Growth and magnetic properties of vertically aligned epitaxial CoNi nanowires in (Sr, Ba)TiO3 with diameters in the 1.8-6 nm range.

The growth by pulsed laser deposition of fully epitaxial nanocomposites made of Co x Ni1-x nanowires (NW) vertically self-assembled in Sr0.5Ba0.5TiO3/SrTiO3(001) layers is reported. The diameter of the wires can be tuned in the 1.8-6 nm range. The composition of the wires can be controlled, with the growth sequence and the fcc crystallographic structure of the wires preserved for Co content up to 78%. The nanocomposite systems obtained display a uniaxial magnetic anisotropy with out-of-plane easy axis as shown through analysis of ferromagnetic resonance measurements. It is shown that the magnitude of the magnetic anisotropy depends sensitively on the structural quality of the nanocomposites.The energy barrier for magnetization reversal scales as the square of the diameter of the NW and reaches 60 [Formula: see text] for 6 nm diameter, with T amb = 300 K.

Modeling magnetization curves in magnetic thin films with striped patterns.

In this work, we study magnetic thin films presenting magnetic stripe patterns. A fingerprint of such domains is a linear behavior of the in-plane magnetization curves below a given saturation field. We present free energy models for the in-plane magnetization curves which permit us to extract key geometrical information about the stripe patterns, such as the maximum canted angle of the magnetization and the domain wall width. As an example, we discuss in this work magnetization curves for Fe(1-x)Ga(x) magnetic films which present a stripe pattern with a period of 160 nm and we found a typical maximum canted angle of 85° and a domain wall width around 30 nm.

Grain structure and magnetic relaxation of self-assembled Co nanowires.

The magnetic relaxation of Co nanowires assemblies embedded in CeO(2)/SrTiO(3)(001) epilayers has been investigated by magnetization decay measurements. Two different samples were studied, with nanowires having distinct crystallographic structures and diameters of 3 and 5 nm. The structure of the nanowires was derived from high-resolution transmission electron microscopy analysis. The 3 nm diameter nanowires are made of hcp Co grains with the c-axis pointing along one of the four <111> directions of the CeO(2) matrix, separated by fcc Co regions. In the 5 nm diameter nanowires, the grains are smaller and the density of stacking faults is much higher. The magnetic viscosity coefficient (S) of these two systems was measured as a function of the applied field and of the temperature. Analysis of the variation of S and of the activation volume for magnetization reversal reveals distinct behaviors for the two systems. In the nanowires assembly with 5 nm diameter, the results can be described by considering an energy barrier distribution related to shape anisotropy and are consistent with a thermally activated reversal of the magnetization. In contrast, the anomalous behavior of the 3 nm diameter wires indicates that additional sources of anisotropy have to be considered in order to describe the distribution of energy barriers and the reversal process. The distinct magnetic behaviors observed in these two systems can be rationalized by considering the grain structure of the nanowires and the resulting effective magnetocrystalline anisotropy.

Mechanism of localization of the magnetization reversal in 3 nm wide Co nanowires.

The mechanism of magnetization reversal has been studied in a model system of self-assembled cobalt nanowires with a 3 nm diameter. The structure, orientation and size of grains within the nanowires could be determined by high resolution transmission electron microscopy. The magnetic properties were probed using static and dynamic magnetization measurements. Micromagnetic modeling based on the structural analysis allows us to correlate the structure and the magnetic behavior of the wires, revealing competition between shape anisotropy, magnetocrystalline anisotropy and exchange in the localized reversal within Co hcp oriented grains. These results provide direct experimental evidence of the link between anisotropy fluctuations and reversal localization in nanowires.

A highly immunogenic trivalent T cell receptor peptide vaccine for multiple sclerosis.

