921 research outputs found

    Krill’s Disease: A Newer Management Option

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    Purpose: To report a case of a young female who presented with scotoma in the right eye for few days. Case Report: Krill’s disease or acute retinal pigment epithelitis (ARPE) is a self-limiting retinal disease with no specific treatment. Typical clinical and imaging features helped us to diagnose her with ARPE. Intravenous methylprednisolone (IVMP), which gives a rapid anti-inflammatory response, was advised. An SD-OCT scan post-injection showed a reduction in hyperreflectivity and height of lesion at day 3 and near total resolution by day 5. Conclusion: This case suggests rapid resolution of ARPE with the use of IVM

    Odessa's Intellectuals In the 1920s: the activities of the All-Ukrainian Committee for the Promotion of Scientists

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    У статті аналізуються усі сфери суспільного життя в Україні у перше десятиліття більшовицького режиму. Досліджується основні напрямків діяльності Всеукраїнського комітету сприяння вченим у 1920 рр. у великому науковому центрі України – Одесі.В статье анализируются все сферы общественной жизни в Украине в первое десятилетие большевистского режима. Исследуется основные направления деятельности Всеукраинского комитета содействия ученым в 1920 в большом научном центре Украины - Одессе.The article analyzes all spheres of public life in Ukraine in the first decade of the Bolshevik regime. The main directions of activity of the All-Ukrainian Committee for the Facilitation of Scientists in 1920 in the large scientific center of Ukraine - Odessa were investigated

    Концепція реформування літературної освіти в середній школі (предмет – українська література)

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    This paper provides a technique that minimize the cruise drag (or maximize L/D) fora blended wing body transport with a number of constraints. The wing shape design isdone by splitting the problem into 2D airfoil design and 3D twist optimization with a frozenplanform. A 45% to 50% reduction of inviscid drag is nally obtained, with desired pitchingmoment. The results indicate that further improvement can be obtained by modifying theplanform and varying the camber more aggressively.QC 20121113NOVEMO

    Interplay of strong and weak hydrogen bonding in molecular complexes of some 4,4'-disubstituted biphenyls with urea, thiourea and water

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    The crystal chemistry and engineering of a new family of host-guest complexes is described. 4,4'-Dicyanobiphenyl (DCBP) forms a 1:1 complex, 1 with urea wherein the DCBP host forms large hexagonal channels via C-H···N hydrogen bonds and the urea guest molecules are arranged in N-H···O ribbons which fit completely within the host channels. By analogy, 4,4'-bipyridine N,N'-dioxide (BPNO) was selected as a molecule that can form a corresponding C-H…O based channel. BPNO forms complexes with urea (2), thiourea (3) and water (4). Structures 2 and 3 provide some points of comparison with the structure of 1 but are not fully equivalent to it. In structure 4, the smaller guest water is able to fit neatly within the smaller hexagonal channel of BPNO and in this sense, the degree of structural predictability is satisfactory. To obtain another structure similar to that of 1, 4,4'-dinitrobiphenyl (DNBP) was identified as an alternative host compound. This choice was justified by the structure of its 1:1 complex, 5 with urea. In all cases, the guest molecules interact with each other via strong hydrogen bonds and form an essential template for the weak hydrogen bonded assembly of the host network structure but the latter is still of some significance. One finds consequently, in complexes 1-5, a constructive interplay of strong and weak hydrogen bonds

    Molecular networks in the crystal structures of tetrakis(4-iodophenyl)methane and (4-iodophenyl)triphenylmethane

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    The crystal structure of tetrakis(4-iodophenyl)methane is analysed in terms of molecular networks wherein the tetraphenylmethane moieties and I4 synthons are considered as molecular and supramolecular nodes. This I4 cluster plays the same role in generating molecular networks as does the Br4 cluster in the isomorphous tetrakis(4-bromophenyl)methane derivative. (4-Iodophenyl)triphenylmethane crystallises in a lower symmetry space group but features an unusual I···Ph interaction. In this series of halo-substituted tetraphenylmethanes the molecules exhibit similar columnar packing in the solid state, accounting for their crystallisation in non-centrosymmetric space groups

    Comparison between the for-profit human milk industry and nonprofit human milk banking: Time for regulation?

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    Human milk (HM) is a highly evolutionary selected, complex biofluid, which provides tailored nutrition, immune system support and developmental cues that are unique to each maternal-infant dyad. In the absence of maternal milk, the World Health Organisation recommends vulnerable infants should be fed with screened donor HM (DHM) from a HM bank (HMB) ideally embedded in local or regional lactation support services. However, demand for HM products has arisen from an increasing awareness of the developmental and health impacts of the early introduction of formula and a lack of prioritisation into government-funded and nonprofit milk banking and innovation. This survey of global nonprofit milk bank leaders aimed to outline the trends, commonalities and differences between nonprofit and for-profit HM banking, examine strategies regarding the marketing and placement of products to hospital and public customers and outline the key social, ethical and human rights concerns. The survey captured information from 59 milk bank leaders in 30 countries from every populated continent. In total, five companies are currently trading HM products with several early-stage private milk companies (PMCs). Products tended to be more expensive from PMC than HMB, milk providers were financially remunerated and lactation support for milk providers and recipients was not a core function of PMCs. Current regulatory frameworks for HM vary widely, with the majority of countries lacking any framework, and most others placing HM within food legislation, which does not include the support and care of milk donors and recipient prioritisation. Regulation as a Medical Product of Human Origin was only in place to prevent the sale of HM in four countries; export and import of HM was banned in two countries. This paper discusses the safety and ethical concerns raised by the commodification of HM and the opportunities policymakers have globally and country-level to limit the potential for exploitation and the undermining of breastfeeding

