The effect of Windbreaks on Railway Overheads subject to Cross-Winds at O Eixo Viaduct

A measurement investigation, at ADIF's test site at the O Eixo viaduct which is on the Spanish Santiago-Ourense high speed railway line, has been carried out during the last year. The main goal of the investigation is to study the effect of the cross-wind on railway overheads (catenaries) and the influence of the presence of windbreaks on the wind-induced motion of the railway overhead. A description of the O Eixo viaduct test site is presented in this paper, including the installed windbreaks, the sensor and power supply systems. Three catenary spans has been instrumented at the center point of the catenary span contact wire with one ultrasonic anemometer and two unidirectional accelerometers. Additionally, another ultrasonic anemometer placed in the central catenary span has been installed to provide reference wind data. Wind roses of wind speed and standard deviation of the accelerometers are presented. As expected, the four wind roses look very similar and the two dominant directions close to the perpendicular to the bridge longitudinal axes, north and south have been identified. The wind roses of the standard deviation of the acceleration shows that the acceleration of the catenary contact wire is related to the directions of the two dominant winds. The vertical standard deviation of the acceleration is higher than the horizontal one for the spans with windbreaks. It has also been observed that the presence of the windbreaks modifies the wind flow leading to a wind-induced motion of the catenary contact wire which shows a higher variability than the corresponding unprotected case. On the one hand, the baseline southerly wind configuration (south wind, windbreaks in the windward side and catenary in the leeward side) influence both the mean speed at the catenary and the turbulence intensity. On the other hand, the northerly wind configuration, windbreaks in the leeward side and catenary in the windward side, provide a reference to the response of the catenary for an unprotected railway overhead, and, as it is expected, the windbreak influence is much more reduced compared to the southerly wind configuration. Both the height of the windbreak and the eaves contribute to the increase in the turbulence intensity at the catenary contact wire height. It can be seen that the height of the windbreak plays a crucial role in the increase of turbulence intensity, much more intense than the presence of the windbreak eave.

Comparison of different MIMO antenna arrays and user's effect on their performances

Multiple-input multiple-output (MIMO) systems have entailed a great enhancement in wireless communications performances. The use of multiple antennas at each side of the radio link has been included in recent drafts and standards such as WLAN, WIMAX, or DVB-T2. The MIMO performances depend on the antenna array characteristics and thus several aspects have to be taken into account to design MIMO antennas. In the literature, many articles can be found in terms of capacity or antenna design, but in this article, different types of antenna arrays for MIMO systems are measured in a reverberation chamber with and without a phantom as a user's head. As a result, the MIMO performances are degraded by the user in terms of efficiency, diversity gain, and capacity. Omnidirectional antennas such as monopoles with high radiation efficiency offer the highest performance for a rich scattering nonline of sight indoor environment.

Effect of fire on the microstructure and mechanical response of structural steels for building construction

The research is an exhaustive study of the microstructure and of the stress-strain curves of structural steel S460N at temperatures typical of a fire. It includes a fractographic study of the fracture suifaces of cylindrical specimens, tensile tested at different fire scenarios, explaining the relationship between the failure micromechanisms and temperature. The paper ends with the comparison between the experimentally found strain-stress curves with that one's proposed by the EUROCODE EC3, resulting that in the case of steel S460N these are on the side ofsafety.

Sophisticated security verification on routing repaired balanced cell-based dual-rail logic against side channel analysis

Conventional dual-rail precharge logic suffers from difficult implementations of dual-rail structure for obtaining strict compensation between the counterpart rails. As a light-weight and high-speed dual-rail style, balanced cell-based dual-rail logic (BCDL) uses synchronised compound gates with global precharge signal to provide high resistance against differential power or electromagnetic analyses. BCDL can be realised from generic field programmable gate array (FPGA) design flows with constraints. However, routings still exist as concerns because of the deficient flexibility on routing control, which unfavourably results in bias between complementary nets in security-sensitive parts. In this article, based on a routing repair technique, novel verifications towards routing effect are presented. An 8 bit simplified advanced encryption processing (AES)-co-processor is executed that is constructed on block random access memory (RAM)-based BCDL in Xilinx Virtex-5 FPGAs. Since imbalanced routing are major defects in BCDL, the authors can rule out other influences and fairly quantify the security variants. A series of asymptotic correlation electromagnetic (EM) analyses are launched towards a group of circuits with consecutive routing schemes to be able to verify routing impact on side channel analyses. After repairing the non-identical routings, Mutual information analyses are executed to further validate the concrete security increase obtained from identical routing pairs in BCDL.

