Integrin-Mediated Cell-Matrix Interaction in Physiological and Pathological Blood Vessel Formation

Physiological as well as pathological blood vessel formation are fundamentally dependent on cell-matrix interaction. Integrins, a family of major cell adhesion receptors, play a pivotal role in development, maintenance, and remodeling of the vasculature. Cell migration, invasion, and remodeling of the extracellular matrix (ECM) are integrin-regulated processes, and the expression of certain integrins also correlates with tumor progression. Recent advances in the understanding of how integrins are involved in the regulation of blood vessel formation and remodeling during tumor progression are highlighted. The increasing knowledge of integrin function at the molecular level, together with the growing repertoire of integrin inhibitors which allow their selective pharmacological manipulation, makes integrins suited as potential diagnostic markers and therapeutic targets

Syk-dependent Phosphorylation of CLEC-2: A Novel Mechanism of Hem-Immunoreceptor Tyrosine-Based Activation Motif Signaling

The C-type lectin-like receptor CLEC-2 signals via phosphorylation of a single cytoplasmic YXXL sequence known as a hem-immunoreceptor tyrosine-based activation motif (hemITAM). In this study, we show that phosphorylation of CLEC-2 by the snake toxin rhodocytin is abolished in the absence of the tyrosine kinase Syk but is not altered in the absence of the major platelet Src family kinases, Fyn, Lyn, and Src, or the tyrosine phosphatase CD148, which regulates the basal activity of Src family kinases. Further, phosphorylation of CLEC-2 by rhodocytin is not altered in the presence of the Src family kinase inhibitor PP2, even though PLCγ2 phosphorylation and platelet activation are abolished. A similar dependence of phosphorylation of CLEC-2 on Syk is also seen in response to stimulation by an IgG mAb to CLEC-2, although interestingly CLEC-2 phosphorylation is also reduced in the absence of Lyn. These results provide the first definitive evidence that Syk mediates phosphorylation of the CLEC-2 hemITAM receptor with Src family kinases playing a critical role further downstream through the regulation of Syk and other effector proteins, providing a new paradigm in signaling by YXXL-containing receptors

Hole spin dephasing time associated to hyperfine interaction in quantum dots

The spin interaction of a hole confined in a quantum dot with the surrounding nuclei is described in terms of an effective magnetic field. We show that, in contrast to the Fermi contact hyperfine interaction for conduction electrons, the dipole-dipole hyperfine interaction is anisotropic for a hole, for both pure or mixed hole states. We evaluate the coupling constants of the hole-nuclear interaction and demonstrate that they are only one order of magnitude smaller than the coupling constants of the electron-nuclear interaction. We also study, theoretically, the hole spin dephasing of an ensemble of quantum dots via the hyperfine interaction in the framework of frozen fluctuations of the nuclear field, in absence or in presence of an applied magnetic field. We also discuss experiments which could evidence the dipole-dipole hyperfine interaction and give information on hole mixing.Comment: 35 pages, 7 figures and 2 table

Collaborative Course Design in Scientific Writing: Experimentation and Productive Failure

English 3820: Scientific Writing, a writing-intensive (WI) course offered by the Department of English at East Carolina University (ECU), serves primarily science majors. According to the course catalog, it provides students with “practice in assimilation and written presentation of scientific information.� The course asks students to consider the situated nature of scientific writing and also to produce scientific writing for various audiences. Throughout the course, students examine theories, methodologies, and ideologies that undergird scientific writing with an eye to perfecting both critique and imitation of scientific styles

Bistability of the Nuclear Polarisation created through optical pumping in InGaAs Quantum Dots

We show that optical pumping of electron spins in individual InGaAs quantum dots leads to strong nuclear polarisation that we measure via the Overhauser shift (OHS) in magneto-photoluminescence experiments between 0 and 4T. We find a strongly non-monotonous dependence of the OHS on the applied magnetic field, with a maximum nuclear polarisation of 40% for intermediate magnetic fields. We observe that the OHS is larger for nuclear fields anti-parallel to the external field than in the parallel configuration. A bistability in the dependence of the OHS on the spin polarization of the optically injected electrons is found. All our findings are qualitatively understood with a model based on a simple perturbative approach.Comment: Phys Rev B (in press

Phosphorylation of CLEC-2 is dependent on lipid rafts, actin polymerization,secondary mediators, and Rac

