CXCR4 signaling regulates metastatic onset by controlling neutrophil motility and response to malignant cells

Developing tumors interact with the surrounding microenvironment. Myeloid cells exert both anti- and pro-tumor functions and chemokines are known to drive immune cell migration towards cancer cells. It is documented that CXCR4 signaling supports tumor metastasis formation in tissues where CXCL12, its cognate ligand, is abundant. On the other hand, the role of the neutrophilic CXCR4 signaling in driving cancer invasion and metastasis formation is poorly understood. Here, we use the zebrafish xenotransplantation model to study the role of CXCR4 signaling in driving the interaction between invasive human tumor cells and host neutrophils, supporting early metastasis formation. We found that zebrafish cxcr4 (cxcr4b) is highly expressed in neutrophils and experimental micrometastases fail to form in mutant larvae lacking a functional Cxcr4b. We demonstrated that Cxcr4b controls neutrophil number and motility and showed that Cxcr4b transcriptomic signature relates to motility and adhesion regulation in neutrophils in tumor-naïve larvae. Finally, Cxcr4b deficient neutrophils failed to interact with cancer cells initiating early metastatic events. In conclusion, we propose that CXCR4 signaling supports the interaction between tumor cells and host neutrophils in developing tumor metastases. Therefore, targeting CXCR4 on tumor cells and neutrophils could serve as a double bladed razor to limit cancer progression

Violation of the Nernst heat theorem in the theory of thermal Casimir force between Drude metals

We give a rigorous analytical derivation of low-temperature behavior of the Casimir entropy in the framework of the Lifshitz formula combined with the Drude dielectric function. An earlier result that the Casimir entropy at zero temperature is not equal to zero and depends on the parameters of the system is confirmed, i.e. the third law of thermodynamics (the Nernst heat theorem) is violated. We illustrate the resolution of this thermodynamical puzzle in the context of the surface impedance approach by several calculations of the thermal Casimir force and entropy for both real metals and dielectrics. Different representations for the impedances, which are equivalent for real photons, are discussed. Finally, we argue in favor of the Leontovich boundary condition which leads to results for the thermal Casimir force that are consistent with thermodynamics.Comment: 24 pages, 3 figures, accepted for publication in Phys. Rev.

Embryonic zebrafish xenograft assay of human cancer metastasis

) embryos, however, offer many advantages as a model system for studying the complex, multi-step processes involved during cancer metastasis. This article describes a detailed method for the analysis of human cancer cell invasion and metastasis in zebrafish embryos before they reach protected status at 5 days post fertilisation. Results demonstrate that human cancer cells actively invade within a zebrafish microenvironment, and form metastatic tumours at secondary tissue sites, suggesting that the mechanisms involved during the different stages of metastasis are conserved between humans and zebrafish, supporting the use of zebrafish embryos as a viable model of human cancer metastasis. We suggest that the embryonic zebrafish xenograft model of human cancer is a tractable laboratory model that can be used to understand cancer biology, and as a direct replacement of mice for the analysis of drugs that target cancer invasion and metastasis.Animal science

Options for a high heat flux enabled helium cooled First Wall for DEMO

Helium is considered as coolant in the plasma facing first wall of several blanket concepts for DEMO fusion reactors, due to the favorable properties of flexible temperature range, chemical inertness, no activation, comparatively low effort to remove tritium from the gas and no chemical corrosion. Existing blanket designs have shown the ability to use helium cooled first walls with heat flux densities of 0.5 MW/m2. Average steady state heat loads coming from the plasma for current EU DEMO concepts are expected in the range of 0.3 MW/m2. The definition of peak values is still ongoing and depends on the chosen first wall shape, magnetic configuration and assumptions on the fraction of radiated power and power fall off lengths in the scrape off layer of the plasma. Peak steady state values could reach and excess 1 MW/m2. Higher short-term transient loads are expected. Design optimization approaches including heat transfer enhancement, local heat transfer tuning and shape optimization of the channel cross section are discussed. Design points to enable a helium cooled first wall capable to sustain heat flux densities of 1 MW/m2 at an average shell temperature lower than 500 °C are developed based on experimentally validated heat transfer coefficients of structured channel surfaces. The required pumping power is in the range of 3–5% of the collected thermal power. The FEM stress analyses show code-acceptable stress intensities. Several manufacturing methods enabling the application of the suggested heat transfer enhanced first wall channels are explored. An alternative cooling technology is suggested, extending the tolerable heat loads up to 3 MW/m

Microscopic Structure of the Calcium Isotopes

This research was sponsored by the National Science Foundation Grant NSF PHY 87-1440

Viscous Brane Cosmology with a Brane-Bulk Energy Interchange Term

We assume a flat brane located at y=0, surrounded by an AdS space, and consider the 5D Einstein equations when the energy flux component of the energy-momentum tensor is related to the Hubble parameter through a constant Q. We calculate the metric tensor, as well as the Hubble parameter on the brane, when Q is small. As a special case, if the brane is tensionless, the influence from Q on the Hubble parameter is absent. We also consider the emission of gravitons from the brane, by means of the Boltzmann equation. Comparing the energy conservation equation derived herefrom with the energy conservation equation for a viscous fluid on the brane, we find that the entropy change for the fluid in the emission process has to be negative. This peculiar effect is related to the fluid on the brane being a non-closed thermodynamic system. The negative entropy property for non-closed systems is encountered in other areas in physics also, in particular, in connection with the Casimir effect at finite temperature.Comment: 12 pages, latex, no figure

