Domain-wall pinning by local control of anistropy in Pt/Co/Pt strips-

We theoretically and experimentally analyze the pinning of a magnetic domain wall (DW) at engineered anisotropy variations in Pt/Co/Pt strips with perpendicular magnetic anisotropy. An analytical model is derived showing that a step in the anisotropy acts as an energy barrier for the DW. Quantitative measurements are performed showing that the anisotropy can be controlled by focused ion beam irradiation with Ga ions. This tool is used to experimentally study the field-induced switching of nanostrips which are locally irradiated. The boundary of the irradiated area indeed acts as a pinning barrier for the domain wall and the pinning strength increases with the anisotropy difference. Varying the thickness of the Co layer provides an additional way to tune the anisotropy, and it is shown that a thinner Co layer gives a higher starting anisotropy thereby allowing tunable DW pinning in a wider range of fields. Finally, we demonstrate that not only the anisotropy itself, but also the width of the anisotropy barrier can be tuned on the length scale of the domain wall

Domain-wall pinning by local control of anistropy in Pt/Co/Pt strips-

We theoretically and experimentally analyze the pinning of a magnetic domain wall (DW) at engineered anisotropy variations in Pt/Co/Pt strips with perpendicular magnetic anisotropy. An analytical model is derived showing that a step in the anisotropy acts as an energy barrier for the DW. Quantitative measurements are performed showing that the anisotropy can be controlled by focused ion beam irradiation with Ga ions. This tool is used to experimentally study the field-induced switching of nanostrips which are locally irradiated. The boundary of the irradiated area indeed acts as a pinning barrier for the domain wall and the pinning strength increases with the anisotropy difference. Varying the thickness of the Co layer provides an additional way to tune the anisotropy, and it is shown that a thinner Co layer gives a higher starting anisotropy thereby allowing tunable DW pinning in a wider range of fields. Finally, we demonstrate that not only the anisotropy itself, but also the width of the anisotropy barrier can be tuned on the length scale of the domain wall

Magnetic effects in FeNi structures codeposited with atom nanolithography

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The antibody response in the bovine mammary gland is influenced by the adjuvant and the site of subcutaneous vaccination

Intramammary infections in cattle resulting in mastitis have detrimental effects on cows' well-being, lifespan and milk production. In the host defense against S. aureus mastitis antibodies are thought to play an important role. To explore potential ways to increase antibody titers in the bovine mammary gland the effects of various adjuvants on the magnitude, isotype, and neutralizing capacity of antibodies produced following subcutaneous vaccine administration at different immunization sites were analyzed. In this study, α-toxoid was used as a model antigen and formulated in three different alum-based adjuvants: Alum-Saponin, Alum-Oil, and Alum-Saponin-Oil. Vaccines were administered near the suspensory ligament of the udder or in the lateral triangular area of the neck. At both immunization sites, immunization with α-toxoid in Alum-Saponin-Oil resulted in higher specific antibody titers in milk and serum as compared with Alum-Oil and Alum-Saponin, without favoring an IgG1, IgG2, or IgA response. Furthermore, the neutralizing capacity of milk serum and serum following immunization near the udder and in the neck was higher when Alum-Saponin-Oil was used as adjuvant compared with Alum-Oil and Alum-Saponin. Prime immunizations near the udder effectively increased both antibody isotype titers and neutralization titers, while prime plus boost immunizations were required to induce similar effects following immunization in the neck. Results indicate that subcutaneous administration of an Alum-Saponin-Oil based vaccine near the udder could be further explored for the development of a one-shot vaccination strategy to efficiently increase intramammary antibody responses

Overproduction of the poly(ADP-ribose)polymerase DNA-binding domain blocks alkylation-induced DNA repair synthesis in mammalian cells.

The zinc-finger DNA-binding domain (DBD) of poly (ADP-ribose) polymerase (PARP, EC 2.4.2.30) specifically recognizes DNA strand breaks induced by various DNA-damaging agents in eukaryotes. This, in turn, triggers the synthesis of polymers of ADP-ribose linked to nuclear proteins during DNA repair. The 46 kDa DBD of human PARP, and several derivatives thereof mutated in its first or second zinc-finger, were overproduced in Escherichia coli, in CV-1 monkey cells or in human fibroblasts to study their DNA-binding properties, the trans-dominant inhibition of resident PARP activity, and the consequences on DNA repair, respectively. A positi

Mutational analysis of the human nucleotide excision repair gene ERCC1.

The human DNA repair protein ERCC1 resides in a complex together with the ERCC4, ERCC11 and XP-F correcting activities, thought to perform the 5' strand incision during nucleotide excision repair (NER). Its yeast counterpart, RAD1-RAD10, has an additional engagement in a mitotic recombination pathway, probably required for repair of DNA cross-links. Mutational analysis revealed that the poorly conserved N-terminal 91 amino acids of ERCC1 are dispensable for both repair functions, in contrast to a deletion of only four residues from the C-terminus. A database search revealed a strongly conserved motif in this C-terminus sharing sequence homology with many DNA break processing proteins, indicating that this part is primarily required for the presumed structure-specific endonuclease activity of ERCC1. Most missense mutations in the central region give rise to an unstable protein (complex). Accordingly, we found that free ERCC1 is very rapidly degraded, suggesting that protein-protein interactions provide stability. Survival experiments show that the removal of cross-links requires less ERCC1 than UV repair. This suggests that the ERCC1-dependent step in cross-link repair occurs outside the context of NER and provides an explanation for the phenotype of the human repair syndrome xeroderma pigmentosum group F

Trio-based whole exome sequencing in patients with suspected sporadic inborn errors of immunity: A retrospective cohort study

Background: De novo variants (DNVs) are currently not routinely evaluated as part of diagnostic whole exome sequencing (WES) analysis in patients with suspected inborn errors of immunity (IEI). Methods: This study explored the potential added value of systematic assessment of DNVs in a retrospective cohort of 123 patients with a suspected sporadic IEI that underwent patient-parent trio-based WES. Results: A (likely) molecular diagnosis for (part) of the immunological phenotype was achieved in 12 patients with the diagnostic in silico IEI WES gene panel. Systematic evaluation of rare, non-synonymous DNVs in coding or splice site regions led to the identification of 14 candidate DNVs in genes with an annotated immune function. DNVs were found in IEI genes (NLRP3 and RELA) and in potentially novel candidate genes, including PSMB10, DDX1, KMT2C, and FBXW11. The FBXW11 canonical splice site DNV was shown to lead to defective RNA splicing, increased NF-κB p65 signalling, and elevated IL-1β production in primary immune cells extracted from the patient with autoinflammatory disease. Conclusions: Our findings in this retrospective cohort study advocate the implementation of trio-based sequencing in routine diagnostics of patients with sporadic IEI. Furthermore, we provide functional evidence supporting a causal role for FBXW11 loss-of-function mutations in autoinflammatory disease