A study of the thermal behavior of different test patterns used in differential high resolution electromigration measurements

The differential high-resolution electromigration (EM) measurement technique requires special test patterns since for the implementation of this technique the presence of two metal lines is necessary, one metal line to be stressed with a high current density (‘test’ or ‘stressed’ resistor) and a second line (‘monitor’ or ‘reference’ resistor) to compensate for the thermal instabilities of the stressed one. It is accepted that due to Joule heating the stressed line always acquires higher temperature than the reference line and, therefore, additional resistance changes due to thermally induced phenomena, like precipitation of additional elements, will affect the measurement. In order to minimize these unwanted effects, an optimal high-resolution EM test structure should show a minimum temperature difference between the stressed and the reference lines. Based on this requirement, in this work we simulated three different test structures being used by various research groups for high-resolution measurements and subsequently compared these test structures on account of their thermal behavior. Each test structure was examined for the case of two different widths of metal lines, 4 and 0.5 μm. The results obtained from the simulation of these test patterns demonstrated that the test pattern comprised of two parallel stress and reference lines shows better thermal behavior than the ‘lined-up’ (continuous) metal lines where the stress and reference lines are actually part of the same line. In particular, the test pattern comprised of two parallel straight lines has slightly better behavior than the one with meandered lines in terms of minimization of the temperature difference between the stressed and the reference resistors. The difference between the thermal behavior of the two structures though is very small. For that reason, the parallel lines should be preferred from the meandered ones only if layout restrictions do not require the choice of a more compact (i.e., meandered) solution. Both test structures have shown a better thermal behavior than the ‘lined-up’ metal lines.     

The anti-aggregatory effect of chloramine derivatives of amino acids on platelets in the presence of plasma

Rabbit platelet aggregation induced by ADP is suppressed equally by the group of the chloramine derivatives of uncharged amino acid with the high molecular masses (N-chlorphenylalanine, N-chlorglutamine, N-chlorleucine). The effects of the derivatives of other uncharged amino acids are different, the inhibition degree increasing sharply at the decrease of molecular mass of amino acid chloramines. Ratio of the rate constant for the reaction of these chloramines with platelets and the rate constant for the reaction with plasma components raises exponentially at the molecular mass reduction.     

Preparation and properties of membranes obtained by radiation induced grafting of 4-vinylpyridine onto polytetrafluoroethylene films

The preparation and properties of membranes obtained by radiation induced grafting are described, using vinylpyridine (VPy) on a polytetrafluoroethylene (PTFE) matrix. Subsequent quaternarization of the pyridine groups improves greatly the hyperfiltration properties of these membranes, considering both flux and rejection, and they may be developed for desalination purposes.The dependence of grafting yields on irradiation times was studied as well as the thermal and chemical properties of the membranes obtained. Flux and rejection to NaCl of quaternarized VPy/PTFE membranes was measured as a function of various chemical and physical properties.     

Monte Carlo model of nonlinear chromatography

A stochastic approach to the nonlinear chromatography theory, based on the Monte Carlo simulation method, is presented. A computer program, acting as a "virtual chromatograph" and performing a discrete event simulation, is described. Such a program allows one to choose the column type, operating conditions, sample composition, injection method, mobile-phase dispersion model, and stationary-phase sorption-desorption kinetics. Nonlinearity is accounted for by continuously monitoring and updating both the column and the solute status and by moving individual molecules step by step along the column according to specific random modes. The program has been validated through a series of statistical tests and comparing the results with the well-known achievements of the classical stochastic theory. A first application is presented, referred to a real case benzene elution on a gas solid capillary column, where the Langmuir adsorption isotherm is assumed. The effect of both the sorption modes and the site capacity are investigated. Possible applications to investigate open problems in several fields of separation science are emphasized. In addition, several specific points such as the down-scaling of a real case and the correspondence of specific adsorption dynamics with the equilibrium Langmuir isotherm are described.     

Synthesis and characterization of poly(butylene terephthalate‐co‐triethylene terephthalate) copolyesters

Poly(butylene terephthalate‐co‐triethylene terephthalate) random copolymers of various compositions and molecular weights were synthesized in bulk and characterized in terms of their chemical structure and thermal and rheological properties. At room temperature all the copolymers were partially crystalline and showed good thermal stability. The main effect of copolymerization was a decrease in the melting and glass‐transition temperatures with respect to the poly(butylene tere‐ phthalate) homopolymer. The fusion temperatures were well correlated with the composition by the Baur equation and the equilibrium melting temperature and the heat of fusion extrapolated values for poly(butylene terephthalate) were in good agreement with those reported elsewhere. Triethylene terephthalate units were found to influence the rheological behavior in the melt, the viscosity being significantly higher than that of the poly(butylene terephthalate‐co‐diethylene terephthalate) copolymers investigated previously. © 2001 John Wiley & Sons, Inc. J Appl Polym Sci 81: 981–990, 2001     

Molecular weights of grafted polystyrene onto γ-preirradiated cellulose diacetate

The behavior of molecular weights of grafted polystyrene onto γ-preirradiated cellulose diacetate was studied. The grafting of styrene onto cellulose diacetate was kinetically followed with particular attention paid to the polystyrene molecular weight behavior. The molecular weight was evaluated with the polymer fractions obtained by acid hydrolysis of the grafted copolymer. From the experimental results it appeared that the grafted chain molecular weight is completely controlled by the physical properties of the polymeric matrix either during a “bulk” or a “front” grafting.     