Effect of fire on the microstructure and mechanical response of structural steels for building construction

The research is an exhaustive study of the microstructure and of the stress-strain curves of structural steel S460N at temperatures typical of a fire. It includes a fractographic study of the fracture suifaces of cylindrical specimens, tensile tested at different fire scenarios, explaining the relationship between the failure micromechanisms and temperature. The paper ends with the comparison between the experimentally found strain-stress curves with that one's proposed by the EUROCODE EC3, resulting that in the case of steel S460N these are on the side ofsafety.

A swarm intelligence approach based on coupled oscillators: an application in demand side management with photovoltaic distributed generation

Esta Tesis aborda los problemas de eficiencia de las redes eléctrica desde el punto de vista del consumo. En particular, dicha eficiencia es mejorada mediante el suavizado de la curva de consumo agregado. Este objetivo de suavizado de consumo implica dos grandes mejoras en el uso de las redes eléctricas: i) a corto plazo, un mejor uso de la infraestructura existente y ii) a largo plazo, la reducción de la infraestructura necesaria para suplir las mismas necesidades energéticas. Además, esta Tesis se enfrenta a un nuevo paradigma energético, donde la presencia de generación distribuida está muy extendida en las redes eléctricas, en particular, la generación fotovoltaica (FV). Este tipo de fuente energética afecta al funcionamiento de la red, incrementando su variabilidad. Esto implica que altas tasas de penetración de electricidad de origen fotovoltaico es perjudicial para la estabilidad de la red eléctrica. Esta Tesis trata de suavizar la curva de consumo agregado considerando esta fuente energética. Por lo tanto, no sólo se mejora la eficiencia de la red eléctrica, sino que también puede ser aumentada la penetración de electricidad de origen fotovoltaico en la red. Esta propuesta conlleva grandes beneficios en los campos económicos, social y ambiental. Las acciones que influyen en el modo en que los consumidores hacen uso de la electricidad con el objetivo producir un ahorro energético o un aumento de eficiencia son llamadas Gestión de la Demanda Eléctrica (GDE). Esta Tesis propone dos algoritmos de GDE diferentes para cumplir con el objetivo de suavizado de la curva de consumo agregado. La diferencia entre ambos algoritmos de GDE reside en el marco en el cual estos tienen lugar: el marco local y el marco de red. Dependiendo de este marco de GDE, el objetivo energético y la forma en la que se alcanza este objetivo son diferentes. En el marco local, el algoritmo de GDE sólo usa información local. Este no tiene en cuenta a otros consumidores o a la curva de consumo agregado de la red eléctrica. Aunque esta afirmación pueda diferir de la definición general de GDE, esta vuelve a tomar sentido en instalaciones locales equipadas con Recursos Energéticos Distribuidos (REDs). En este caso, la GDE está enfocada en la maximización del uso de la energía local, reduciéndose la dependencia con la red. El algoritmo de GDE propuesto mejora significativamente el auto-consumo del generador FV local. Experimentos simulados y reales muestran que el auto-consumo es una importante estrategia de gestión energética, reduciendo el transporte de electricidad y alentando al usuario a controlar su comportamiento energético. Sin embargo, a pesar de todas las ventajas del aumento de auto-consumo, éstas no contribuyen al suavizado del consumo agregado. Se han estudiado los efectos de las instalaciones locales en la red eléctrica cuando el algoritmo de GDE está enfocado en el aumento del auto-consumo. Este enfoque puede tener efectos no deseados, incrementando la variabilidad en el consumo agregado en vez de reducirlo. Este efecto se produce porque el algoritmo de GDE sólo considera variables locales en el marco local. Los resultados sugieren que se requiere una coordinación entre las instalaciones. A través de esta coordinación, el consumo debe ser modificado teniendo en cuenta otros elementos de la red y buscando el suavizado del consumo agregado. En el marco de la red, el algoritmo de GDE tiene en cuenta tanto información local como de la red eléctrica. En esta Tesis se ha desarrollado un algoritmo autoorganizado para controlar el consumo de la red eléctrica de manera distribuida. El objetivo de este algoritmo es el suavizado del consumo agregado, como en las implementaciones