One of the requirements for tumor growth is the ability to recruit a blood supply, a process known as angiogenesis. Angiogenesis begins early in the progression of cervical disease from mild to severe dysplasia and on to invasive cancer. We have previously reported that expression of human papillomavirus type 16 E6 and E7 (HPV16 E6E7) proteins in primary foreskin keratinocytes (HFKs) decreases expression of two inhibitors and increases expression of two angiogenic inducers [Toussaint-Smith, E., Donner, D.B., Roman, A., 2004. Expression of human papillomavirus type 16 E6 and E7 oncoproteins in primary foreskin keratinocytes is sufficient to alter the expression of angiogenic factors. Oncogene 23, 2988-2995]. Here we report that HPV-induced early changes in the keratinocyte phenotype are sufficient to alter endothelial cell behavior both in vitro and in vivo. Conditioned media from HPV16 E6E7 expressing HFKs as well as from human cervical keratinocytes containing the intact HPV16 were able to stimulate proliferation and migration of human microvascular endothelial cells. In addition, introduction of the conditioned media into immunocompetent mice using a Matrigel plug model resulted in a clear angiogenic response. These novel data support the hypothesis that HPV proteins contribute not only to the uncontrolled keratinocyte growth seen following HPV infection but also to the angiogenic response needed for tumor formation.
The development of qualitatively new measurement capabilities is often a prerequisite for critical scientific and technological advances. The dramatic progress made by modern probe techniques to uncover the microscopic structure of matter is fundamentally rooted in our control of two defining traits of quantum mechanics: discreteness of physical properties and interference phenomena. Magnetic Resonance Imaging, for instance, exploits the fact that protons have spin and can absorb photons at frequencies that depend on the medium to image the anatomy and physiology of living systems. Scattering techniques, in which photons, electrons, protons or neutrons are used as probes, make use of quantum interference to directly image the spatial position of individual atoms, their magnetic structure, or even unveil their concomitant dynamical correlations. None of these probes have so far exploited a unique characteristic of the quantum world: entanglement. Here we introduce a fundamentally new quantum probe, an entangled neutron beam, where individual neutrons can be entangled in spin, trajectory and energy. Its tunable entanglement length from nanometers to microns and energy differences from peV to neV will enable new investigations of microscopic magnetic correlations in systems with strongly entangled phases, such as those believed to emerge in unconventional superconductors. We develop an interferometer to prove entanglement of these distinguishable properties of the neutron beam by observing clear violations of both Clauser-Horne-Shimony-Holt and Mermin contextuality inequalities in the same experimental setup. Our work opens a pathway to a future era of entangled neutron scattering in matter. Text:A most amazing aspect of quantum reality is the possibility to share information non-locally between two or more spacelike separated subsystems, a "spooky action at a distance", as Einstein liked to call it and Bell epitomized in an inequality 1,2 . The fact that measuring compatible observables does not unveil predetermined physical properties, as pointed out by Kochen and Specker 3,4 , reveals the contextual nature of quantum measurements. Behind all these non-classical statistical correlations is the property of entanglement wherein "the state of the whole is more than the sum of its [constituent] parts'' 5 . Developing novel quantum probes that exploit these correlations as a means for investigating entanglement in matter could lead to novel insight into some of the most interesting materials studied today, such as frustrated magnets hosting quantum spin liquids and unconventional superconductors with strange metallic behavior 6 .
A magnetic Wollaston prism can spatially split a polarized neutron beam into two beams with different neutron spin states, in a manner analogous to an optical Wollaston prism. Such a Wollaston prism can be used to encode the trajectory of neutrons into the Larmor phase associated with their spin degree of freedom. This encoding can be used for neutron phase-contrast radiography and in spin echo scattering angle measurement (SESAME). In this paper, we show that magnetic Wollaston prisms with highly uniform magnetic fields and low Larmor phase aberration can be constructed to preserve neutron polarization using high temperature superconducting (HTS) materials. The Meissner effect of HTS films is used to confine magnetic fields produced electromagnetically by current-carrying HTS tape wound on suitably shaped soft iron pole pieces. The device is cooled to ~30 K by a closed cycle refrigerator, eliminating the need to replenish liquid cryogens and greatly simplifying operation and maintenance. A HTS film ensures that the magnetic field transition within the prism is sharp, well-defined, and planar due to the Meissner effect. The spin transport efficiency across the device was measured to be ~98.5% independent of neutron wavelength and energizing current. The position-dependent Larmor phase of neutron spins was measured at the NIST Center for Neutron Research facility and found to agree well with detailed simulations. The phase varies linearly with horizontal position, as required, and the neutron beam shows little depolarization. Consequently, the device has advantages over existing devices with similar functionality and provides the capability for a large neutron beam (20 mm × 30 mm) and an increase in length scales accessible to SESAME to beyond 10 μm. With further improvements of the external coupling guide field in the prototype device, a larger neutron beam could be employed.
The spin echo modulated small‐angle neutron scattering technique has been implemented using two superconducting magnetic Wollaston prisms at a reactor neutron source. The density autocorrelation function measured for a test sample of colloidal silica in a suspension agrees with that obtained previously by other neutron scattering methods on an identically prepared sample. The reported apparatus has a number of advantages over competing technologies: it should allow larger length scales (up to several micrometres) to be probed; it has very small parasitic neutron scattering and attenuation; the magnetic fields within the device are highly uniform; and the neutron spin transport across the device boundaries is very efficient. To understand quantitatively the results of the reported experiment and to guide future instrument development, Monte Carlo simulations are presented, in which the evolution of the neutron polarization through the apparatus is based on magnetic field integrals obtained from finite‐element simulations of the various magnetic components. The Monte Carlo simulations indicate that the polarization losses observed in the experiments are a result of instrumental artifacts that can be easily corrected in future experiments.
We present a new instrument for spin echo small angle neutron scattering (SESANS) developed at the Low Energy Neutron Source (LENS) at Indiana University. A description of the various instrument components is given along with the performance of these components. At the heart of the instrument are a series of resistive coils to encode the neutron trajectory into the neutron polarisation. These are shown to work well over a broad wavelength range of neutron wavelengths. Neutron polarisation analysis is accomplished using a continuously-operating neutron spin filter polarised by Rb-spin exchange optical pumping of 3 He. We describe the performance of the analyser along with a study of the 3 He polarisation stability and its implications for SESANS measurements. Scattering from silica Stöber particles is investigated and agrees with samples run on similar instruments.
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