A fast magnetic vector characterization method for quasi two-dimensional systems and heterostructures.

The use of magnetic vector tomography/laminography has opened a 3D experimental window to access the magnetization at the nanoscale. These methods exploit the dependence of the magnetic contrast in transmission to recover its 3D configuration. However, hundreds of different angular projections are required leading to large measurement times. Here we present a fast method to dramatically reduce the experiment time specific for quasi two-dimensional magnetic systems. The algorithm uses the Beer-Lambert equation in the framework of X-ray transmission microscopy to obtain the 3D magnetic configuration of the sample. It has been demonstrated in permalloy microstructures, reconstructing the magnetization vector field with a reduced number of angular projections obtaining quantitative results. The throughput of the methodology is × 10-× 100 times faster than conventional magnetic vector tomography, making this characterization method of general interest for the community.

Planar refraction and lensing of highly confined polaritons in anisotropic media.

Refraction between isotropic media is characterized by light bending towards the normal to the boundary when passing from a low- to a high-refractive-index medium. However, refraction between anisotropic media is a more exotic phenomenon which remains barely investigated, particularly at the nanoscale. Here, we visualize and comprehensively study the general case of refraction of electromagnetic waves between two strongly anisotropic (hyperbolic) media, and we do it with the use of nanoscale-confined polaritons in a natural medium: α-MoO3. The refracted polaritons exhibit non-intuitive directions of propagation as they traverse planar nanoprisms, enabling to unveil an exotic optical effect: bending-free refraction. Furthermore, we develop an in-plane refractive hyperlens, yielding foci as small as λp/6, being λp the polariton wavelength (λ0/50 compared to the wavelength of free-space light). Our results set the grounds for planar nano-optics in strongly anisotropic media, with potential for effective control of the flow of energy at the nanoscale.

Transcervical drainage of abdominal-pelvic abscess after laparoscopic sacrocolpopexy.

INTRODUCTION AND HYPOTHESIS: Abdominopelvic abscess is a serious, but infrequent, postoperative complication of sacrocolpopexy, which a priori requires a second surgery to debride the affected tissue and dry out the infected mesh in addition to a prolonged broad-spectrum antibiotic therapy. METHODS: We present two cases of post-surgical abdominopelvic abscesses, treated with conservative management using ultrasound-guided transcervical drainage and prolonged antibiotic therapy. Both patients underwent a favorable evolution without needing the removal of the mesh. CONCLUSIONS: Because of the search for new alternatives to avoid mesh removal and the comorbidity associated with a second surgery, transcervical drainage is a treatment to be considered in selected cases.

Revealing 3D magnetization of thin films with soft X-ray tomography: magnetic singularities and topological charges.

The knowledge of how magnetization looks inside a ferromagnet is often hindered by the limitations of the available experimental methods which are sensitive only to the surface regions or limited in spatial resolution. Here we report a vector tomographic reconstruction based on soft X-ray transmission microscopy and magnetic dichroism data, which has allowed visualizing the three-dimensional magnetization in a ferromagnetic thin film heterostructure. Different non-trivial topological textures have been resolved and the determination of their topological charge has allowed us to identify a Bloch point and a meron-like texture. Our method relies only on experimental data and might be of wide application and interest in 3D nanomagnetism.

Chiral asymmetry detected in a 2D array of permalloy square nanomagnets using circularly polarized x-ray resonant magnetic scattering.

The sensitivity of circularly polarized x-ray resonant magnetic scattering (CXRMS) to chiral asymmetry has been demonstrated. The study was performed on a 2D array of Permalloy (Py) square nanomagnets of 700 nm lateral size arranged in a chess pattern, in a square lattice of 1000 nm lattice parameter. Previous x-ray magnetic circular dichroism photoemission electron microscopy (XMCD-PEEM) images on this sample showed the formation of vortices at remanence and a preference in their chiral state. The magnetic hysteresis loops of the array along the diagonal axis of the squares indicate a non-negligible and anisotropic interaction between vortices. The intensity of the magnetic scattering using circularly polarized light along one of the diagonal axes of the square magnets becomes asymmetric in intensity in the direction transversal to the incident plane at fields where the vortex states are formed. The asymmetry sign is inverted when the direction of the applied magnetic field is inverted. The result is the expected in the presence of an unbalanced chiral distribution. The effect is observed by CXRMS due to the interference between the charge scattering and the magnetic scattering.

