286 research outputs found

    Photonic band mixing in linear chains of optically coupled micro-spheres

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    The paper deals with optical excitations arising in a one-dimensional chain of identical spheres due optical coupling of whispering gallery modes (WGM). The band structure of these excitations depends significantly on the inter-mixing between WGMs characterized by different values of angular quantum number, ll. We develop a general theory of the photonic band structure of these excitations taking these effects into account and applied it to several cases of recent experimental interest. In the case of bands originating from WQMs with the angular quantum number of the same parity, the calculated dispersion laws are in good qualitative agreement with recent experiment results. Bands resulting from hybridization of excitations resulting from whispering gallery modes with different parity of ll exhibits anomalous dispersion properties characterized by a gap in the allowed values of \emph{wave numbers} and divergence of group velocity.Comment: RevTex, 28 pages, 7 Figure

    Publix Supermarkets, Inc.

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    All traditional brick-and-mortar retailers are struggling with how best to deal with threats from online retailers. However, the supermarket industry is also dealing with pressure from new foreign entrants like Aldi and Lidl. Perhaps nowhere is this more evident than in the southeastern United States, where Publix operates. Publix is an employee-owned supermarket chain with excellent service, high margins and strong growth in sales and profits. The company has also had some success with Internet offerings. However, is the company’s business model going to sustain it in this increasingly competitive industry, or are changes needed? This case focuses on the entrance of Publix into the Richmond Virginia market

    Nanocarriers Of Fe3O4 As A Novel Method For Delivery Of The Antineoplastic Agent Doxorubicin Into Hela Cells In Vitro

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    Here we report the synthesis and in vitro characterization of a redox-sensitive, magnetically inducible nanoparticle carrier system based on the doxorubicin (DOX) drug delivery model. Each quantal nanocarrier unit consists of a magnetite Fe3O4 nanoparticle core that is further encapsulated in self-assembled micelles of the redox-responsive polyethylene glycol derivative, DSPE-SS-mPEG. The nanocarrier system was prepared using a combination of ultrasonication and dialysis to produce the microenvironment sensitive delivery system. The final synthesized and DOX-loaded magnetic nanocarriers had an average size of ~150 nm when assembled with a 6.9% DOX payload. The release rate of DOX from these redox-responsive magnetic nanocarriers was shown to be accelerated in vitro when in the presence of glutathione (GSH). Furthermore, we demonstrated that more redox-responsive magnetic nanocarriers could be taken up by HeLa cells when a local magnetic field was applied. Once internalized within a cell, the micelles of the outer nanocarrier complex were broken down in the presence of higher concentrations of GSH, which accelerated the release of DOX. This produces a particle with dual operating characteristics that can be controlled via a specific cellular environment coupled with an exogenously applied signal in the form of a magnetic field triggering release

    Promiscuous actions of small molecule inhibitors of the protein kinase D-class IIa HDAC axis in striated muscle

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    AbstractPKD-mediated phosphorylation of class IIa HDACs frees the MEF2 transcription factor to activate genes that govern muscle differentiation and growth. Studies of the regulation and function of this signaling axis have involved MC1568 and Gö-6976, which are small molecule inhibitors of class IIa HDAC and PKD catalytic activity, respectively. We describe unanticipated effects of these compounds. MC1568 failed to inhibit class IIa HDAC catalytic activity in vitro, and exerted divergent effects on skeletal muscle differentiation compared to a bona fide inhibitor of these HDACs. In cardiomyocytes, Gö-6976 triggered calcium signaling and activated stress-inducible kinases. Based on these findings, caution is warranted when employing MC1568 and Gö-6976 as pharmacological tool compounds to assess functions of class IIa HDACs and PKD

    Sasang Constitution as a Risk Factor for Diabetes Mellitus: A Cross-Sectional Study

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    Sasang Constitutional Medicine, which is a branch of traditional Korean medicine, states that medications for diabetes should be individualized according to the patient's individual constitution. However, the effect of constitution on diabetes has not been evaluated to date. Therefore, this study was conducted to determine if constitution is an independent risk factor for diabetes by comparing the prevalence and odds ratios (ORs) of the disease according to constitution. The medical records of 1443 adults who had been examined and classified based on their constitution at Kyung Hee University Hospital in Seoul, Korea were reviewed. A chi-squared test and Fisher's exact test were used to compare the prevalence of diabetes according to constitution, and multiple logistic regression was used to calculate the ORs for diabetes. The prevalence of diabetes differed significantly according to constitution (χ2 = 36.20, df = 2, P < 0.001). Specifically, the prevalence of the disease was higher in Tae-eumin (11.4%) individuals than in Soyangin (5.0%) or Soeumin (1.7%) individuals. In addition, multiple logistic regression revealed that Tae-eumin individuals had a greater risk for diabetes than Soeumin individuals. When compared to Soeumin individuals, the adjusted ORs were 2.01 (95% CI 0.77–5.26) for Soyangin individuals and 3.96 (95% CI 1.48–10.60) for Tae-eumin individuals. These results show that constitution has a significant and independent association with diabetes, which suggests that constitution is an independent risk factor for diabetes that should be considered when attempting to detect and prevent the disease