The C-type lectin-like receptor 2 (CLEC-2)activates platelets through Src and Syk tyrosine kinases via a single cytoplasmic YxxL motif known as a hem immunoreceptor tyrosine-based activation motif (hemITAM).Here, we demonstrate using sucrose gradient ultracentrifugation and methyl--cyclodextrin treatment that CLEC-2 translocates to lipid rafts upon ligand engagement and that translocation is essential for hemITAM phosphorylation and signal initiation. HemITAM phosphorylation, but not translocation, is also critically dependent on actin polymerization,Rac1 activation, and release of ADP and thromboxane A2 (TxA2). The role of ADP and TxA2 in mediating hosphorylation is dependent on ligand engagement and rac activation but is independent of platelet aggregation. In contrast,tyrosine phosphorylation of the GPVIFcR -chain ITAM, which has 2 YxxL motifs,is independent of actin polymerization and secondary mediators. These results reveal a unique series of proximal events in CLEC-2 phosphorylation involving actin polymerization, secondary mediators,and Rac activation

Demagnetization of Quantum Dot Nuclear Spins: Breakdown of the Nuclear Spin Temperature Approach

The physics of interacting nuclear spins arranged in a crystalline lattice is typically described using a thermodynamic framework: a variety of experimental studies in bulk solid-state systems have proven the concept of a spin temperature to be not only correct but also vital for the understanding of experimental observations. Using demagnetization experiments we demonstrate that the mesoscopic nuclear spin ensemble of a quantum dot (QD) can in general not be described by a spin temperature. We associate the observed deviations from a thermal spin state with the presence of strong quadrupolar interactions within the QD that cause significant anharmonicity in the spectrum of the nuclear spins. Strain-induced, inhomogeneous quadrupolar shifts also lead to a complete suppression of angular momentum exchange between the nuclear spin ensemble and its environment, resulting in nuclear spin relaxation times exceeding an hour. Remarkably, the position dependent axes of quadrupolar interactions render magnetic field sweeps inherently non-adiabatic, thereby causing an irreversible loss of nuclear spin polarization.Comment: 15 pages, 3 figure

Etiology of pure tricuspid regurgitation based on anular circumference and leaflet area: Analysis of 45 necropsy patients with clinical and morphologic evidence of pure tricuspid regurgitation

Despite recent renewed interest in the detection of tricuspid valve regurgitation by echocardiographic and Doppler techniques, little morphologic information is available on dysfunctioning tricuspid valves. This report describes 45 necropsy patients with clinical and morphologic evidence of pure(no element of stenosis) tricuspid regurgitation and provides morphometric observations (anular circumference, leaflet area) of the tricuspid valve useful in determining the etiology of pure tricuspid regurgitation. Of 45 patients, 24 (53%) had pure tricuspid regurgitation resulting from an anatomically abnormal valve (prolap9e in 7, papillary muscle dysfunction in 6, rheumatic disease in 5, Ebstein's anomaly in 3, infective endocarditis in 2, carcinoid tumor in 1), and 21(47%) had an anatomically normal valve with systolic pulmonary artery hypertension (cor pulmonary in 12, mitral stenosis in 9). Anular circumference was dilated (> 12 cm) in patients with various causes of pulmonary hypertension, floppy valve and Ebstein's tricuspid anomaly. Leaflet area was increased in floppy valve and Ebstein's anomaly.Of the 45 patients, 24 had pulmonary systolic artery pressure measurements available for correlation with tricuspid valve morphology. Pulmonary artery pressures accurately predicted morphologically normal from abnormal valves in 16 patients (89 %). Morphologic overlap occurred in six patients with pulmonary pressures of 41 to 54 mm Hg. Of these six, the additional knowledge of normal or dilated anular circumference correctly separated valves with normal and abnormal leaflets

Full Stokes imaging polarimetry using dielectric metasurfaces

Polarization is a degree of freedom of light carrying important information that is usually absent in intensity and spectral content. Imaging polarimetry is the process of determining the polarization state of light, either partially or fully, over an extended scene. It has found several applications in various fields, from remote sensing to biology. Among different devices for imaging polarimetry, division of focal plane polarization cameras (DoFP-PCs) are more compact, less complicated, and less expensive. In general, DoFP-PCs are based on an array of polarization filters in the focal plane. Here we demonstrate a new principle and design for DoFP-PCs based on dielectric metasurfaces with the ability to control polarization and phase. Instead of polarization filtering, the method is based on splitting and focusing light in three different polarization bases. Therefore, it enables full-Stokes characterization of the state of polarization, and overcomes the 50% theoretical efficiency limit of the polarization-filter-based DoFP-PCs.Comment: 20 pages, 4 figure