A novel derivative of the chelon desferrioxamine for site-specific conjugation to antibodies.

We describe the preparation of the modified chelator aminooxyacetyl-ferrioxamine, and the replacement of its iron atom by 67Ga at high specific activity. The aminooxy function of this compound was allowed to react with the aldehyde groups generated by the periodate oxidation of the oligosaccharide of a mouse IgG1 monoclonal antibody (MAb) directed against carcino-embryonic antigen (CEA). The use of the aminooxy group allowed a stable bond to be formed between the chelon and the antibody with no need for reduction. Iron was removed from the ferrioxamine moiety and replaced by 67Ga either before or after conjugation of the chelon to the antibody. In either case the labelled antibody was injected into nude mice bearing a human colon carcinoma having the appropriate antigenicity. Unoxidized antibody, labelled with 125I by conventional methods, was co-injected as an internal control. Additional control experiments were carried out with a non-immune IgG using the same 67Ga-labelled modified chelon as above. The in vivo distribution of the modified antibodies was evaluated at various times between 24 and 96 hr after injection. The methods used were gamma-camera imaging and, more quantitatively, gamma-counting of the various organs after dissection. Interestingly, with the metal-chelon-labelled antibody, the intensity and specificity of tumor labelling was comparable and in some cases superior to the results obtained with radio-iodinated antibody. In particular, there was almost no increase in liver and spleen uptake of radioactive metal relative to radio-iodine, contrary to what has been observed with most antibodies labelled with 111In after conjugation with DTPA.

Focused ion beam scanning electron microscopy in biology.

Since the end of the last millennium, the focused ion beam scanning electron microscopy (FIB-SEM) has progressively found use in biological research. This instrument is a scanning electron microscope (SEM) with an attached gallium ion column and the 2 beams, electrons and ions (FIB) are focused on one coincident point. The main application is the acquisition of three-dimensional data, FIB-SEM tomography. With the ion beam, some nanometres of the surface are removed and the remaining block-face is imaged with the electron beam in a repetitive manner. The instrument can also be used to cut open biological structures to get access to internal structures or to prepare thin lamella for imaging by (cryo-) transmission electron microscopy. Here, we will present an overview of the development of FIB-SEM and discuss a few points about sample preparation and imaging.

Asymptotic analysis of the Gunn effect with realistic boundary conditions

A general asymptotic analysis of the Gunn effect in n-type GaAs under general boundary conditions for metal-semiconductor contacts is presented. Depending on the parameter values in the boundary condition of the injecting contact, different types of waves mediate the Gunn effect. The periodic current oscillation typical of the Gunn effect may be caused by moving charge-monopole accumulation or depletion layers, or by low- or high-field charge-dipole solitary waves. A new instability caused by multiple shedding of (low-field) dipole waves is found. In all cases the shape of the current oscillation is described in detail: we show the direct relationship between its major features (maxima, minima, plateaus, etc.) and several critical currents (which depend on the values of the contact parameters). Our results open the possibility of measuring contact parameters from the analysis of the shape of the current oscillation.

Magnetization reversal and magnetic anisotropies in epitaxial Fe/MgO and Fe/MgO/Fe heterostructures grown on Si(001)

Epitaxial Fe/MgO heterostructures have been grown on Si(001) by a combination of sputtering and laser ablation deposition techniques. The growth of MgO on Si(001) is mainly determined by the nature of the interface, with large lattice mismatch and the presence of an amorphous layer of unclear origin. Reflection high energy electron diffraction patterns of this MgO buffer layer are characteristic of an epitaxial, but disordered, structure. The structural quality of subsequent Fe and MgO layers continuously improves due to the better lattice match and the burial of defects. A weak uniaxial in-plane magnetic anisotropy is found superimposed on the expected cubic biaxial anisotropy. This additional anisotropy, of interfacial nature and often found in Fe/MgO and Fe/MgO/GaAs(001) systems, is less intense here due to the poorer MgO/Si interface quality compared with that of other systems. From the evolution of the anisotropy field with film thickness, magnetic anisotropy is also found to depend on the crystal quality. Kerr measurements of a Fe/MgO multilayered structure grown on Si show two different switching fields, suggesting magnetic coupling of two of the three Fe layers. Nevertheless, due to the little sensitivity to the bottom Fe film, independent switching of the three layers cannot be ruled out.

