Test Targets 9.0: A Collaborative effort exploring the use of scientific methods for color imaging and process control

Painters spend their lifetime to master visual media by expressing the sense of beauty through conscious arrangement of color and patt erns. Tools and materials they use are prett y standard, but their creativity, as refl ected in their artwork, diff ers from artist to artist and from era to era. RIT School of Print Media publishes Test Targets annually using standard writing and publishing tools to turn ideas into printed pages. Our creativity is refl ected in the exploration of diff erent print media technologies and the visual eff ect they achieve. Th is introduction off ers readers a glance of the topics addressed by RIT students, faculty, and staff in Test Targets 9.0. Th e process ranges from experimentation, documentation, peer review, to fi nished manuscripts. It also describes how we benchmark two diff erent printing technologies, off set and highspeed inkjet, in terms of their tone and color capabilities, and how we use color management to achieve color agreement between these two dissimilar printing technologies

Test Targets 10: A Collaborative effort exploring the use of scientific methods for color imaging and process control

Th ere are six papers that were written, peer reviewed, and published in Test Targets 10. Two papers focus on printing standardization and conformity assessment. Chung describes aims and tolerances specified in ISO 12647-2 and the use of color measurement and data analysis for conformity assessment. Urbain and Khoury describe data reception requirements in ISO 12647-2 and ISO 15930 and the use of a test pdf file to assess conformity of any pdf workflow. Test Targets 10 will likely be remembered as the publication that covers OBA (optical brightening agents). Two papers focus on OBA. Tian and Chung report the effect of paper containing OBA on printed colors and how such effect can be corrected using different mathematics. Sigg and Millward report the stability of OBA as a function of exposure to light over time. In addition, Gallery of Visual Interest shows side-by-side the visual effect of pictorial and synthetic color images printed on paper with and without OBA. Printing conformity is result-oriented and does not dictate the press calibration method used. The fifth paper, authored by Wang, compares the compatibility of two press calibration methods, TVI and G7, by means of gradation compensation and press run simulation. Printing conformity requires that correct inks and paper be used. Verifying that correct inks are used is outside the capability of a printer. Th e sixth paper, authored by Zhang, explores an alternative ink drawdown and ink verification method that could be implemented by printers. Test Forms is a regular feature of Test Targets. We are pleased to showcase pictorial color reference images, Roman 16 Reference Images, courtesy of Bundesverband Druck und Medien e.V. (bvdm), and many possible uses of these images for printing process control and for color management studies. For example, we can compare the appearance of an image printed from the supplied CMYK file with the image from a supplied RGB file that was converted to CMYK by a color management application

Prognostic relevance of CCDC88C (Daple) transcripts in the peripheral blood of patients with cutaneous melanoma

A loss of balance between G protein activation and deactivation has been implicated in the initiation of melanomas, and non-canonical Wnt signaling via the Wnt5A/Frizzled (FZD) pathway has been shown to be critical for the switch to an invasive phenotype. Daple [CCDC88C], a cytosolic guanine nucleotide exchange modulator (GEM) which enhances non-canonical Wnt5A/FZD signaling via activation of trimeric G protein, Gαi, has been shown to serve opposing roles-as an inducer of EMT and invasiveness and a potent tumor suppressor-via two isoforms, V1 (full-length) and V2 (short spliced isoform), respectively. Here we report that the relative abundance of these isoforms in the peripheral circulation, presumably largely from circulating tumor cells (CTCs), is a prognostic marker of cutaneous melanomas. Expression of V1 is increased in both the early and late clinical stages (p \u3c 0.001, p = 0.002, respectively); V2 is decreased exclusively in the late clinical stage (p = 0.003). The two isoforms have opposing prognostic effects: high expression of V2 increases relapse-free survival (RFS; p = 0.014), whereas high expression of V1 tends to decrease RFS (p = 0.051). Furthermore, these effects are additive, in that melanoma patients with a low V2-high V1 signature carry the highest risk of metastatic disease. We conclude that detection of Daple transcripts in the peripheral blood (i.e., liquid biopsies) of patients with melanoma may serve as a prognostic marker and an effective strategy for non-invasive long-term follow-up of patients with melanoma