BACKGROUND: T cell receptor (TCR) peptide vaccination is a novel approach to treating multiple sclerosis (MS). The low immunogenicity of previous vaccines has hindered the development of TCR peptide vaccination for MS. OBJECTIVE: To compare the immunogenicity of intramuscular injections of TCR BV5S2, BV6S5 and BV13S1 CDR2 peptides in incomplete Freunds adjuvant (IFA) with intradermal injections of the same peptides without IFA. METHODS: MS subjects were randomized to receive TCR peptides/IFA, TCR peptides/saline or IFA alone. Subjects were on study for 24 weeks. RESULTS: The TCR peptides/IFA vaccine induced vigorous T cell responses in 100% of subjects completing the 24-week study (9/9) compared with only 20% (2/10) of those receiving the TCR peptides/saline vaccine (P =0.001). IFA alone induced a weak response in only one of five subjects. Aside from injection site reactions, there were no significant adverse events attributable to the treatment. CONCLUSIONS: The trivalent TCR peptide in IFA vaccine represents a significant improvement in immunogenicity over previous TCR peptide vaccines and warrants investigation of its ability to treat MS.

Effect of dipolar interaction on the antiferromagnetic resonance spectra of NiO.

We have investigated the antiferromagnetic (AF) resonance modes (AFMR) of NiO, theoretically using a model that includes the effects of exchange, dipolar coupling, and a small cubic anisotropy, and experimentally using Brillouin scattering. Using only superexchange between next nearest Ni atoms the model accounts for the observed AF structure with a [112] spin orientation. The model predicts that there are four, weakly coupled, AF lattices that should therefore exhibit eight AFMR modes. Because of degeneracies, only five distinct frequencies are predicted by the model. Three of these frequencies are consistent with the doublet observed by Raman scattering and the central peak reported in Brillouin experiments. Using Brillouin scattering we report the observation of the two missing modes.

Inflammatory myopathy on HTLV-I infection: case report.

We describe a 41 years old woman who 17 years ago presented hypotonia and proximal muscular weakness in the upper and lower limbs. On neurological examination, the biceps, triceps and Achilles reflexes were absent; the brachioradialis reflexes were decreased and the patellar reflexes were normal. There was bilateral Babinski sign. The remainder of the neurological examination was unremarkable. In the investigation a myopathic pattern was found in the electromyography. The nerve-conduction study was normal; a ELISA method for HTLV-I antibodies was positive in the blood and in the cerebral spinal fluid. The muscle biopsy showed inflammatory myopathy, compatible with polymyositis. This paper focuses the polymyositis in the beginning of an HTLV-I infection case.

A replication-deficient rSV40 mediates liver-directed gene transfer and a long-term amelioration of jaundice in gunn rats.

BACKGROUND & AIMS: In the quest for a recombinant viral vector for liver-directed gene therapy that would permit both prolonged and efficient transgene expression in quiescent hepatocytes in vivo and repeated administration, we evaluated a recombinant simian virus 40 (rSV40). METHODS: The rSV40 was generated through replacement of the DNA encoding for the T antigens (Tag) by the coding region of human bilirubin-uridine 5'-diphosphate-glucuronosyl-transferase (BUGT) complementary DNA (SV-hBUGT). Helper-free rSV40 units were generated at infectious titers of 5 x 10(9) to 1 x 10(10) infectious units (IU)/mL in a Tag-producing packaging cell line (COS-7 cells). RESULTS: After 1, 3, or 7 daily infusions of 3 x 10(9) IU of SV-hBUGT through an indwelling portal vein catheter in bilirubin-UGT-deficient jaundiced Gunn rats, mean serum bilirubin concentrations decreased by 40%, 60% and 70%, respectively, in 3 weeks and remained at those levels throughout the duration of the study (40 days). Results of liver biopsies from SV-hBUGT-treated Gunn rats, but not from controls, were positive for human BUGT DNA, messenger RNA, and protein. Bilirubin-UGT activity in liver homogenates was 8%-12% of normal, and bilirubin glucuronides were excreted in bile. Immunostaining showed that >50%-60% of hepatocytes stably expressed the transgene. Portal vein infusion of an rSV40 expressing hepatitis B surface antigen (HBsAg) in a naive Gunn rat and a Gunn rat that had received 7 injections of SV-BUGT resulted in approximately equal levels of hepatic expression of HBsAg, indicating that multiple inoculations of SV-BUGT did not elicit neutralizing antibodies. Plasma alanine aminotransferase levels and liver histology remained normal despite repeated injections of rSV40. CONCLUSIONS: rSV40 vectors may represent a significant advance toward gene therapy for metabolic diseases.

