Failure analysis case study on a Cu/low-k technology in package: New front-side approach using laser and plasma de-processing

Because of its advantages (reduction of thickness, improvement of the signal delay and of the thermal dissipation…), Cu/low-k technologies are more and more used for RF applications in semiconductor industry. The failure analysis of such devices becomes a new challenge. This paper deals with a failure analysis case study on copper and low-k dielectric structure encapsulated in a plastic package. It shows the limitations of the techniques used in a standard failure analysis flow and presents a new sample preparation combining laser package ablation and specific RIE process for front-side decapsulation. This innovative sample preparation flow has been found mandatory for solving the failure analysis case: it was demonstrated that there was not any defect at the surface of the die and this method enabled the access to an EOS defect located between two metal layers.     

Techniques to measure sorption and migration between small molecules and packaging. A critical review

The mass transfer parameters diffusion and sorption in food and packaging or between them are the key parameters for assessing a food product's shelf‐life in reference to consumer safety. This has become of paramount importance owing to the legislations set by the regulated markets. The technical capabilities that can be exploited for analyzing product–package interactions have been growing rapidly. Different techniques categorized according to the state of the diffusant (gas or liquid) in contact with the packaging material are emphasized in this review. Depending on the diffusant and on the analytical question under review, the different ways to study sorption and/or migration are presented and compared. Some examples have been suggested to reach the best possible choice, consisting of a single technique or a combination of different approaches. © 2014 Society of Chemical Industry     

Fluoride exposure in cervids inhabiting areas adjacent to aluminum smelters in Norway. I. Residue levels

Mandibular fluorine concentrations were determined in 1,425 red deer (Cervus elaphus), 240 moose (Alces alces), and 424 roe deer (Capreolus capreolus) collected in Norway from 1990 to 1993 in seven municipalities in which aluminum smelters are located, in eight neighboring municipalities, and in eight reference areas representing background levels. Background fluorine concentration was significantly correlated with age in all three species. Roe deer had the highest mean background fluorine level in each age group, followed by red deer. Due to differences in fluoride exposure, large variations in bone fluorine residues were evident between locations. In Ardal, the district most severely exposed to fluoride contamination, nine of ten cervids had fluorine concentrations exceeding background levels. The proportions of red deer with fluorine residues exceeding background levels also were high in neighboring municipalities to Ardal. We propose that roe deer are a better biomonitor of local fluoride exposure than red deer and moose, due to their more sedentary behavior.     

Chemometric Classification of Comb and Cuticular Waxes of the Honeybee Apis Mellifera Carnica

Waxes are important as building material and for the chemical communication of the honeybee Apis mellifera carnica. In this study chemometric tools were established for classifying the different waxes inside the hive. By using gas chromatography in combination with mass spectrometry, components of different types of waxes were analyzed. By considering different substance classes of waxes, discriminant function analyses revealed distinct subtypes of comb waxes and of cuticular waxes. It is shown that the aging of comb wax is in part a spontaneous physicochemical process due to differential volatilities of compound classes with different chain length ranges. On the other hand it is directly influenced by the bees by adding lipolytic enzymes to the comb wax. The data suggest that the varying cuticular wax and comb wax compositions could serve as cues for bees to recognize castes, sexes, or comb age.     

Dynamic Features of the Rumen Metabolism of Linoleic Acid,Linolenic Acid and Linseed Oil Measured in Vitro