Topologically protected superconducting ratchet effect generated by spin-ice nanomagnets.

We have designed, fabricated and tested a robust superconducting ratchet device based on topologically frustrated spin ice nanomagnets. The device is made of a magnetic Co honeycomb array embedded in a superconducting Nb film. This device is based on three simple mechanisms: (i) the topology of the Co honeycomb array frustrates in-plane magnetic configurations in the array yielding a distribution of magnetic charges which can be ordered or disordered with in-plane magnetic fields, following spin ice rules; (ii) the local vertex magnetization, which consists of a magnetic half vortex with two charged magnetic Néel walls; (iii) the interaction between superconducting vortices and the asymmetric potentials provided by the Néel walls. The combination of these elements leads to a superconducting ratchet effect. Thus, superconducting vortices driven by alternating forces and moving on magnetic half vortices generate a unidirectional net vortex flow. This ratchet effect is independent of the distribution of magnetic charges in the array.

Magnetic order and disorder in nanomagnets probed by superconducting vortices.

We have studied two nanomagnet systems with strong (Co/Pd multilayers) and weak (NdCo alloy films) stray magnetic fields by probing the out-of-plane magnetic states with superconducting vortices. The hybrid samples are made of array of nanomagnets embedded in superconducting Nb thin films. The vortex motion detects relevant magnetic state features, since superconducting vortices are able to discriminate between different magnetic stray field strengths and directions. The usual matching effect between the superconducting vortex lattice and the periodic pinning array can be quenched by means of disorder magnetic potentials with strong stray fields at random. Ordered stray fields retrieve the matching effect and yield asymmetry and shift in the vortex dissipation signal. Furthermore vortices can discriminate the sizes of the nanomagnet magnetic domains, detecting magnetic domain sizes as small as 70 nm. In addition, we observe that the vortex cores play the crucial role instead of the supercurrents around the vortex.

A real-time stress classification system based on arousal analysis of the nervous system by an F-state machine.

BACKGROUND AND OBJECTIVE: Detection and labelling of an increment in the human stress level is a contribution focused principally on improving the quality of life of people. This work is aimed to develop a biophysical real-time stress identification and classification system, analysing two noninvasive signals, the galvanic skin response and the heart rate variability. METHODS: An experimental procedure was designed and configured in order to elicit a stressful situation that is similar to those found in real cases. A total of 166 subjects participated in this experimental stage. The set of registered signals of each subject was considered as one experiment. A preliminary qualitative analysis of the signals collected was made, based on previous counselling received from neurophysiologists and psychologists. This study revealed a relationship between changes in the temporal signals and the induced stress states in each subject. To identify and classify such states, a subsequent quantitative analysis was performed in order to determine specific numerical information related to the above mentioned relationship. This second analysis gives the particular details to design the finally proposed classification algorithm, based on a Finite State Machine. RESULTS: The proposed system is able to classify the detected stress stages at three levels: low, medium, and high. Furthermore, the system identifies persistent stress situations or momentary alerts, depending on the subject's arousal. The system reaches an F1 score of 0.984 in the case of high level, an F1 score of 0.970 for medium level, and an F1 score of 0.943 for low level. CONCLUSION: The resulting system is able to detect and classify different stress stages only based on two non invasive signals. These signals can be collected in people during their monitoring and be processed in a real-time sense, as the system can be previously preconfigured. Therefore, it could easily be implemented in a wearable prototype that could be worn by end users without feeling to be monitored. Besides, due to its low computational, the computation of the signals slopes is easy to do and its deployment in real-time applications is feasible.

[Presumed perinatal ischemic stroke: risk factors and clinical and radiological findings]. / Ictus isquemico presumiblemente perinatal: factores de riesgo, hallazgos clinicos y radiologicos.

