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  • 1
    Language: English
    In: Physical review letters, 08 February 2013, Vol.110(6), pp.067203
    Description: We determine magnetoresistance effects in stable and clean Permalloy nanocontacts of variable cross section, fabricated by UHV deposition and in situ electromigration. To ascertain the magnetoresistance (MR) effects originating from a magnetic domain wall, we measure the resistance values with and without such a wall at zero applied field. In the ballistic transport regime, the MR ratio reaches up to 50% and exhibits a previously unobserved sign change. Our results can be reproduced by recent atomistic calculations for different atomic configurations of the nanocontact, highlighting the importance of the detailed atomic arrangement for the MR effect.
    Keywords: Condensed Matter - Mesoscale And Nanoscale Physics;
    ISSN: 00319007
    E-ISSN: 1079-7114
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  • 2
    Language: English
    In: Journal of Physics: Condensed Matter, 2014, Vol.26(47), p.474207 (9pp)
    Description: The study of magnetic domain walls in constrained geometries is an important topic, yet when dealing with extreme nanoscale magnetic systems artefacts can often dominate the measurements and obscure the effects of intrinsic magnetic origin. In this work we study the evolution of domain wall depinning in electromigrated ferromagnetic junctions which are both initially fabricated and subsequently tailored in-situ in clean ultra-high vacuum conditions. Carefully designed Ni 80 Fe 20 (Permalloy) notched half-ring structures are fabricated and investigated as a function of constriction width by tailoring the size of the contact using controlled in-situ electromigration. It is found that the domain wall pinning strength is increased on reducing the contact size in line with a reduction of the wall energy in narrower constrictions. Furthermore, the angular dependency and symmetry of the depinning field is measured to determine the full pinning potential for a domain wall in a system with a narrow constriction.
    Keywords: Walls ; Constrictions ; Ferromagnetism ; Contact ; Domain Walls ; Condensed Matter ; Pinning ; Nanostructure ; Condensed Matter Physics (General) (So) ; Magnetic Domain Walls ; Pinning Potential ; Electromigration ; Break-Junctions;
    ISSN: 0953-8984
    E-ISSN: 1361-648X
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  • 3
    Language: English
    In: Cancer research, 15 April 2017, Vol.77(8), pp.2134-2147
    Description: Many tumors display intracellular heterogeneity with subsets of cancer stem cells (CSC) that sustain tumor growth, recurrence, and therapy resistance. Cancer-associated fibroblasts (CAF) have been shown to support and regulate CSC function. Here, we investigate the interactions between CSCs and CAFs in mammary gland tumors driven by combined activation of Wnt/β-catenin and Hgf/Met signaling in mouse mammary epithelial cells. In this setting, CSCs secrete the Hedgehog ligand SHH, which regulate CAFs via paracrine activation of Hedgehog signaling. CAFs subsequently secrete factors that promote expansion and self-renewal of CSCs. treatment of tumors with the Hedgehog inhibitor vismodegib reduce CAF and CSC expansion, resulting in an overall delay of tumor formation. Our results identify a novel intracellular signaling module that synergistically regulates CAFs and CSCs. Targeting CAFs with Hedgehog inhibitors may offer a novel therapeutic strategy against breast cancer. .