Wave-vector dependence of spin and density multipole excitations in quantum dots

We have employed time-dependent local-spin density-functional theory to analyze the multipole spin and charge density excitations in GaAs-AlxGa1-xAs quantum dots. The on-plane transferred momentum degree of freedom has been taken into account, and the wave-vector dependence of the excitations is discussed. In agreement with previous experiments, we have found that the energies of these modes do not depend on the transferred wave vector, although their intensities do. Comparison with a recent resonant Raman scattering experiment [C. Schüller et al., Phys. Rev. Lett. 80, 2673 (1998)] is made. This allows us to identify the angular momentum of several of the observed modes as well as to reproduce their energies

Asymptotic analysis of the Gunn effect with realistic boundary conditions

A general asymptotic analysis of the Gunn effect in n-type GaAs under general boundary conditions for metal-semiconductor contacts is presented. Depending on the parameter values in the boundary condition of the injecting contact, different types of waves mediate the Gunn effect. The periodic current oscillation typical of the Gunn effect may be caused by moving charge-monopole accumulation or depletion layers, or by low- or high-field charge-dipole solitary waves. A new instability caused by multiple shedding of (low-field) dipole waves is found. In all cases the shape of the current oscillation is described in detail: we show the direct relationship between its major features (maxima, minima, plateaus, etc.) and several critical currents (which depend on the values of the contact parameters). Our results open the possibility of measuring contact parameters from the analysis of the shape of the current oscillation.

Ferromagnetic shape memory alloys: structural and thermal properties

The most extensively studied Heusler alloys are those based on the Ni-Mn-Ga system. However, to overcome the high cost of Gallium and the usually low martensitic transformation temperature, the search for Ga-free alloys has been recently attempted, particularly, by introducing In, Sn or Sb. In this work, two alloys (Mn50Ni35.5In14.5 and Ni50Mn35In15) have been obtained by melt spinning. We outline their structural and thermal behaviour. Mn50Ni35.5In14.5 alloy has the transformation above room temperature whereas Ni50Mn35In15 does not have this transformation in the temperature range here analyzed

Modeling and manufacturability assessment of bistable quantum-dot cells

We have investigated the behavior of bistable cells made up of four quantum dots and occupied by two electrons, in the presence of realistic confinement potentials produced by depletion gates on top of a GaAs/AlGaAs heterostructure. Such a cell represents the basic building block for logic architectures based on the concept of quantum cellular automata (QCA) and of ground state computation, which have been proposed as an alternative to traditional transistor-based logic circuits. We have focused on the robustness of the operation of such cells with respect to asymmetries derived from fabrication tolerances. We have developed a two-dimensional model for the calculation of the electron density in a driven cell in response to the polarization state of a driver cell. Our method is based on the one-shot configuration-interaction technique, adapted from molecular chemistry. From the results of our simulations, we conclude that an implementation of QCA logic based on simple ¿hole arrays¿ is not feasible, because of the extreme sensitivity to fabrication tolerances. As an alternative, we propose cells defined by multiple gates, where geometrical asymmetries can be compensated for by adjusting the bias voltages. Even though not immediately applicable to the implementation of logic gates and not suitable for large scale integration, the proposed cell layout should allow an experimental demonstration of a chain of QCA cells.

Magnetic and transport properties of InGaAs quantum wells with Mn

In the present work structural, magnetic and transport properties of InGaAs quantum wells (QW) prepared by MBE with an remote Mn layer are investigated. By means of high-resolution X-ray diffractometry the structure of the samples is analyzed. It is shown that Mn ions penetrate into the QW. Influence of the thickness of GaAs spacer and annealing at 286 ºС on the properties of the system is shown. It is shown that annealing of the samples led to Mn activation and narrowing of the Mn layer. Substantial role of 2D holes in ferromagnetic ordering in Mn layer is shown. Evidence for that is observation of maximum at 25 – 55 K on the resistivity temperature dependence. Position of maximum, which is used for quantitative assessment of the Curie temperature, correlates with calculations of the Curie temperature for structures with indirect interaction via 2D holes’ channel. Dependence of the Curie temperature on the spacer thickness shows, that creation of applicable spintronic devices needs high-precision equipment to manufacture extra fine structures. The magnetotransport measurements show that charge carrier mobility is very low. This leads to deficiency of the anomalous Hall effect. At the same time, magnetic field dependences of the magnetization at different temperatures demonstrate that systems are ferromagnetically ordered. These facts, most probably, give evidence of presence of the ferromagnetic MnAs clusters.