INTRODUCTION: Presumed perinatal ischemic stroke is a frequent cause of neurological sequelae. We aimed to describe the different clinical findings and risk factors and to analyse the differences according the vascular origin. PATIENTS AND METHODS: Retrospective, descriptive study of patients diagnosed with presumed perinatal ischemic stroke attended at a tertiary pediatric hospital from 1990 to 2015. RESULTS: 44 patients were included. A total of 24 patients (55%) had arterial ischemic stroke and 20 (45%) had periventricular venous infarction. Delay in diagnosis was significantly higher in patients with periventricular venous infarction compared to those with arterial ischemic stroke (14 and 8 months respectively; p = 0.025). Most patients presented with asymmetrical motor development (90%), only < 5% with seizures or non motor delays. Subsequent epilepsy at follow-up was significantly more prevalent in arterial ischemic stroke group (p = 0.020). We determined risk factors theoretically involved in the pathogenesis of presumed perinatal ischemic stroke: prenatal, obstetrical, perinatal, prothrombotic and cardiac. No significant differences between risk factors and vascular origin were found. Prothrombotic abnormalities were common (48.3%). CONCLUSIONS: Investigation in risk factors implicated in presumed perinatal ischemic stroke is required to develop prevention strategies. Delay in diagnosis is higher in periventricular venous infarction group.

TITLE: Ictus isquemico presumiblemente perinatal: factores de riesgo, hallazgos clinicos y radiologicos.Introduccion. El ictus isquemico presumiblemente perinatal es una causa frecuente de secuelas neurologicas importantes. Los objetivos del estudio son describir las caracteristicas clinicas y los factores de riesgo implicados, y analizar las diferencias segun su origen vascular. Pacientes y metodos. Estudio descriptivo retrospectivo que incluye pacientes con diagnostico de ictus isquemico presumiblemente perinatal atendidos en un hospital terciario entre 1990-2015. Resultados. Se incluyeron 44 pacientes: 24 (55%) fueron de origen arterial, frente a 20 (45%) de origen venoso. El diagnostico fue significativamente mas tardio en los de origen venoso que en los de origen arterial (14 y 8 meses respectivamente; p = 0,025). La mayoria comenzo con un deficit motor (90%), y las crisis epilepticas y el retraso psicomotor global fueron menos frecuentes en ambos grupos (< 5%). La prevalencia de epilepsia posterior fue significativamente mas frecuente entre los de origen arterial (p = 0,020). Se analizaron los factores de riesgo teoricamente implicados en su patogenia: prenatales, obstetricos, perinatales, protromboticos y cardiacos, sin hallarse diferencias significativas en la presencia de estos entre los infartos arteriales y los venosos. Encontramos la presencia de al menos una alteracion en el estudio de hipercoagulabilidad en el 48,3% de los pacientes. Conclusion. Es preciso investigar el papel que desempeñan los factores de riesgo implicados en el ictus isquemico presumiblemente perinatal para establecer medidas preventivas. Su diagnostico es mas tardio si el origen es venoso.

Nanoscale imaging of buried topological defects with quantitative X-ray magnetic microscopy.

Advances in nanoscale magnetism increasingly require characterization tools providing detailed descriptions of magnetic configurations. Magnetic transmission X-ray microscopy produces element specific magnetic domain images with nanometric lateral resolution in films up to ∼100 nm thick. Here we present an imaging method using the angular dependence of magnetic contrast in a series of high resolution transmission X-ray microscopy images to obtain quantitative descriptions of the magnetization (canting angles relative to surface normal and sense). This method is applied to 55-120 nm thick ferromagnetic NdCo5 layers (canting angles between 65° and 22°), and to a NdCo5 film covered with permalloy. Interestingly, permalloy induces a 43° rotation of Co magnetization towards surface normal. Our method allows identifying complex topological defects (merons or ½ skyrmions) in a NdCo5 film that are only partially replicated by the permalloy overlayer. These results open possibilities for the characterization of deeply buried magnetic topological defects, nanostructures and devices.

Unravelling the tunable exchange bias-like effect in magnetostatically-coupled two dimensional hybrid (hard/soft) composites.