    The Unique a4(1)/(2)a4 Agonist Binding Site in (a4) 3 (b2) 2 Subtype Nicotinic Acetylcholine Receptors Permits Differential Agonist Desensitization Pharmacology versus the (a4) 2 (b2) 3 Subtype s

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    ABSTRACT Selected nicotinic agonists were used to activate and desensitize high-sensitivity (HS) (a4) 2 (b2) 3 ) or low-sensitivity (LS) (a4) 3 (b2) 2 ) isoforms of human a4b2-nicotinic acetylcholine receptors (nAChRs). Function was assessed using 86 Rb 1 efflux in a stably transfected SH-EP1-ha4b2 human epithelial cell line, and twoelectrode voltage-clamp electrophysiology in Xenopus laevis oocytes expressing concatenated pentameric HS or LS a4b2-nAChR constructs (HSP and LSP). Unlike previously studied agonists, desensitization by the highly selective agonists A-85380 [3-(2(S)-azetidinylmethoxy)pyridine] and sazetidine-A (Saz-A) preferentially reduced a4b2-nAChR HS-phase versus LS-phase responses. The concatenated-nAChR experiments confirmed that approximately 20% of LS-isoform acetylcholine-induced function occurs in an HS-like phase, which is abolished by Saz-A preincubation. Six mutant LSPs were generated, each targeting a conserved agonist binding residue within the LS-isoform-only a4(1)/(2)a4 interface agonist binding site. Every mutation reduced the percentage of LS-phase function, demonstrating that this site underpins LS-phase function. Oocyte-surface expression of the HSP and each of the LSP constructs was statistically indistinguishable, as measured using b2-subunit-specific [ 125 I]mAb295 labeling. However, maximum function is approximately five times greater on a &quot;per-receptor&quot; basis for unmodified LSP versus HSP a4b2-nAChRs. Thus, recruitment of the a4(1)/(2)a4 site at higher agonist concentrations appears to augment otherwisesimilar function mediated by the pair of a4(1)/(2)b2 sites shared by both isoforms. These studies elucidate the receptor-level differences underlying the differential pharmacology of the two a4b2-nAChR isoforms, and demonstrate that HS versus LS a4b2-nAChR activity can be selectively manipulated using pharmacological approaches. Since a4b2 nAChRs are the predominant neuronal subtype, these discoveries likely have significant functional implications, and may provide important insights for drug discovery and development

    Nanocarriers of Fe3O4 as a Novel Method for Delivery of the Antineoplastic Agent Doxorubicin Into HeLa Cells in vitro

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    Here we report the synthesis and in vitro characterization of a redox-sensitive, magnetically inducible nanoparticle carrier system based on the doxorubicin (DOX) drug delivery model. Each quantal nanocarrier unit consists of a magnetite Fe3O4 nanoparticle core that is further encapsulated in self-assembled micelles of the redox-responsive polyethylene glycol derivative, DSPE-SS-mPEG. The nanocarrier system was prepared using a combination of ultrasonication and dialysis to produce the microenvironment sensitive delivery system. The final synthesized and DOX-loaded magnetic nanocarriers had an average size of ~150 nm when assembled with a 6.9% DOX payload. The release rate of DOX from these redox-responsive magnetic nanocarriers was shown to be accelerated in vitro when in the presence of glutathione (GSH). Furthermore, we demonstrated that more redox-responsive magnetic nanocarriers could be taken up by HeLa cells when a local magnetic field was applied. Once internalized within a cell, the micelles of the outer nanocarrier complex were broken down in the presence of higher concentrations of GSH, which accelerated the release of DOX. This produces a particle with dual operating characteristics that can be controlled via a specific cellular environment coupled with an exogenously applied signal in the form of a magnetic field triggering release

    High-throughput analysis of the mutagenic and cytotoxic properties of DNA lesions by next-generation sequencing

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    Human cells are constantly exposed to environmental and endogenous agents which can induce damage to DNA. Understanding the implications of these DNA modifications in the etiology of human diseases requires the examination about how these DNA lesions block DNA replication and induce mutations in cells. All previously reported shuttle vector-based methods for investigating the cytotoxic and mutagenic properties of DNA lesions in cells have low-throughput, where plasmids containing individual lesions are transfected into cells one lesion at a time and the products from the replication of individual lesions are analyzed separately. The advent of next-generation sequencing (NGS) technology has facilitated investigators to design scientific approaches that were previously not technically feasible or affordable. In this study, we developed a new method employing NGS, together with shuttle vector technology, to have a multiplexed and quantitative assessment of how DNA lesions perturb the efficiency and accuracy of DNA replication in cells. By using this method, we examined the replication of four carboxymethylated DNA lesions and two oxidatively induced bulky DNA lesions including (5′S) diastereomers of 8,5′-cyclo-2′-deoxyguanosine (cyclo-dG) and 8,5′-cyclo-2′-deoxyadenosine (cyclo-dA) in five different strains of Escherichia coli cells. We further validated the results obtained from NGS using previously established methods. Taken together, the newly developed method provided a high-throughput and readily affordable method for assessing quantitatively how DNA lesions compromise the efficiency and fidelity of DNA replication in cells
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