Síntese, caracterização e estudo das propriedades de um novo complexo mononuclear contendo quercetina e íon Ga(III)

Flavonoids are one of the most important compound groups applied as medicine given their antioxidant properties, but several intrinsic properties can be improved through structural modifications to their molecules. Here, the synthesis and characterization of a new gallium (III) complex with quercetin is described. Electrochemical properties, as well as antioxidant and cytotoxic activities, were investigated and compared to the free flavonoid molecule. The mononuclear complex obtained, [Ga(C15H9O7)3].2H2O.2CH3OH.CH3CH2OH, seems more active as a DPPH radical scavenger given its lower oxidation potential compared to quercetin. The new complex cytotoxic responses have shown to be more effective than those of the free flavonoid and of lapachol used as a control.

Synthesis, characterization and thermal studies of solid state 4-methylbenzylidenepyruvate of some trivalent metal ions

Solid state compounds of 4-methylbenzylidenepyruvate with Al(III), Ga(III), In(III) and Sc(III) have been synthesized. Complexometry, X-ray powder diffractometry, infrared spectroscopy and simultaneous thermogravimetry-differential thermal analysis (TG-DTA) have been used to characterize and to study the thermal behavior of these compounds. The results provided information concerning the stoichiometry, crystallinity, thermal stability and thermal decomposition of these compounds.

Epäpuhtausmetallien talteenotto sinkkiprosessissa

There are small amounts of valuable metals, such as indium, gallium and germanium, in zinc process solutions. Their solvent extraction was studied in this work in sulphate solutions containing zinc and other metals present in industrial solutions. It was discovered, that a commercial bis(2-ethylhexyl)phosphate (D2EHPA) extractant can be used to extract indium and gallium. Indium was extracted separately at a higher acid concentration than gallium. Zinc was co-extracted faster than gallium and almost as much as gallium at the same pH. However, the scrubbing of zinc was possible using a dilute sulphuric acid and a short contact time while gallium losses were small. Both indium and gallium were stripped with sulphuric acid. Germanium was extracted with 5,8-diethyl-7-hydroxydodecane-6-oxime with the commercial name of LIX 63. Unlike other metals in the solution the extraction of germanium increased with different extractants as the acidity increased. Germanium extraction isotherm was measured for a 125 g/L sulfuric acid solution. The loaded organic phase was washed with pure water. It removed the co-extracted acid and part of the germanium and extracted impurities such as iron and copper. Germanium was stripped using a NaOH solution. A process model utilizing own experimentally determined extraction, scrubbing and stripping isotherms was made with HSC Sim software developed by Outotec Oyj. The model based on McCabe–Thiele diagrams was used in sizing the necessary amount of stages and phase ratios in a recovery process. It was concluded, that indium, gallium and germanium can be recovered in the process from a feed where their concentrations are low (<300 ppm). In an example case the feed contained also more than 20 g/L zinc and 2–8 g/L iron, aluminium and copper. The recoveries of indium, gallium and germanium were more than 90 % when 1–3 stages were used in each extraction, scrubbing and stripping section. Since the number of stages is small mixer-settlers would be well suited for this purpose.