Hybrid 2D hard-soft composites have been fabricated by combining soft (Co73Si27) and hard (NdCo5) magnetic materials with in-plane and out-of-plane magnetic anisotropies, respectively. They have been microstructured in a square lattice of CoSi anti-dots with NdCo dots within the holes. The magnetic properties of the dots allow us to introduce a magnetostatic stray field that can be controlled in direction and sense by their last saturating magnetic field. The magnetostatic interactions between dot and anti-dot layers induce a completely tunable exchange bias-like shift in the system's hysteresis loops. Two different regimes for this shift are present depending on the lattice parameter of the microstructures. For large parameters, dipolar magnetostatic decay is observed, while for the smaller one, the interaction between the adjacent anti-dot's characteristic closure domain structures enhances the exchange bias-like effect as clarified by micromagnetic simulations.

Ovarian hydatid disease.

Hydatid disease, also known as Echinococcosis is a zoonosis caused by the larval stage of Echinococcus. The human cystic variant primarily affects liver and lungs. The pelvic location of the disease is a rare finding usually secondary to a ruptured liver cyst, although it may also appear as a primary lesion affecting the genital organs. Despite its rarity, in endemic areas, pelvic hydatid disease should be considered in the differential diagnosis of complex adnexal cystic mass, to make an appropriate treatment strategy. The suspected diagnosis is based on imaging studies and serodiagnostic techniques, in which a new field of research attempts to find a standardized test with sufficient sensitivity and specificity. We report a case of primary pelvic hydatid disease in postmenopausal women operated for suspected ovarian cancer.

Magnetic behavior of high density arrays of Co bars with strong magnetostatic coupling.

Magnetization reversal processes have been analyzed by Magnetic Force Microscopy in dense arrays of Co bars with well defined shape anisotropy and strong magnetostatic interactions. Two different geometries have been used: rectangular and rhombic so that the sign of dipolar interactions between adjacent chains of bars is changed from antiferromagnetic (rectangular array) to ferromagnetic (rhombic array), having a profound influence on the shape of a nucleus of inversion at the magnetization reversal.

Topological defects and misfit strain in magnetic stripe domains of lateral multilayers with perpendicular magnetic anisotropy.

Stripe domains are studied in perpendicular magnetic anisotropy films nanostructured with a periodic thickness modulation that induces the lateral modulation of both stripe periods and in-plane magnetization. The resulting system is the 2D equivalent of a strained superlattice with properties controlled by interfacial misfit strain within the magnetic stripe structure and shape anisotropy. This allows us to observe, experimentally for the first time, the continuous structural transformation of a grain boundary in this 2D magnetic crystal in the whole angular range. The magnetization reversal process can be tailored through the effect of misfit strain due to the coupling between disclinations in the magnetic stripe pattern and domain walls in the in-plane magnetization configuration.

Discovery of a series of imidazopyrazine small molecule inhibitors of the kinase MAPKAPK5, that show activity using in vitro and in vivo models of rheumatoid arthritis.

MAPKAPK5 has been proposed to play a role in regulation of matrix metalloprotease expression and so to be a potential target for intervention in rheumatoid arthritis. We present here the identification of a series of compounds against this target which are effective in both biochemical and cell assays. The expansion of the series is described, along with early SAR and pharmacokinetics for some representative compounds.

Pulsed rf-GD-TOFMS for depth profile analysis of ultrathin layers using the analyte prepeak region.

Direct solid analysis of ultrathin layers is investigated using pulsed radiofrequency (rf) glow discharge (GD) time-of-flight mass spectrometry (TOFMS). In particular, previous studies have always integrated the detected ion signals in the afterglow region of the rf-GD pulse, which is known to be the most sensitive one. Nevertheless, the analytical capabilities of other pulse time regions have not been evaluated in detail. Therefore, in this work, we investigate the analyte prepeak region, which is the pulse region where the analyte ions peak after the initial sputtering process of each GD pulse, aiming at obtaining improved depth profile analysis with high depth resolution and with minimum polyatomic spectral interferences. To perform these studies, challenging ultrathin Si-Co bilayers deposited on a Si substrate were investigated. The thickness of the external Si layer was 30 nm for all the samples, whilst the internal Co layer thicknesses were 30, 10, 5, 2 and 1 nm, respectively. It should be remarked that the top layer and the substrate have the same matrix composition (Si > 99.99%). Therefore, the selected samples are suitable to evaluate the response of the Si ion signal in the presence of an ultrathin Co layer as well as the possible oxygen contaminations or its reactions. Additionally, these samples have been evaluated using time-of-flight secondary ion mass spectrometry, and the results compare well to those obtained by our pulsed rf-GD time-of-flight mass spectrometry results.

