Engineering buffer layers to improve temperature resilience of magnetic tunnel junction sensors.

Improving the thermal resilience of magnetic tunnel junctions (MTJs) broadens their applicability as sensing devices and is necessary to ensure their operation under harsh environments. In this work, we are address the impact of temperature on the degradation of the magnetic reference in field sensor stacks based on MgO-MTJs. Our study starts by simple MnIr/CoFe bilayers to gather enough insights into the role of critical morphological and magnetic parameters and their impact in the temperature dependent behavior. The exchange bias coupling field (Hex), coercive field (Hc), and blocking temperature (Tb) distribution are tuned, combining tailored growth conditions of the antiferromagnet and different buffer layer materials and stackings. This is achieved by a unique combination of ion beam deposition and magnetron sputtering, without vaccum break. Then, the work then extends beyond bilayers into more complex state-of-the-art MgO MTJ stacks as those employed in commercial sensing applications. We systematically address their characteristic fields, such as the width of the antiferromagnetic coupling plateau ΔH, and study their dependence on temperature. Although, [Ta/CuN] buffers showed higher key performance indications (e.g.Hex) at room temperature in both bilayers and MTJs, [Ta/Ru] buffers showed an overall wider ΔHup to 200 °C, more suitable to push high temperature operations. This result highlights the importance of properly design a suitable buffer layer system and addressing the complete MTJ behavior as function of temperature, to deliver the best stacking design with highest resilience to high temperature environments.

Benzodiazepine partially reverses tonic-clonic seizures induced by thiocolchicoside.

Seizures are a disorder caused by structural brain lesions, life-threatening metabolic derangements, or drug toxicity. The present study describes the behavior related to proconvulsant activity induced by thiocolchicoside (TCC) in rats and investigates the electrocorticographic patterns of this behavior and the effectiveness of classic antiepileptic drugs used to control these seizures. Forty-nine adult male Wistar rats were used and divided into two phases of our experimental design: 1) evaluation of seizure-related behavior and electrocorticographic patterns induced by TCC and 2) evaluation of the efficacy of classical antiepileptic drugs to control the proconvulsive activity caused by TCC. Our results showed that TCC induced tonic-clonic seizures that caused changes in electrocorticographic readings, characteristic of convulsive activity, with average amplitude greater than that induced by pentylenetetrazole. Treatment with anticonvulsants, especially diazepam, reduced the electrocorticographic outbreaks induced by TCC. The results suggested that TCC caused seizures with increased power in brain oscillations up to 40 Hz and that diazepam may partially reverse the effects.

Benzodiazepine partially reverses tonic-clonic seizures induced by thiocolchicoside

Seizures are a disorder caused by structural brain lesions, life-threatening metabolic derangements, or drug toxicity. The present study describes the behavior related to proconvulsant activity induced by thiocolchicoside (TCC) in rats and investigates the electrocorticographic patterns of this behavior and the effectiveness of classic antiepileptic drugs used to control these seizures. Forty-nine adult male Wistar rats were used and divided into two phases of our experimental design: 1) evaluation of seizure-related behavior and electrocorticographic patterns induced by TCC and 2) evaluation of the efficacy of classical antiepileptic drugs to control the proconvulsive activity caused by TCC. Our results showed that TCC induced tonic-clonic seizures that caused changes in electrocorticographic readings, characteristic of convulsive activity, with average amplitude greater than that induced by pentylenetetrazole. Treatment with anticonvulsants, especially diazepam, reduced the electrocorticographic outbreaks induced by TCC. The results suggested that TCC caused seizures with increased power in brain oscillations up to 40 Hz and that diazepam may partially reverse the effects.

Resistive switching of silicon-silver thin film devices in flexible substrates.

Novel applications for memory devices demand nanoscale flexible structures. In particular, resistive switching (RS) devices are promising candidates for wearable and implantable technologies. Here, the Pt/Si/Ag/TiW metal-insulator-metal structure was fabricated and characterized on top of flexible substrates using a straightforward microfabrication process. We also showed that these substrates are compatible with sputtering deposition. RS was successfully achieved using both commercial cellulose cleanroom paper and bacterial cellulose, and polymer (PET) substrates. The bipolar switching behavior was observed for both flat and bent (under a radius of 3.5 mm) configurations. The observed phenomenon was explained by the formation/rupture of metallic Ag filaments in the otherwise insulating Si host layer.

All-spinel oxide Josephson junctions for high-efficiency spin filtering.

