314 research outputs found

    Building block libraries and structural considerations in the self-assembly of polyoxometalate and polyoxothiometalate systems

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    Inorganic metal-oxide clusters form a class of compounds that are unique in their topological and electronic versatility and are becoming increasingly more important in a variety of applications. Namely, Polyoxometalates (POMs) have shown an unmatched range of physical properties and the ability to form structures that can bridge several length scales. The formation of these molecular clusters is often ambiguous and is governed by self-assembly processes that limit our ability to rationally design such molecules. However, recent years have shown that by considering new building block principles the design and discovery of novel complex clusters is aiding our understanding of this process. Now with current progress in thiometalate chemistry, specifically polyoxothiometalates (POTM), the field of inorganic molecular clusters has further diversified allowing for the targeted development of molecules with specific functionality. This chapter discusses the main differences between POM and POTM systems and how this affects synthetic methodologies and reactivities. We will illustrate how careful structural considerations can lead to the generation of novel building blocks and further deepen our understanding of complex systems

    Rapid Discovery of Pyrido[3,4- d ]pyrimidine Inhibitors of Monopolar Spindle Kinase 1 (MPS1) Using a Structure-Based Hybridization Approach

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    Monopolar spindle 1 (MPS1) plays a central role in the transition of cells from metaphase to anaphase and is one of the main components of the spindle assembly checkpoint. Chromosomally unstable cancer cells rely heavily on MPS1 to cope with the stress arising from abnormal numbers of chromosomes and centrosomes and are thus more sensitive to MPS1 inhibition than normal cells. We report the discovery and optimization of a series of new pyrido[3,4-d]pyrimidine based inhibitors via a structure-based hybridization approach from our previously reported inhibitor CCT251455 and a modestly potent screening hit. Compounds in this novel series display excellent potency and selectivity for MPS1, which translates into biomarker modulation in an in vivo human tumor xenograft mode

    Prostate-specific antigen at or before age 50 as a predictor of advanced prostate cancer diagnosed up to 25 years later: A case-control study

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    BACKGROUND: Based on a large, representative unscreened cohort from Malmö, Sweden, we have recently reported that a single prostate-specific antigen (PSA) measurement at or before age 50 is a strong predictor of prostate cancer occurring up to 25 years subsequently. We aimed to determine whether this association holds for advanced cancers, defined as clinical stage T3 or higher, or skeletal metastasis at the time of the cancer diagnosis. METHODS: In 1974-1986 blood samples were obtained from a cohort of 21,277 men aged up to 50. Through 1999, 498 men were diagnosed with prostate cancer, and of these 161 had locally advanced or metastatic prostate cancers. Three controls, matched for age and date of venipuncture, were selected for each case. Conditional logistic regression was used to test associations between molecular markers and advanced cancer. RESULTS: Median time from venipuncture to diagnosis was 17 years. Levels of all PSA forms and hK2 were associated with case status. Total PSA was a strong and statistically significant predictor of subsequent advanced cancer (area under the curve 0.791; p < 0.0005). Two-thirds of the advanced cancer cases occurred in men with the top 20% of PSA levels (0.9 ng/ml or higher). CONCLUSION: A single PSA test taken at or before age 50 is a very strong predictor of advanced prostate cancer diagnosed up to 25 years later. This suggests the possibility of using an early PSA test to risk-stratify patients so that men at highest risk are the focus of the most intensive screening efforts

    Small bowel MRI in adult patients: not just Crohn’s disease—a tutorial

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    To provide an overview of less well-known small bowel and mesenteric diseases found at small bowel magnetic resonance (MR) enterography/enteroclysis and to review the imaging findings. MR enterography and enteroclysis are important techniques for evaluation of small bowel diseases. In most centres these techniques are primarily used in Crohn's disease, and most radiologists are familiar with these MRI findings. However, the knowledge of findings in other diseases is often sparse, including diseases that may cause similar clinical symptoms to those of Crohn's disease. We present a spectrum of less common and less well-known bowel and mesenteric diseases (e.g. internal hernia, intussusception, neuroendocrine tumour) from our small bowel MR database of over 2,000 cases. These diseases can be found in patients referred for bowel obstruction, abdominal pain or rectal blood loss. Further, in patients with (or suspected to have) Crohn's disease, some of these diseases (e.g. neuroendocrine tumour, familial Mediterranean fever) may mislead radiologists to erroneously diagnose active Crohn's disease. Radiologists should be familiar with diseases affecting the small bowel other than Crohn's disease, including diseases that may mimic Crohn's diseas

    Search for a Technicolor omega_T Particle in Events with a Photon and a b-quark Jet at CDF

