Microstructure evolution of the Sn–Ag–y%Cu interconnect

The lead free Sn–Ag–y%Cu (y = 0.0, 0.5, 1.0 and 2.0) interconnect interfacial microstructures and the microstructure evolution under thermal treatment (isothermal aging, 150 °C/1000 h) were studied in detail by using surface microetching microscopy and cross section microscopy. The corresponding mechanical and reliability behaviors were evaluated by performing shear test and fracture mode analysis before and after the thermal treatment. The results indicate: (i) The interconnects could have different microstructures and intermetallic compound (IMC), depending on the Cu content. The Cu–Sn IMC could have microstructures that were clusters or protrusion-like, Augustine grass leaf-like, scissor-like, tweezers-like, etc. (ii) Ag₃Sn IMCs were not observed at time zero for any interconnect groups, but they occurred after the aging for all groups. The Ag₃Sn IMC could have different microstructures, again depending on Cu content. For low Cu content, the Ag₃Sn IMCs were granules or nodules; for higher Cu content, Ag₃Sn IMCs were plate-like. (iii) The growth of Ag₃Sn plates was promoted by the growth of Cu–Sn IMCs, but indirectly linked to the Cu content. (iv) High Cu content (1.0 wt% and higher) could degrade the mechanical and reliability performances of the LF interconnect by providing a brittle joint, which was mainly achieved through the substantial growth of Cu–Sn IMCs and Ag₃Sn plates.     

A game theory approach to constrained minimax state estimation

This paper presents a game theory approach to the constrained state estimation of linear discrete time dynamic systems. In the application of state estimators, there is often known model or signal information that is either ignored or dealt with heuristically. For example, constraints on the state values (which may be based on physical considerations) are often neglected because they do not easily fit into the structure of the state estimator. This paper develops a method for incorporating state equality constraints into a minimax state estimator. The algorithm is demonstrated on a simple vehicle tracking simulation.     

Effect of Anisotropy and Destructuration on the Behavior of Murro Test Embankment

This paper investigates the influence of anisotropy and destructuration on the behavior of a test embankment on soft clay. The test embankment at Murro, Finland, was commissioned in 1993 by the Finnish Road Administration and has been monitored for over 10?years. The construction and consolidation of Murro test embankment is analyzed with finite element method using three different constitutive models to represent the soft soil. The results are compared with field observations. The constitutive models used include two recently proposed constitutive models, namely S-CLAY1 that accounts for initial and plastic strain induced anisotropy and its extension, called S-CLAY1S. The S-CLAY1S model accounts, additionally, for interparticle bonding and degradation of bonds. For comparison, the test embankment is also analyzed using the isotropic Modified Cam Clay model. The simulations demonstrate that for this type of problem, it is important to account for the anisotropy, whereas destructuration appears to have less influence on predicted deformations. However, only a model incorporating destructuration can explain the decrease in undrained shear strength during consolidation that was measured in field.     

Revisiting the Roles of Filaggrin in Atopic Dermatitis

The discovery in 2006 that loss-of-function mutations in the filaggrin gene (FLG) cause ichthyosis vulgaris and can predispose to atopic dermatitis (AD) galvanized the dermatology research community and shed new light on a skin protein that was first identified in 1981. However, although outstanding work has uncovered several key functions of filaggrin in epidermal homeostasis, a comprehensive understanding of how filaggrin deficiency contributes to AD is still incomplete, including details of the upstream factors that lead to the reduced amounts of filaggrin, regardless of genotype. In this review, we re-evaluate data focusing on the roles of filaggrin in the epidermis, as well as in AD. Filaggrin is important for alignment of keratin intermediate filaments, control of keratinocyte shape, and maintenance of epidermal texture via production of water-retaining molecules. Moreover, filaggrin deficiency leads to cellular abnormalities in keratinocytes and induces subtle epidermal barrier impairment that is sufficient enough to facilitate the ingress of certain exogenous molecules into the epidermis. However, although FLG null mutations regulate skin moisture in non-lesional AD skin, filaggrin deficiency per se does not lead to the neutralization of skin surface pH or to excessive transepidermal water loss in atopic skin. Separating facts from chaff regarding the functions of filaggrin in the epidermis is necessary for the design efficacious therapies to treat dry and atopic skin.     