Obtaining high efficiency spin filtering at room temperature using spinel ferromagnetic tunnel barriers has been hampered by the formation of antiphase boundaries due to their difference in lattice parameters between barrier and electrodes. In this work we demonstrate the use of LiTi2O4 thin films as electrodes in an all-spinel oxide CoFe2O4-based spin filter devices. These structures show nearly perfect epitaxy maintained throughout the structure and so minimise the potential for APBs formation. The LiTi2O4 in these devices is superconducting and so measurements at low temperature have been used to explore details of the tunnelling and Josephson junction behaviour.

EWSR1 rearrangement is a frequent event in papillary thyroid carcinoma and in carcinoma of the thyroid with Ewing family tumor elements (CEFTE).

Carcinomas of the thyroid with Ewing family tumor element (CEFTEs) are small-cell thyroid tumors with epithelial differentiation that disclose p63 expression and EWSR1-FLI1 rearrangement, carry a favorable prognosis and may co-exist with papillary thyroid carcinoma (PTC) foci. Two histogenetic hypotheses have been advanced regarding the origin of CEFTEs: arising in PTCs or in solid cell nests (SCN). A total of 3 CEFTEs, 54 PTCs, and 10 SCNs were reviewed, and fluorescence in situ hybridization (FISH) technique was performed in all cases to search for the presence of EWSR1 rearrangements. The three CEFTEs disclosed the EWSR1-FLI1 rearrangement both in the small cell and in the PTC component. Out of the 54 PTC cases, 28 (51.9%) were positive, 20 (37.0%) were negative, and 6 (11.1%) were inconclusive for EWSR1 rearrangement; in two of the positive PTC cases, the EWSR1-FLI1 rearrangement was detected. Classic PTC disclosed more often the EWSR1 rearrangement than other PTC variants (p = 0.031). PTCs with EWSR1 rearrangement disclosed a lower percentage of nuclei with EWSR1 polysomy than those without EWSR1 rearrangement (p = 0.001). Out of the 10 SCNs, 7 (70.0%) were negative and 3 (30.0%) were inconclusive for the EWSR1 rearrangement. Monosomic nuclei were more frequent (mean of 44.3%) in SCNs than in PTCs (p < 0.001). The presence of the EWSR1-FLI1 rearrangement in PTC component of all studied CEFTEs and the existence of the EWSR1 rearrangement in some PTCs favor the origin of CEFTE from PTC. The high frequency of EWSR1 rearrangements in PTC may represent a new diagnostic marker of these tumors.

Co nanostructures in ordered templates: comparative FORC analysis.

A comparative study on the structural and magnetic properties of highly ordered hexagonal arrays of Co nanoholes, nanowires, nanopillars and nanotubes, with tuned pore/wire/tube diameters, is here presented. The magnetic interactions and their dependence on the geometric features of the arrays were studied using first-order reversal curves (FORCs). For all nanostructures we observe an increase of the magnetostatic interactions with the templates' pore diameter, with the higher (smaller) values found for the nanowire (nanohole) arrays. For the smallest diameters studied (35 nm), all types of arrays could be considered as almost isolated nanostructures, where local interactions prevail. In particular, both nanotube and nanohole arrays exhibit considerable local magnetostatic interactions coming from the stray fields within each void or empty core. On the other hand, the coercivity is found to decrease with diameter for the elongated nanostructures, while it increases with the pore diameter for the nanohole arrays. This behavior is associated with the magnetization reversal mechanisms present in each array. This work highlights a versatile route to tailor the size, geometrical arrangement and magnetostatic interactions of ordered arrays and demonstrates their importance for the tuning of the magnetic behavior of nanometric devices.

Correlations among magnetic, electrical and magneto-transport properties of NiFe nanohole arrays.

In this work, we use anodic aluminum oxide (AAO) templates to build NiFe magnetic nanohole arrays. We perform a thorough study of their magnetic, electrical and magneto-transport properties (including the resistance R(T), and magnetoresistance MR(T)), enabling us to infer the nanohole film morphology, and the evolution from granular to continuous film with increasing thickness. In fact, different physical behaviors were observed to occur in the thickness range of the study (2 nm < t < 100 nm). For t < 10 nm, an insulator-to-metallic crossover was visible in R(T), pointing to a granular film morphology, and thus being consistent with the presence of electron tunneling mechanisms in the magnetoresistance. Then, for 10 nm < t < 50 nm a metallic R(T) allied with a larger anisotropic magnetoresistance suggests the onset of morphological percolation of the granular film. Finally, for t > 50 nm, a metallic R(T) and only anisotropic magnetoresistance behavior were obtained, characteristic of a continuous thin film. Therefore, by combining simple low-cost bottom-up (templates) and top-down (sputtering deposition) techniques, we are able to obtain customized magnetic nanostructures with well-controlled physical properties, showing nanohole diameters smaller than 35 nm.

