ERK/MAPK Is Essential for Endogenous Neuroprotection in SCN2.2 Cells

Glutamate (Glu) is essential to central nervous system function; however excessive Glu release leads to neurodegenerative disease. Strategies to protect neurons are underdeveloped, in part due to a limited understanding of natural neuroprotective mechanisms, such as those present in the suprachiasmatic nucleus (SCN). This study tests the hypothesis that activation of ERK/MAPK provides essential protection to the SCN after exposure to excessive Glu using the SCN2.2 cells as a model.Immortalized SCN2.2 cells (derived from SCN) and GT1-7 cells (neurons from the neighboring hypothalamus) were treated with 10 mM Glu in the presence or absence of the ERK/MAPK inhibitor PD98059. Cell death was assessed by Live/Dead assay, MTS assay and TUNEL. Caspase 3 activity was also measured. Activation of MAPK family members was determined by immunoblot. Bcl2, neuritin and Bid mRNA (by quantitative-PCR) and protein levels (by immunoblot) were also measured.As expected Glu treatment increased caspase 3 activity and cell death in the GT1-7 cells, but Glu alone did not induce cell death or affect caspase 3 activity in the SCN2.2 cells. However, pretreatment with PD98059 increased caspase 3 activity and resulted in cell death after Glu treatment in SCN2.2 cells. This effect was dependent on NMDA receptor activation. Glu treatment in the SCN2.2 cells resulted in sustained activation of the anti-apoptotic pERK/MAPK, without affecting the pro-apoptotic p-p38/MAPK. In contrast, Glu exposure in GT1-7 cells caused an increase in p-p38/MAPK and a decrease in pERK/MAPK. Bcl2-protein increased in SCN2.2 cells following Glu treatment, but not in GT1-7 cells; bid mRNA and cleaved-Bid protein increased in GT1-7, but not SCN2.2 cells.Facilitation of ERK activation and inhibition of caspase activation promotes resistance to Glu excitotoxicity in SCN2.2 cells.Further research will explore ERK/MAPK as a key molecule in the prevention of neurodegenerative processes

On finitely ambiguous B\"uchi automata

Unambiguous B\"uchi automata, i.e. B\"uchi automata allowing only one accepting run per word, are a useful restriction of B\"uchi automata that is well-suited for probabilistic model-checking. In this paper we propose a more permissive variant, namely finitely ambiguous B\"uchi automata, a generalisation where each word has at most $k$ accepting runs, for some fixed $k$. We adapt existing notions and results concerning finite and bounded ambiguity of finite automata to the setting of $\omega$-languages and present a translation from arbitrary nondeterministic B\"uchi automata with $n$ states to finitely ambiguous automata with at most $3^n$ states and at most $n$ accepting runs per word

Further Development of the Sextupole and Decapole Spool Corrector Magnets for the LHC

In the Large Hadron Collider (LHC) the main dipoles will be equipped with sextupole (MCS) and decapole (MCD) spool correctors to meet the very high demands of field quality required for the satisfactory operation of the machine. Each decapole corrector will in addition have an octupole insert (MCO) and the assembly of the two is designated MCDO. These correctors are needed in relatively large quantities, i.e. 2464 MCS Sextupoles and 1232 MCDO Decapole-Octupole assemblies. Half the number of the required spool correctors will be made in India through a collaboration between CERN and CAT (Centre for Advanced Technology, Indore, India), the other half will be built by European industry. The paper describes final choices concerning design, materials, production techniques, and testing so as to assure economic magnet manufacture but while maintaining a homogenous magnetic quality that results in a robust product

Experience with the Fabrication and Testing of the Sextupole Superconducting Corrector Magnets for the LHC

The LHC main dipoles will be equipped with sextupole corrector magnets with a field strength of 1700 x2 (T,m) and a magnetic length of 110 mm to correct sextupole field errors. Within the LHC magnet programme CERN has developed in collaboration with CAT a cosine-q type of design where much emphasis has been put on the cost reduction. The magnet features a two-layer racetrack coil, without end spacers, wound from a rectangular NbTi-wire. The two layers are wound simultaneously turning in opposite directions. The yoke is made of a scissor-type of lamination, which allows bringing the iron close to the coil for field enhancement. In this paper we review the manufacturing experiences with the first 12 prototypes built at CERN and CAT. The results of the training at 4.2 K and 1.9 K are presented along with the magnetic field quality measured at room temperature and at 1.9 K

Molecular markers for discriminating Streptococcus pyogenes and S. dysgalactiae subspecies equisimilis

Given the increasing aetiological importance of Streptococcus dysgalactiae subspecies equisimilis in diseases which are primarily attributed to S. pyogenes, molecular markers are essential to distinguish these species and delineate their epidemiology more precisely. Many clinical microbiology laboratories rely on agglutination reactivity and biochemical tests to distinguish them. These methods have limitations which are particularly exacerbated when isolates with mixed properties are encountered. In order to provide additional distinguishing parameters that could be used to unequivocally discriminate these two common pathogens, we assess here three molecular targets: the speB gene, intergenic region upstream of the scpG gene (IRSG) and virPCR. Of these, the former two respectively gave positive and negative results for S. pyogenes, and negative and positive results for S. dysgalactiae subsp. equisimilis. Thus, a concerted use of these nucleic acid-based methods is particularly helpful in epidemiological surveillance to accurately assess the relative contribution of these species to streptococcal infections and diseases