Oxy210, a Semi-Synthetic Oxysterol,Exerts Anti-Inflammatory Effects in Macrophages via Inhibition of Toll-like Receptor (TLR) 4 and TLR2 Signaling and Modulation of Macrophage Polarization

Inflammatory responses by the innate and adaptive immune systems protect against infections and are essential to health and survival. Many diseases including atherosclerosis, osteoarthritis, rheumatoid arthritis, psoriasis, and obesity involve persistent chronic inflammation. Currently available anti-inflammatory agents, including non-steroidal anti-inflammatory drugs, steroids, and biologics, are often unsafe for chronic use due to adverse effects. The development of effective non-toxic anti-inflammatory agents for chronic use remains an important research arena. We previously reported that oral administration of Oxy210, a semi-synthetic oxysterol, ameliorates non-alcoholic steatohepatitis (NASH) induced by a high-fat diet in APOE*3-Leiden.CETP humanized mouse model of NASH and inhibits expression of hepatic and circulating levels of inflammatory cytokines. Here, we show that Oxy210 also inhibits diet-induced white adipose tissue inflammation in APOE*3-Leiden.CETP mice, evidenced by the inhibition of adipose tissue expression of IL-6, MCP-1, and CD68 macrophage marker. Oxy210 and related analogs exhibit anti-inflammatory effects in macrophages treated with lipopolysaccharide in vitro, mediated through inhibition of toll-like receptor 4 (TLR4), TLR2, and AP-1 signaling, independent of cyclooxygenase enzymes or steroid receptors. The anti-inflammatory effects of Oxy210 are correlated with the inhibition of macrophage polarization. We propose that Oxy210 and its structural analogs may be attractive candidates for future therapeutic development for targeting inflammatory diseases.     

Smaller,Stronger, More Stable: Peptide Variants of a SARS-CoV-2 Neutralizing Miniprotein

Based on the structure of a de novo designed miniprotein (LCB1) in complex with the receptor binding domain (RBD) of the SARS-CoV-2 spike protein, we have generated and characterized truncated peptide variants of LCB1, which present only two of the three LCB1 helices, and which fully retained the virus neutralizing potency against different SARS-CoV-2 variants of concern (VOC). This antiviral activity was even 10-fold stronger for a cyclic variant of the two-helix peptides, as compared to the full-length peptide. Furthermore, the proteolytic stability of the cyclic peptide was substantially improved, rendering it a better potential candidate for SARS-CoV-2 therapy. In a more mechanistic approach, the peptides also served as tools to dissect the role of individual mutations in the RBD for the susceptibility of the resulting virus variants to neutralization by the peptides. As the peptides reported here were generated through chemical synthesis, rather than recombinant protein expression, they are amenable to further chemical modification, including the incorporation of a wide range of non-proteinogenic amino acids, with the aim to further stabilize the peptides against proteolytic degradation, as well as to improve the strength, as well the breadth, of their virus neutralizing capacity.     

Relationship between microscopic and macroscopic structures of organic thin films for SHG

The experiments described in this paper were undertaken in order to obtain information about the relationship between the structure and non-linear optical properties (second-harmonic generation) of organic thin films. For this purpose, two closely related dyes, diones and tetrones, were compared, both of which are shown to have large hyperpolarisabilities. Their microscopic properties are investigated by conformational analysis and electron diffraction. It could be shown that detailed knowledge about the structure and the adjacent neighbour packing can be obtained from conformational analysis and electron diffraction in order to understand the non-linear optical properties of the two dyes.     

Cloning and Functional Characterization of Dog OCT1 and OCT2: Another Step in Exploring Species Differences in Organic Cation Transporters

OCT1 and OCT2 are polyspecific membrane transporters that are involved in hepatic and renal drug clearance in humans and mice. In this study, we cloned dog OCT1 and OCT2 and compared their function to the human and mouse orthologs. We used liver and kidney RNA to clone dog OCT1 and OCT2. The cloned and the publicly available RNA-Seq sequences differed from the annotated exon-intron structure of OCT1 in the dog genome CanFam3.1. An additional exon between exons 2 and 3 was identified and confirmed by sequencing in six additional dog breeds. Next, dog OCT1 and OCT2 were stably overexpressed in HEK293 cells and the transport kinetics of five drugs were analyzed. We observed strong differences in the transport kinetics between dog and human orthologs. Dog OCT1 transported fenoterol with 12.9-fold higher capacity but 14.3-fold lower affinity (higher K_M) than human OCT1. Human OCT1 transported ipratropium with 5.2-fold higher capacity but 8.4-fold lower affinity than dog OCT1. Compared to human OCT2, dog OCT2 showed 10-fold lower transport of fenoterol and butylscopolamine. In conclusion, the functional characterization of dog OCT1 and OCT2 reported here may have implications when using dogs as pre-clinical models as well as for drug therapy in dogs.     

Decarbonylation Kinetics of Formic Acid in Aqueous Sulphuric Acid Solutions

Decarbonylation of formic acid in 46.6–80.2% (6.5–14.1 m) sulphuric acid was studied by driving CO out of the reaction medium by an air current followed by its photometrical determination with Ag-Na-sulphamoyl-benzoate. The logarithm of the reaction rate constant increases straight with the acidity of the medium in the 6.5–12.6 M H₂SO₄ range. The data obtained argue in favour of a possible implication of a sulphuric acid molecule respectively hydrogensulphate ion in a rate controlling step.