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    If the Technicolor omega_T particle exists, a likely decay mode is omega_T -> gamma pi_T, followed by pi_T -> bb-bar, yielding the signature gamma bb-bar. We have searched 85 pb^-1 of data collected by the CDF experiment at the Fermilab Tevatron for events with a photon and two jets, where one of the jets must contain a secondary vertex implying the presence of a b quark. We find no excess of events above standard model expectations. We express the result of an exclusion region in the M_omega_T - M_pi_T mass plane.Comment: 14 pages, 2 figures. Available from the CDF server (PS with figs): http://www-cdf.fnal.gov/physics/pub98/cdf4674_omega_t_prl_4.ps FERMILAB-PUB-98/321-

    Measurement of the B0 anti-B0 oscillation frequency using l- D*+ pairs and lepton flavor tags

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    The oscillation frequency Delta-md of B0 anti-B0 mixing is measured using the partially reconstructed semileptonic decay anti-B0 -> l- nubar D*+ X. The data sample was collected with the CDF detector at the Fermilab Tevatron collider during 1992 - 1995 by triggering on the existence of two lepton candidates in an event, and corresponds to about 110 pb-1 of pbar p collisions at sqrt(s) = 1.8 TeV. We estimate the proper decay time of the anti-B0 meson from the measured decay length and reconstructed momentum of the l- D*+ system. The charge of the lepton in the final state identifies the flavor of the anti-B0 meson at its decay. The second lepton in the event is used to infer the flavor of the anti-B0 meson at production. We measure the oscillation frequency to be Delta-md = 0.516 +/- 0.099 +0.029 -0.035 ps-1, where the first uncertainty is statistical and the second is systematic.Comment: 30 pages, 7 figures. Submitted to Physical Review

    Search for New Particles Decaying to top-antitop in proton-antiproton collisions at squareroot(s)=1.8 TeV

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    We use 106 \ipb of data collected with the Collider Detector at Fermilab to search for narrow-width, vector particles decaying to a top and an anti-top quark. Model independent upper limits on the cross section for narrow, vector resonances decaying to \ttbar are presented. At the 95% confidence level, we exclude the existence of a leptophobic \zpr boson in a model of topcolor-assisted technicolor with mass M_{\zpr} << 480 \gev for natural width Γ\Gamma = 0.012 M_{\zpr}, and M_{\zpr} << 780 \gev for Γ\Gamma = 0.04 M_{\zpr}.Comment: The CDF Collaboration, submitted to PRL 25-Feb-200

    A Measurement of the Differential Dijet Mass Cross Section in p-pbar Collisions at sqrt{s}=1.8 TeV

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    We present a measurement of the cross section for production of two or more jets as a function of dijet mass, based on an integrated luminosity of 86 pb^-1 collected with the Collider Detector at Fermilab. Our dijet mass spectrum is described within errors by next-to-leading order QCD predictions using CTEQ4HJ parton distributions, and is in good agreement with a similar measurement from the D0 experiment.Comment: 18 pages including 2 figures and 3 tables. Submitted to Phys. Rev. D Rapid Communication

    Glacial vicariance drives phylogeographic diversification in the amphi-boreal kelp Saccharina latissima

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    Glacial vicariance is regarded as one of the most prevalent drivers of phylogeographic structure and speciation among high-latitude organisms, but direct links between ice advances and range fragmentation have been more difficult to establish in marine than in terrestrial systems. Here we investigate the evolution of largely disjunct (and potentially reproductively isolated) phylogeographic lineages within the amphi-boreal kelp Saccharina latissima s.l. Using molecular data (COI, microsatellites) we confirm that S. latissima comprises also the NE Pacific S. cichorioides complex and is composed of divergent lineages with limited range overlap and genetic admixture. Only a few genetic hybrids were detected throughout a Canadian Arctic/NW Greenland contact zone. The degree of genetic differentiation and sympatric isolation of phylogroups suggest that S. latissima s.l. represents a complex of incipient species. Phylogroup distributions compared with paleo-environmental reconstructions of the cryosphere further suggest that diversification within S. latissima results from chronic glacial isolation in disjunct persistence areas intercalated with ephemeral interglacial poleward expansions and admixture at high-latitude (Arctic) contact zones. This study thus supports a role for glaciations not just in redistributing pre-existing marine lineages but also as a speciation pump across multi-glacial cycles for marine organisms otherwise exhibiting cosmopolite amphi-boreal distributions.Pew Foundation (USA); Portuguese FCT (Fundacao para a Ciencia e a Tecnologia) through program GENEKELP [PTDC/MAR-EST/6053/2014]; Portuguese FCT (Fundacao para a Ciencia e a Tecnologia) through program MARFOR [Biodiversa/0004/2015]; Portuguese FCT (Fundacao para a Ciencia e a Tecnologia) [UID/Multi/04326/2013, SFRH/BPD/88935/2012, SFRH/BPD/111003/2015]; NSERC; FRQNT; Canada Foundation for Innovation; New Brunswick Innovation Foundation; European Union's Seventh Framework Programme [226248]; Danish Environmental Protection Agency within the Danish Cooperation for Environment in the Arctic (DANCEA)info:eu-repo/semantics/publishedVersio
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