Surface-impedance approach solves problems with the thermal Casimir force between real metals

The surface impedance approach to the description of the thermal Casimir effect in the case of real metals is elaborated starting from the free energy of oscillators. The Lifshitz formula expressed in terms of the dielectric permittivity depending only on frequency is shown to be inapplicable in the frequency region where a real current may arise leading to Joule heating of the metal. The standard concept of a fluctuating electromagnetic field on such frequencies meets difficulties when used as a model for the zero-point oscillations or thermal photons in the thermal equilibrium inside metals. Instead, the surface impedance permits not to consider the electromagnetic oscillations inside the metal but taking the realistic material properties into account by means of the effective boundary condition. An independent derivation of the Lifshitz-type formulas for the Casimir free energy and force between two metal plates is presented within the impedance approach. It is shown that they are free of the contradictions with thermodynamics which are specific to the usual Lifshitz formula for dielectrics in combination with the Drude model. We demonstrate that in the impedance approach the zero-frequency contribution is uniquely fixed by the form of impedance function and does not need any of the ad hoc prescriptions intensively discussed in the recent literature. As an example, the computations of the Casimir free energy between two gold plates are performed at different separations and temperatures. It is argued that the surface impedance approach lays a reliable framework for the future measurements of the thermal Casimir force.Comment: 21 pages, 3 figures, to appear in Phys. Rev.

Zebrafish microenvironment elevates EMT and CSC-Like phenotype of engrafted prostate cancer cells

Animal science

Stereotactic Radiosurgery for Postoperative Spine Malignancy: A Systematic Review and International Stereotactic Radiosurgery Society Practice Guidelines.

To determine safety and efficacy of postoperative spine stereotactic body radiation therapy (SBRT) in the published literature, and to present practice recommendations on behalf of the International Stereotactic Radiosurgery Society. A systematic review of the literature was performed, specific to postoperative spine SBRT, using PubMed and Embase databases. A meta-analysis for 1-year local control (LC), overall survival (OS), and vertebral compression fracture probability was conducted. The literature search revealed 251 potentially relevant articles after duplicates were removed. Of these 56 were reviewed in-depth for eligibility and 12 met all the inclusion criteria for analysis. 7 studies were retrospective, 2 prospective observational and 3 were prospective phase 1 and 2 clinical trials. Outcomes for a total of 461 patients and 499 spinal segments were reported. Ten studies used a magnetic resonance imaging (MRI) scan fused to computed tomography (CT) simulation for treatment planning, and 2 investigations reported on all patients receiving a CT-myelogram at the time of planning. Meta-analysis for 1 year LC and OS was 88.9% and 57%, respectively. The crude reported vertebral compression fracture rate was 5.6%. One case of myelopathy was described in a patient with a previously irradiated spinal segment. One patient developed an esophageal fistula requiring surgical repair. Postoperative spine SBRT delivers a high 1-year LC with acceptably low toxicity. Patients who may benefit from this include those with oligometastatic disease, radioresistant histology, paraspinal masses, or those with a history of prior irradiation to the affected spinal segment. The International Stereotactic Radiosurgery Society recommends a minimum interval of 8 to 14 days after invasive surgery before simulation for SBRT, with initiation of radiation therapy within 4 weeks of surgery. An MRI fused to the planning CT, or the use of a CT-myelogram, are necessary for target and organ-at-risk delineation. A planning organ-at-risk volume (PRV) of 1.5 to 2 mm for the spinal cord is advised

How Many CMEs Have Flux Ropes? Deciphering the Signatures of Shocks, Flux Ropes, and Prominences in Coronagraph Observations of CMEs

We intend to provide a comprehensive answer to the question on whether all Coronal Mass Ejections (CMEs) have flux rope structure. To achieve this, we present a synthesis of the LASCO CME observations over the last sixteen years, assisted by 3D MHD simulations of the breakout model, EUV and coronagraphic observations from STEREO and SDO, and statistics from a revised LASCO CME database. We argue that the bright loop often seen as the CME leading edge is the result of pileup at the boundary of the erupting flux rope irrespective of whether a cavity or, more generally, a 3-part CME can be identified. Based on our previous work on white light shock detection and supported by the MHD simulations, we identify a new type of morphology, the `two-front' morphology. It consists of a faint front followed by diffuse emission and the bright loop-like CME leading edge. We show that the faint front is caused by density compression at a wave (or possibly shock) front driven by the CME. We also present high-detailed multi-wavelength EUV observations that clarify the relative positioning of the prominence at the bottom of a coronal cavity with clear flux rope structure. Finally, we visually check the full LASCO CME database for flux rope structures. In the process, we classify the events into two clear flux rope classes (`3-part', `Loop'), jets and outflows (no clear structure). We find that at least 40% of the observed CMEs have clear flux rope structures. We propose a new definition for flux rope CMEs (FR-CMEs) as a coherent magnetic, twist-carrying coronal structure with angular width of at least 40 deg and able to reach beyond 10 Rsun which erupts on a time scale of a few minutes to several hours. We conclude that flux ropes are a common occurrence in CMEs and pose a challenge for future studies to identify CMEs that are clearly not FR-CMEs.Comment: 26 pages, 9 figs, to be published in Solar Physics Topical Issue "Flux Rope Structure of CMEs