clásicas de GDE. El enfoque distribuido significa que la GDE se realiza desde el lado de los consumidores sin seguir órdenes directas emitidas por una entidad central. Por lo tanto, esta Tesis propone una estructura de gestión paralela en lugar de una jerárquica como en las redes eléctricas clásicas. Esto implica que se requiere un mecanismo de coordinación entre instalaciones. Esta Tesis pretende minimizar la cantidad de información necesaria para esta coordinación. Para lograr este objetivo, se han utilizado dos técnicas de coordinación colectiva: osciladores acoplados e inteligencia de enjambre. La combinación de estas técnicas para llevar a cabo la coordinación de un sistema con las características de la red eléctrica es en sí mismo un enfoque novedoso. Por lo tanto, este objetivo de coordinación no es sólo una contribución en el campo de la gestión energética, sino también en el campo de los sistemas colectivos. Los resultados muestran que el algoritmo de GDE propuesto reduce la diferencia entre máximos y mínimos de la red eléctrica en proporción a la cantidad de energía controlada por el algoritmo. Por lo tanto, conforme mayor es la cantidad de energía controlada por el algoritmo, mayor es la mejora de eficiencia en la red eléctrica. Además de las ventajas resultantes del suavizado del consumo agregado, otras ventajas surgen de la solución distribuida seguida en esta Tesis. Estas ventajas se resumen en las siguientes características del algoritmo de GDE propuesto: • Robustez: en un sistema centralizado, un fallo o rotura del nodo central provoca un mal funcionamiento de todo el sistema. La gestión de una red desde un punto de vista distribuido implica que no existe un nodo de control central. Un fallo en cualquier instalación no afecta el funcionamiento global de la red. • Privacidad de datos: el uso de una topología distribuida causa de que no hay un nodo central con información sensible de todos los consumidores. Esta Tesis va más allá y el algoritmo propuesto de GDE no utiliza información específica acerca de los comportamientos de los consumidores, siendo la coordinación entre las instalaciones completamente anónimos. • Escalabilidad: el algoritmo propuesto de GDE opera con cualquier número de instalaciones. Esto implica que se permite la incorporación de nuevas instalaciones sin afectar a su funcionamiento. • Bajo coste: el algoritmo de GDE propuesto se adapta a las redes actuales sin requisitos topológicos. Además, todas las instalaciones calculan su propia gestión con un bajo requerimiento computacional. Por lo tanto, no se requiere un nodo central con un alto poder de cómputo. • Rápido despliegue: las características de escalabilidad y bajo coste de los algoritmos de GDE propuestos permiten una implementación rápida. No se requiere una planificación compleja para el despliegue de este sistema. ABSTRACT This Thesis addresses the efficiency problems of the electrical grids from the consumption point of view. In particular, such efficiency is improved by means of the aggregated consumption smoothing. This objective of consumption smoothing entails two major improvements in the use of electrical grids: i) in the short term, a better use of the existing infrastructure and ii) in long term, the reduction of the required infrastructure to supply the same energy needs. In addition, this Thesis faces a new energy paradigm, where the presence of distributed generation is widespread over the electrical grids, in particular, the Photovoltaic (PV) generation. This kind of energy source affects to the operation of the grid by increasing its variability. This implies that a high penetration rate of photovoltaic electricity is pernicious for the electrical grid stability. This Thesis seeks to smooth the aggregated consumption considering this energy source. Therefore, not only the efficiency of the electrical grid is improved, but also the penetration of photovoltaic electricity into the grid can be increased. This proposal brings great benefits in the economic, social and environmental fields. The actions that influence the way that consumers use electricity in order to achieve energy savings or higher efficiency in energy use are called Demand-Side Management (DSM). This Thesis proposes two different DSM algorithms to meet the aggregated consumption smoothing objective. The difference between both DSM algorithms lie in the framework in which they take place: the local framework and the grid framework. Depending on the DSM framework, the energy goal and the procedure