189 research outputs found

    Brand Singapore: How businesses can align with their country's branding in a Covid-19-plagued world

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    Four-particle condensate in strongly coupled fermion systems

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    Four-particle correlations in fermion systems at finite temperatures are investigated with special attention to the formation of a condensate. Instead of the instability of the normal state with respect to the onset of pairing described by the Gorkov equation, a new equation is obtained which describes the onset of quartetting. Within a model calculation for symmetric nuclear matter, we find that below a critical density, the four-particle condensation (alpha-like quartetting) is favored over deuteron condensation (triplet pairing). This pairing-quartetting competition is expected to be a general feature of interacting fermion systems, such as the excition-biexciton system in excited semiconductors. Possible experimental consequences are pointed out.Comment: LaTeX, 11 pages, 2 figures, uses psfig.sty (included), to be published in Phys. Rev. Lett., tentatively scheduled for 13 April 1998 (Volume 80, Number 15

    Neuronal calcium sensor-1 enhancement of InsP3 receptor activity is inhibited by therapeutic levels of lithium

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    Author Posting. © American Society for Clinical Investigation, 2006. This article is posted here by permission of American Society for Clinical Investigation for personal use, not for redistribution. The definitive version was published in Journal of Clinical Investigation 116 (2006): 1668-1674, doi:10.1172/JCI22466.Regulation and dysregulation of intracellular calcium (Ca2+) signaling via the inositol 1,4,5-trisphosphate receptor (InsP3R) has been linked to many cellular processes and pathological conditions. In the present study, addition of neuronal calcium sensor-1 (NCS-1), a high-affinity, low-capacity, calcium-binding protein, to purified InsP3R type 1 (InsP3R1) increased the channel activity in both a calcium-dependent and -independent manner. In intact cells, enhanced expression of NCS-1 resulted in increased intracellular calcium release upon stimulation of the phosphoinositide signaling pathway. To determine whether InsP3R1/NCS-1 interaction could be functionally relevant in bipolar disorders, conditions in which NCS-1 is highly expressed, we tested the effect of lithium, a salt widely used for treatment of bipolar disorders. Lithium inhibited the enhancing effect of NCS-1 on InsP3R1 function, suggesting that InsP3R1/NCS-1 interaction is an essential component of the pathomechanism of bipolar disorder.This work was supported by a grant from the NIH (GM63496 to B.E. Ehrlich), German National Merit Foundation scholarships (C. Schlecker and W. Boehmerle), and a National Kidney Foundation Fellowship (A. Varshney)

    New Human Papilloma Virus E2 Transcription Factor Mimics: A Tripyrrole-Peptide Conjugate with Tight and Specific DNA-Recognition

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    BACKGROUND: Human papillomavirus (HPV) is the main causative agent of cervical cancer, particularly high risk strains such us HPV-16, -18 and -31. The viral encoded E2 protein acts as a transcriptional modulator and exerts a key role in viral DNA replication. Thus, E2 constitutes an attractive target for developing antiviral agents. E2 is a homodimeric protein that interacts with the DNA target through an α-helix of each monomer. However, a peptide corresponding to the DNA recognition helix of HPV-16 E2 binds DNA with lower affinity than its full-length DNA binding domain. Therefore, in an attempt to promote the DNA binding of the isolated peptide, we have designed a conjugate compound of the E2 α-helix peptide and a derivative of the antibiotic distamycin, which involves simultaneous minor- and major-groove interactions. METHODOLOGY/PRINCIPAL FINDINGS: An E2 α-helix peptide-distamycin conjugate was designed and synthesized. It was characterized by NMR and CD spectroscopy, and its DNA binding properties were investigated by CD, DNA melting and gel shift experiments. The coupling of E2 peptide with distamycin does not affect its structural properties. The conjugate improves significantly the affinity of the peptide for specific DNA. In addition, stoichiometric amounts of specific DNA increase meaningfully the helical population of the peptide. The conjugate enhances the DNA binding constant 50-fold, maintaining its specificity. CONCLUSIONS/SIGNIFICANCE: These results demonstrate that peptide-distamycin conjugates are a promising tool to obtain compounds that bind the E2 target DNA-sequences with remarkable affinity and suggest that a bipartite major/minor groove binding scaffold can be a useful approach for therapeutic treatment of HPV infection

    Thriving under Stress: Selective Translation of HIV-1 Structural Protein mRNA during Vpr-Mediated Impairment of eIF4E Translation Activity

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    Translation is a regulated process and is pivotal to proper cell growth and homeostasis. All retroviruses rely on the host translational machinery for viral protein synthesis and thus may be susceptible to its perturbation in response to stress, co-infection, and/or cell cycle arrest. HIV-1 infection arrests the cell cycle in the G2/M phase, potentially disrupting the regulation of host cell translation. In this study, we present evidence that HIV-1 infection downregulates translation in lymphocytes, attributable to the cell cycle arrest induced by the HIV-1 accessory protein Vpr. The molecular basis of the translation suppression is reduced accumulation of the active form of the translation initiation factor 4E (eIF4E). However, synthesis of viral structural proteins is sustained despite the general suppression of protein production. HIV-1 mRNA translation is sustained due to the distinct composition of the HIV-1 ribonucleoprotein complexes. RNA-coimmunoprecipitation assays determined that the HIV-1 unspliced and singly spliced transcripts are predominantly associated with nuclear cap binding protein 80 (CBP80) in contrast to completely-spliced viral and cellular mRNAs that are associated with eIF4E. The active translation of the nuclear cap binding complex (CBC)-bound viral mRNAs is demonstrated by ribosomal RNA profile analyses. Thus, our findings have uncovered that the maintenance of CBC association is a novel mechanism used by HIV-1 to bypass downregulation of eIF4E activity and sustain viral protein synthesis. We speculate that a subset of CBP80-bound cellular mRNAs contribute to recovery from significant cellular stress, including human retrovirus infection

    Staging Singapore’s cultural economy

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    Singapore 1994-1996: Bibliographies

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    10.1177/002200949803300306The Journal of Commonwealth Literature333134-15

    Subacute abdominal pain requiring hospitalization in a systemic lupus erythematosus patient: a retrospective analysis and review of the literature

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    In the systemic lupus erythematosus (SLE) patient, abdominal pain is a common problem. Intra-abdominal vasculitis must be excluded as the source because of its potentially high mortality rate. We retrospectively reviewed the charts of 56 SLE patients with 75 admissions for predominantly subacute abdominal pain (abdominal pain without peritoneal signs) severe enough to require hospital admission, comparing the diagnostic modalities used, ultimate diagnoses, and use of corticosteroids before admission with 56 age- and sex-matched patients without SLE admitted for abdominal pain during the same time interval. SLE patients were further subdivided by disease activity at presentation using the SELENA SLEDAI score. The in-hospital mortality for all patients in this review was 0%. There were no statistically significant differences in the use of computed tomography between SLE and control patients. Intestinal vasculitis was diagnosed in 5.4% of SLE patients compared with 0% of control patients (P = 0.0433). Only patients with SLEDAI scores >8 developed vasculitis (P 8 and subacute abdominal pain. All SLE patients with SLEDAI scores ≤8 and subacute abdominal pain should be evaluated for a cause of abdominal pain other than vasculitis
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