Direct chemical in-depth profile analysis and thickness quantification of nanometer multilayers using pulsed-rf-GD-TOFMS.

Nanometer depth resolution is investigated using an innovative pulsed-radiofrequency glow discharge time-of-flight mass spectrometer (pulsed-rf-GD-TOFMS). A series of ultra-thin (in nanometers approximately) Al/Nb bilayers, deposited on Si wafers by dc-magnetron sputtering, is analyzed. An Al layer is first deposited on the Si substrate with controlled and different values of the layer thickness, t(Al). Samples with t(Al) = 50, 20, 5, 2, and 1 nm have been prepared. Then, a Nb layer is deposited on top of the Al one, with a thickness t(Nb) = 50 nm that is kept constant along the whole series. Qualitative depth profiles of those layered sandwich-type samples are determined using our pulsed-rf-GD-TOFMS set-up, which demonstrated to be able to detect and measure ultra-thin layers (even of 1 nm). Moreover, Gaussian fitting of the internal Al layer depth profile is used here to obtain a calibration curve, allowing thickness estimation of such nanometer layers. In addition, the useful yield (estimation of the number of detected ions per sputtered atom) of the employed pulsed-rf-GD-TOFMS system is evaluated for Al at the selected operating conditions, which are optimized for the in-depth profile analysis with high depth resolution.

Crossed-ratchet effects for magnetic domain wall motion.

We study both experimentally and theoretically the driven motion of domain walls in extended amorphous magnetic films patterned with a periodic array of asymmetric holes. We find two crossed-ratchet effects of opposite sign that change the preferred sense for domain wall propagation, depending on whether a flat or a kinked wall is moving. By solving numerically a simple phi(4) model we show that the essential physical ingredients for this effect are quite generic and could be realized in other experimental systems involving elastic interfaces moving in multidimensional ratchet potentials.

REPLACE: a strategy for iterative design of cyclin-binding groove inhibitors.

We describe a drug-design strategy termed REPLACE (REplacement with Partial Ligand Alternatives through Computational Enrichment) in which nonpeptidic surrogates for specific determinants of known peptide ligands are identified in silico by using a core peptide-bound protein structure as a design anchor. In the REPLACE application example, we present the effective replacement of two critical binding motifs in a lead protein-protein interaction inhibitor pentapeptide with more druglike phenyltriazole and diphenyl ether groups. These were identified through docking of fragment libraries into the volume of the cyclin-binding groove of CDK2/cyclin A vacated through truncation of the inhibitor peptide-binding determinants. Proof of concept for this strategy was obtained through the generation of potent peptide-small-molecule hybrids and by the confirmation of inhibitor-binding modes in X-ray crystal structures. This method therefore allows nonpeptide fragments to be identified without the requirement for a high-sensitivity binding assay and should be generally applicable in replacing amino acids as individual residues or groups in peptide inhibitors to generate pharmaceutically acceptable lead molecules.

Expediting drug discovery: recent advances in fast medicinal chemistry--optimization of hits and leads.

This article reviews the literature from January 2004 to January 2006 relating to the use of parallel chemistry compound libraries in drug discovery. Examples of libraries that have yielded active compounds across a range of biological targets are presented, together with synthetic details where relevant. The background of the biological target, and any structure-activity relationship that can be discerned from members of a library series, are also commented upon. A brief discussion of new technological developments in library design and synthesis, and likely future directions for parallel chemistry in the context of drug discovery, is also presented.