to reach this goal are different. In the local framework, the DSM algorithm only uses local information. It does not take into account other consumers or the aggregated consumption of the electrical grid. Although this statement may differ from the general definition of DSM, it makes sense in local facilities equipped with Distributed Energy Resources (DERs). In this case, the DSM is focused on the maximization of the local energy use, reducing the grid dependence. The proposed DSM algorithm significantly improves the self-consumption of the local PV generator. Simulated and real experiments show that self-consumption serves as an important energy management strategy, reducing the electricity transport and encouraging the user to control his energy behavior. However, despite all the advantages of the self-consumption increase, they do not contribute to the smooth of the aggregated consumption. The effects of the local facilities on the electrical grid are studied when the DSM algorithm is focused on self-consumption maximization. This approach may have undesirable effects, increasing the variability in the aggregated consumption instead of reducing it. This effect occurs because the algorithm only considers local variables in the local framework. The results suggest that coordination between these facilities is required. Through this coordination, the consumption should be modified by taking into account other elements of the grid and seeking for an aggregated consumption smoothing. In the grid framework, the DSM algorithm takes into account both local and grid information. This Thesis develops a self-organized algorithm to manage the consumption of an electrical grid in a distributed way. The goal of this algorithm is the aggregated consumption smoothing, as the classical DSM implementations. The distributed approach means that the DSM is performed from the consumers side without following direct commands issued by a central entity. Therefore, this Thesis proposes a parallel management structure rather than a hierarchical one as in the classical electrical grids. This implies that a coordination mechanism between facilities is required. This Thesis seeks for minimizing the amount of information necessary for this coordination. To achieve this objective, two collective coordination techniques have been used: coupled oscillators and swarm intelligence. The combination of these techniques to perform the coordination of a system with the characteristics of the electric grid is itself a novel approach. Therefore, this coordination objective is not only a contribution in the energy management field, but in the collective systems too. Results show that the proposed DSM algorithm reduces the difference between the maximums and minimums of the electrical grid proportionally to the amount of energy controlled by the system. Thus, the greater the amount of energy controlled by the algorithm, the greater the improvement of the efficiency of the electrical grid. In addition to the advantages resulting from the smoothing of the aggregated consumption, other advantages arise from the distributed approach followed in this Thesis. These advantages are summarized in the following features of the proposed DSM algorithm: • Robustness: in a centralized system, a failure or breakage of the central node causes a malfunction of the whole system. The management of a grid from a distributed point of view implies that there is not a central control node. A failure in any facility does not affect the overall operation of the grid. • Data privacy: the use of a distributed topology causes that there is not a central node with sensitive information of all consumers. This Thesis goes a step further and the proposed DSM algorithm does not use specific information about the consumer behaviors, being the coordination between facilities completely anonymous. • Scalability: the proposed DSM algorithm operates with any number of facilities. This implies that it allows the incorporation of new facilities without affecting its operation. • Low cost: the proposed DSM algorithm adapts to the current grids without any topological requirements. In addition, every facility calculates its own management with low computational requirements. Thus, a central computational node with a high computational power is not required. • Quick deployment: the scalability and low cost features of the proposed DSM algorithms allow a quick deployment. A complex schedule of the deployment of this system is not required.

