Observation of electromigration at low temperature

Electromigration and mean time-to-failure were investigated for unglassed thin Al stripes over the temperature range of 223 K to 347 K. Thermal effects are minimized by sinking heat from the linestrip through the substrate to a miniature cryogenic refrigerator. This test technique allows the investigation of structure and current interactions while suppressing the effects of an added temperature factor. The circuit was stressed by direct current densities greater than 4×10⁶ A/cm². Electromigration damage was induced in a test stripe at temperatures near 0°C. For the temperature range of 347 K to 267 K, an activation energy of 0.30 eV was calculated, indicating that surface migration is the dominant failure mechanism. For temperatures between 267 K and 223 K, a calculated activation energy of 0.12 eV suggests a different failure mechanism, which was subsequently identified as stripe separation from the substrate     

People and processes — The Key Elements to Information Security

With the near ubiquitous use of the Internet to connect suppliers, partners and customers, enterprises are looking to technology to protect their data. Companies often assume that technology such as firewalls, virtual private networks (VPNs) and intrusion detection systems (IDS) will take care of their security problems. But in order for these to be effective, skilled people and clearly defined processes are also needed to safeguard information.     

Discovering small-molecule estrogen receptor α/coactivator binding inhibitors: high-throughput screening, ligand development, and models for enhanced potency

Small molecules, namely coactivator binding inhibitors (CBIs), that block estrogen signaling by directly inhibiting the interaction of the estrogen receptor (ER) with coactivator proteins act in a fundamentally different way to traditional antagonists, which displace the endogenous ligand estradiol. To complement our prior efforts at CBI discovery by de?novo design, we used high-throughput screening (HTS) to identify CBIs of novel structure and subsequently investigated two HTS hits by analogue synthesis, finding many compounds with low micromolar potencies in cell-based reporter gene assays. We examined structure-activity trends in both series, using induced-fit computational docking to propose binding poses for these molecules in the coactivator binding groove. Analysis of the structure of the ER-steroid receptor coactivator (SRC) complex suggests that all four hydrophobic residues within the SRC nuclear receptor box sequence are important binding elements. Thus, insufficient water displacement upon binding of the smaller CBIs in the expansive complexation site may be limiting the potency of the compounds in these series, which suggests that higher potency CBIs might be found by screening compound libraries enriched with larger molecules.     

Binding of guanine nucleotides to bronchial membranes: effect of maturation

Guanosine 5-[y-thio]triphosphate ([35S]GTP gamma S) binding to guinea pig bronchial membranes from immature and mature guinea pigs was rapid (Kon: 3.8 x 10(5) mol-1 min-1), saturable (Bmax: 160 pmoles/mg protein) and of high affinity (Kd: 0.6 microM). [35S]GTP gamma S rapidly dissociated in the absence of magnesium (Koff: 0.06 min-1), but 50 mM magnesium inhibited the dissociation. Maturation did not alter the affinity of the ligand, but Bmax (pmoles/mg DNA) was greater in preparations from mature animals (929 +/- 16 vs. 620 +/- 64). [35S]GTP gamma S was displaced by guanine nucleotides with a rank order of potency of GDP beta S = Gpp(NH)p > GDP > GTP, but not by ATP. We conclude that [35S]GTP gamma S is a specific and useful method to quantitate bronchial membrane-bound GTP-binding proteins. The technique shows that there is a significant increase in the cellular content of G-proteins during maturation.     

Synthesis,Characterization, and Biological Activity Evaluation of Magnetite-Functionalized Eugenol

This work reports the magnetite-functionalization and biological evaluation of eugenol by the co-precipitation method employed only Fe²⁺ under mild conditions and control from the amount of the incorporated magnetite. Magnetic nanoparticles were characterized by scanning electron microscopy (SEM), X-ray diffraction (XRD), Fourier transform infrared (FTIR), hydrodynamic size distribution (Zetasizer), and vibrating sample magnetometer (VSM). SEM images showed that EUG·Fe₃O₄ similar in shape to a nanoflower. The FTIR spectrum confirmed the presence of characteristic EUG and Fe₃O₄ bands in the EUG·Fe₃O₄ sample, the XRD analysis showed that the magnetite functionalization with eugenol slightly affected the Fe₃O₄ crystal structure, while the VSM measurements demonstrate that EUG·Fe₃O₄ 1:1 shows a superparamagnetic behavior, suggesting small non-interacting particles. The in vitro safety profile and cytotoxicity of free eugenol, magnetite pristine, EUG·Fe₃O₄ 1:1, EUG·Fe₃O₄ 1:5, and EUG·Fe₃O₄ 1:10 was investigated using human cell lines (keratinocytes and melanoma). The results demonstrate the high biocompatibility of EUG·Fe₃O₄ in HaCat cells and the greater specificity for the A375 cell line. Furthermore, the magnetite-functionalization with eugenol decreased the toxic effects of free eugenol on healthy cells. Antibacterial tests were performed in different bacterial strains. The experimental data showed that among the magnetic compounds, the microorganisms were only sensitive to treatment with EUG·Fe₃O₄ 1:1. Regarding the antibiofilm activity assay, it can be observed that only the EUG·Fe₃O₄ caused a significant decrease in biomass when compared to the positive control. Finally, it can be concluded that EUG·Fe₃O₄ proves to be a potential candidate for future studies for drug delivery of cancer and bacterial infections treatments.

Graphical Abstract