The Memory Activation of NK Cells: New Methods in Cancer Immunotherapy

Cancer remains a main cause of mortality, despite the research efforts to unravel molecular mechanisms and for developing personalized targeted therapies with acceptable side effects. In cancer, both players, the aggressor (tumor cells) and the endogenous defenders (immune cells), are key therapeutic targets. Immunotherapy is nowadays considered the fourth therapeutical approach in cancer, complementing and sometimes replacing surgery and chemo‐ and radiotherapy. Natural killer (NK) cells, generally considered part of the innate immune system, play a critical role in defense against pathogens and tumors. Immunological memory is a hallmark of the adaptive immune system. However, NK cells have been shown to mediate Ag‐specific recall responses and acquire immunological memory in a manner similar to that of T and B cells. This chapter summarizes evidence for NK cell immunotherapy, evidence and characteristics of NK cell memory and mechanisms involved in the generation and survival of these cells. There is no doubt that NK cells have major role in cancer treatments and viral infections, and in the future, NK cell immunotherapy from “a new hope” may become “a reality” for malignant diseases

Metal-Organic Complexes at Surfaces

The adsorption of different metal-organic complexes at surfaces was investigated by spectroscopic techniques (x-ray photoemission spectroscopy, x-ray absorption spectroscopy, resonant photoemission spectroscopy) and by scanning tunnelling microscopy. The investigation methods are able to provide atomic scale information on the studied systems, which moreover originates from the top-most atomic layers in a sample, meaning that they are surface sensitive techniques. Since the interest is always directed towards adsorbate-substrate interfaces, surface sensitivity is essential. The spectroscopic techniques also ensure atomic and chemical specificity. The information obtained relates to the electronic and geometric structure of the adsorbates on surfaces. The systems studied are iron phthalocyanine, oxalic acid and bi-isonicotinic acid molecules on different supports (Au(111), Cu(111) and highly oriented pyrolitic graphite). A significant part of the research deals with the study of iron phthalocyanine at surfaces and its interaction with different small gas molecules such as ammonia, pyridine, carbon monoxide and nitric oxide. It is interesting to note that the iron phthalocyanine shows different coupling strength on a Au(111) substrate compared to highly oriented pyrolitic graphite. On Au(111), the adsorbate-substrate coupling is relatively strong resulting in covalent-type interactions, while on graphite the coupling is weak and of van der Waals type. The adsorption of different gases on iron phthalocyanine structures on Au(111) results in the formation of bonds between the iron atom and the gas molecule which acts as a molecular ligand. This leads to significant changes in the electronic structure of the phthalocyanine molecular network. First, a decoupling of the phthalocyanine adsorbates from the Au(111) substrate is observed and second, the spin state of the phthalocyanine molecule is significantly changed. The spin changes range from a lowering of the spin to a complete spin quench, depending on the gas molecule that is bound to the iron site. By comparing the adsorption of different molecules it is possible to show that the spin state can be tuned to different values by using different gas molecules. On the other hand the adsorption of oxalic acid on Cu(111) shows the possibility of forming an iron –oxalate coordination network on a Cu(111) surface by incorporation of iron atoms inside a previously formed oxalate network. The study of of bi-isonicotinic acid on Au(111) by resonant photoemission spectroscopy shows the possibility of femtosecond charge transfer from the substrate to the bi-isonicotinic acid molecules, while charge transfer in the opposite direction does not seem to take place

Non-newtonian 3D ciliary fluid flow in a semi-infinite domain

This paper was presented at the 3rd Micro and Nano Flows Conference (MNF2011), which was held at the Makedonia Palace Hotel, Thessaloniki in Greece. The conference was organised by Brunel University and supported by the Italian Union of Thermofluiddynamics, Aristotle University of Thessaloniki, University of Thessaly, IPEM, the Process Intensification Network, the Institution of Mechanical Engineers, the Heat Transfer Society, HEXAG - the Heat Exchange Action Group, and the Energy Institute.Continuing our previous investigations in ciliary fluid transportation (Isvoranu et al., 2010) our present paper looks into the matter of non-newtonian fluid flow. Naturally, in constant properties fluids (newtonian fluids) ciliary transportation is based on a non-symmetric actuation mechanism meaning different geometrical configuration of the cilium during the active and passive stroke. Artificial cilia can mimick this behaviour through asymmetric magnetic actuation as discused in (Isvoranu et. al., 2008). What happens when fluid properties (eg. viscosity) are not constant throughout a beating cycle? Such situation is expected to be encountered when dealing with biological fluids like saliva, for example. In the case of a shear-thinning fluid, like the above mentioned one, the motion can also become asymetric due to deformation rate dependent viscosity that ultimately leads to different time scales of the forward and backward strokes. In the present paper we are investigating a 3D flow generated by an array of cilia embedded in a non-newtonian fluid whose viscosity is characterized by a power low shear rate dependency. The same magnetic actuation mechanism is considered