Transmitter-side antennas correlation in SVD-assisted MIMO systems

MIMO techniques allow increasing wireless channel performance by decreasing the BER and increasing the channel throughput and in consequence are included in current mobile communication standards. MIMO techniques are based on benefiting the existence of multipath in wireless communications and the application of appropriate signal processing techniques. The singular value decomposition (SVD) is a popular signal processing technique which, based on the perfect channel state information (PCSI) knowledge at both the transmitter and receiver sides, removes inter-antenna interferences and improves channel performance. Nevertheless, the proximity of the multiple antennas at each front-end produces the so called antennas correlation effect due to the similarity of the various physical paths. In consequence, antennas correlation drops the MIMO channel performance. This investigation focuses on the analysis of a MIMO channel under transmitter-side antennas correlation conditions. First, antennas correlation is analyzed and characterized by the correlation coefficients. The analysis describes the relation between antennas correlation and the appearance of predominant layers which significantly affect the channel performance. Then, based on the SVD, pre- and post-processing is applied to remove inter-antenna interferences. Finally, bit- and power allocation strategies are applied to reach the best performance. The resulting BER reveals that antennas correlation effect diminishes the channel performance and that not necessarily all MIMO layers must be activated to obtain the best performance.

Side effects of modern pesticides on adults of the predatory mite Amblyseius swirskii (Athias-Henriot) (Acari: Phytoseiidae) under laboratory conditions

Amblyseius swirskii (Athias-Henriot) is a polyphagous predatory mite which feeds on pollen and small arthropod preys like whiteflies, thrips and mites. This species is widely used in IPM programs in greenhouses, being essential for its success, to obtain information about the non target effects of the pesticides currently used in those crops where the mite is artificially released. This work describes a laboratory contact residual test for evaluating lethal (mortality after 72 hour exposure to fresh residues) and sublethal effects (fecundity and fertility of the surviving mites) of eleven modern pesticides to adults of A. swirskii. Spiromesifen is lipogenesis inhibitor; flonicamid a selective feeding inhibitor with a mode of action not totally known; flubendiamide a modulator of the rhyanodin receptor, sulfoxaflor has a complex mode of action not totally ascertained; metaflumizone is a voltage dependent sodium channel blocker; methoxyfenozide is an IGR, spirotetramat inhibits lipids; abamectin and emamectin activate the Cl- channel; spinosad is a neurotix naturalyte and deltamethrin a pyrethroid used as positive standard. Selected pesticides are effective against different key pests present in horticultural crop areas and were always applied at the maximum field recommended concentration in Spain if registered, or at the concentration recommended by the supplier. Out of the tested pesticides, spiromesifen, flonicamid, flubendiamide, sulfoxaflor, metaflumizone, methoxyfenozide and spirotetramat were harmless to adults of the predatory mite (IOBC toxicity class 1). The rest of pesticides exhibited some negative effects: emamectin was slightly harmful (IOBC 2), deltamethrin moderately harmful (IOBC 3) and spinosad and abamectin harmful (IOBC 4). Further testing under more realistic conditions is needed for those pesticides having some harmful effect on the mite prior deciding their joint use or not. Key words: Amblyseius swirskii, adults, laboratory, residual test, spiromesifen, flonicamid, flubendiamide, sulfoxaflor, metaflumizone, methoxyfenozide, spirotetramat, emamectin, deltamethrin, abamectin, spinosad.

The N-terminal domain of a K+ channel β subunit increases the rate of C-type inactivation from the cytoplasmic side of the channel

Voltage-gated K+ channels are complexes of membrane-bound, ion-conducting α and cytoplasmic ancillary (β) subunits. The primary physiologic effect of coexpression of α and β subunits is to increase the intrinsic rate of inactivation of the α subunit. For one β subunit, Kvβ1.1, inactivation is enhanced through an N-type mechanism. A second β subunit, Kvβ1.2, has been shown to increase inactivation, but through a distinct mechanism. Here we show that the degree of enhancement of Kvβ1.2 inactivation is dependent on the amino acid composition in the pore mouth of the α subunit and the concentration of extracellular K+. Experimental conditions that promote C-type inactivation also enhance the stimulation of inactivation by Kvβ1.2, showing that this β subunit directly stimulates C-type inactivation. Chimeric constructs containing just the nonconserved N-terminal region of Kvβ1.2 fused with an α subunit behave in a similar fashion to coexpressed Kvβ1.2 and α subunit. This shows that it is the N-terminal domain of Kvβ1.2 that mediates the increase in C-type inactivation from the cytoplasmic side of the pore. We propose a model whereby the N terminus of Kvβ1.2 acts as a weakly binding “ball” domain that associates with the intracellular vestibule of the α subunit to effect a conformational change leading to enhancement of C-type inactivation.

