Search

Introduction: The reported prevalence of ALK receptor tyrosine kinase gene (ALK) rearrangement in NSCLC ranges from 2% to 7%. The primary standard diagnostic method is fluorescence in situ hybridization (FISH). Recently, immunohistochemistry (IHC) has also proved to be a reproducible and sensitive technique. Reverse-transcriptase polymerase chain reaction (RT-PCR) has also been advocated, and most recently, the advent of targeted next-generation sequencing (NGS) for ALK and other fusions has become possible. This study compares anaplastic lymphoma kinase (ALK) evaluation with all four techniques in resected NSCLC from the large European Thoracic Oncology Platform Lungscape cohort. Methods: A total of 96 cases from the European Thoracic Oncology Platform Lungscape iBiobank, with any ALK immunoreactivity were examined by FISH, central RT-PCR, and NGS. An H-score higher than 120 defines IHC positivity. RNA was extracted from the same formalin-fixed, paraffin-embedded tissues. For RT-PCR, primers covered the most frequent ALK translocations. For NGS, the Oncomine Solid Tumour Fusion Transcript Kit (Thermo Fisher Scientific, Waltham, MA) was used. The concordance was assessed using the Cohen κ coefficient (two-sided α ≤ 5%). Results: NGS provided results for 77 of the 95 cases tested (81.1%), whereas RT-PCR provided results for 77 of 96 (80.2%). Concordance occurred in 55 cases of the 60 cases tested with all four methods (43 ALK negative and 12 ALK positive). Using ALK copositivity for IHC and FISH as the criterion standard, we derived a sensitivity for RT-PCR/NGS of 70.0%/85.0%, with a specificity of 87.1%/79.0%. When either RT-PCR or NGS was combined with IHC, the sensitivity remained the same, whereas the specificity increased to 88.7% and 83.9% respectively. Conclusion: NGS evaluation with the Oncomine Solid Tumour Fusion transcript kit and RT-PCR proved to have high sensitivity and specificity, advocating their use in routine practice. For maximal sensitivity and specificity, ALK status should be assessed by using two techniques and a third one in discordant cases. We therefore propose a customizable testing algorithm. These findings significantly influence existing testing paradigms and have clear clinical and economic impact. © 2017 International Association for the Study of Lung Cancer

Introduction: Phosphatase and tensin homolog (PTEN) loss is frequently observed in NSCLC and associated with both phosphoinositide 3-kinase activation and tumoral immunosuppression. PTEN immunohistochemistry is a valuable readout, but lacks standardized staining protocol and cutoff value. Methods: After an external quality assessment using SP218, 138G6 and 6H2.1 anti-PTEN antibodies, scored on webbook and tissue microarray, the European Thoracic Oncology Platform cohort samples (n = 2245 NSCLC patients, 8980 tissue microarray cores) were stained with SP218. All cores were H-scored by pathologists and by computerized pixel-based intensity measurements calibrated by pathologists. Results: All three antibodies differentiated six PTEN+ versus six PTEN- cases on external quality assessment. For 138G6 and SP218, high sensitivity and specificity was found for all H-score threshold values including prospectively defined 0, calculated 8 (pathologists), and calculated 5 (computer). High concordance among pathologists in setting computer-based intensities and between pathologists and computer in H-scoring was observed. Because of over-integration of the human eye, pixel-based computer H-scores were overall 54% lower. For all cutoff values, PTEN- was associated with smoking history, squamous cell histology, and higher tumor stage (p < 0.001). In adenocarcinomas, PTEN- was associated with poor survival. Conclusion: Calibration of immunoreactivity intensities by pathologists following computerized H-score measurements has the potential to improve reproducibility and homogeneity of biomarker detection regarding epitope validation in multicenter studies. © 2018 International Association for the Study of Lung Cancer

