Evaluation of expanded gamut software solutions for spot color reproduction

Expanded gamut printing is an approach in color reproduction that expands the color gamut of conventional CMYK printing processes via the use of additional colorants, such as Orange, Green, and Violet inks. This study evaluates the ability of commercial color management software to create an accurate solution for an expanded gamut printing system. In this study, two printing processes were used, an Epson SureColor P9000 inkjet printer/proofer and an HP Indigo 7900 digital production press, both with 7-color expanded gamut ink sets. Software solutions from Alwan, CGS ORIS, ColorLogic, GMG Color, Heidelberg, and Kodak were evaluated. The systems were tested to see how well they could reproduce the colors in the entire PANTONE+ Solid Coated spot color library. It is shown that the solutions are able to reproduce 89% to 94% of the spot colors on the Epson P9000 inkjet printer and 77% to 87% of the library on the Indigo 7900, both to less than two CIEDE2000 (a typical tolerance in label and packaging work). The number of color patches in expanded gamut characterization test charts was noted, as this is still an area of proprietary, nonstandardized working practice. There are many different colorant combinations that can make the same color in expanded gamut printing. The ink build created by the different software solutions was studied, as it relates to press stability through appropriate choice of colorants. Pantone and Adobe provide everyday commercial tools for expanded color workflows. The study identified some issues with products from these companies that could confuse a less-skilled user in a busy production environment. The conclusion of the study is that expanded gamut solutions for spot color printing produce totally acceptable results for digital printing processes; expanded gamut printing is ready, here and now. The findings show that expanded gamut printing can replace cumbersome conventional spot color workflows creating considerable savings and advantages, especially for label and packaging printers.     

Viral dynamics of primary viremia and antiretroviral therapy in simian immunodeficiency virus infection

Mathematical modeling of viral replication dynamics, based on sequential measurements of levels of virion-associated RNA in plasma during antiretroviral treatment, has led to fundamental new insights into human immunodeficiency virus type 1 pathogenesis. We took advantage of the simian immunodeficiency virus (SIV)-infected macaque model to perform detailed measurements and mathematical modeling during primary infection and during treatment of established infection with the antiretroviral drug (R)-9-(2-phosphonylmethoxypropyl)adenine (PMPA). The calculated clearance half-life for productively infected cells during resolution of the peak viremia of primary infection was on the order of 1 day, with slightly shorter clearance half-lives calculated during PMPA treatment. Viral reproduction rates upon discontinuation of PMPA treatment after 2 weeks were approximately twofold greater than those obtained just prior to initiation of treatment in the same animals, likely reflecting accumulation of susceptible target cells during treatment. The basic reproductive ratio (R0) for the spread of SIV infection in vivo, which represents the number of productively infected cells derived from each productively infected cell at the beginning of infection, was also estimated. This parameter quantifies the extent to which antiviral therapy or vaccination must limit the initial spread of virus to prevent establishment of chronic disseminated infection. The results thus provide an important guide for efforts to develop vaccines against SIV and, by extension, human immunodeficiency virus.     

Polymeric prodrugs of mitomycin C designed for tumour tropism and sustained activation

Prodrugs of mitomycin C (MMC) based on soluble poly-[N-(2-hydroxyethyl)-L-glutamine] (pHEG) polymers have been evaluated as tumour-targeted drugs. These materials are designed to exploit the enhanced permeability of tumour vasculature, combining a passive tumour tropism with decreased systemic liberation of free MMC. A tri- or tetrapeptide linkage (e.g. Gly-Phe-Ala-Leu) between pHEG and the aziridine nitrogen of MMC can combine good hydrolytic stability with rapid cleavage by lysosomal enzymes, releasing free MMC. The conjugates showed decreased systemic toxicity and could be administered to mice at a total MMC dose of 15 mg/kg i.v., compared with just 6 mg/kg for free MMC. Conjugates also showed better activity against animal models of established tumours, achieving up to 77% increased life span (ILS) against solid P388 leukaemia, compared with only 23% for free MMC, and up to 121% ILS against solid C26 colorectal carcinoma, compared with no activity for the free drug. Improving the therapeutic index of anticancer drugs by combining tumour tropism with decreased systemic toxicity is a versatile approach that should produce a new generation of improved anticancer agents.     

