in their daily practice to do not have universally agreed answers, but patients increasingly demand the 'best practice' from their doctors. In addition time pressures mean that clinicians are unable to keep up with the full spectrum of published research and current resources that collate evidence for clinicians have few if any resources for cardiothoracic surgeons. We have adopted an approach pioneered in emergency medicine, namely the Best Evidence Topic or BestBET. Clinicians select a clinical scenario from their daily practice that highlighted an area of controversy. From this, a three-part question is generated and this is used to search Medline for relevant papers. Once the relevant papers are found, these papers are critically appraised using validated checklists and the results are summarized. A clinical bottom line is reached after this process. To add confidence to the quality of the search a second author and then an Evidence Based Journal Club checks the BET to ensure that no relevant evidence is missed. These BETs will then be posted on the ICVTS website prior to publication for widespread commentary. The resulting BETs, written by practising cardiothoracic surgeons, will then provide robust evidence-based answers to important clinical questions asked during our daily practice.
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTOrganic Metals and Superconductors Based on BETS (BETS = Bis(ethylenedithio)tetraselenafulvalene)Hayao Kobayashi, HengBo Cui, and Akiko KobayashiView Author Information Institute for Molecular Science and CREST, Okazaki 444-8585, Japan Research Center for Spectrochemistry, Graduate School of Science, The University of Tokyo, Hongo, Bunkyo-ku, Tokyo 113-0033, Japan Cite this: Chem. Rev. 2004, 104, 11, 5265–5288Publication Date (Web):August 18, 2004Publication History Received9 March 2004Published online18 August 2004Published inissue 1 November 2004https://pubs.acs.org/doi/10.1021/cr030657dhttps://doi.org/10.1021/cr030657dresearch-articleACS PublicationsCopyright © 2004 American Chemical SocietyRequest reuse permissionsArticle Views2593Altmetric-Citations277LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose SUBJECTS:Anions,Electrical conductors,Magnetic properties,Metals,Superconductors Get e-Alerts
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We present a model with leverage and margin constraints that vary across investors and time. We find evidence consistent with each of the model's five central predictions: (1) Because constrained investors bid up high-beta assets, high beta is associated with low alpha, as we find empirically for US equities, 20 international equity markets, Treasury bonds, corporate bonds, and futures. (2) A betting against beta (BAB) factor, which is long leveraged low-beta assets and short high-beta assets, produces significant positive risk-adjusted returns. (3) When funding constraints tighten, the return of the BAB factor is low. (4) Increased funding liquidity risk compresses betas toward one. (5) More constrained investors hold riskier assets.
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Innate immunity serves as the rapid and first-line defense against invading pathogens, and this process can be regulated at various levels, including epigenetic mechanisms. The bromodomain and extraterminal domain (BET) family of proteins consists of four conserved mammalian members (BRD2, BRD3, BRD4, and BRDT) that regulate the expression of many immunity-associated genes and pathways. In particular, in response to infection and sterile inflammation, abnormally expressed or dysfunctional BETs are involved in the activation of pattern recognition receptor (e.g., TLR, NLR, and CGAS) pathways, thereby linking chromatin machinery to innate immunity under disease or pathological conditions. Mechanistically, the BET family controls the transcription of a wide range of proinflammatory and immunoregulatory genes by recognizing acetylated histones (mainly H3 and H4) and recruiting transcription factors (e.g., RELA) and transcription elongation complex (e.g., P-TEFb) to the chromatin, thereby promoting the phosphorylation of RNA polymerase II and subsequent transcription initiation and elongation. This review covers the accumulating data about the roles of the BET family in innate immunity, and discusses the attractive prospect of manipulating the BET family as a new treatment for disease.
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T-bet is a member of the T-box family of transcription factors that appears to regulate lineage commitment in CD4 T helper (TH) lymphocytes in part by activating the hallmark TH1 cytokine, interferon-gamma (IFN-gamma). IFN-gamma is also produced by natural killer (NK) cells and most prominently by CD8 cytotoxic T cells, and is vital for the control of microbial pathogens. Although T-bet is expressed in all these cell types, it is required for control of IFN-gamma production in CD4 and NK cells, but not in CD8 cells. This difference is also apparent in the function of these cell subsets. Thus, the regulation of a single cytokine, IFN-gamma, is controlled by distinct transcriptional mechanisms within the T cell lineage.
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The MYC transcription factor is a master regulator of diverse cellular functions and has been long considered a compelling therapeutic target because of its role in a range of human malignancies. However, pharmacologic inhibition of MYC function has proven challenging because of both the diverse mechanisms driving its aberrant expression and the challenge of disrupting protein-DNA interactions. Here, we demonstrate the rapid and potent abrogation of MYC gene transcription by representative small molecule inhibitors of the BET family of chromatin adaptors. MYC transcriptional suppression was observed in the context of the natural, chromosomally translocated, and amplified gene locus. Inhibition of BET bromodomain-promoter interactions and subsequent reduction of MYC transcript and protein levels resulted in G(1) arrest and extensive apoptosis in a variety of leukemia and lymphoma cell lines. Exogenous expression of MYC from an artificial promoter that is resistant to BET regulation significantly protected cells from cell cycle arrest and growth suppression by BET inhibitors. MYC suppression was accompanied by deregulation of the MYC transcriptome, including potent reactivation of the p21 tumor suppressor. Treatment with a BET inhibitor resulted in significant antitumor activity in xenograft models of Burkitt's lymphoma and acute myeloid leukemia. These findings demonstrate that pharmacologic inhibition of MYC is achievable through targeting BET bromodomains. Such inhibitors may have clinical utility given the widespread pathogenetic role of MYC in cancer.
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