243 research outputs found

    Coherent control of the Goos-Hanchen shift

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    Journals published by the American Physical Society can be found at http://publish.aps.org/The behavior of the Goos-Hanchen (GH) shifts in the reflected and transmitted light beam which is incident on a cavity containing an intracavity medium of three-level or four-level atoms with electromagnetically induced transparency (EIT) is discussed. We report a coherent control of the GH shift in a fixed configuration or device via superluminal and subluminal wave propagation. For superluminal wave propagation, we observe negative GH shifts in the reflected part of the incident light whereas the shifts are positive in the transmitted light beam. This corresponds to the negative group index of the cavity in the former case and positive group index of the cavity in the latter. For subluminal wave propagation, the behavior of the GH shifts in the reflected light changes and positive shifts appearhowever, the GH shifts in the transmitted light remains positive. The corresponding group index of the cavity is positive in both cases

    Potentiation of the anticancer effect of valproic acid, an antiepileptic agent with histone deacetylase inhibitory activity, by the kinase inhibitor Staurosporine or its clinically relevant analogue UCN-01

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    Histone deacetylase inhibitors (HDACIs) are novel anticancer agents with potent cytotoxicity against a wide range of malignancies. We have previously demonstrated that either Calphostin C (CC) (a protein kinase C (PKC) inhibitor) or Parthenolide (an NF-ĪŗB inhibitor) abrogates HDACI-induced transcriptional activation of NF-ĪŗB and p21, which is associated with profound potentiation of HDACI-mediated induction of apoptosis. Valproic acid (VA), a commonly used antiepileptic agent, has recently been shown to be an HDACI. This study was aimed to evaluate the anticancer property of VA in thoracic cancer cells and the development of clinically relevant strategies to enhance VA-mediated induction of apoptosis using kinase inhibitors Staurosporine (STP) or its analogue UCN-01. Treating cultured thoracic cancer cells with VA (0.62ā€“10.0ā€‰mM) resulted in significant cell line- and dose-dependent growth inhibition (IC50 values: 4.1ā€“6.0ā€‰mM) and cell cycle arrest at G1/S checkpoint with profound accumulation of cells at G0/G1 phase but little induction of apoptosis. Valproic acid, being an HDACI, caused significant dose-dependent accumulation of hyperacetylated histones, following 24ā€‰h of treatment. Valproic acid-mediated 5ā€“20-fold upregulation of transcriptional activity of NF-ĪŗB was substantially (50ā€“90%) suppressed by cotreatment with CC, STP or UCN-01. Whereas minimal death (<20%) was observed in cells treated with either VA (1.0 or 5.0ā€‰mM) alone or kinase inhibitors alone, 60ā€“90% of cells underwent apoptosis following exposure to combinations of VA+kinase inhibitors. Kinase inhibitor-mediated suppression of NF-ĪŗB transcriptional activity played an important role in sensitising cancer cells to VA as direct inhibition of NF-ĪŗB by Parthenolide drastically synergised with VA to induce apoptosis (VA+Parthenolide: 60ā€“90% compared to <20% following single-drug treatments). In conclusion, VA, a well-known antiepileptic drug, has mild growth-inhibitory activity on cultured cancer cells. The weak VA-mediated induction of apoptosis of thoracic cancer cells can be profoundly enhanced either by Parthenolide, a pharmacologic inhibitor of NF-ĪŗB, or by UCN-01 a kinase inhibitor that has already undergone phase I clinical development. Combinations of VA with either a PKC inhibitor or an NF-ĪŗB inhibitor are promising novel molecularly targeted therapeutics for thoracic cancers

    Scaling up, sustaining, and enhancing school-based sexuality education programs in resource-constrained and conservative contexts: Replicable lessons from positive-deviant countries

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    Despite considerable efforts, progress in the implementationof sexuality education (SE) has been uneven. This study identi-fied six ā€œpositive-deviantā€ low- and middle-income countries,i.e., countries that had scaled up, sustained and enhancedtheir SE programs when many othersā€”in similar social, cul-tural and economic circumstancesā€”were not able to do so. Inother words, they were significantly and consistently moresuccessful than the norm. Countries were shortlisted using avalidated framework and were analyzed using three other vali-dated frameworks on political priority setting, scaling up, andstakeholder engagement. The study found that India, Pakistan,Nigeria, Senegal, Mexico, and Uruguay had scaled up (eithernationwide or in some states/provinces), sustained andenhanced their SE programs in very different contexts. In allsix, SE was a political priority, the national or state/provincelevel SE scale up effort had been carefully planned and man-aged, and a mix of methods were used to build support and/or to overcome resistance. The study points to what needs tobe done better/more energetically/differently in research, pro-gram support-tool development, and policy and program sup-port to change the status quo

    PACE Technical Report Series, Volume 6: Data Product Requirements and Error Budgets Consensus Document

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    This chapter summarizes ocean color science data product requirements for the Plankton, Aerosol, Cloud,ocean Ecosystem (PACE) mission's Ocean Color Instrument (OCI) and observatory. NASA HQ delivered Level-1 science data product requirements to the PACE Project, which encompass data products to be produced and their associated uncertainties. These products and uncertainties ultimately determine the spectral nature of OCI and the performance requirements assigned to OCI and the observatory. This chapter ultimately serves to provide context for the remainder of this volume, which describes tools developed that allocate these uncertainties into their components, including allowable OCI systematic and random uncertainties, observatory geo location uncertainties, and geophysical model uncertainties

    Micronutrient Sprinkles to Control Childhood Anaemia

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    Over 750 million children have iron-deficiency anemia. A simple powdered sachet may be the key to addressing this global proble