Probing the quality of Ni filled nanoporous alumina templates by magnetic techniques.

Pulsed electrodeposition prepared porous alumina templates with Ni nanowires pore filling ranged from 1 to 100%, depending on the alumina barrier-layer thickness, were probed by continuous wave ferromagnetic resonance at room temperature. For completely filled samples, a single resonance peak was observed in the whole range of angles between the applied magnetic field and normal to the sample plane. Its position was described by Kittel formula that takes into account shape anisotropy of individual Ni wires and dipolar interactions between them. For the samples with lower pore filling the effective anisotropy field decreased and the resonance linewidth in the perpendicular configuration increased. Also a quite intense second peak was observed at lower fields for these samples. These changes are associated with reduction of pore filling percentage that can lead to decrease of dipolar interactions between nanowires and to appearance of magnetic inhomogeneities inside wires.

Tailoring the physical properties of thin nanohole arrays grown on flat anodic aluminum oxide templates.

The introduction of voids in a magnetic thin-film alters the stray field distribution and enables the tailoring of the corresponding physical properties. Here we present a detailed study on thin magnetic nanohole arrays (NhAs) grown on top of hexagonally-ordered anodic aluminum oxide (AAO) substrates. We address the effect of AAO topography on the corresponding electrical and magneto-transport properties. Optimization of the AAO topography led to NhAs with improved resistance and magnetoresistance responses, while retaining their most important feature of enhanced coercivity. This opens new pathways for the growth of more complex structures on AAO substrates, a crucial aspect for their technological viability.

Tunning pore filling of anodic alumina templates by accurate control of the bottom barrier layer thickness.

The role of the alumina barrier layer thickness (δ(b)) on the growth of Ni nanowires (NWs) in porous anodic alumina (PAA) has been revealed. By varying the final anodization voltage to form dendrites at the bottom of the nanoporous structure, we are able to optimize δ(b) (in the 2-16 nm range), allowing us to obtain a Ni pore filling percentage (f(p)) of almost 100% for δ(b) = 10 nm. However, deviations from this optimal δ(b)-value led to a strong decrease of f(p). Moreover, an increase of the electrodeposition efficiency (EE) and NW homogeneity was also verified for δ(b) up to 10 nm. Such increase in nominal δ(b) leads to a consistent growth rate in all pores and consequently a complete and uniform nanopore filling. On the other hand, the decrease in electrodeposition efficiency visible for δ(b) > 10 nm is related with hydrogen evolution and dielectric breakdown of the insulator layer due to the required high deposition voltages. Non-uniform NW growth is then visible, with the consequent decrease in f(p). The control of the pore filling and length homogeneity of the fabricated 1D metallic nanostructures, combined with the ability to adjust the pore dimensions of PAA, can bring novel approaches for the fabrication of nano-objects and thus exciting new applications.

Rapid synthesis of ordered manganite nanotubes by microwave irradiation in alumina templates.

Highly ordered La2/3Ca1/3MnO3 nanotube arrays were successfully synthesized by a simple and rapid process, combining nanoporous alumina template-assisted synthesis with microwave irradiation. The method offers a quick hands-on route to produce manganite bulk sample and nanotube arrays at relative low-temperatures. We obtain thin wall nanotubes of uniform diameter of 80 nm. The growth mechanism of nanotubes is briefly discussed. Magnetic measurements indicate that the ferromagnetic transition temperature T(c) of the nanotubes is depleted with respect to its bulk counterpart possibly due to the geometric confinement imposed by the thin wall of the nanotubes.

A method to investigate the electron scattering characteristics of ultrathin metallic films by in situ electrical resistance measurements.

In this article, a method to measure the electrical resistivity/conductivity of metallic thin films during layer growth on specific underlayers is described. The in situ monitoring of an underlayer electrical resistance, its change upon the incoming of new material atoms/molecules, and the growth of a new layer are presented. The method is easy to implement and allows obtaining in situ experimental curves of electrical resistivity dependence upon film thickness with a subatomic resolution, providing insight in film growth microstructure characteristics, specular/diffuse electron scattering surfaces, and optimum film thicknesses.

Influence of grain size dispersion on the magnetic properties of nanogranular BaTiO3-CoFe2O4 thin films.

