Molecular Subtyping of Invasive Breast Cancer Using a PAM50-Based Multigene Expression Test-Comparison with Molecular-Like Subtyping by Tumor Grade/Immunohistochemistry and Influence on Oncologist’s Decision on Systemic Therapy in a Real-World Setting

In intermediate risk hormone receptor (HR) positive, HER2 negative breast cancer (BC), the decision regarding adjuvant chemotherapy might be facilitated by multigene expression tests. In all, 142 intermediate risk BCs were investigated using the PAM50-based multigene expression test Prosigna® in a prospective multicentric study. In 119/142 cases, Prosigna® molecular subtyping was compared with local and two central (C1 and C6) molecular-like subtypes relying on both immunohistochemistry (IHC; HRs, HER2, Ki-67) and IHC + tumor grade (IHC+G) subtyping. According to local IHC, 35.4% were Luminal A-like and 64.6% Luminal B-like subtypes (local IHC+G subtype: 31.9% Luminal A-like; 68.1% Luminal B-like). In contrast to local and C1 subtyping, C6 classified >2/3 of cases as Luminal A-like. Pairwise agreement between Prosigna® subtyping and molecular-like subtypes was fair to moderate depending on molecular-like subtyping method and center. The best agreement was observed between Prosigna® (53.8% Luminal A; 44.5% Luminal B) and C1 surrogate subtyping (Cohen’s kappa = 0.455). Adjuvant chemotherapy was suggested to 44.2% and 88.6% of Prosigna® Luminal A and Luminal B cases, respectively. Out of all Luminal A-like cases (locally IHC/IHC+G subtyping), adjuvant chemotherapy was recommended if Prosigna® testing classified as Prosigna® Luminal A at high / intermediate risk or upgraded to Prosigna® Luminal B.     

Characterization of expression of a plant oleate desaturase in yeast

We have expressed the oleate desaturase gene of Arabidopsis thaliana in Saccharomyces cerevisiae by means of a galactose-inducible promoter. Transfer of yeast cells to galactose-containing media and growth at 30°C resulted in the production of active oleate desaturase, as shown by the appearance of the diunsaturated octadecadienoic acid (18:2) and hexadecadienoic acid (16:2). The highest level of these two fatty acids was 46.2%. In induced cultures, 18:2 appeared before 16:2, and we show that both of these fatty acids were present first on phosphatidylcholine and then appeared in other phospholipids and a neutral lipid fraction. We raised antibodies against the C-terminal 100 amino acids of oleate desaturase and demonstrated that this protein was in the microsomal fraction of induced cells.     

Tobacco etch virus protease: mechanism of autolysis and rational design of stable mutants with wild-type catalytic proficiency

Because of its stringent sequence specificity, the catalyticdomain of the nuclear inclusion protease from tobacco etch virus(TEV) is a useful reagent for cleaving genetically engineeredfusion proteins. However, a serious drawback of TEV proteaseis that it readily cleaves itself at a specific site to generatea truncated enzyme with greatly diminished activity. The rateof autoinactivation is proportional to the concentration ofTEV protease, implying a bimolecular reaction mechanism. Yet,a catalytically active protease was unable to convert a catalyticallyinactive protease into the truncated form. Adding increasingconcentrations of the catalytically inactive protease to a fixedamount of the wild-type enzyme accelerated its rate of autoinactivation.Taken together, these results suggest that autoinactivationof TEV protease may be an intramolecular reaction that is facilitatedby an allosteric interaction between protease molecules. Inan effort to create a more stable protease, we made amino acidsubstitutions in the P2 and P1' positions of the internal cleavagesite and assessed their impact on the enzyme's stability andcatalytic activity. One of the P1' mutants, S219V, was not onlyfar more stable than the wild-type protease (~100-fold), butalso a more efficient catalyst.     

Assessment of Post-Earthquake Fire Behavior of a Steel MRF Building in a Low Seismic Region

International Journal of Steel Structures - Building-level response to post-earthquake fire hazards in steel buildings has been assessed using primarily two-dimensional analyses of the lateral...     

Strength and Microstructure of Silicon Nitride Ceramics Brazed with Nickel-Chromium-Silicon Alloys

Joining of sintered Si₃N₄ was performed using a high-temperature brazing technique. Ni-based brazing alloys having the same Ni:Cr ratio as AWS BNi-5 (Ni·18Cr·19Si (at. %)) but different Si content were used as the brazing filler metals. Joining experiments were performed at 1220°C under a N₂ partial pressure of 15 Pa for different times between 5 to 15 min. The highest room-temperature four-point bend strength of the joints was 115 MPa, whereas 220 MPa was achieved when the joints were tested at 900°C. The high strength of the experimental joints was attributed to the reduction in residual stresses and formation of a CrN reaction layer at the ceramic/filler metal interface.     

Factors Affecting the Study of Chemistry in Different Countries Around the World: Findings from an International Survey

Improving teaching and student learning in chemistry classrooms is an important goal that is constantly researched. Several comparative studies of science teaching have been carried out on different parameters, e. g. misconceptions which science teachers and students may have regarding the scientific concepts they learn and teach. Here we describe science teaching in general, and chemistry teaching in particular, in 12 countries including Israel. Different parameters are compared, including the hours that are devoted to science, the subjects included, the pedagogy, and teachers′ salaries. The survey covers all school levels: elementary school, secondary school and high school. At the high‐school level, the comparison focused on chemistry studies. In this study the variances variables, such as the hours that are allocated for science teaching, did not show an appreciable effect on students′ achievements. It was also found that, in countries where chemistry studies at the high‐school level are not mandatory, innovative pedagogies are more likely to replace the traditional chemistry teaching methods where chemistry is taught according to the structure of the subject based on basic concepts that underlie the curriculum. The study provided an additional support to the importance of the professional development of science and chemistry teachers and suggest that the autonomy that is given to them could influence the quality of science teaching and students′ achievements.