Magnetic control of large room-temperature polarization

Numerous authors have referred to room-temperature magnetic switching of large electric polarizations as The Holy Grail of magnetoelectricity.We report this long-sought effect using a new physical process of coupling between magnetic and ferroelectric relaxor nano-regions. Here we report magnetic switching between the normal ferroelectric state and the ferroelectric relaxor state. This gives both a new room-temperature, single-phase, multiferroic magnetoelectric, PbZr0.46Ti0.34Fe0.13W0.07O3, with polarization, loss (<4%), and resistivity (typically 108 -109 ohm.cm) equal to or superior to BiFeO3, and also a new and very large magnetoelectric effect: switching not from +Pr to negative Pr with applied H, but from Pr to zero with applied H of less than a Tesla. This switching of the polarization occurs not because of a conventional magnetically induced phase transition, but because of dynamic effects: Increasing H lengthens the relaxation time by x500 from 100 ?s, and it couples strongly the polarization relaxation and spin relaxations. The diverging polarization relaxation time accurately fits a modified Vogel-Fulcher Equation in which the freezing temperature Tf is replaced by a critical freezing field Hf that is 0.92 positive/negative 0.07 Tesla. This field dependence and the critical field Hc are derived analytically from the spherical random bond random field (SRBRF) model with no adjustable parameters and an E2H2 coupling. This device permits 3-state logic (+Pr,0,negative Pr) and a condenser with >5000% magnetic field change in its capacitance.Comment: 20 pages, 5 figure

Bounds on the Complexity of Halfspace Intersections when the Bounded Faces have Small Dimension

We study the combinatorial complexity of D-dimensional polyhedra defined as the intersection of n halfspaces, with the property that the highest dimension of any bounded face is much smaller than D. We show that, if d is the maximum dimension of a bounded face, then the number of vertices of the polyhedron is O(n^d) and the total number of bounded faces of the polyhedron is O(n^d^2). For inputs in general position the number of bounded faces is O(n^d). For any fixed d, we show how to compute the set of all vertices, how to determine the maximum dimension of a bounded face of the polyhedron, and how to compute the set of bounded faces in polynomial time, by solving a polynomial number of linear programs

The Liquisolid technique: an overview

A novel "Powder Solution Technology" involves absorption and adsorption efficiency which makes use of liquid medications, drug suspensions admixed with suitable carriers, coating materials and formulated into free flowing, dry looking, non adherent and compressible powder forms. Based upon a new mathematical model expression, improved flow characteristics and hardness of the formulation has been achieved by changing the proportion of Avicel ® PH 200 and Aerosil ® PH 200 from 50:1 ratio to 5:1 and in which the drug is dispersed in an almost molecularly state. Due to their significantly improved wetting properties a greater drug surface area is exposed to the dissolution media, resulting in an increased dissolution rate and bio availability. By using the Liquisolid technique, sustained drug delivery systems were developed for the water soluble drugs in which hydrophobic non-volatile solvents are used as vehicles.A nova "Tecnologia da Solução Sólida" envolve eficiência de absorção e de adsorção, faz uso de medicações líquidas, suspensões de fármacos e misturas com transportadores adequados, materiais de cobertura e é formulada em formas sólidas em fluxo livre, secas, não aderentes e compressíveis. Com base em novo modelo matemático, características aprimoradas de fluxo e dureza da formulação foram alcançadas modificando-se a proporção de Avicel ® PH 200 e Aerosil ® PH 200 de 50:1 para 5:1, na qual o fármaco é disperso quase que no estado molecular. Devido às propriedades de umidificação significativamente aprimoradas e à área do fármaco exposta ao meio de dissolução, que resulta na velocidade de dissolução, a biodisponibilidade foi aumentada. Utilizando a técnica Liquisólido, desenvolveram-se sistemas de liberação controlada de fármacos solúveis em água, nos quais solventes hidrofóbicos não voláteis foram usados como veículos

Tracking planar orientations of active MRI needles

Purpose: To determine and track the planar orientation of active interventional devices without using localizing RF microcoils. Materials and Methods: An image-based tracking method that determines a device's orientation using projection images was developed. An automated and a manual detection scheme were implemented. The method was demonstrated in an in vivo mesocaval puncture procedure in swine, which required accurate orientation of an active transvascular needle catheter. Results: The plane of the catheter was determined using two projection images. The scan plane was adjusted automatically to follow the catheter plane, and its orientation with respect to a previously acquired target plane was displayed. The algorithm facilitated navigation for a fast and accurate puncture. Conclusion: Using image-based techniques, with no mechanical design changes, the orientation of an active intravascular probe could be tracked. © 2007 Wiley-Liss, Inc