Harvinaisten metallien talteenotto epäorgaanisista jätevirroista

Taloudellisesti tärkeiden metallien varannot ja tuotanto eivät ole jakautuneet tasaisesti. Maantieteelliset alueet, joilla ei ole omia varantoja ovat riippuvaisia muualta tuoduista raaka-aineista. Euroopan komissio ja USA:n energiaministeriö ovat luokitelleet tietyt metallit kriittisiksi niiden taloudellisen merkittävyyden ja saatavuuteen liittyvien epävarmuustekijöiden johdosta. Tällaisten metallien saatavuutta voitaisiin mahdollisesti parantaa lisäämällä niiden talteenottoa jätteistä. Tutkimuksessa kartoitettiin Euroopan komission kriittiseksi luokittelemien metallien pitoisuuksia eräissä jätevirroissa. Kartoitetut jätteet olivat teollisissa poltto-prosesseissa syntyneitä polttojätteitä, prosessiteollisuuden jätesakkoja ja sähkö- ja elektroniikkajätteitä. Kartoituksen perusteella valittiin lupaavimmat jätteet ja suoritettiin niille talteenottokokeita. Talteenottokokeita suoritettiin kolmelle jätteelle. Yhdestä jätesakasta liuotettiin indiumia rikki- ja suolahapoilla. Kahden eri polttojätteen seoksesta liuotettiin galliumia rikkihapolla. Käytettyjen loisteputkien käsittelyprosessista peräisin olleesta sakasta liuotettiin maametalleja rikki- ja suolahapoilla sekä rikki- ja typpihapon seoksella. Indium liukeni heikosti (korkeintaan 25 %) huoneenlämmössä rikkihapolla. Suolahapolla se liukeni paremmin (68 %). Polttojätteen liuotuskokeissa galliumin talteenottoasteen todettiin riippuvan käytetyn liuottimen määrästä. Loisteputkijätesakasta liukeni yttriumia ja europiumia kaikilla käytetyillä happoliuoksilla noin 70–100 %. Käytetyillä happokonsentraatioilla ei havaittu suuria eroja yttriumin ja europiumin liukoisuuksissa. Näitä metalleja voitaisiin mahdollisesti ottaa talteen tämän tyyppisestä sakasta liuottamalla ne happoliuoksella ja saostamalla oksalaattina. Tarvittaessa liuokset voitaisiin puhdistaa tai metallit erottaa toisistaan neste–nesteuutolla, joka on tärkein maametallien tuotantoon käytetty hydrometallurginen menetelmä.

In vivo imaging of vascular adhesion protein 1 - preclinical studies with positron emission tomography

The golden standard in nuclear medicine imaging of inflammation is the use of radiolabeled leukocytes. Although their diagnostic accuracy is good, the preparation of the leukocytes is both laborious and potentially hazardous for laboratory personnel. Molecules involved in leukocyte migration could serve as targets for the development of inflammation imaging agents. An excellent target would be a molecule that is absent or expressed at low level in normal tissues, but is induced or up-regulated at the site of inflammation. Vascular adhesion protein-1 (VAP-1) is a very promising target for in vivo imaging, since it is translocated to the endothelial cell surface when inflammation occurs. VAP-1 functions as an endothelial adhesion molecule that participates in leukocyte recruitment to inflamed tissues. Besides being an adhesion molecule, VAP-1 also has enzymatic activity. In this thesis, the targeting of VAP-1 was studied by using Gallium-68 (68Ga) labeled peptides and an Iodine-124 (124I) labeled antibody. The peptides were designed based on molecular modelling and phage display library searches. The new imaging agents were preclinically tested in vitro, as well as in vivo in animal models. The most promising imaging agent appeared to be a peptide belonging to the VAP-1 leukocyte ligand, Siglec-9 peptide. The 68Ga-labeled Siglec-9 peptide was able to detect VAP-1 positive vasculature in rodent models of sterile skin inflammation and melanoma by positron emission tomography. In addition to peptides, the 124I-labeled antibody showed VAP-1 specific binding both in vitro and in vivo. However, the estimated human radiation dose was rather high, and thus further preclinical studies in disease models are needed to clarify the value of this imaging agent. Detection of VAP-1 on endothelium was demonstrated in these studies and this imaging approach could be used in the diagnosis of inflammatory conditions as well as melanoma. These studies provide a proof-of-concept for PET imaging of VAP-1 and further studies are warranted.

Positron measurements in Mg-doped GaN and development of digital Doppler broadening spectroscopy

In this work parameters of Mg-doped GaN samples were studied using positron annihilation spectroscopy and analyzed. It is shown that gallium vacancies exist in an unintentionally doped sample. Next, the sample with higher concentration of Mg and low growth temperature contains vacancy clusters. In case of low concentration of Mg the growth temperature does not affect the formation of defects. Analog electronics can be replaced by a modern digital device. While promising a high quantity of benefits, the performance of these digitizers requires thorough adjustment. A 14-bit two channel digitizer has been tested in order to achieve better performance than the one of a traditional analog setup, and the adjustment process is described. It has been shown that the digital device is unable to achieve better energy resolution, but it is quite close to the corresponding attribute of the available analog system, which had been used for measurements in Mg-doped GaN.