    Activation of Human T-Helper/Inducer Cell, T-Cytotoxic Cell, B-Cell, and Natural Killer (NK)-Cells and induction of Natural Killer Cell Activity against K562 Chronic Myeloid Leukemia Cells with Modified Citrus Pectin

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    <p>Abstract</p> <p>Background</p> <p>Modified citrus pectin (MCP) is known for its anti-cancer effects and its ability to be absorbed and circulated in the human body. In this report we tested the ability of MCP to induce the activation of human blood lymphocyte subsets like T, B and NK-cells.</p> <p>Methods</p> <p>MCP treated human blood samples were incubated with specific antibody combinations and analyzed in a flow cytometer using a 3-color protocol. To test functionality of the activated NK-cells, isolated normal lymphocytes were treated with increasing concentrations of MCP. Log-phase PKH26-labeled K562 leukemic cells were added to the lymphocytes and incubated for 4 h. The mixture was stained with FITC-labeled active form of caspase 3 antibody and analyzed by a 2-color flow cytometry protocol. The percentage of K562 cells positive for PKH26 and FITC were calculated as the dead cells induced by NK-cells. Monosaccharide analysis of the MCP was performed by high-performance anion-exchange chromatography with pulse amperometric detection (HPAEC-PAD).</p> <p>Results</p> <p>MCP activated T-cytotoxic cells and B-cell in a dose-dependent manner, and induced significant dose-dependent activation of NK-cells. MCP-activated NK-cells demonstrated functionality in inducing cancer cell death. MCP consisted of oligogalacturonic acids with some containing 4,5-unsaturated non-reducing ends.</p> <p>Conclusions</p> <p>MCP has immunostimulatory properties in human blood samples, including the activation of functional NK cells against K562 leukemic cells in culture. Unsaturated oligogalacturonic acids appear to be the immunostimulatory carbohydrates in MCP.</p

    Calpain activation through galectin-3 inhibition sensitizes prostate cancer cells to cisplatin treatment

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    Prostate cancer will develop chemoresistance following a period of chemotherapy. This is due, in part, to the acquisition of antiapoptotic properties by the cancer cells and, therefore, development of novel strategies for treatment is of critical need. Here, we attempt to clarify the role of the antiapoptotic molecule galectin-3 in prostate cancer cells using siRNA and antagonist approaches. The data showed that Gal-3 inhibition by siRNA or its antagonist GCS-100/modified citrus pectin (MCP) increased cisplatin-induced apoptosis of PC3 cells. Recent studies have indicated that cisplatin-induced apoptosis may be mediated by calpain, a calcium-dependent protease, as its activation leads to cleavage of androgen receptor into an androgen-independent isoform in prostate cancer cells. Thus, we examined whether calpain activation is associated with the Gal-3 function of regulating apoptosis. Here, we report that Gal-3 inhibition by siRNA or GCS-100/MCP enhances calpain activation, whereas Gal-3 overexpression inhibits it. Inhibition of calpain using its inhibitor and/or siRNA attenuated the proapoptotic effect of Gal-3 inhibition, suggesting that calpain activation may be a novel mechanism for the proapoptotic effect of Gal-3 inhibition. Thus, a paradigm shift for treating prostate cancer is suggested whereby a combination of a non-toxic anti-Gal-3 drug together with a toxic chemotherapeutic agent could serve as a novel therapeutic modality for chemoresistant prostate cancers

    Novel Inhibitors of Rad6 Ubiquitin Conjugating Enzyme: Design, Synthesis, Identification, and Functional Characterization

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    Protein ubiquitination is important for cell signaling, DNA repair, and proteasomal degradation, and it is not surprising that alterations in ubiquitination occur frequently in cancer. Ubiquitin-conjugating enzymes (E2) mediate ubiquitination by selective interactions with ubiquitin-activating (E1) and ubiquitin ligase (E3) enzymes, and thus selective E2 small molecule inhibitor (SMI) will provide specificity unattainable with proteasome inhibitors. Here we describe synthesis and functional characterization of the first SMIs of human E2 Rad6B, a fundamental component of translesion synthesis DNA repair. A pharmacophore model for consensus E2 ubiquitin-binding sites was generated for virtual screening to identify E2 inhibitor candidates. Twelve triazine (TZ) analogs screened in silico by molecular docking to the Rad6B X-ray structure were verified by their effect on Rad6B ubiquitination of histone H2A. TZs #8 and 9 docked to the Rad6B catalytic site with highest complementarity. TZs #1, 2, 8, and 9 inhibited Rad6B-ubiquitin thioester formation and subsequent ubiquitin transfer to histone H2A. SMI #9 inhibition of Rad6 was selective as BCA2 ubiquitination by E2 UbcH5 was unaffected by SMI #9. SMI #9 more potently inhibited proliferation, colony formation, and migration than SMI #8, and induced MDA-MB-231 breast cancer cell G2–M arrest and apoptosis. Ubiquitination assays using Rad6 immunoprecipitated from SMI #8- or 9-treated cells confirmed inhibition of endogenous Rad6 activity. Consistent with our previous data showing Rad6B-mediated polyubiquitination stabilizes β-catenin, MDA-MB-231 treatment with SMIs #8 or 9 decreased β-catenin protein levels. Together these results describe identification of the first Rad6 SMIs
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