Thin film nanogranular composites of cobalt ferrite (CoFe2O4) dispersed in a barium titanate (BaTiO3) matrix were deposited by laser ablation with different cobalt ferrite concentrations (x). Their structural and magnetic properties were characterized. The films were polycrystalline and composed by a mixture of tetragonal-BaTiO3 and CoFe2O4 with the cubic spinel structure. A slight (111) barium titanate phase orientation and (311) CoFe2O4 phase orientation were observed. The lattice parameter of the CoFe2O4 was always smaller than the bulk value indicating that the cobalt ferrite was under compressive stress. From atomic force microscopy a broad distribution of grain sizes was observed in the nanocomposites, with a significant amount of smaller grains (<40 nm) from the CoFe2O4 phase. The magnetic measurements show an increase of the magnetic moment from the low concentration region where the magnetic grains are more isolated and their magnetic interaction is small, towards the bulk value for higher CoFe2O4 content in the films. A corresponding decrease of coercive field with increasing cobalt ferrite concentration was also observed, due to the higher inter-particle magnetic interaction (and reduced stress) of the agglomerated grains.

Association of ERBB2 gene status with histopathological parameters and disease-specific survival in gastric carcinoma patients.

The clinical significance of ERBB2 amplification/overexpression in gastric cancer remains unclear. In this study, we evaluated the ERBB2 status in 463 gastric carcinomas using immunohistochemistry (IHC) and fluorescence in situ hybridisation (FISH), and compared the findings with histopathological characteristics and with disease-specific survival. ERBB2 overexpression (2+ and 3+) and amplification (ratio ERBB2/CEP17 >or= 2) were found in 43 (9.3%) and 38 (8.2%) gastric carcinomas, respectively. Perfect IHC/FISH correlation was found for the 19 cases scored as 0 (all negative by FISH), and also for the 25 cases scored as 3+ (all positive by FISH). One out of six carcinomas scored as 1+ and 12 out of 18 carcinomas scored as 2+ were positive by FISH. ERBB2 amplification was associated with gastric carcinomas of intestinal type (P=0.007) and with an expansive growth pattern (P=0.021). ERBB2 amplification was detected in both histological components of two mixed carcinomas, indicating a common clonal origin. A statistically significant association was found between ERBB2 amplification and worse survival in patients with expansive gastric carcinomas (P=0.011). We conclude that ERBB2 status may have clinical significance in subsets of gastric cancer patients, and that further studies are warranted to evaluate whether patients whose gastric carcinomas present ERBB2 amplification/overexpression may benefit from therapy targeting this surface receptor.

Toluene permeabilization differentially affects F- and P-type ATPase activities present in the plasma membrane of Streptococcus mutans

Streptococcus mutans membrane-bound P- and F-type ATPases are responsible for H+ extrusion from the cytoplasm thus keeping intracellular pH appropriate for cell metabolism. Toluene-permeabilized bacterial cells have long been used to study total membrane-bound ATPase activity, and to compare the properties of ATPase in situ with those in membrane-rich fractions. The aim of the present research was to determine if toluene permeabilization can significantly modify the activity of membrane-bound ATPase of both F-type and P-type. ATPase activity was assayed discontinuously by measuring phosphate release from ATP as substrate. Treatment of S. mutans membrane fractions with toluene reduced total ATPase activity by approximately 80 percent and did not allow differentiation between F- and P-type ATPase activities by use of the standard inhibitors vanadate (3 µM) and oligomycin (4 µg/mL). Transmission electron microscopy shows that, after S. mutans cells permeabilization with toluene, bacterial cell wall and plasma membrane are severely injured, causing cytoplasmic leakage. As a consequence, loss of cell viability and disruption of H+ extrusion were observed. These data suggest that treatment of S. mutans with toluene is an efficient method for cell disruption, but care should be taken in the interpretation of ATPase activity when toluene-permeabilized cells are used, because results may not reflect the real P- and F-type ATPase activities present in intact cell membranes. The mild conditions used for the preparation of membrane fractions may be more suitable to study specific ATPase activity in the presence of biological agents, since this method preserves ATPase selectivity for standard inhibitors.

Toluene permeabilization differentially affects F- and P-type ATPase activities present in the plasma membrane of Streptococcus mutans.

