S. Cardoso

Insulin is a Two-Edged Knife on the Brain

Insulin, long known as an important regulator of blood glucose levels, plays important and multifaceted roles in the brain. It has been reported that insulin is an important neuromodulator, contributing to several neurobiological processes in particular energy homeostasis and cognition. Dysregulation of insulin signaling has been linked to aging and metabolic and neurodegenerative disorders. The first part of this review is devoted to discussion of the critical role of insulin signaling in normal brain function. Then the involvement of impaired insulin signaling in the pathophysiology of diabetes, Alzheimers, Parkinsons and Huntingtons diseases and amyotrophic lateral sclerosis will be discussed. Finally, the potential therapeutic effect of insulin and insulin sensitizers will be examined.

Study of the dynamic magnetic properties of soft CoFeB films

We study the magnetization damping in ion-beam deposited Co72Fe18B10 thin films as a function of film thickness and crystalline state. As-deposited amorphous layers showed low damping (αapp=0.006) that is thickness independent. 40nm Co80Fe20 with no boron content exhibited a value twice higher (αapp=0.013). Crystallization in Co72Fe18B10, triggered by annealing at 280°C, results in increased magnetization as well as a strong increase in damping, by a factor of 5 for 40nm films. For lower thicknesses the damping increase upon annealing is less pronounced. The exchange stiffness constant for amorphous films is deduced from perpendicular standing spin waves to be 28.4×10−12J∕m. The annealing dependence of damping should have consequences for the spin-transfer switching in CoFeB∕MgO∕CoFeB magnetic tunnel junctions.

Insulin signaling, glucose metabolism and mitochondria: Major players in Alzheimer's disease and diabetes interrelation

Many epidemiological studies have shown that diabetes, particularly type 2 diabetes, significantly increases the risk to develop Alzheimers disease. Both diseases share several common abnormalities including impaired glucose metabolism, increased oxidative stress, insulin resistance and deposition of amyloidogenic proteins. It has been suggested that these two diseases disrupt common cellular and molecular pathways and each disease potentiates the progression of the other. This review discusses clinical and biochemical features shared by Alzheimers disease and diabetes, giving special attention to the involvement of insulin signaling, glucose metabolism and mitochondria. Understanding the key mechanisms underlying this deleterious interaction may provide opportunities for the design of effective therapeutic strategies.

Collective states of interacting ferromagnetic nanoparticles

Abstract Discontinuous magnetic multilayers [CoFe/Al 2 O 3 ] are studied by use of magnetometry, susceptometry and numeric simulations. Soft ferromagnetic Co 80 Fe 20 nanoparticles are embedded in a diamagnetic insulating a-Al 2 O 3 matrix and can be considered as homogeneously magnetized superspins exhibiting randomness of size (viz. moment), position and anisotropy. Lacking intra-particle core-surface ordering, generic freezing processes into collective states rather than individual particle blocking are encountered. With increasing particle density one observes first superspin glass and then superferromagnetic domain state behavior. The phase diagram resembles that of a dilute disordered ferromagnet. Criteria for the identification of the individual phases are given.

Size dependence of the exchange bias field in NiO/Ni nanostructures

NiO/Ni wires have been investigated as a function of their width in order to investigate the size dependence of exchange bias. The samples have been prepared by e-beam lithography and ion milling of ion beam sputtered thin films. For NiO/Ni wires narrower than 3 μm, the exchange bias field significantly depends on the wire width. A NiO/Ni film shows an exchange bias field of −78 Oe whereas the exchange bias field of wires narrower than 200 nm is reduced to approximately −40 Oe. The coercive field of the NiO/Ni film is 28 Oe and increases to 210 Oe for the narrowest wires. The decrease of the exchange bias field for the narrowest wires is consistent with a recent microscopic model of exchange bias where the appearance of a unidirectional anisotropy in ferromagnet/antiferromagnet bilayers has been attributed to the presence of antiferromagnetic domains in the bulk of the antiferromagnet. A possible onset of a transition from a multidomain to a single-domain state of the antiferromagnet as a function of the ...

Femtomolar limit of detection with a magnetoresistive biochip.

In this paper the biological limit of detection of a spin-valve-based magnetoresistive biochip applied to the detection of 20 mer ssDNA hybridization events is presented. Two reactional variables and their impact on the biomolecular recognition efficiency are discussed. Both the influence of a 250 nm diameter magnetic particle attached to the target molecule during the hybridization event and the effect of a magnetic focusing system in the hybridization of pre-labeled target DNA (assisted hybridization) are addressed. The particles carrying the target molecules are attracted to the probe active sensor sites by applying a 40 mA DC current on U-shaped aluminium current lines. Experiments comparing pre-hybridization versus post-hybridization magnetic labeling and passive versus magnetically assisted hybridization were conducted. The efficiency of a passive hybridization is reduced by about 50% when constrained to the operational conditions (sample volume, reaction time, temperature and magnetic label) of an on-chip real-time hybridization assay. This reduction has shown to be constant and independent from the initial target concentration. Conversely, the presence of the magnetic label improved the limit of detection when a magnetically assisted hybridization was performed. The use of a labeled target focusing system has permitted a gain of three orders of magnitude (from 1 pM down to 1 fM) in the sensitivity of the device, as compared with passive, diffusion-controlled hybridization.

