Molecular Genetics of Conjunctival Melanoma and Prognostic Value of TERT Promoter Mutation Analysis

The aim of this study was exploration of the genetic background of conjunctival melanoma (CM) and correlation with recurrent and metastatic disease. Twenty-eight CM from the Rotterdam Ocular Melanoma Study group were collected and DNA was isolated from the formalin-fixed paraffin embedded tissue. Targeted next-generation sequencing was performed using a panel covering GNAQ, GNA11, EIF1AX, BAP1, BRAF, NRAS, c-KIT, PTEN, SF3B1, and TERT genes. Recurrences and metastasis were present in eight (29%) and nine (32%) CM cases, respectively. TERT promoter mutations were most common (54%), but BRAF (46%), NRAS (21%), BAP1 (18%), PTEN (14%), c-KIT (7%), and SF3B1 (4%) mutations were also observed. No mutations in GNAQ, GNA11, and EIF1AX were found. None of the mutations was significantly associated with recurrent disease. Presence of a TERT promoter mutation was associated with metastatic disease (p-value = 0.008). Based on our molecular findings, CM comprises a separate entity within melanoma, although there are overlapping molecular features with uveal melanoma, such as the presence of BAP1 and SF3B1 mutations. This warrants careful interpretation of molecular data, in the light of clinical findings. About three quarter of CM contain drug-targetable mutations, and TERT promoter mutations are correlated to metastatic disease in CM.     

Sign language applications: preliminary modeling

For deaf persons to have ready access to information and communication technologies (ICTs), the latter must be usable in sign language (SL), i.e., include interlanguage interfaces. Such applications will be accepted by deaf users if they are reliable and respectful of SL specificities—use of space and iconicity as the structuring principles of the language. Before developing ICT applications, it is necessary to model these features, both to enable analysis of SL videos and to generate SL messages by means of signing avatars. This paper presents a signing space model, implemented within a context of automatic analysis and automatic generation, which are currently under development.

Scaffolding information problem solving in web-based collaborative inquiry learning

This study investigated the impact of different modes of scaffolding on students who are learning science through a web-based collaborative inquiry project in authentic classroom settings and explored the interaction effects with students’ characteristics. The intervention study aimed to improve domain-specific knowledge and metacognitive awareness during online information problem solving (IPS) as part of an online inquiry project. Three experimental conditions (teacher-enhanced scaffolding, technology-enhanced scaffolding, and both forms of scaffolding) were compared with a control condition in a two-by-two factorial quasi-experimental design. Moreover, gender and prior knowledge were examined as two factors which may have a significant impact on Web-based learning. In a four-week field study in secondary science education, pretest-posttest differences were measured. In total 347 students from 18 secondary school classes were involved and the classes were randomly distributed over the 4 conditions. Our findings support the notion of multiple scaffolding as an approach to enhance both knowledge acquisition and metacognitive awareness with respect to IPS-processes and to meet a mix of students with different needs within the context of a web-based inquiry learning project.     

Influence of FeO/SiO2 and CaO/SiO2 Ratios in Iron‐Saturated ZnO‐Rich Fayalite Slags on the Corrosion of MgO

The corrosion behavior of MgO in iron‐saturated ZnO‐rich fayalite (ZFS) slags having various FeO/SiO₂ ratio and CaO/SiO₂ ratio was investigated using MgO crucible tests for 12 h at 1200°C. The FeO/SiO₂ and CaO/SiO₂ ratios in the ZFS slags were varied from 1.0 to 2.2, and from 0.04 to 0.32, respectively. In all of the tests, it was observed that MgO dissolves into ZFS slags and that (Zn,Fe,Mg)₂SiO₄ olivine and (Zn,Fe,Mg)O solid solution are formed at the crucible/slag interface. The MgO dissolution decreased with the FeO/SiO₂ ratio up to a value of 1.7 and then slightly increased, whereas it continuously increased with the CaO/SiO₂ ratio. There is no obvious relationship between the amount of olivine and the FeO/SiO₂ ratio or CaO/SiO₂ ratio. In comparison, the formation of (Zn,Fe,Mg)O solid solution is enhanced by increasing the FeO/SiO₂ ratio or CaO/SiO₂ ratio in ZFS slags. The results suggest that MgO corrosion is the lowest for FeO/SiO₂ and CaO/SiO₂ ratios around 1.7 and 0, respectively.     

Inorganic polymers made of fayalite slag: On the microstructure and behavior of Fe

The microstructure of inorganic polymers (IP) formed from fayalite slag was investigated as a function of the composition of different activating solutions. The starting slag was 80 wt% amorphous, and after activation using sodium silicate solutions with varying SiO₂/Na₂O molar ratios, the amorphous phase dissolved and a binder phase was formed. The morphology of this binder, including the population and size of remnant particles and pores, was dependent on the particular activating solution used, and became denser as the level of silicate rose. ⁵⁷Fe Mössbauer spectroscopy revealed that the IP synthesis reaction is combined with the oxidation of Fe²⁺ from the fayalite slag to Fe³⁺ in the inorganic polymer binder. The reaction extent varied and could be quantified using the absorption areas of these ions. Data corroborate that the Fe²⁺ ions in the amorphous part of the fayalite slag and the Fe³⁺ ions in the new binder phase had an average oxygen‐coordination number of 5.     

Hedgehog Signaling in Prostate Cancer and Its Therapeutic Implication

Activation of Hedgehog (Hh) signaling is implicated in the development and progression of several tumor types, including prostate cancer, which is still the most common non-skin malignancy and the third leading cause of cancer-related mortality in men in industrialized countries worldwide. Several studies have indicated that the Hh pathway plays a crucial role in the development as well as in the progression of this disease to more aggressive and even therapy-resistant disease states. Moreover, preclinical data have shown that inhibition of Hh signaling has the potential to reduce prostate cancer invasiveness and metastatic potential. Clinical trials investigating the benefit of Hh inhibitors in patients with prostate cancer have recently been initiated. However, acquired drug resistance has already been observed in other tumor types after long-term Hh inhibition. Therefore, combining Hh inhibitors with ionizing radiation, chemotherapy or other molecular targeted agents could represent an alternative therapeutic strategy. In this review, we will highlight the role of Hh signaling in the development and progression of prostate cancer and summarize the different therapeutic applications of Hedgehog inhibition.     

Untersuchungen zur H2O2-Behandlung der Milch II. Mitteilung Einflu? von H2O2 auf Butterfett und einige fettl?sliche Vitamine

Zusammenfassung Milch wird mit Wasserstoffperoxyd in Konzentrationen bis 1% einer 30%igen Lösung versetzt (Einwirkungszeit bis 24 Std bei 30° C oder 1/2 Std bei 51° C) und der Einfluß auf das Butterfett und die fettlöslichen Vitamine untersucht.Unter den angegebenen Bedingungen lassen sich keine oxydativen Veränderungen im Butterfett feststellen. Der Gehalt der Milch an -Carotin, Vitamin A und E wird nicht verändert.Inalkoholischer Lösung sind die Vitamine A und D₃ sowie -Carotin bei H₂O₂-Einwirkung relativ stabil; nur Tokopherol wird schnell zerstört.