    Electrochemically Induced Mesomorphism Switching in a Chlorpromazine Hydrochloride Lyotropic Liquid Crystal

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    The discovery of electrochemical switching of the LĪ± phase of chlorpromazine hydrochloride in water is reported. The phase is characterized using polarizing microscopy, X-ray scattering, rheological measurements, and microelectrode voltammetry. Fast, heterogeneous oxidation of the lyotropic liquid crystal is shown to cause a phase change resulting from the disordering of the structural order in a stepwise process. The underlying molecular dynamics is considered to be a cooperative effect of both increasing electrostatic interactions and an unfolding of the monomers from "butterfly"-shaped in the reduced form to planar in the oxidized form

    Apoptosis screening of human chromosome 21 proteins reveals novel cell death regulators

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    The functional analysis of chromosome 21 (Chr21) proteins is of great medical relevance. This refers, in particular, to the trisomy of human Chr21, which results in Downā€™s syndrome, a complex developmental and neurodegenerative disease. In a previous study we analyzed 89 human Chr21 genes for the subcellular localization of their encoded proteins using a transfected-cell array technique. In the present study, the results of the follow-up investigation are presented in which 52 human Chr21 genes were over-expressed in HEK cells using the transfected-cell array platform, and the effect of this protein over-expression on the induction of apoptosis has been analyzed. We found that the over-expression of two Chr21 proteins (claudin-14 and -8) induced cell death independent of the classic caspase-mediated apoptosis. Our results strongly suggest the functional involvement of claudins in the control of the cell cycle and regulation of the cell death induction mechanism

    Bak Compensated for Bax in p53-null Cells to Release Cytochrome c for the Initiation of Mitochondrial Signaling during Withanolide D-Induced Apoptosis

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    The goal of cancer chemotherapy to induce multi-directional apoptosis as targeting a single pathway is unable to decrease all the downstream effect arises from crosstalk. Present study reports that Withanolide D (WithaD), a steroidal lactone isolated from Withania somnifera, induced cellular apoptosis in which mitochondria and p53 were intricately involved. In MOLT-3 and HCT116p53+/+ cells, WithaD induced crosstalk between intrinsic and extrinsic signaling through Bid, whereas in K562 and HCT116p53āˆ’/āˆ’ cells, only intrinsic pathway was activated where Bid remain unaltered. WithaD showed pronounced activation of p53 in cancer cells. Moreover, lowered apoptogenic effect of HCT116p53āˆ’/āˆ’ over HCT116p53+/+ established a strong correlation between WithaD-mediated apoptosis and p53. WithaD induced Bax and Bak upregulation in HCT116p53+/+, whereas increase only Bak expression in HCT116p53āˆ’/āˆ’ cells, which was coordinated with augmented p53 expression. p53 inhibition substantially reduced Bax level and failed to inhibit Bak upregulation in HCT116p53+/+ cells confirming p53-dependent Bax and p53-independent Bak activation. Additionally, in HCT116p53+/+ cells, combined loss of Bax and Bak (HCT116Baxāˆ’Bakāˆ’) reduced WithaD-induced apoptosis and completely blocked cytochrome c release whereas single loss of Bax or Bak (HCT116Baxāˆ’Bak+/HCT116Bax+Bakāˆ’) was only marginally effective after WithaD treatment. In HCT116p53āˆ’/āˆ’ cells, though Bax translocation to mitochondria was abrogated, Bak oligomerization helped the cells to release cytochrome c even before the disruption of mitochondrial membrane potential. WithaD also showed in vitro growth-inhibitory activity against an array of p53 wild type and null cancer cells and K562 xenograft in vivo. Taken together, WithaD elicited apoptosis in malignant cells through Bax/Bak dependent pathway in p53-wild type cells, whereas Bak compensated against loss of Bax in p53-null cells

    The Role of Cytokines Produced via the NLRP3 Inflammasome in Mouse Macrophages Stimulated with Dental Calculus in Osteoclastogenesis

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    Dental calculus (DC) is a common deposit in periodontitis patients. We have previously shown that DC contains both microbial components and calcium phosphate crystals that induce an osteoclastogenic cytokine IL-1Ī² via the NLRP3 inflammasome in macrophages. In this study, we examined the effects of cytokines produced by mouse macrophages stimulated with DC on osteoclastogenesis. The culture supernatants from wild-type (WT) mouse macrophages stimulated with DC accelerated osteoclastogenesis in RANKL-primed mouse bone marrow macrophages (BMMs), but inhibited osteoclastogenesis in RANKL-primed RAW-D cells. WT, but not NLRP3-deficient, mouse macrophages stimulated with DC produced IL-1Ī² and IL-18 in a dose-dependent manner, indicating the NLRP3 inflammasome-dependent production of IL-1Ī² and IL-18. Both WT and NLRP3-deficient mouse macrophages stimulated with DC produced IL-10, indicating the NLRP3 inflammasome-independent production of IL-10. Recombinant IL-1Ī² accelerated osteoclastogenesis in both RANKL-primed BMMs and RAW-D cells, whereas recombinant IL-18 and IL-10 inhibited osteoclastogenesis. These results indicate that DC induces osteoclastogenic IL-1Ī² in an NLRP3 inflammasome-dependent manner and anti-osteogenic IL-18 and IL-10 dependently and independently of the NLRP3 inflammasome, respectively. DC may promote alveolar bone resorption via IL-1Ī² induction in periodontitis patients, but suppress resorption via IL-18 and IL-10 induction in some circumstances
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