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We report the levitation of a superconducting lead-tin sphere with 100 µm diameter (corresponding to a mass of 5.6 µg) in a static magnetic trap formed by two coils in an anti-Helmholtz configuration, with adjustable resonance frequencies up to 240 Hz. The center-of-mass motion of the sphere is monitored magnetically using a dc superconducting quantum interference device as well as optically and exhibits quality factors of up to 2.6×10^{7}. We also demonstrate 3D magnetic feedback control of the motion of the sphere. The setup is housed in a dilution refrigerator operating at 15 mK. By implementing a cryogenic vibration isolation system, we can attenuate environmental vibrations at 200 Hz by approximately 7 orders of magnitude. The combination of low temperature, large mass, and high quality factor provides a promising platform for testing quantum physics in previously unexplored regimes with high mass and long coherence times.
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We present a method to fabricate nanometer scale gaps within InAs nanowires by selectively etching InAs/InP heterostructure nanowires. We used vapor-liquid-solid grown InAs nanowires with embedded InP segments of 10-60 nm length and developed an etching recipe to selectively remove the InP segment. A photo-assisted wet etching process in a mixture of acetic acid and hydrobromic acid gave high selectivity, with accurate removal of InP segments down to 20 nm, leaving the InAs wire largely unattacked, as verified using scanning electron and transmission electron microscopy. The obtained nanogaps in InAs wires have potential as semiconducting electrodes to investigate electronic transport in nanoscale objects. We demonstrate this functionality by dielectrophoretically trapping 30 nm diameter gold nanoparticles into the gap.
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Using an optimally coupled nanometer-scale SQUID, we measure the magnetic flux originating from an individual ferromagnetic Ni nanotube attached to a Si cantilever. At the same time, we detect the nanotube's volume magnetization using torque magnetometry. We observe both the predicted reversible and irreversible reversal processes. A detailed comparison with micromagnetic simulations suggests that vortexlike states are formed in different segments of the individual nanotube. Such stray-field free states are interesting for memory applications and noninvasive sensing.
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Engineered gold nanostructured arrays with feature separation in the sub-10-nm range were fabricated and used for highly sensitive surface enhanced Raman scattering (SERS) detection of biomarkers. Nanostructuring is achieved by combining electron beam lithography with the so-called shadow evaporation technique which involves a two-step Au vapor deposition through a suspended Ge mask while the substrate is tilted in opposite directions. This results in a regular triangular surface pattern with extremely small gap distances that allow positive enhancement of the local electric fields by enabling improvements in the electromagnetic coupling between adjacent nanoparticles. The resulting SERS active surfaces are suitable for the realization of reference procedures for quantifying marker molecules like urea or creatinine at physiologically relevant concentrations.
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Biomarcadores/química , Análisis por Micromatrices/instrumentación , Nanotecnología/métodos , Espectrometría Raman/instrumentación , Benzoatos/química , Creatinina/química , Diseño de Equipo , Oro/química , Análisis por Micromatrices/métodos , Espectrometría Raman/métodos , Compuestos de Sulfhidrilo/química , Propiedades de Superficie , Urea/químicaRESUMEN
Management of patients with metastatic squamous cell skin cancer, refractory to initial therapy with standard chemotherapy and radiation protocols, remains difficult with poor overall prognosis and limited therapeutic options. Recently, promising response rates with nivolumab, a programmed death receptor-1-blocking antibody, in squamous cancer of the head and neck have been demonstrated. Considering the similar histological patterns of squamous cell cancer of the skin and squamous cell cancer of the head and neck, we assumed that nivolumab could also be effective in our patients with refractory metastatic squamous cell cancer of the skin. So far, there have been no clinical data on the therapeutic efficacy of nivolumab in squamous cell skin cancer. We here present a case of a patient with metastatic squamous cell skin cancer refractory to previous therapies, who showed a good response to nivolumab over a period of 5 months, but developed a serious hemolytic crisis under nivolumab treatment after eight applications.