Okra is one of the widely grown vegetables for the commercial market in the United States Virgin Islands and the rest of the Caribbean. Plant biostimulants or agricultural biostimulants include diverse substances and microorganisms that are derived from commercial marine algae extracts, enhance plant growth of fruits and vegetables. Plants of eight cultivars of okra (Abelmoschus esculentus) were treated weekly with Stimplex® (5 mL/L) liquid seaweed extract of Ascophyllum nodosum and Biozest® (100 mL/5L) crop hiostimulant as foliar spray to assess their influence on yields. Half of the plants in a row (5 plants) were sprayed weekly and half of the plants (5plants) were untreated (control). Eight cultivars of okra ca. Clemson Spineless 80, Red Burgundy, Clemson Spineless, Jambalaya, Red Velvet, Annie Oakley II, Perkins Mammoth and Chant were investigated. The experimental design was a randomized complete block with 3 replications and consisted of rows spaced 3' apart and spaced 2' between the plants within a row. They were organically managed. Results showed that Biozest® treated plants of most of the cultivars responded positively. Marketable yields were higher with Biozest® treated plants of Clemson Spineless 80 (0.5%), Annie Oakley II (27.9%), Perkins Mammoth (49%), jambalaya (41.2), Chant (16%) and Red Burgundy (60%) than with the untreated control. Higher marketable yields were obtained with Stimplex® treated plants of Jambalaya (62%), Red Burgundy (58%) and Perkins Mammoth (30%) than with the untreated control. Cultivars produced lower or non-significant yields with Clemson Spineless 80, Clemson Spineless, Red Velvet, Annie Oakley II and Chant. The results show that biostimulants may increase yields in okra. However, further research trials are needed to fully explain the effects of biostimulants in commercial production.

Crop bio-stimulants derived from commercial marine algae extracts have been known to improve yields in fruits and vegetable crops in conventional production system. Therefore, studies of biostimulants in organic management system are needed to determine their potential impact on yield. In organic management system ten cultivars of eggplant (Nubia, Fairy Tale, Dancer, Beatrice, Calliope, Orient Charm, Barbarella, RosaBianca, Machiaw and Shooting Stars) were selected to evaluate bio-stimulant effect. Ten cultivars of eggplant (Solanum melongena L.) were treated weekly with Stimplex® (5 mL/L) (liquid seaweed extract of Ascophyllum nodosum) and Biozest® (20 mL/L) crop bio-stimulants as foliar spray. Half of the plants in a row (5 plants) were sprayed weekly and the other half of the plants (5 plants) were untreated as a control. The organically managed, experimental design was a randomized complete block with 3 replications consisting of rows spaced 3' apart with plants spaced 2' between each plant within a row. Results showed that Stimplex® treated plants performed better than biozest treated plants. Marketable yields were higher in Stimplex® treated plants of Nubia (10.7%), Fairy Tale (42.5%), Dancer (31.9%), Beatrice (27.8%), Barbarella (13.9%), Machiaw (84.2%) and Shooting Stars (9.9%) than their respective untreated controls. Higher marketable yields were obtained in Biozest® treated plants of Nubia (35.8%), Beatrice (10.3%), Orient Charm (1%), Rosa Bianca (68.8), and Shooting Stars (55%) relative to their respective untreated controls. The remaining cultivars produced lower or non-significant yields. These results suggest that bio-stimulants may increase yields in eggplant. Additional research trials are needed to fully explain the effects of bio-stimulants in organically managed commercial production of eggplant.

Organic farming provides an opportunity to positively impact the environment, human health, and future yields. Tomato (Solanum lycopersicum L.) is a high value vegetable grown for the fresh market in the United States Virgin Islands. Four cultivars: “Mountain Fresh”, “Red Defender”, “Security 28”, and “Defiant” were evaluated for yield potential in an on-farm trial with farmer’s participation at Sejah Farm, St. Croix. The experimental design was a complete randomized block with three replications. The trial was conducted from November, 2012 through March, 2013. Crops were grown using National Organic Program standards and approved practices. Seeds were planted in seedling trays containing organic (farmer produced) compost, reared in the greenhouse, then transplanted into the field 21 days after germination. Plots consisted of three rows spaced 1.2 m apart and in-row plant spacing at 0.6m for a total of 13,883 plants per hectare. Organic fertilizer (Nature’s Nectar 5-4-5) was applied on a weekly basis using standard commercial fertilization rates through drip tape fertigation. The field was monitored for diseases and insect pests periodically by staff and our extension entomologist. Weeds were controlled manually and mechanically. Data on average fruit and yield per plant and overall yield was collected from eight harvests during the growing season. No significant differences were observed between the four cultivars tested for marketable, unmarketable, or total yield (marketable plus unmarketable yield). “Mountain Fresh” produced numerically higher total fruit yield with 37.1t/ha. “Defiant” produced numerically higher marketable (US #1) fruit yield with 25.0t/ha and also had numerically lower unmarketable fruit with 10.5t/ha. Based on these observations, all four cultivars tested can be recommended for commercial organic production in the USVI.