Učinak stope zagrijavanja na temperaturi staklastog prijelaza umreženih smola za baze proteza

The purpose of the study was to investigate the effect of different heating rates in the evaluation of the transition glass temperature of a dough-moulded poly(methylmethacrylate) denture base material Cross-linking agent ethylene glycol dimethacrylate (EGDMA) was added to the MM A monomer component: in concentration of 10% by volume. The polymer component was an unpigmented PMMA homopolymer. A comparison group of specimens was made by use of monomer liquid without any cross-linking agent. Specimens were produced in moulds according to conventional dental flasking and curing procedures. Measurements of Tg were determined by thermomechanical analysis using a Stanton Redcroft TMA, Model 790 (PL Thermal Science Ltd., Epson, UK). Heating rates of 5 °C/min, 10 °C/min and 15 °C/min were selected for this investigation. It was concluded that the addition of cro- os-linking agent would affect Tg denture base resins. Tg values were highly dependent on the heating rates used in thermomechanical analysis, being very significantly increased with a heating rate increase.Svrha istraživanja bila je ispitati učinak različitih brzina zagrijavanja kod procjene temperature staklastoga prijelaza toplopolimerizirajućih poli (metilmetalkrilnih) smola za baze proteza. Umrezivač etilen glikol dimetakrilat dodan je monomer-komponenti MMA u koncentraciji od 10% po volumenu. Polimerna komponenta bila je nepigmentirani PMMA homopolimer. Napravljena je poredbena skupina uzoraka uporabom monomerne tekućine bez umrezivača. Pripravci su napravljeni u kalupima, u skladu s uobičajenom kivetnom tehnikom. Mjerenja Tg određena su termomehaničkom raščlambom uporabom Stanton Redcroft TMA Model 790 (PL Thermal Sciences Ltd., Epson, UK), Za to istraživanje odabrane su brzine zagrijavanja od 5 °C/min, 10 °C/min i 15 °C/min. Zaključeno je da dodavanje umrezivača utječe na Tg smola za baze proteza. Tg vrijednosti jako su ovisne o brzinama zagrijavanja upotrijebljenih tijekom termomehaničke raščlambe s tim da se uvelike povisuju povećavanja brzine zagrijavanja

Membrane Anchoring of the Diras3 N-terminal Extension Permits Tumor Suppressor Function

DIRAS3 is an imprinted tumor suppressor gene encoding a GTPase that has a distinctive N-terminal extension (NTE) not found in other RAS proteins. This NTE and the prenylated C-terminus are required for DIRAS3-mediated inhibition of RAS/MAP signaling and PI3K activity at the plasma membrane. In this study, we applied biochemical, biophysical, and computational methods to characterize the structure and function of the NTE. The NTE peptide recognizes phosphoinositides PI(3,4,5)P3 and PI(4,5)P2 with rapid kinetics and strong affinity. Lipid binding induces NTE structural change from disorder to amphipathic helix. Mass spectrometry identified N-myristoylation of DIRAS3. All-atom molecular dynamic simulations predict DIRAS3 could adhere to the membrane through both termini, suggesting the NTE is involved in targeting and stabilizing DIRAS3 on the membrane by double anchoring. Overall, our results are consistent with DIRAS3\u27s function as a tumor suppressor, whereby the membrane-bound DIRAS3 can effectively target PI3K and KRAS at the membrane

A Phase I, First-in-Human Study of GSK2849330, an Anti-HER3 Monoclonal Antibody, in HER3-Expressing Solid Tumors