Vector network analyzer ferromagnetic resonance of thin films on coplanar waveguides : Comparison of different evaluation methods

We have carried out two-port network analyzer ferromagnetic resonance measurements on a coplanar waveguide. We present a detailed description on how to calculate from the raw measurement data a value proportional to the complex susceptibility and permittivity of the ferromagnetic material. Necessary corrections for errors due to imprecise sample placement on the waveguide and the sample dimensions are presented. Evaluated data up to 15 GHz are provided for two model samples: a 40 nm Co80Fe20 layer showing a large linewidth (≈900 MHz) and a 40 nm Co72Fe18B10 layer yielding a small linewidth (≈360 MHz). Using these experimental data the presented evaluation scheme based on all four scattering parameters is then compared to commonly used approximate evaluation schemes relying on only one S parameter. These approximate methods show close agreement for the ferromagnetic resonance frequencies (the relative error is below 1%). However, the resonance linewidths show a relative error that can reach 10% in comparis...

Ion beam deposition and oxidation of spin-dependent tunnel junctions

Spin dependent tunnel junctions showing tunnel magnetoresistance (TMR) values of 39/spl sim/41% were fabricated using Ion Beam Deposition (IBD). Both the electrodes and the aluminum layer deposition were done by IBD. The aluminum oxidation was performed using the assist gun with an oxygen beam (+30 V acceleration voltage applied on the grids) using mixed O/sub 2//Ar plasma. The oxidation was monitored in real time with a residual gas analyzer (RGA). The junction area is defined by lithography, down to 3/spl times/2 /spl mu/m/sup 2/. As-deposited junctions with 15 /spl Aring/ of Al showed TMR of 27/spl sim/29%, independent of the junction area, with resistance-area products of 0.8/spl sim/1.6 M/spl Omega//spl times//spl mu/m/sup 2/. This TMR value reached 40% upon annealing at 290/spl deg/C, with resistance decreasing to 0.5/spl sim/0.8 M/spl Omega//spl times//spl mu/m/sup 2/.

Metabolic Alterations Induced by Sucrose Intake and Alzheimer’s Disease Promote Similar Brain Mitochondrial Abnormalities

Evidence shows that diabetes increases the risk of developing Alzheimer’s disease (AD). Many efforts have been done to elucidate the mechanisms linking diabetes and AD. To demonstrate that mitochondria may represent a functional link between both pathologies, we compared the effects of AD and sucrose-induced metabolic alterations on mouse brain mitochondrial bioenergetics and oxidative status. For this purpose, brain mitochondria were isolated from wild-type (WT), triple transgenic AD (3xTg-AD), and WT mice fed 20% sucrose-sweetened water for 7 months. Polarography, spectrophotometry, fluorimetry, high-performance liquid chromatography, and electron microscopy were used to evaluate mitochondrial function, oxidative status, and ultrastructure. Western blotting was performed to determine the AD pathogenic protein levels. Sucrose intake caused metabolic alterations like those found in type 2 diabetes. Mitochondria from 3xTg-AD and sucrose-treated WT mice presented a similar impairment of the respiratory chain and phosphorylation system, decreased capacity to accumulate calcium, ultrastructural abnormalities, and oxidative imbalance. Interestingly, sucrose-treated WT mice presented a significant increase in amyloid β protein levels, a hallmark of AD. These results show that in mice, the metabolic alterations associated to diabetes contribute to the development of AD-like pathologic features.

Tunnel magnetoresistance and magnetic ordering in ion-beam sputtered Co80Fe20/Al2O3 discontinuous multilayers

Discontinuous multilayered Co80Fe20(t)/Al2O3(30 A) thin films have been prepared by ion-beam sputtering. We report on structural, magnetic, and transport (for current in plane geometry) results obtained in this system. With growing nominal thickness t of the metal layers, which effectively characterizes the granular structure, a transition from tunnel to metallic conductance is observed, indicating the onset of infinite conducting paths at t>18 A. At t 13 A was detected from the magnetization data which display here a transition from superparamagnetic to ferromagnetic behavior. The measurements of tunnel magnetoresistance (MR) show that a sharp maximum of MR sensitivity to field takes place at this thickness, reaching ∼24%/kOe at room temperature. At least, MR itself as a function of t has a break at the same value. All these features suggest that some specific kind of percolation with respect to magnetic order occurs in o...