Rotating magnetic field actuation of a multicilia configuration

This paper was presented at the 2nd Micro and Nano Flows Conference (MNF2009), which was held at Brunel University, West London, UK. The conference was organised by Brunel University and supported by the Institution of Mechanical Engineers, IPEM, the Italian Union of Thermofluid dynamics, the Process Intensification Network, HEXAG - the Heat Exchange Action Group and the Institute of Mathematics and its Applications.The current paper continues the analysis of a completely novel method of fluid manipulation technology in micro-fluidics systems, inspired by nature, namely by the mechanisms found in ciliates. More information on this subject can be found at http://www.hitech-projects.com/euprojects/artic/. In order to simulate the drag forces acting on an array of artificial cilia, we have developed a computer code that is based on fundamental solutions of Stokes flow in a semi-infinite domain. The actuation mechanism consists of a bi-directional rotating excitation magnetic field. The magnetization induced by the magnetic field was calculated in a separate routine based on the Integral Nonlinear Equations Approach with 1D discretization of wire (cilium). Time averaged x-coordinate mass flow rates are computed for several cilium configurations resulting. The outcome and originality of this paper consist on assessing magnetic actuation as a practical tool for obtaining a consistent one-directional fluid flow.This work has been supported through grant ARTIC FP6-2004-NMP-TI4

Aerodynamic behavior of the bridge of a capacitive RF MEMS switch

This paper was presented at the 4th Micro and Nano Flows Conference (MNF2014), which was held at University College, London, UK. The conference was organised by Brunel University and supported by the Italian Union of Thermofluiddynamics, IPEM, the Process Intensification Network, the Institution of Mechanical Engineers, the Heat Transfer Society, HEXAG - the Heat Exchange Action Group, and the Energy Institute, ASME Press, LCN London Centre for Nanotechnology, UCL University College London, UCL Engineering, the International NanoScience Community, www.nanopaprika.eu.The present paper proposes a coupled 3D multi-physics model and presents the results of its transient simulation, for a RF MEMS capacitive switch of bridge-type. The fluid structure interaction (FSI) simulation sustains time-varying viscous damping and modified time response of the bridge deflection compared to the actuation modulation above closing of the switch. Complex 3D geometries of the bridge were rarely taken into account in viscous damping assessment much less in the simulation of the full flow around the bridge of the switch. The final goal of the paper is to obtain the dependency of an equivalent damping coefficient with respect to time, to be used in subsequent reduced order models for the switch, that include the aerodynamic behaviour of the switch

The importance of early arthritis in patients with rheumatoid arthritis

Rheumatoid arthritis (RA) is a systemic inflammatory disorder that manifests predominantly in the synovial joint, where it causes a chronic inflammatory process, leading to early osteoarticular destructions. These destructions are progressive and irreversible, generating a significant functional deficiency. During the last years, the diagnostic approach of RA has focused on early arthritis. Early arthritis can develop into established RA or another established arthropathy, like systemic lupus erythematosus or psoriatic arthritis. It can have a spontaneous resolution or may remain undifferentiated for indefinite periods of time. The management of early arthritis has changed considerably in the past few years, under the influence of new concepts of diagnosis and new effective therapies. The treatment goal of early arthritis should now be the clinical remission and prevention of joint destruction. Methotrexate is the first line of therapy, used to treat early arthralgia and to reverse or limit impending exacerbation to RA. Biological treatment is used as a second line therapy in patients with severe disease who do not respond or have a contraindication to disease-modifying antirheumatic drugs (DMARDs). Patients with early arthritis should usually be identified and directed to rheumatologists to confirm the presence of arthritis, and to establish the correct diagnosis plus to initiate the proper treatment strategies