3D magnetization profile and multi-axes exchange bias in Co antidot arrays

Cu/Co/Cu trilayers have been deposited on nanoporous alumina membranes. Magnetic properties of the resulting Co antidot arrays are investigated using SQUID magnetometry. Hysteresis loops of these arrays show two-step magnetization reversal. In addition, exchange bias is observed, whether the cooling field is applied within or perpendicular to the surface plane. In the former case, the exchange bias changes sign close to the blocking temperature, and becomes positive. We attribute these effects to the local, crescent shape of the Co films, induced by the surface morphology of the alumina membranes. This morphology leads to a three-dimensional magnetization distribution at the nanoscale.Comment: 3 pages, 3 figure

Hyperammonemia-induced toxicity for the developing central nervous system

In pediatric patients, hyperammonemia can be caused by various acquired or inherited disorders such as urea cycle deficiencies or organic acidemias. The brain is much more susceptible to the deleterious effects of ammonium during development than in adulthood. Hyperammonemia can provoke irreversible damages to the developing central nervous system that lead to cortical atrophy, ventricular enlargement and demyelination, responsible for cognitive impairment, seizures and cerebral palsy. Until recently, the mechanisms leading to these irreversible cerebral damages were poorly understood. Using experimental models allowing the analysis of the neurotoxic effects of ammonium on the developing brain, these last years have seen the emergence of new clues showing that ammonium exposure alters several amino acid pathways and neurotransmitter systems, as well as cerebral energy metabolism, nitric oxide synthesis, oxidative stress, mitochondrial permeability transition and signal transduction pathways. Those alterations may explain neuronal loss and impairment of axonal and dendritic growth observed in the different models of congenital hyperammonemia. Some neuroprotective strategies such as the potential use of NMDA receptor antagonists, nitric oxide inhibitors, creatine and acetyl-l-carnitine have been suggested to counteract these toxic effects. Unraveling the molecular mechanisms involved in the chain of events leading to neuronal dysfunction under hyperammonemia may be useful to develop new potential strategies for neuroprotection

Role of caspases, calpain and cdk5 in ammonia-induced cell death in developing brain cells.

Hyperammonemia in neonates and infants causes irreversible damages in the developing CNS due to brain cell loss. Elucidating the mechanisms triggering ammonia-induced cell death in CNS is necessary for the development of neuroprotective strategies. We used reaggregated developing brain cell cultures derived from fetal rat telencephalon exposed to ammonia as an experimental model. Ammonia induced neuronal and oligodendroglial death, triggered apoptosis and activated caspases and calpain. Probably due to calpain activation, ammonia caused the cleavage of the cyclin-dependent kinase 5 activator, p35, to p25, the cdk5/p25 complex being known to lead to neurodegeneration. Roscovitine, a cdk5 inhibitor, protected neurons from ammonia-induced cell death. However, roscovitine also impaired axonal growth, probably through inhibition of the remaining cdk5/p35 activity, which is involved in neurite outgrowth. Thus, cdk5 appears as a promising therapeutic target for treating hyperammonemic newborns and infants, especially if one develops specific cdk5/p25 inhibitors

CNTF protects oligodendrocytes from ammonia toxicity: intracellular signaling pathways involved.

In pediatric patients, hyperammonemia can provoke irreversible damages to developing CNS like cortical atrophy, ventricular enlargement, demyelination or gray and white matter hypodensities which are concordant with alterations of neurons and oligodendrocytes. Cerebral injury triggers endogenous protective mechanisms that can prevent or limit brain damage. Understanding these mechanisms may lead to new therapeutic strategies. We investigated whether ciliary neurotrophic factor (CNTF), a cytokine-like protein expressed by astrocytes and described as an injury-associated survival factor, was up-regulated by ammonia in developing reaggregated 3D brain cell cultures. We showed that CNTF is up-regulated by ammonia exposure, through mediation of p38 MAPK activation in astrocytes. We also observed that SAPK/JNK and Erk1/2 activations in oligodendrocytes and neurons, respectively, also play indirect roles in CNTF synthesis by astrocytes. Co-treatment with exogenous CNTF demonstrated strong protective effects on oligodendrocytes, but not on neurons, against ammonia toxicity. These protective effects involved JAK/STAT, SAPK/JNK and c-jun proteins

Electrochemical machining of stainless steel microelements with ultrashort voltage pulses

An electrochemical pulse technique enables the fabrication of three-dimensional microelements from stainless steel. The method is based on the application of ultrashort (nanosecond) voltage pulses, whereupon electrochemical reactions are locally confined with submicrometer precision. Employing properly shaped tool electrodes enables the machining of freestanding cantilevers or microstructures directly to a metal sheet. Due to gentle removal of the material, the grain structure of the material is revealed without any chemical or mechanical modifications. This is demonstrated by measuring the vibration frequency of a cantilever, and agrees well with the value derived from the bulk material properties

Quantitative analysis of shadow X-ray Magnetic Circular Dichroism Photo-Emission Electron Microscopy