Involvement of a cytosine side chain in proton transfer in the rate-determining step of ribozyme self-cleavage

Ribozymes of hepatitis delta virus have been proposed to use an active-site cytosine as an acid-base catalyst in the self-cleavage reaction. In this study, we have examined the role of cytosine in more detail with the antigenomic ribozyme. Evidence that proton transfer in the rate-determining step involved cytosine 76 (C76) was obtained from examining cleavage activity of the wild-type and imidazole buffer-rescued C76-deleted (C76Δ) ribozymes in D2O and H2O. In both reactions, a similar kinetic isotope effect and shift in the apparent pKa indicate that the buffer is functionally substituting for the side chain in proton transfer. Proton inventory of the wild-type reaction supported a mechanism of a single proton transfer at the transition state. This proton transfer step was further characterized by exogenous base rescue of a C76Δ mutant with cytosine and imidazole analogues. For the imidazole analogues that rescued activity, the apparent pKa of the rescue reaction, measured under kcat/KM conditions, correlated with the pKa of the base. From these data a Brønsted coefficient (β) of 0.51 was determined for the base-rescued reaction of C76Δ. This value is consistent with that expected for proton transfer in the transition state. Together, these data provide strong support for a mechanism where an RNA side chain participates directly in general acid or general base catalysis of the wild-type ribozyme to facilitate RNA cleavage.

Template-nucleated alanine-lysine helices are stabilized by position-dependent interactions between the lysine side chain and the helix barrel.

The helicity in water has been determined for several series of alanine-rich peptides that contain single lysine residues and that are N-terminally linked to a helix-inducing and reporting template termed Ac-Hel1. The helix-propagating constant for alanine (sAla value) that best fits the properties of these peptides lies in the range of 1.01-1.02, close to the value reported by Scheraga and coworkers [Wojcik, J., Altmann, K.-H. & Scheraga, H.A. (1990) Biopolymers 30, 121-134], but significantly lower than the value assigned by Baldwin and coworkers [Chakrabartty, A., Kortemme, T. & Baldwin, R.L. (1994) Protein Sci. 3,843-852]. From a study of conjugates Ac-Hel1-Ala(n)-Lys-Ala(m)-NH2 and analogs in which the methylene portion of the lysine side chain is truncated, we find that the unusual helical stability of Ala(n)Lys peptides is controlled primarily by interactions of the lysine side chain with the helix barrel, and only passively by the alanine matrix. Using 1H NMR spectroscopy, we observe nuclear Overhauser effect crosspeaks consistent with proton-proton contacts expected for these interactions.

Mice deficient in the orphan receptor steroidogenic factor 1 lack adrenal glands and gonads but express P450 side-chain-cleavage enzyme in the placenta and have normal embryonic serum levels of corticosteroids.

The orphan nuclear receptor steroidogenic factor 1 (SF-1) is expressed in the adrenal cortex and gonads and regulates the expression of several P450 steroid hydroxylases in vitro. We examined the role of SF-1 in the adrenal glands and gonads in vivo by a targeted disruption of the mouse SF-1 gene. All SF-1-deficient mice died shortly after delivery. Their adrenal glands and gonads were absent, and persistent Mullerian structures were found in all genotypic males. While serum levels of corticosterone in SF-1-deficient mice were diminished, levels of adrenocorticotropic hormone (ACTH) were elevated, consistent with intact pituitary corticotrophs. Intrauterine survival of SF-1-deficient mice appeared normal, and they had normal serum level of corticosterone and ACTH, probably reflecting transplacental passage of maternal steroids. We tested whether SF-1 is required for P450 side-chain-cleavage enzyme (P450scc) expression in the placenta, which expresses both SF-1 and P450scc, and found that in contrast to its strong activation of the P450scc gene promoter in vitro, the absence of SF-1 had no effect on P450scc mRNA levels in vivo. Although the region targeted by our disruption is shared by SF-1 and by embryonal long terminal repeat-binding protein (ELP), a hypothesized alternatively spliced product, we believe that the observed phenotype reflects absent SF-1 alone, as PCR analysis failed to detect ELP transcripts in any mouse tissue, and sequences corresponding to ELP are not conserved across species. These results confirm that SF-1 is an important regulator of adrenal and gonadal development, but its regulation of steroid hydroxylase expression in vivo remains to be established.