Background GSK2849330, an anti-HER3 monoclonal antibody that blocks HER3/Neuregulin 1 (NRG1) signaling in cancer cells, is engineered for enhanced antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity. This phase I, first-in-human, open-label study assessed the safety, pharmacokinetics (PK), pharmacodynamics, and preliminary activity of GSK2849330 in patients with HER3-expressing advanced solid tumors. Patients and Methods Patients with various tumor types were prospectively selected for HER3 expression by immunohistochemistry; a subset was also screened for NRG1 mRNA expression. In the dose-escalation phase, patients received GSK2849330 1.4-30 mg/kg every 2 weeks, or 3 mg/kg or 30 mg/kg weekly, intravenously (IV). In the dose-expansion phase, patients received 30 mg/kg GSK2849330 IV weekly. Results Twenty-nine patients with HER3-expressing cancers, of whom two expressed NRG1, received GSK2849330 (dose escalation: n = 18, dose expansion: n = 11). GSK2849330 was well tolerated. No dose-limiting toxicities were observed. The highest dose, of 30 mg/kg weekly, expected to provide full target engagement, was selected for dose expansion. Treatment-emergent adverse events (AEs) were mostly grade 1 or 2. The most common AEs were diarrhea (66%), fatigue (62%), and decreased appetite (31%). Dose-proportional plasma exposures were achieved, with evidence of HER3 inhibition in paired tissue biopsies. Of 29 patients, only 1 confirmed partial response, lasting 19 months, was noted in a patient with CD74-NRG1-rearranged non-small cell lung cancer (NSCLC). Conclusion GSK2849330 demonstrated a favorable safety profile, dose-proportional PK, and evidence of target engagement, but limited antitumor activity in HER3-expressing cancers. The exceptional response seen in a patient with CD74-NRG1-rearranged NSCLC suggests further exploration in NRG1-fusion-positive cancers. Implications for Practice This first-in-human study confirms that GSK2849330 is well tolerated. Importantly, across a variety of HER3-expressing advanced tumors, prospective selection by HER3/NRG1 expression alone was insufficient to identify patients who could benefit from treatment with this antibody-dependent cell-mediated cytotoxicity- and complement-dependent cytotoxicity-enhanced anti-HER3 antibody. The only confirmed durable response achieved was in a patient with CD74-NRG1-rearranged lung cancer. This highlights the potential utility of screening for NRG1 fusions prospectively across tumor types to enrich potential responders to anti-HER3 agents in ongoing trials

Conserved Orb6 Phosphorylation Sites Are Essential for Polarized Cell Growth in Schizosaccharomyces pombe

The Ndr-related Orb6 kinase is a key regulator of polarized cell growth in fission yeast, however the mechanism of Orb6 activation is unclear. Activation of other Ndr kinases involves both autophosphorylation and phosphorylation by an upstream kinase. Previous reports suggest that the Nak1 kinase functions upstream from Orb6. Supporting this model, we show that HA-Orb6 overexpression partially restored cell polarity in nak1 ts cells. We also demonstrated by coimmunoprecipitation and in vitro binding assays that Nak1 and Orb6 physically interact, and that the Nak1 C-terminal region is required forNak1/Orb6 complex formation in vivo. However, results from in vitro kinase assays did not show phosphorylation of recombinant Orb6 by HA-Nak1, suggesting that Orb6 activation may not involve direct phosphorylation by Nak1. To investigate the role of Orb6 phosphorylation and activity, we substituted Ala at the ATP-binding and conserved phosphorylation sites. Overexpression of kinase-dead HA-Orb6K122A in wild-type cells resulted in a loss of cell polarity, suggesting that it has a dominant-negative effect, and it failed to rescue the polarity defect of nak1 or orb6 ts mutants. Recombinant GST-Orb6S291A did not autophosphorylate in vitro suggesting that Ser291 is the primary autophosphorylation site. HA-Orb6S291A overexpression only partially rescued the orb6 polarity defect and failed to rescue the nak1 defect, suggesting that autophosphorylation is important for Orb6 function. GST-Orb6T456A autophosphorylated in vitro, indicating that the conserved phosphorylation site at Thr456 is not essential for kinase activity. However, HA-Orb6T456A overexpression had similar effects as overexpressing kinase-dead HA-Orb6K122A, suggesting that Thr456 is essential for Orb6 function in vivo. Also, we found that both phosphorylation site mutations impaired the ability of Myc-Nak1 to coimmunoprecipitate with HA-Orb6. Together, our results suggest a model whereby autophosphorylation of Ser291 and phosphorylation of Thr456 by an upstream kinase promote Nak1/Orb6 complex formation and Orb6 activation