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We have recently shown the CD44 variant isoform 10 (CD44v10) to be expressed on reactive as well as malignant cutaneous lymphocytes; however, the functional consequences of CD44v10 expression on lymphocytes are not elucidated. By using appropriately transfected lymphatic cells we analyzed the role of CD44v10 on lymphocytes in cell-matrix adhesion and homotypic and heterotypic cell-cell adhesion assays. Despite a low binding affinity to hyaluronan, CD44v10-expressing lymphocytes exhibited heterotypic cell-cell adhesion to inflamed dermal microvascular endothelium and keratinocytes, as indicated by Stamper-Woodruff assays on tissue sections of delayed type hypersensitivity reactions and adhesion assays with cultured keratinocytes and cytokine-stimulated human dermal microvascular endothelial cells. Antibody-blocking assays excluded interaction of CD44v10 with the principal CD44 ligand hyaluronan as well as involvement of selectins or integrins in these heterotypic cell-cell adhesion assays. In contrast, cellular aggregation assays with fluorescence-labeled CD44v10- and CD44H-expressing lymphocytes revealed homotypic CD44v10/CD44v10 binding as well as binding of CD44v10 with CD44H. Heterotypic cell-cell adhesion assays with ultraviolet-A-irradiated CD44v-negative cytokine-stimulated endothelial cells demonstrated binding kinetics of CD44v10-expressing lymphocytes paralleling those of endothelial CD44H expression. These results imply that a hyaluronan-independent CD44v10/CD44H-mediated pathway is involved in lymphocyte infiltration into the dermis and epidermis of inflamed skin and suggest modulation of CD44H expression on inflamed dermal microvascular endothelium as a mechanism of ultraviolet-A-induced therapeutic effects on the skin.
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Endotelio Vascular/fisiología , Receptores de Hialuranos/análisis , Ácido Hialurónico/fisiología , Queratinocitos/fisiología , Linfocitos/fisiología , Piel/irrigación sanguínea , Adhesión Celular , Células Cultivadas , Endotelio Vascular/citología , Exones , Variación Genética , Humanos , Receptores de Hialuranos/metabolismo , Receptores de Hialuranos/fisiología , Ácido Hialurónico/metabolismo , Integrinas/fisiología , Microcirculación , Selectinas/fisiologíaRESUMEN
Using the differentiation antigen Pmel17/gp100 to genetically immunize C57BL/6 mice (H-2(b)), we and colleagues noticed that only mice that had received the human homolog but not animals injected with the murine counterpart were protected against the growth of syngeneic B16 melanoma cells. The goal of this study was to determine whether the state of nonresponsiveness to the autoantigen Pmel17/gp100 can be broken by immunization with a plasmid DNA construct encoding the autologous form of the molecule. A construct containing the murine form of Pmel17 was administered intradermally to DBA/2 mice (H-2(d)), which were then investigated for the presence of Pmel17/gp100-specific immunity. We show that administration of plasmid DNA coding for the autologous melanoma-associated antigen Pmel17/gp100 protects DBA/2 mice against the growth of Pmel17-positive M3 melanoma cells but not against Pmel17-negative M3 melanoma cells or unrelated P815 mastocytoma cells. Cell depletion experiments demonstrated that this protective effect is mediated by T lymphocytes. The notion that Pmel17/gp100 represents the biologically relevant target in this system was supported by the observations (i) that recipients of Pmel17/gp100 DNA mount an antigen-specific cytotoxic T lymphocyte response and (ii) that M3 tumors growing in mice immunized with autologous Pmel17/gp100 had lost expression of this melanoma-associated antigen whereas M3 melanomas appearing in control-vector-treated animals were still Pmel17/gp100-positive. These results indicate that intracutaneous genetic immunization with autologous melanoma-associated antigen Pmel17/gp100 encoding plasmid DNA can lead to protection against melanoma cells as a result of the induction of a melanoma-associated antigen-specific and protective T-cell-mediated immune response. J Invest Dermatol 115:1082-1087 2000