A catalytic antioxidant metalloporphyrin blocks hydrogen peroxide-induced mitochondrial DNA damage.

Reactive oxygen species (ROS) have been implicated as the cause of cumulative damage to DNA, proteins and lipids that can ultimately result in cell death. A common problem when measuring oxidative DNA damage has been the introduction of modifications in the native state of the molecule by many DNA isolation methods. We circumvented this problem by employing direct PCR (DPCR) of whole cell lysates. DPCR of mouse lung fibroblasts performed better than PCRs containing template acquired by phenol/chloroform extraction or a commercially available genomic DNA isolation kit. We investigated the direct use of whole cell preparations in the polymerase chain reaction (PCR) to detect hydrogen peroxide (H(2)O(2))-mediated DNA damage. We observed a concentration-dependent decrease in amplification efficiency of a 4.3 kb mitochondrial (mt)DNA target in H(2)O(2)-treated mouse lung fibroblasts (MLFs). At low doses the efficiency of amplification returns to control levels over 24 h. We detected no change in amplification efficiency of a plasmid control containing our mtDNA target under any of the culture conditions employed in these studies. Treatment of MLFs with the catalytic antioxidant manganese(III) meso -tetrakis(4-benzoic acid)porphyrin (MnTBAP) attenuates the effects of H(2)O(2)exposure. When quantitated with an external standard the use of DPCR in tandem with a PCR amplification efficiency assay provides a powerful approach to assess oxidative mtDNA damage.

Selective in vivo mobilization with granulocyte macrophage colony-stimulating factor (GM-CSF)/granulocyte-CSF as compared to G-CSF alone of dendritic cell progenitors from peripheral blood progenitor cells in patients with advanced breast cancer undergoing autologous transplantation.

Dendritic cells (DCs) are potent antigen-presenting cells that are essential for the initiation of T cell-mediated immunity. DCs develop from myeloid progenitor populations under the influence of granulocyte macrophage colony-stimulating factor (GM-CSF) and pass through an intermediate stage of maturation that is characterized by CD14 expression. Interest has focused on generating human-derived DCs for antigen-specific tumor vaccines to be used as adjuvant immunotherapy in minimal disease settings, such as after autologous transplantation. In the present study, mobilized peripheral blood progenitor cells (PBPCs) were obtained from 18 patients with locally advanced or metastatic breast cancer preparing to undergo autologous stem cell transplantation. PBPCs mobilized in 10 patients with GM-CSF for 1 week, followed by the combination of GM-CSF and G-CSF, were compared with those obtained from patients receiving G-CSF alone with respect to the presence of DC progenitors and the capacity to generate functionally active mature DCs. PBPCs mobilized with GM-CSF/G-CSF were markedly enriched for CD14+ DC progenitor cells as compared with those mobilized with G-CSF alone. Consistent with an immature progenitor population, the CD14+ cells express Ki-67 antigen but not nonspecific esterase. CD14+ cells purified by fluorescence-activated cell sorting from PBPCs mobilized with either regimen and cultured for 1 week in GM-CSF and interleukin-4 generated nearly pure populations of cells with characteristic DC phenotype and function. The addition of GM-CSF to the mobilization regimen resulted in greater yields of functionally active DCs for potential use in posttransplant immunotherapy.

Effects of overexpression of Ran/TC4 mammalian cells in vitro.

