New players in the preventive treatment of migraine.

Migraine is a common, chronic disorder of the brain causing much disability, as well as personal, familial and societal impact. Several oral preventive agents are available in different countries for the prevention of migraine, but none have performed better than 50% improvement in 50% of patients in a clinical trial. Additionally, each has various possible adverse events making their tolerability less than optimal. Recently, three monoclonal antibodies targeting the calcitonin gene-related peptide (CGRP) ligand (LY2951742, ALD403 and TEV-48125) and one targeting the CGRP receptor (AMG 334) have completed phase 2 trials, and the results have been reported. These early results show them all to be somewhat more effective than placebo, with no serious adverse events. Three have been studied for episodic migraine, and only TEV-48125 has been studied for both high frequency episodic and chronic migraine. Moreover, preliminary data suggests that neurostimulation is effective in migraine treatment, including stimulation of the sphenopalatine ganglion, transcutaneous supraorbital and supratrochlear nerve, and transcutaneous vagus nerve. In this article, these innovative therapies will be reviewed

Direct-Write Fabrication of Integrated, Multilayer Ceramic Components

The need for advanced (electronic) ceramic components with smaller size, greater functionality, and enhanced reliability requires the ability to integrate electronic ceramics in complex 3-D architectures. For rapid prototyping and small-lot manufacturing, traditional tape casting and screen printing approaches are poorly suited. To address this need, we are developing a direct-write approach for fabricating highly integrated, multilayer components using a micropen to deposit slurries in precise patterns. With this technique, components can be constructed layer by layer, simplifying fabrication. It can also be used to produce structures combining several materials in a single layer. The parts are either cofired or sequentially fired, after each layer is deposited. Since differential shrinkage can lead to defects in these multilayer structures, we are characterizing the sintering behavior ofindividua1layers. This technique has been used to fabricate devices such integrated RC filters, multilayer voltage transformers, and other passive components. The direct-write approach provides the ability to fabricate multifunctional, multimaterial integrated ceramic components (MMICCs) in an agile and rapid way.Mechanical Engineerin

Laser engineered net shaping for direct fabrication of metal components

Sandia National Laboratories is developing a new technology to fabricate three-dimensional metallic components directly from CAD solid models. This process, called Laser Engineered Net Shaping (LENS{trademark}), exhibits enormous potential to revolutionize the way in which metal parts, such as complex prototypes, tooling, and small lot production parts, are produced. To perform the process, metal powder is injected into a molten pool created by a focused, high powered laser beam. Simultaneously, the substrate on which the deposition is occurring is scanned under the beam/powder interaction zone to fabricate the desired cross-sectional geometry. Consecutive layers are sequentially deposited, thereby producing a three-dimensional metal component

Correlation between the electric and acoustic signals emitted during compression of brittle materials

An experimental protocol is described including a series of uniaxial compression tests of three brittle materials (marble, mortar and glass). The Acoustic Emission (AE) technique and the Pressure Stimulated Currents (PSC) one are used since the recordings of both techniques are strongly related to the formation of cracking in brittle materials. In the present paper, the correlation of these techniques is investigated, which is finally proven to be very satisfactory

Critical currents in Josephson junctions with macroscopic defects

The critical currents in Josephson junctions of conventional superconductors with macroscopic defects are calculated for different defect critical current densities as a function of the magnetic field. We also study the evolution of the different modes with the defect position, at zero external field. We study the stability of the solutions and derive simple arguments, that could help the defect characterization. In most cases a reentrant behavior is seen, where both a maximum and a minimum current exist.Comment: 17 pages with 16 figures, submitted to Supercond. Sci. Techno

Aging, cellular senescence, and progressive Multiple Sclerosis

Aging is one of the most important risk factors for the development of several neurodegenerative diseases including progressive multiple sclerosis (MS). Cellular senescence (CS) is a key biological process underlying aging. Several stressors associated with aging and MS pathology, such as oxidative stress, mitochondrial dysfunction, cytokines and replicative exhaustion are known triggers of cellular senescence. Senescent cells exhibit stereotypical metabolic and functional changes, which include cell-cycle arrest and acquiring a pro-inflammatory phenotype secreting cytokines, growth factors, metalloproteinases and reactive oxygen species. They accumulate with aging and can convert neighboring cells to senescence in a paracrine manner. In MS, accelerated cellular senescence may drive disease progression by promoting chronic non-remitting inflammation, loss or altered immune, glial and neuronal function, failure of remyelination, impaired blood-brain barrier integrity and ultimately neurodegeneration. Here we discuss the evidence linking cellular senescence to the pathogenesis of MS and the putative role of senolytic and senomorphic agents as neuroprotective therapies in tackling disease progression

Development and integration of applique decoupling capacitors

For high-speed integrated circuit applications, it is important to interconnect decoupling capacitors and integrated circuits (ICs) as intimately as possible, to minimize parasitic impedances. This can be achieved by mounting free-standing, thin film capacitors directly onto ICs as part of a chip-scale packaging approach. These applique capacitors utilize a chemically-prepared PLZT dielectric, which is nominally 1 {micro}m thick. The small size and weight of applique capacitors can be used to improve packaging efficiency. Applique capacitors, which are initially fabricated on silicon wafers, have high permittivity ({var_epsilon} {approx_equal} 1,000), low loss (tan{delta} {approx_equal} 0.01) and high breakdown strength (E{sub b} {approx_equal} 1 MV/cm) and leakage resistance ({rho} > 10{sup 14} {Omega}-cm {at} 125 C). Various processes being developed to remove the capacitors from the silicon substrate and reattach them to ICs is described. In addition, a concept for interconnecting the capacitors using a repatterning process is discussed

Inter- and intragrain currents in bulk melt-grown YBaCuO rings

A simple contactless method suitable to discern between the intergrain (circular) current, which flows in the thin superconducting ring, and the intragrain current, which does not cross the weakest link, has been proposed. At first, we show that the intergrain current may directly be estimated from the magnetic flux density $B(\pm z_0)$ measured by the Hall sensor positioned in the special points $\pm z_0$ above/below the ring center. The experimental and the numerical techniques to determine the value $z_0$ are discussed. Being very promising for characterization of a current flowing across the joints in welded YBaCuO rings (its dependencies on the temperature and the external magnetic field as well as the time dissipation), the approach has been applied to study corresponding properties of the intra- and intergrain currents flowing across the $a$-twisted grain boundaries which are frequent in bulk melt-textured YBaCuO samples. We present experimental data related to the flux penetration inside a bore of MT YBaCuO rings both in the non-magnetized, virgin state and during the field reversal. The shielding properties and their dependence on external magnetic fields are also studied. Besides, we consider the flux creep effects and their influence on the current re-distribution during a dwell.Comment: 13 pages, 16 figures (EPS), RevTeX4. In the revised version, corrections to perturbing effects near the weak links are introduced, one more figure is added. lin