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Proteínas/inmunología , Animales , Antígenos de Neoplasias , Epítopos , Femenino , Humanos , Inmunidad Celular , Inmunización , Inyecciones Intradérmicas , Antígenos Específicos del Melanoma , Glicoproteínas de Membrana , Ratones , Ratones Endogámicos C57BL , Ratones Endogámicos DBA , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/inmunología , Neoplasias/prevención & control , Proteínas/genética , Linfocitos T/inmunología , Vacunación , Antígeno gp100 del MelanomaRESUMEN
Tumor cells with alterations in the MHC class I peptide-loading complex are unable to load peptide antigens onto MHC class I molecules. These alterations result in destabilization of MHC class I expression on the tumor cell surface and thus play a critical role in escape from immunological recognition by the acquired cellular immune system. By forming physical links between class I heavy chains and TAP molecules, a component of the class I peptide-loading complex, tapasin, plays an important role in the assembly of MHC class I molecules with peptides in the endoplasmic reticulum. In the present study, we compared 104 human melanoma lesions representing different stages of tumor progression for their expression of tapasin in tumor cells by immunohistochemistry. Tapasin downregulation was significantly associated with tumor progression. Whereas 100% of melanomata in situ and 96.2% of primary melanomas with a Breslow index of
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Antiportadores/metabolismo , Inmunoglobulinas/metabolismo , Melanoma/metabolismo , Neoplasias Cutáneas/metabolismo , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Progresión de la Enfermedad , Regulación hacia Abajo , Femenino , Humanos , Inmunohistoquímica/métodos , Masculino , Proteínas de Transporte de Membrana , Persona de Mediana Edad , Coloración y EtiquetadoRESUMEN
Measurements performed on superconductive networks shaped in the form of planar graphs display anomalously large currents when specific branches are biased. The temperature dependences of these currents evidence that their origin is due to Cooper pair hopping through the Josephson junctions connecting the superconductive islands of the array. The experimental data are discussed in terms of theoretical models which predict, for the system under consideration, an inhomogeneous Cooper pair distribution on the superconductive islands of the network as a consequence of a Bose-Einstein condensation phenomenon.
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Cobre/química , Conductividad Eléctrica , Modelos Teóricos , Teoría Cuántica , Simulación por Computador , TemperaturaRESUMEN
The electrical properties of single ZnO nanowires grown by vapor phase transport were investigated. While some samples were contacted by Ti/Au electrodes, another set of samples was investigated using a manipulator tip in a low energy electron point-source microscope. The deduced resistivities range from 1 to 10(3) Ωcm. Additionally, the resistivities of nanowires from multiple publications were brought together and compared to the values obtained from our measurements. The overview of all data shows enormous differences (10(-3)-10(5) Ωcm) in the measured resistivities. In order to reveal the origin of the discrepancies, the influence of growth parameters, measuring methods, contact resistances, crystal structures and ambient conditions are investigated and discussed in detail.
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CD44 is a family of cell-surface receptors on human lymphocytes that act as co-stimulatory molecules leading to the induction of effector functions in T cells. We have analyzed primary cutaneous malignant melanomas with clinical and histologic signs of tumor regression using immunohistochemistry and observed the predominant expression of the CD44 variant isoform v10 on CD3 CD4/CD8 co-expressing tumor-infiltrating lymphocytes (TIL). We further analyzed the role of CD44v10 in adhesion of lymphocytes to human melanoma cells. In contrast to CD44- lymphatic cells, CD44v10+ lymphatic cells strongly bound to cultured human melanoma cells and to frozen tissue samples of melanomas. Antibody blocking studies revealed a hyaluronan-, integrin-, and selectin-independent pathway of adhesion. Furthermore, CD44v10+ lymphatic cells exhibited significantly higher invasiveness in three-dimensional collagen matrices as compared with CD44H+ and CD44-negative lymphocytes. These results indicate that expression of CD44v10 on TIL may mediate adhesion to melanoma cells and result in gain of novel invasive properties.