We investigated the effect of overexpression of Ran/TC4 on cell cycle progression. Ran/TC4 (ras-related nuclear protein) is a highly conserved 25-kDa GTP-binding protein that, in concert with its guanine-nucleotide-exchange factor RCC1, is involved in signal transduction. Ran and RCC1 act on nuclear transport of RNA and protein, cell cycle regulation at the G1/S interphase, chromatin decondensation after mitosis, and chromosome stability. These two proteins are essential for the coupling of DNA synthesis with the onset of mitosis. The cDNA for rabbit Ran/TC4 was identified in a cDNA library using degenerate oligonucleotide probes devised on the basis of deduced protein sequence data. This cDNA was cloned into pCDM8 expression vector to yield a plasmid, pTC4, in which Ran/TC4 expression is driven by the cytomegalovirus intermediate early promoter. Both a human tumor cell line, MCF7, and a normal rabbit fibroblast line, RK-13, were tested. Following transfection with pTC4 we observed an increase in Ran/TC4 transcript levels. Transfection with pTC4 prolonged the duration of S phase in both MCF7 and RK-13 cells and led to reduced cell proliferation and decreased total cell numbers. DNA fragmentation was seen in pTC4-transfected cultures but not in control cultures. These findings underscore the function of Ran/TC4 as a molecular switch that guides the cell to completion of DNA synthesis before it enters mitosis and suggest that its overexpression may greatly alter cell cycle kinetics and cell viability.

Use of SV40-based vectors to transduce foreign genes to normal human peripheral blood mononuclear cells.

Stable, efficient gene transfer to normal human peripheral blood mononuclear cells (PBMC) is a prerequisite for therapy of a number of diseases, both hereditary and acquired, affecting these cells. Current approaches to gene transfer to PBMC entail ex vivo mitogenic stimulation and multiple transduction steps followed by selection, usually of progenitor populations. Thus, the ability to transfer gene expression to normal, resting PBMC could complement gene transfer strategies that target dividing precursor cells. We report successful short-term transduction of human PBMC using two different SV40-derived viral vectors SV40-derivative viruses were constructed by cloning cDNAs for firefly luciferase (luc), or hepatitis B surface antigen (HBSAg), into shuttle plasmids to create the SV40 derivative viruses SVluc and SV(HBS) respectively. Both genes were cloned downstream from SV40 early promoter. Normal, resting, human PBMC were exposed to these viruses, and unselected cultured cells were assayed 24 to 48 h later for expression of transduced genes by immunochemistry and Northern blot analysis. Expression of both luciferase and HBSAg was detected using both approaches. Levels of expression of luciferase were slightly higher in PBMC which were stimulated with concanavalin A (con A). Conversely, expression of HBSAg was less in con A-stimulation did not alter infectivity of PBMC by SV40-derivative virus. While longevity and stability of expression in vitro are as yet unknown, this demonstration of successful gene transfer to resting, normal human PBMC, assayed on unselected cells, suggests that SV40-based transduction systems may be potential candidates for use in transient gene transfer to mononuclear blood cells.

SV40 mediates stable gene transfer in vivo.

Gene transfer in vivo requires an efficient, nonreplicating, transfer agent. We report here the efficacy of recombinant, replication-deficient SV40 in transferring firefly luciferase (luc) production to murine hematopoietic cells and selected internal organs in vivo. Replication-deficient SV40 was made by replacing the large T antigen gene (Tag) with a polylinker, into which luc cDNA (luc) was cloned. Luc expression was controlled by SV40 early promoter. Tag-, luc+ SV40 DNA was transfected into Tag-expressing cells to yield a replication-deficient SV40-derivative virus containing luc (SVluc). The ability of SVluc to transfer luc production in vivo was tested in two ways: SVluc was inoculated into BALB/C mice intravenously; also bone marrow cells treated with SVluc were infused into syngeneic hosts. Luc production was followed for 105 days by immunochemical analysis of peripheral blood and selected internal organs using anti-luciferase antibody, and by assay of luc enzyme activity in peripheral blood. Luc was found in 20-25% of peripheral blood nucleated cells from day 20 until > or = 105 days. Luc-producing cells were also identified in liver, spleen, brain, kidney, skin and colon from day 20, also until > or = 105 days. Analysis of whole blood showed fluctuating levels of functionally active luc enzyme beginning on day 21, and remaining substantially and significantly greater than control values to day 105. Thus, SV40 may transfer sustained expression of foreign genes to bone marrow and other organs, for at least 3 months.