Shadow X-ray Magnetic Circular Dichroism Photo-Emission Electron Microscopy (XMCD-PEEM) is a recent technique, in which the photon intensity in the shadow of an object lying on a surface, may be used to gather information about the three-dimensional magnetization texture inside the object. Our purpose here is to lay the basis of a quantitative analysis of this technique. We first discuss the principle and implementation of a method to simulate the contrast expected from an arbitrary micromagnetic state. Text book examples and successful comparison with experiments are then given. Instrumental settings are finally discussed, having an impact on the contrast and spatial resolution : photon energy, microscope extraction voltage and plane of focus, microscope background level, electric-field related distortion of three-dimensional objects, Fresnel diffraction or photon scattering

Determination of the local concentrations of Mn interstitials and antisite defects in GaMnAs

We present a method for the determination of the local concentrations of interstitial and substitutional Mn atoms and As antisite defects in GaMnAs. The method relies on the sensitivity of the structure factors of weak reflections to the concentrations and locations of these minority constituents. High spatial resolution is obtained by combining structure factor measurement and X-ray analysis in a transmission electron microscope. We demonstrate the prevalence of interstitials with As nearest neighbors in as-grown layers.Comment: 10 pages, 4 figure

Rapid and Continued T-Cell Differentiation into Long-term Effector and Memory Stem Cells in Vaccinated Melanoma Patients.

<b>Purpose:</b> Patients with cancer benefit increasingly from T-cell-based therapies, such as adoptive T-cell transfer, checkpoint blockade, or vaccination. We have previously shown that serial vaccinations with Melan-A <sup>MART-1</sup> <sub>26-35</sub> peptide, CpG-B, and incomplete Freund adjuvant (IFA) generated robust tumor-specific CD8 T-cell responses in patients with melanoma. Here, we describe the detailed kinetics of early- and long-term establishment of T-cell frequency, differentiation (into memory and effector cells), polyfunctionality, and clonotype repertoire induced by vaccination. <b>Experimental Design:</b> Twenty-nine patients with melanoma were treated with multiple monthly subcutaneous vaccinations consisting of CpG-B, and either the native/EAA ( <i>n</i> = 13) or the analogue/ELA ( <i>n</i> = 16) Melan-A <sup>MART-1</sup> <sub>26-35</sub> peptide emulsified in IFA. Phenotypes and functionality of circulating Melan-A-specific CD8 T cells were assessed directly <i>ex vivo</i> by multiparameter flow cytometry, and TCR clonotypes were determined <i>ex vivo</i> by mRNA transcript analyses of individually sorted cells. <b>Results:</b> Our results highlight the determining impact of the initial vaccine injections on the rapid and strong induction of differentiated effector T cells in both patient cohorts. Moreover, long-term polyfunctional effector T-cell responses were associated with expansion of stem cell-like memory T cells over time along vaccination. Dominant TCR clonotypes emerged early and persisted throughout the entire period of observation. Interestingly, one highly dominant clonotype was found shared between memory and effector subsets. <b>Conclusions:</b> Peptide/CpG-B/IFA vaccination induced powerful long-term T-cell responses with robust effector cells and stem cell-like memory cells. These results support the further development of CpG-B-based cancer vaccines, either alone or as specific component of combination therapies. <i>Clin Cancer Res; 23(13); 3285-96. ©2016 AACR</i>

Emerging Opportunities of Radiotherapy Combined With Immunotherapy in the Era of Breast Cancer Heterogeneity.

The association of radiotherapy and immunotherapy has recently emerged as an exciting combination that might improve outcomes in many solid tumor settings. In the context of breast cancer, this opportunity is promising and under investigation. Given the heterogeneity of breast cancer, it might be meaningful to study the association of radiotherapy and immunotherapy distinctly among the various breast cancer subtypes. The use of biomarkers, such as tumor infiltrating lymphocytes, which are also associated to breast cancer heterogeneity, might provide an opportunity for tailored studies. This review highlights current knowledge of the association of radiotherapy and immunotherapy in the setting of breast cancer and attempts to highlight the therapeutic opportunities among breast cancer heterogeneity

Design of a pulse power supply unit for micro-ECM

Electrochemical micro-machining (μECM) requires a particular pulse power supply unit (PSU) to be developed in order to achieve desired machining performance. This paper summarises the development of a pulse PSU meeting the requirements of μECM. The pulse power supply provides tens of nanosecond pulse duration, positive and negative bias voltages and a polarity switching functionality. It fulfils the needs for tool preparation with reversed pulsed ECM on the machine. Moreover, the PSU is equipped with an ultrafast overcurrent protection which prevents the tool electrode from being damaged in case of short circuits. The developed pulse PSU was used to fabricate micro-tools out of 170 μm WC-Co alloy shafts via micro-electrochemical turning and drill deep holes via μECM in a disk made of 18NiCr6. The electrolyte used for both processes was a mixture of sulphuric acid and NaNO3 aqueous solutions.The research reported in this paper is supported by the European Commission within the project “Minimizing Defects in Micro-Manufacturing Applications (MIDEMMA)” (FP7-2011-NMP-ICT-FoF-285614