Efficacy of Combined Use of Everolimus and Second-Generation Pan-EGRF Inhibitors in KRAS Mutant Non-Small Cell Lung Cancer Cell Lines

Background: EGFR mutations are present in approximately 15–50% of non-small cell lung cancer (NSCLC), which are predictive of anti-EGFR therapies. At variance, NSCLC patients harboring KRAS mutations are resistant to those anti-EGFR approaches. Afatinib and allitinib are second-generation pan-EGFR drugs, yet no predictive biomarkers are known in the NSCLC context. In the present study, we evaluated the efficacy of pan-EGFR inhibitors in a panel of 15 lung cancer cell lines associated with the KRAS mutations phenotype. Methods: KRAS wild-type sensitive NCI-H292 cell line was further transfected with KRAS mutations (p.G12D and p.G12S). The pan-EGFR inhibitors’ activity and biologic effect of KRAS mutations were evaluated by cytotoxicity, MAPK phospho-protein array, colony formation, migration, invasion, and adhesion. In addition, in vivo chicken chorioallantoic membrane assay was performed in KRAS mutant cell lines. The gene expression profile was evaluated by NanoString. Lastly, everolimus and pan-EGFR combinations were performed to determine the combination index. Results: The GI₅₀ score classified two cell lines treated with afatinib and seven treated with allitinib as high-sensitive phenotypes. All KRAS mutant cell lines demonstrated a resistant profile for both therapies (GI₅₀ < 30%). The protein array of KRAS edited cells indicated a significant increase in AKT, CREB, HSP27, JNK, and, importantly, mTOR protein levels compared with KRAS wild-type cells. The colony formation, migration, invasion, adhesion, tumor perimeter, and mesenchymal phenotype were increased in the H292 KRAS mutated cells. Gene expression analysis showed 18 dysregulated genes associated with the focal adhesion-PI3K-Akt-mTOR-signaling correlated in KRAS mutant cell lines. Moreover, mTOR overexpression in KRAS mutant H292 cells was inhibited after everolimus exposure, and sensitivity to afatinib and allitinib was restored. Conclusions: Our results indicate that allitinib was more effective than afatinib in NSCLC cell lines. KRAS mutations increased aggressive behavior through upregulation of the focal adhesion-PI3K-Akt-mTOR-signaling in NSCLC cells. Significantly, everolimus restored sensibility and improved cytotoxicity of EGFR inhibitors in the KRAS mutant NSCLC cell lines.     

TRK Protein Expression in Merkel Cell Carcinoma Is Not Caused by NTRK Fusions

Merkel cell carcinoma (MCC) is a rare and aggressive cutaneous malignant tumor with neuroendocrine differentiation, with a rapidly growing incidence rate, high risk of recurrence, and aggressive behavior. The available therapeutic options for advanced disease are limited and there is a pressing need for new treatments. Tumors harboring fusions involving one of the neurotrophin receptor tyrosine kinase (NTRK) genes are now actionable with targeted inhibitors. NTRK-fused genes have been identified in neuroendocrine tumors of other sites; thus, a series of 76 MCCs were firstly analyzed with pan-TRK immunohistochemistry and the positive ones with real-time RT-PCR, RNA-based NGS, and FISH to detect the eventual underlying gene fusion. Despite 34 MCCs showing pan-TRK expression, NTRK fusions were not found in any cases. As in other tumors with neural differentiation, TRK expression seems to be physiological and not caused by gene fusions.     

Reliability assessment of multi-via Cu-damascene structures by wafer-level isothermal electromigration tests

In this paper, the isothermal wafer-level electromigration test method has been used to compare the resistance to electromigration damage of multi-level structures, realized by dual-damascene copper technology with a variable number of vias. “Upstream” and “downstream” structures have been defined, depending on the metal level where the line under test was located, with respect to the metal level where current and voltage taps were drawn. Not unexpectedly, the most critical current path for electromigration has been found in downstream structures, where the electron flow is entering the line under test. Worthy of note, a well defined dependence of the time to failure on the number of vias has been observed for these structures. Activation energy and current-density acceleration coefficient have been extracted and a quantitative relation is proposed to relate the lifetime expectancy to the number of vias.