    Keywords: Cancer-Associated Fibroblasts -- Metabolism ; Hedgehog Proteins -- Metabolism ; Mammary Neoplasms, Experimental -- Metabolism ; Neoplastic Stem Cells -- Metabolism
    ISSN: 00085472
    E-ISSN: 1538-7445
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  • 4
    In: EMBO Journal, 03 June 2015, Vol.34(11), pp.1493-1508
    Description: In this study, we have used techniques from cell biology, biochemistry, and genetics to investigate the role of the tyrosine phosphatase Shp2 in tumor cells of mouse mammary glands. Genetic ablation or pharmacological inhibition of Shp2 induces senescence, as determined by the activation of senescence‐associated β‐gal (‐β‐gal), cyclin‐dependent kinase inhibitor 1B (p27), p53, and histone 3 trimethylated lysine 9 (H3K9me3). Senescence induction leads to the inhibition of self‐renewal of tumor cells and blockage of tumor formation and growth. A signaling cascade was identified that acts downstream of Shp2 to counter senescence: Src, focal adhesion kinase, and Map kinase inhibit senescence by activating the expression of (), (), and the Notch ligand (), which block and . Remarkably, the expression of and of selected target genes predicts human breast cancer outcome. We conclude that therapies, which rely on senescence induction by inhibiting Shp2 or controlling its target gene products, may be useful in blocking breast cancer. Ablation or inhibition of the tyrosine phosphatase Shp2 in mammary gland cancers of mice induces senescence via the inactivation of Src, Fak, and Mek and subsequent downregulation of the genes ,, and . Small molecule inhibitors that target Shp2 block tumor growth by inducing senescence. Shp2 is highly upregulated in PyMT‐induced mammary gland cancers in mice. Ablation of the Shp2 gene blocks tumor formation by inducing senescence. Shp2 ablation or inhibition blocks the downstream signaling molecules Fak, Src, and Mek to inhibit the genes Skp2, Aurka, and Dll1, which suppress p27‐ and p53‐dependent senescence. Shp2 and downstream gene signatures predict relapse‐free survival of patients with breast cancer. Inhibition of Shp2 enzyme activity by small molecules blocks tumor growth in mice. Tyrosine phosphatase Shp2, upregulated in human breast cancer, regulates Src, , and signaling pathway to suppress senescence and promote tumorigenesis in mouse models.
    Keywords: Kaplan–Meier Analysis ; Pro‐Senescence Therapy ; Ptpn 11 ; Relapse‐Free Survival ; Shp2‐Dependent Gene Signature
    ISSN: 0261-4189
    E-ISSN: 1460-2075
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  • 5
    In: EMBO Journal, 14 September 2015, Vol.34(18), pp.2383-2383
    ISSN: 0261-4189
    E-ISSN: 1460-2075
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  • 6
    Language: English
    In: Proceedings of the National Academy of Sciences of the United States of America, 25 September 2007, Vol.104(39), pp.15376-81
    Description: Gab1 is a multiadaptor protein that has been shown to be required for multiple processes in embryonic development and oncogenic transformation. Gab1 functions by amplifying signal transduction downstream of various receptor tyrosine kinases through recruitment of multiple signaling effectors, including phosphatidylinositol 3-kinase and Shp2. Until now, the functional significance of individual interactions in vivo was not known. Here we have generated knockin mice that carry point mutations in either the P13K or Shp2 binding sites of Gab1. We show that different effector interactions with Gab1 play distinct biological roles downstream of Gab1 during the development of different organs. Recruitment of phosphatidylinositol 3-kinase by Gab1 is essential for EGF receptor-mediated embryonic eyelid closure and keratinocyte migration, and the Gab1-Shp2 interaction is crucial for Met receptor-directed placental development and muscle progenitor cell migration to the limbs. Furthermore, we investigate the dual association of Gab1 with the Met receptor. By analyzing knockin mice with mutations in the Grb2 or Met binding site of Gab1, we show that the requirements for Gab1 recruitment to Met varies in different biological contexts. Either the direct or the indirect interaction of Gab1 with Met is sufficient for Met-dependent muscle precursor cell migration, whereas both modes of interaction are required and neither is sufficient for placenta development, liver growth, and palatal shelf closure. These data demonstrate that Gab1 induces different biological responses through the recruitment of distinct effectors and that different modes of recruitment for Gab1 are required in different organs.
    Keywords: Signal Transduction ; Erbb Receptors -- Metabolism ; Phosphoproteins -- Physiology ; Proto-Oncogene Proteins C-Met -- Physiology
    ISSN: 0027-8424
    E-ISSN: 10916490
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  • 7
    In: Cell, May 18, 2001, Vol.105(4), p.533(14)
    Description: Research has been conducted on the beta-catenin, an important molecule in Wnt/wingless signaling which controls steps in embryogenesis. The role of beta-catenin in skin development has been investigated via the conditional mutation of the epidermis and hair follicle gene and the results indicate that beta-catenin mutation has blocked placode formation which generates hair follicles.
