High expression of cannabinoid receptor 2 on cytokine-induced killer cells and multiple myeloma cells

Multiple myeloma (MM) is characterized by aberrant bone marrow plasma cell (PC) proliferation and is one of the most common hematological malignancies. The potential effect of cannabinoids on the immune system and hematological malignancies has been poorly characterized. Cannabidiol (CBD) may be used to treat various diseases. CBD is known to exert immunomodulatory effects through the activation of cannabinoid receptor 2 (CB2), which is expressed in high levels in the hematopoietic system. Cytokine-induced killer (CIK) cells are a heterogeneous population of polyclonal T lymphocytes obtained via ex vivo sequential incubation of peripheral blood mononuclear cells (PBMCs) with interferon-γ (IFN-γ), anti CD3 monoclonal antibody, and IL-2. They are characterized by the expression of CD3+ and CD56+, which are surface markers common to T lymphocytes and natural killer (NK) cells. CIK cells are mainly used in hematological patients who suffer relapse after allogeneic transplantation. Here, we investigated their antitumor effect in combination with pure cannabidiol in KMS-12 MM cells by lactate dehydrogenase LDH cytotoxicity assay, CCK-8 assay, and flow cytometry analysis. The surface and intracellular CB2 expressions on CIK cells and on KMS-12 and U-266 MM cell lines were also detected by flow cytometry. Our findings confirm that the CB2 receptor is highly expressed on CIK cells as well as on MM cells. CBD was able to decrease the viability of tumor cells and can have a protective role for CIK cells. It also inhibits the cytotoxic activity of CIKs against MM at high concentrations, so in view of a clinical perspective, it has to be considered that the lower concentration of 1 µM can be used in combination with CIK cells. Further studies will be required to address the mechanism of CBD modulation of CIK cells in more detail

About the use of antagonistic bacteria and fungi

Microorganisms isolated from the phylloplane of vine and cereal plants inhibiting different phytopathogenic fungi were tested as biological control agents against Plasmopara viticola (downy mildew of grapevine). Based on screening in vitro against Phytophthora infestans, P. parasitica, Pythium ultimum, Botrytis cinerea 62 bacterial isolates were selected for tests with Plasmopara viticola.. Antifungal bacterial strains were assayed for antagonistic activity towards the grapevine dieback fungus Eutypa lata in vitro and on grape wood

Overview study of Space Power Technologies for the advanced energetics program

Space power technologies are reviewed to determine the state-of-the-art and to identify advanced or novel concepts which promise large increases in performance. The potential for incresed performance is judged relative to benchmarks based on technologies which have been flight tested. Space power technology concepts selected for their potentially high performance are prioritized in a list of R & D topical recommendations for the NASA program on Advanced Energetics. The technology categories studied are solar collection, nuclear power sources, energy conversion, energy storage, power transmission, and power processing. The emphasis is on electric power generation in space for satellite on board electric power, for electric propulsion, or for beamed power to spacecraft. Generic mission categories such as low Earth orbit missions and geosynchronous orbit missions are used to distinguish general requirements placed on the performance of power conversion technology. Each space power technology is judged on its own merits without reference to specific missions or power systems. Recommendations include 31 space power concepts which span the entire collection of technology categories studied and represent the critical technologies needed for higher power, lighter weight, more efficient power conversion in space

Improved Activation toward Primary Colorectal Cancer Cells by Antigen-Specific Targeting Autologous Cytokine-Induced Killer Cells

Adoptive therapy of malignant diseases with cytokine-induced killer (CIK) cells showed promise in a number of trials; the activation of CIK cells from cancer patients towards their autologous cancer cells still needs to be improved. Here, we generated CIK cells ex vivo from blood lymphocytes of colorectal cancer patients and engineered those cells with a chimeric antigen receptor (CAR) with an antibody-defined specificity for carcinoembryonic antigen (CEA). CIK cells thereby gained a new specificity as defined by the CAR and showed increase in activation towards CEA+ colon carcinoma cells, but less in presence of CEA− cells, indicated by increased secretion of proinflammatory cytokines. Redirected CIK activation was superior by CAR-mediated CD28-CD3ζ than CD3ζ signaling only. CAR-engineered CIK cells from colon carcinoma patients showed improved activation against their autologous, primary carcinoma cells from biopsies resulting in more efficient tumour cell lysis. We assume that adoptive therapy with CAR-modified CIK cells shows improved selectivity in targeting autologous tumour lesions