Streptococcus mutans membrane-bound P- and F-type ATPases are responsible for H+ extrusion from the cytoplasm thus keeping intracellular pH appropriate for cell metabolism. Toluene-permeabilized bacterial cells have long been used to study total membrane-bound ATPase activity, and to compare the properties of ATPase in situ with those in membrane-rich fractions. The aim of the present research was to determine if toluene permeabilization can significantly modify the activity of membrane-bound ATPase of both F-type and P-type. ATPase activity was assayed discontinuously by measuring phosphate release from ATP as substrate. Treatment of S. mutans membrane fractions with toluene reduced total ATPase activity by approximately 80% and did not allow differentiation between F- and P-type ATPase activities by use of the standard inhibitors vanadate (3 microM) and oligomycin (4 microg/mL). Transmission electron microscopy shows that, after S. mutans cells permeabilization with toluene, bacterial cell wall and plasma membrane are severely injured, causing cytoplasmic leakage. As a consequence, loss of cell viability and disruption of H+ extrusion were observed. These data suggest that treatment of S. mutans with toluene is an efficient method for cell disruption, but care should be taken in the interpretation of ATPase activity when toluene-permeabilized cells are used, because results may not reflect the real P- and F-type ATPase activities present in intact cell membranes. The mild conditions used for the preparation of membrane fractions may be more suitable to study specific ATPase activity in the presence of biological agents, since this method preserves ATPase selectivity for standard inhibitors.

Double-staining immunohistochemistry of canine mammary neoplasms / Dupla marcação imunoistoquímica em neoplasias mamárias caninas

Descreve-se a técnica de dupla-marcação em imunoistoquímica aplicada a tumores mamários em cadelas incluídos em parafina. Foram utilizados dois tipos de neoplasia em que ocorre envolvimento de células epiteliais, mioepiteliais e mesenquimais, tumor misto benigno e carcinossarcoma. Foram testados dois anticorpos, AE1/AE3 para identificação de tecido epitelial e S100 como marcador de células mioepiteliais. A dupla marcarcação em imunoistoquímica pode ser utilizada como ferramenta importante na pesquisa e diagnóstico de lesões mamárias complexas.

c-KIT and PDGFRA in breast phyllodes tumours: overexpression without mutations?

AIM: To study the immunoexpression and mutational status of c-KIT and PDGFRA in a series of benign and malignant phyllodes tumours of the breast. MATERIAL/METHODS: Nineteen phyllodes tumours (13 benign and six malignant) were analysed by immunohistochemistry for the expression of c-KIT and PDGFRA. Direct sequencing of exons 9, 11, 13, and 17 of the c-KIT gene and exons 12 and 18 of PDGFRA was performed to check the mutational status of these two genes. RESULTS: c-KIT expression was found in 12 of the 19 cases (six of the 13 benign cases and all six malignant ones) and PDGFRA expression was seen in two of the 19 cases (one benign and one malignant case); the 2415 C>T alteration in exon 17 of the c-KIT gene was found in two cases (both benign); the intronic insertion IVS17-50insT and the 2866 G>T alteration in the coding region of exon 18 of the PDGFRA gene were also found in two cases (one malignant and one benign). However, the activating mutations described for these genes in gastrointestinal stromal tumours were not present. CONCLUSION: c-KIT expression is a frequent finding in phyllodes tumours, particularly in malignant cases; however, no activating mutations similar to those described for gastrointestinal stromal tumours were found. The PDGFRA does not seem to be an alternative pathway to tumour development in phyllodes tumours because neither expression nor activating mutations were noteworthy.

Clinicopathological significance and survival influence of p53 protein expression in gastric carcinoma.

AIMS: Mutations in the gene coding for p53 protein are among the most frequent genetic alterations observed in human cancers. The relevance and biological significance of p53 expression in gastric carcinoma are far from being fully established. The aim of our study was to evaluate the influence of p53 detected by immunohistochemistry in the clinicopathological behaviour of a series of gastric carcinoma cases. METHODS AND RESULTS: Samples from 163 patients treated by gastric resection for gastric carcinoma between 1988 and 1995 were used. Surgical specimens were evaluated for the presence of p53 protein detected by immunohistochemistry with a monoclonal antibody. Cases were classified as positive or negative for p53. Several clinicopathological parameters and c-erb B-2 expression were analysed in the same series and compared with the expression of p53. Cumulative survival was evaluated using univariate analysis and Cox model regression. p53 expression was identified in 41 carcinomas (25.2%) and was significantly associated with venous invasion (P = 0.049), lymph node metastases (P = 0.01) and c-erb B-2 expression (P = 0.003). All the parameters except gender, tumour size and Laurén's classification influenced survival on univariate analysis. p53 expression correlated with overall survival (P = 0.006) and survival in the subgroup of patients with intestinal type carcinoma (P = 0.04). In the subgroup of patients with carcinomas not expressing c-erb B-2, p53 expression significantly influenced cumulative survival (P = 0.02). CONCLUSIONS: p53 expression is associated with the aggressive biological behaviour of gastric carcinomas and is related to cumulative survival.