Expression of antigenic proteins in the periphery may result in immunologic tolerance, immunologic ignorance, or autoimmunity. It is not clear why some Ags induce tolerance, whereas others activate Ag-reactive T cells. The physical nature of the Ag, the developmental timing of Ag expression, the priming of reactive lymphocytes, and the level of Ag expression are possible factors determining the immunologic response to extra-thymic Ags. Expression of the whole SV40 large T Ag (SV40-T) induces transformation of T antigen-expressing cells in vivo, and this phenomenon has been postulated to be the triggering event that leads to autoimmunity in some transgenic mouse models. Here we present a model in which a nononcogenic, yet antigenic, fragment of the SV40-T (SV40-Tfrag) is expressed specifically in pancreatic islet beta-cells. In contrast to whole SV40-T transgenic mice, SV40-Tfrag mice that are also transgenic for a TCR specific for the SV40-T are ignorant of Ag in vivo. They do not respond in vivo to the tissue-specific SV40-Tfrag Ag even after priming, but are fully responsive in vitro. This immunologic ignorance cannot be broken after activated SV40-T reactive T cells are transferred into sublethally irradiated mice expressing the islet-specific SV40-Tfrag. However, similar adoptive transfer experiments in mice co-expressing B7-1 and SV40-Tfrag on islet cells specifically lead to Ag recognition and diabetes. This demonstrates that in some circumstances the presence of (primed) reactive T cells is not sufficient to break tolerance; rather, costimulation is additionally required to elicit an autoimmune response. This also suggests that SV40-T-induced cellular transformation is important for the autoimmune response directed against SV40-T in other tissue-specific transgenic models.

I tråd med Lissabonstrategien er det de nordiske landes mål, at øge befolkningernes deltagelse i voksen- og efteruddannelse, særligt blandt kortuddannede og tosprogede.Det er baggrunden for undersøgelsen af landenes kompetencepolitiske indsatser til fremme af livslang læring for alle. Undersøgelsen fokuserer på samarbejdet mellem myndigheder og arbejdsmarkedets parter, samspillet mellem uddannelsesinstitutioner og virksomheder, samt indsatser for at styrke voksnes nøglekompetencer.De nordiske strategier for livslang læring har flere fællestræk, herunder:• samarbejde mellem de uddannelses- og de arbejdsmarkedspolitiske myndigheder• øget fokus på realkompetencer, vejledning og rådgivning• tendens til mere offentlig regulering og frivillig koordineringRapporten afsluttes med anbefalinger til opfølgende arbejde og til videre analyser på området.

27th European Photovoltaic Solar Energy Conference and Exhibition; 2948-2949, The company Solaronix and Empa focus on the development of new unsymmetrical heptamethine dyes for application in dye sensitized solar cells. Because of their out-standing physical properties (e.g. high extinction coefficient and absorption maximum above 700 nm), these dyes are very promising NIR sensitizers. By skillful combination of different heterocycles and dianil derivatives, it is possible to synthesize and characterize various functionalized unsymmetrical heptamethine dyes. Furthermore, the efficiency of industrial dye sensitized solar cells prepared with such sensitizers is up to 1.3%. Remarkably, dye sensitized solar cells with heptamethine dyes, which solely absorb light in the NIR, appear in light yellow, the color of the electrolyte.

The qualities of a peripheral Ag that determine whether T cells will be tolerant of or responsive to it are poorly understood. To approach this problem, we studied the T cell response in a line of transgenic mice selectively expressing an oncoprotein in the islets of Langerhans. The SV40 large tumor Ag (SV40-T) is directed to islet beta-cells in Rip1-Tag3 (RT3) mice by a hybrid insulin promoter-SV40-T construct. Ag is first detected on these cells between 10 and 12 wk after birth. RT3 mice were bred with mice expressing a transgenic rearranged TCR recognizing SV40-T in the context of the class I MHC molecule, H-2Kk. T cell response in the resultant RT3/TCR-double transgenic mice was then analyzed. T cells are fully responsive to SV40-T in RT3/TCR-transgenic mice, and T cells infiltrate the islets of both RT3 and RT3/TCR-transgenic mice. This work demonstrates that T cells may remain responsive to self-Ag expressed outside the thymus, and that this responsiveness may result in autoimmunity. The developmentally delayed expression or the oncogenic nature of SV40-T in the RT3-transgenic mice may be important in determining this T cell response.

For years EMPA has made many contributions to research on historical materials and their manufacture and conservation in archaeology, restoration and the preservation of historical monuments; areas that are somewhat exotic for a materials testing and research institute. This involves complex, preferably non-destructive investigations on objects that are often very valuable by means of organic and inorganic analysis methods. The emphasis is on investigations of paints and varnishes on paintings and metals such as gold, silver, copper, bronze and iron. The analysis of various materials and the associated problems are illustrated by a range of examples.