Prolonged tamoxifen exposure selects a breast cancer cell clone that is stable in vitro and in vivo

The effects of long-term tamoxifen exposure on cell growth and cell cycle kinetics were compared between oestrogen receptor (ER)-positive (MCF-7) and ER-negative (MDA-MB-231) cell lines. In the MCF-7 cell line, prolonged tamoxifen exposure (0.5 mumol/l for > 100 days) blocked cells in G0-G1 of the cell cycle, and slowed the doubling time of cells from 30 to 59 h. These effects corresponded to an increase in the cellular accumulation of tamoxifen over time [mean area under concentration curve (AUC) = 77.92 mumoles/10(6)/cells/day]. In contrast, in the MDA-MB-231 cell line, long-term tamoxifen exposure had no obvious effect on the doubling time, and reduced cellular tamoxifen accumulation (mean AUC = 50.50 mumoles/10(6)/cells/day) compared to the MCF-7 cells. Flow cytometric analysis of MDA-MB-231 cells demonstrated that a new tetraploid clone emerged following 56 days of tamoxifen exposure. Inoculation of the MDA-MB-231 tetraploid clone and MDA-MB-231 wildtype cells into the opposite flanks of athymic nude mice resulted in the rapid growth of tetraploid tumours. The tetraploid tumours maintained their ploidy following tamoxifen treatment for nine consecutive serial transplantations. Histological examination of the fifth transplant generation xenografts revealed that the tetraploid tumour had a 25-30 times greater mass, area of haemorrhage and necrosis, a slightly higher mitotic index and was more anaplastic than the control neoplasm. The control wildtype MDA-MB-231 tumours maintained a stable ploidy following tamoxifen treatment until the eighth and ninth transplantation, when a tetraploid population appeared, suggesting that tamoxifen treatment may select for this clone in vivo. These studies suggest that prolonged tamoxifen exposure may select for new, stable, fast growing cell clones in vitro as well as in vivo.     

Another false alarm? apnea monitor activation in a Neonatal Intensive Care Unit graduate

Neonatal emergencies have become more common as increasingly sophisticated Neonatal Intensive Care Units graduate lower birth-weight babies born at younger gestational ages. These patients present a number of challenges to emergency physicians. They are often discharged with apnea monitors, which generate a high number of false alarms. Neonatal Intensive Care Unit graduates, however, are predisposed to a number of conditions that can result in true episodes of apnea. We present such a case and will discuss the unusual underlying cause of apnea, the utility of apnea monitors, and the need for emergency physicians to be prepared to evaluate and treat these potentially complicated patients.     

Activation of the mitogen-activated protein kinase pathway is involved in and sufficient for megakaryocytic differentiation of CMK cells

Activation of the mitogen-activated protein (MAP) kinase pathway has been associated with both cell proliferation and differentiation. Constitutively activated forms of Mek (MAP kinase/Erk kinase) and Erk (MAP kinase) have been previously shown capable of inducing differentiation or proliferation in nonhematopoietic cells. To specifically examine the role of Erk activation in megakaryocytic growth and development, we activated the MAP kinase pathway by the transfection of constitutively activated Mek or Erk cDNA into a human megakaryoblastic cell line, CMK, by electroporation. The CMK transfectant clones that expressed constitutively activated Mek or Erk showed morphologic changes of differentiation. Transfected cells also showed expression of mature megakaryocytic cell surface markers. The MAP kinase pathway was also activated by treatment of the hematopoietic cells with a cytokine that activates Erk. The treatment of CMK cells with stem cell factor (SCF ) caused MAP kinase activation and induced differentiation by the expression of mature megakaryocytic cell surface markers. The effects of the SCF treatment were inhibited by pretreatment with a specific inhibitor of the MAP kinase pathway, PD98059. In this report, we conclude that activation of the MAP kinase pathway was both necessary and sufficient to induce differentiation in this megakaryoblastic cell line.     

Molecular cloning and functional expression of a recombinant 72.5 kDa fragment of the 110 kDa regulatory subunit of smooth muscle protein phosphatase 1M

RATIONALE AND OBJECTIVES: We compared adverse reactions and image quality for hysterosalpingography (HSG) performed with ionic (diatrizoate meglumine combined with iodipamide meglumine [DM + IM]) and nonionic (iohexol) contrast media. METHODS: We performed a study of 95 patients who had HSG and were randomly selected to receive DM + IM or iohexol. Patients reported episodes of abdominal pain and other adverse reactions immediately and 24 hr after the procedure and categorized severity of symptoms on a subjective scale. Two radiologists evaluated image quality for diagnosis. RESULTS: Prevalence of abdominal pain and other reactions both immediately and 24 hr after HSG was lower in patients who received iohexol than in patients who received DM + IM. Moderate or severe abdominal pain was significantly lower in the iohexol group than in the DM + IM group (p < .05). Visualization of the uterine cavity and ampullary rugae was judged excellent with both contrast media (87% with iohexol and 92% with DM + IM). CONCLUSION: Iohexol and DM + IM are excellent contrast media for use during HSG; iohexol 300 may cause fewer episodes of more severe and prolonged abdominal pain.