    Keywords: Cytological Research -- Analysis ; Morphogenesis -- Physiological Aspects ; Stem Cells -- Physiological Aspects ; Hair Follicles -- Genetic Aspects ; Gene Mutation -- Physiological Aspects ; Epidermis -- Genetic Aspects
    ISSN: 0092-8674
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  • 8
    Language: English
    In: Physical Review B, 6/2017, Vol.95(23)
    Description: We investigate the histograms of conductance values obtained during controlled electromigration thinning of Cu thin films. We focus on the question whether the most frequently observed conductance values, apparent as peaks in conductance histograms, can be attributed to the atomic structure of the wire. To this end we calculate the Fourier transform of the conductance histograms. We find all the frequencies matching the highly symmetric crystallographic directions of fcc-Cu. In addition, there are other frequencies explainable by oxidation and possibly formation of hcp-Cu. With these structures we can explain all peaks occurring in the Fourier transform within the relevant range. The results remain the same if only a third of the samples are included. By comparing our results to the ones available in the literature on work-hardened nanowires, we find indications that even at low temperatures of the environment, metallic nanocontacts could show enhanced electromigration at low current densities due to defects enhancing electron scattering.
    Keywords: Crystal Defects ; Crystallography ; Oxidation ; Fourier Transformation ; Electromigration ; Thin Films ; Low Currents ; Fourier Transforms ; Atomic Structure ; Histograms ; Resistance ; Nanowires;
    ISSN: 2469-9950
    E-ISSN: 2469-9969
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  • 9
    Language: English
    In: Journal of Vacuum Science & Technology B, Nanotechnology and Microelectronics: Materials, Processing, Measurement, and Phenomena, 01/2015, Vol.33(1), p.013201
    Description: The authors present the design of a modular sample holder that offers the possibility of in situ fabrication of metallic nanostructures under ultrahigh vacuum. One of the crucial points is to bridge the gap between the macroscopic leads and the nanostructure itself. This problem is solved by using a set of two different masks. For a precise alignment of the two masks, a magnetic tripod connection system has been developed. With this new system, an alignment precision of 26  μ m is obtained. As a result of the fabrication in ultrahigh vacuum, the nanostructures will be accessible to scanning probe techniques without surface contamination. First results show that electrical measurements are indeed possible.
    Keywords: Shop Notes;
    ISSN: 2166-2746
    E-ISSN: 2166-2754
    Source: CrossRef
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  • 10
    In: Nanoscale, 2017, Vol.9(23), pp.7868-7874
    Description: In nano-structures such as thin films electron confinement results in the quantization of energy levels in the direction perpendicular to the film. The discretization of the energy levels leads to the oscillatory dependence of many properties on the film thickness due to quantum size effects. Pb on Si(111) is a specially interesting system because a particular relationship between the Pb atomic layer thickness and its Fermi wavelength leads to a periodicity of the oscillation of two atomic layers. Here, we demonstrate how the combination of scanning force microscopy (SFM) and Kelvin probe force microscopy (KPFM) provides a reliable method to monitor the quantum oscillations in the work function of Pb ultra-thin film nano-structures on Si(111). Unlike other techniques, with SFM/KPFM we directly address single Pb islands, determine their height while suppressing the influence of electrostatic forces, and, in addition, simultaneously evaluate their local work function by measurements close to equilibrium, without current-dependent and non-equilibrium effects. Our results evidence evenodd oscillations in the work function as a function of the film thickness that decay linearly with the film thickness, proving that this method provides direct and precise information on the quantum states.
    Keywords: Condensed Matter - Mesoscale And Nanoscale Physics;
    ISSN: 2040-3364
    E-ISSN: 2040-3372
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