Spin Coulomb drag in the two-dimensional electron liquid

We calculate the spin-drag transresistivity $\rho_{\uparrow \downarrow}(T)$ in a two-dimensional electron gas at temperature $T$ in the random phase approximation. In the low-temperature regime we show that, at variance with the three-dimensional low-temperature result [$\rho_{\uparrow\downarrow}(T) \sim T^2$], the spin transresistivity of a two-dimensional {\it spin unpolarized} electron gas has the form $\rho_{\uparrow\downarrow}(T) \sim T^2 \ln T$. In the spin-polarized case the familiar form $\rho_{\uparrow\downarrow}(T) =A T^2$ is recovered, but the constant of proportionality $A$ diverges logarithmically as the spin-polarization tends to zero. In the high-temperature regime we obtain $\rho_{\uparrow \downarrow}(T) = -(\hbar / e^2) (\pi^2 Ry^* /k_B T)$ (where $Ry^*$ is the effective Rydberg energy) {\it independent} of the density. Again, this differs from the three-dimensional result, which has a logarithmic dependence on the density. Two important differences between the spin-drag transresistivity and the ordinary Coulomb drag transresistivity are pointed out: (i) The $\ln T$ singularity at low temperature is smaller, in the Coulomb drag case, by a factor $e^{-4 k_Fd}$ where $k_F$ is the Fermi wave vector and $d$ is the separation between the layers. (ii) The collective mode contribution to the spin-drag transresistivity is negligible at all temperatures. Moreover the spin drag effect is, for comparable parameters, larger than the ordinary Coulomb drag effect.Comment: 6 figures; various changes; version accepted for publicatio

Electron Spin Injection at a Schottky Contact

We investigate theoretically electrical spin injection at a Schottky contact between a spin-polarized electrode and a non-magnetic semiconductor. Current and electron density spin-polarizations are discussed as functions of barrier energy and semiconductor doping density. The effect of a spin-dependent interface resistance that results from a tunneling region at the contact/semiconductor interface is described. The model can serve as a guide for designing spin-injection experiments with regard to the interface properties and device structure.Comment: 4 pages, 4 figure

A Low Dose of Pure Cannabidiol Is Sufficient to Stimulate the Cytotoxic Function of CIK Cells without Exerting the Downstream Mediators in Pancreatic Cancer Cells

Despite numerous studies conducted over the past decade, the exact role of the cannabinoid system in cancer development remains unclear. Though research has focused on two cannabinoid receptors (CB1, CB2) activated by most cannabinoids, CB2 holds greater attention due to its expression in cells of the immune system. In particular, cytokine-induced killer cells (CIKs), which are pivotal cytotoxic immunological effector cells, express a high-level of CB2 receptors. Herein, we sought to investigate whether inducing CIK cells with cannabidiol can enhance their cytotoxicity and if there are any possible counter effects in its downstream cascade of phosphorylated p38 and CREB using a pancreatic ductal adenocarcinoma cell line (PANC-1). Our results showed that IL-2 modulates primarily the expression of the CB2 receptor on CIK cells used during ex vivo CIK expansion. The autophagosomal-associated scaffold protein p62 was found to co-localize with CB2 receptors in CIK cells and the PANC-1 cell line. CIK cells showed a low level of intracellular phospho-p38 and, when stimulated with cannabidiol (CBD), a donor specific variability in phospho-CREB. CBD significantly decreases the viability of PANC-1 cells presumably by increasing the cytotoxicity of CIK cells. Taken together, in our preclinical in vitro study, we propose that a low effective dose of CBD is sufficient to stimulate the cytotoxic function of CIK without exerting any associated mediator. Thus, the combinatorial approach of non-psychogenic CBD and CIK cells appears to be safe and can be considered for a clinical perspective in pancreatic cancer

Modulating the polarization of broadband terahertz pulses from a spintronic emitter at rates up to 10 kHz

Reliable modulation of terahertz electromagnetic waveforms is important for many applications. Here, we rapidly modulate the direction of the electric field of linearly polarized terahertz electromagnetic pulses with 1–30 THz bandwidth by applying time-dependent magnetic fields to a spintronic terahertz emitter. Polarity modulation of the terahertz field with more than 99% contrast at a rate of 10 kHz is achieved using a harmonic magnetic field. By adding a static magnetic field, we modulate the direction of the terahertz field between angles of, for instance, −53° and 53° at kilohertz rates. We believe our approach makes spintronic terahertz emitters a promising source for low-noise modulation spectroscopy and polarization-sensitive techniques such as ellipsometry at 1–30 THz

The X-ray Background and AGNs

Deep X-ray surveys have shown that the cosmic X-ray background (XRB) is largely due to the accretion onto supermassive black holes, integrated over the cosmic time. These surveys have resolved more than 80% of the 0.1-10 keV X-ray background into discrete sources. Optical spectroscopic identifications show that the sources producing the bulk of the X-ray background are a mixture of unobscured (type-1) and obscured (type-2) AGNs, as predicted by the XRB population synthesis models. A class of highly luminous type-2 AGN, so called QSO-2s, has been detected in the deepest Chandra and XMM-Newton surveys. The new Chandra AGN redshift distribution peaks at much lower redshifts (z~0.7) than that based on ROSAT data, and the new X-ray luminosity function indicates that the space density of Seyfert galaxies peaks at significantly lower redshifts than that of QSOs. It is shown here, that the low redshift peak applies both to absorbed and unabsorbed AGN and is also seen in the 0.5-2 keV band alone. Previous findings of a strong dependence of the fraction of type-2 AGN on luminosity are confirmed with better statistics here. Preliminary results from an 800 ksec XMM-Newton observation of the Lockman Hole are discussed.Comment: Proceedings of the conference: "The restless high energy universe", held in Amsterdam, May 2003. To be published in: Nucl. Physics B. Suppl. Ser., E.P.J. van den Heuvel, J.J.M. in 't Zand, and R.A.M.J. Wijers (eds.). 10 pages, 5 figure