The lipid quality of ruminant products is largely determined by the extent of rumen microbial biohydrogenation (BH) of polyunsaturated fatty acids (FAs) and the substances formed thereby. In vitro batch incubations with mixed rumen bacteria were tracked over 24 h to characterize the profiles and kinetics of the BH products from three lipid sources: pure linoleic acid (c9,c12–18:2), pure linolenic acid (c9,c12,c15–18:3) and linseed oil (mainly c9,c12,c15–18:3 in triacylglycerols). After 24 h of incubation biohydrogenation was more complete for c9,c12–18:2, which gave mainly stearic acid (18:0), than for c9,c12,c15–18:3, which yielded mainly trans-18:1 FAs. This suggests inhibition of the final BH step (18:1 to 18:0). Incubations of c9,c12–18:2 resulted in high levels of carbon 10- and 12-desaturated 18:1, t10,c12- and c9,t11-CLAs. Incubations of c9,c12,c15–18:3 resulted in high levels of t11–18:1, carbon 13- and 15-desaturated 18:1 as well as t11,c15–18:2 and 11,13-CLAs. A comparative study of linolenic acid and linseed oil kinetics revealed that the BH process was not significantly slowed by the esterification of polyunsaturated FAs, but may have been limited by the isomerization step in which the cis12 double bond goes to the trans11 position. The disappearance rates of c9,c12–18:2 and c9,c12,c15–18:3 ranged from 23.6 to 44.6%/h. The wide variety of BH intermediates found here underlines the large number of possible BH pathways. These data help provide a basis for dynamic approaches to BH processes.     

Population-level modeling to account for multigenerational effects of uranium in Daphnia magna

As part of the ecological risk assessment associated with radionuclides in freshwater ecosystems, toxicity of waterborne uranium was recently investigated in the microcrustacean Daphnia magna over a three-generation exposure (F0, F1, and F2). Toxic effects on daphnid life history and physiology, increasing over generations, were demonstrated at the organism level under controlled laboratory conditions. These effects were modeled using an approach based on the dynamic energy budget (DEB). For each of the three successive generations, DEBtox (dynamic energy budget applied to toxicity data) models were fitted to experimental data. Lethal and sublethal DEBtox outcomes and their uncertainty were projected to the population level using population matrix techniques. To do so, we compared two modeling approaches in which experimental results from F0, F1, and F2 generations were either considered separately (F0-, F1-, and F2-based simulations) or together in the actual succession of F0, F1, and F2 generations (multi-F-based simulation). The first approach showed that considering results from F0 only (equivalent to a standard toxicity test) would lead to a severe underestimation of uranium toxicity at the population level. Results from the second approach showed that combining effects in successive generations cannot generally be simplified to the worst case among F0-, F1-, and F2-based population dynamics.     

Development of the First Oral Bioprecursors of Bis‐alkylguanidine Antimalarial Drugs

Plasmodium falciparum is responsible of the most severe form of malaria, and new targets and novel chemotherapeutic scaffolds are needed to fight emerging multidrug‐resistant strains of this parasite. Bis‐alkylguanidines have been designed to mimic choline, resulting in the inhibition of plasmodial de novo phosphatidylcholine biosynthesis. Despite potent in vitro antiplasmodial and in vivo antimalarial activities, a major drawback of these compounds for further clinical development is their low oral bioavailability. To solve this issue, various modulations were performed on bis‐alkylguanidines. The introduction of N‐disubstituents on the guanidino motif improved both in vitro and in vivo activities. On the other hand, in vivo pharmacological evaluation in a mouse model showed that the N‐hydroxylated derivatives constitute the first oral bioprecursors in bis‐alkylguanidine series. This study paves the way for bis‐alkylguanidine‐based oral antimalarial agents targeting plasmodial phospholipid metabolism.     

Synthetic and Biological Studies of Sesquiterpene Polygodial: Activity of 9‐Epipolygodial against Drug‐Resistant Cancer Cells

Polygodial, a terpenoid dialdehyde isolated from Polygonum hydropiper L., is a known agonist of the transient receptor potential vanilloid 1 (TRPV1). In this investigation a series of polygodial analogues were prepared and investigated for TRPV1‐agonist and anticancer activities. These experiments led to the identification of 9‐epipolygodial, which has antiproliferative potency significantly exceeding that of polygodial. 9‐Epipolygodial was found to maintain potency against apoptosis‐resistant cancer cells as well as those displaying the multidrug‐resistant (MDR) phenotype. In addition, the chemical feasibility for the previously proposed mechanism of action of polygodial, involving the formation of a Paal–Knorr pyrrole with a lysine residue on the target protein, was demonstrated by the synthesis of a stable polygodial pyrrole derivative. These studies reveal rich chemical and biological properties associated with polygodial and its direct derivatives. These compounds should inspire further work in this area aimed at the development of new pharmacological agents, or the exploration of novel mechanisms of covalent modification of biological molecules with natural products.