Inhibitory effect of 9-(2-phosphonylmethoxyethyl)adenine on visna virus infection in lambs: a model for in vivo testing of candidate anti-human immunodeficiency virus drugs.

The acyclic nucleoside phosphonate analog 9-(2-phosphonylmethoxyethyl)adenine (PMEA) was recently found to be effective as an inhibitor of visna virus replication and cytopathic effect in sheep choroid plexus cultures. To study whether PMEA also affects visna virus infection in sheep, two groups of four lambs each were inoculated intracerebrally with 10(6.3) TCID50 of visna virus strain KV1772 and treated subcutaneously three times a week with PMEA at 10 and 25 mg/kg, respectively. The treatment was begun on the day of virus inoculation and continued for 6 weeks. A group of four lambs were infected in the same way but were not treated. The lambs were bled weekly or biweekly and the leukocytes were tested for virus. At 7 weeks after infection, the animals were sacrificed, and cerebrospinal fluid (CSF) and samples of tissue from various areas of the brain and from lungs, spleen, and lymph nodes were collected for isolation of virus and for histopathologic examination. The PMEA treatment had a striking effect on visna virus infection, which was similar for both doses of the drug. Thus, the frequency of virus isolations was much lower in PMEA-treated than in untreated lambs. The difference was particularly pronounced in the blood, CSF, and brain tissue. Furthermore, CSF cell counts were much lower and inflammatory lesions in the brain were much less severe in the treated lambs than in the untreated controls. The results indicate that PMEA inhibits the propagation and spread of visna virus in infected lambs and prevents brain lesions, at least during early infection. The drug caused no noticeable side effects during the 6 weeks of treatment.

Efficient in vivo antitumor effect of an immunotoxin based on ribotoxin α-sarcin in nude mice bearing human colorectal cancer xenografts

Tagging of RNases, such as the ribotoxin α-sarcin, with the variable domains of antibodies directed to surface antigens that are selectively expressed on tumor cells endows cellular specificity to their cytotoxic action. A recombinant single-chain immunotoxin based on the ribotoxin α-sarcin (IMTXA33αS), produced in the generally regarded as safe (GRAS) yeast Pichia pastoris, has been recently described as a promising candidate for the treatment of colorectal cancer cells expressing the glycoprotein A33 (GPA33) antigen, due to its high specific and effective cytotoxic effect on in vitro assays against targeted cells. Here we report the in vivo antitumor effectiveness of this immunotoxin on nude mice bearing GPA33-positive human colon cancer xenografts. Two sets of independent assays were performed, including three experimental groups: control (PBS) and treatment with two different doses of immunotoxin (50 or 100 μg/ injection) (n = 8). Intraperitoneal administration of IMTXA33αS resulted in significant dose-dependent tumor growth inhibition. In addition, the remaining tumors excised from immunotoxin-treated mice showed absence of the GPA33 antigen and a clear inhibition of angiogenesis and proliferative capacity. No signs of immunotoxin-induced pathological changes were observed from specimens tissues.Overall these results show efficient and selective cytotoxic action on tumor xenografts, combined with the lack of severe side effects, suggesting that IMTXA33αS is a potential therapeutic agent against colorectal cancer.

Aberrant protective force generation during neural provocation testing and the effect of treatment in patients with neurogenic cervicobrachial pain

Background: Observation of the occurrence of protective muscle activity is advocated in assessment of the peripheral nervous system by means of neural provocation tests. However, no studies have yet demonstrated abnormal force generation in a patient population. Objectives: To analyze whether aberrations in shoulder girdle-elevation force during neural tissue provocation testing for the median nerve (NTPTI) can be demonstrated, and whether possible aberrations can be normalized following cervical mobilization. Study Design: A single-blind randomized comparative controlled study. Setting: Laboratory setting annex in a manual therapy teaching practice. Participants: Twenty patients with unilateral or bilateral neurogenic cervicobrachial pain. Methods: During the NTPTI, we used a load cell and electrogoniometer to record continuously the shoulder-girdle elevation force in relation to the available range of elbow extension. Following randomization, we analyzed the immediate treatment effects of a cervical contralateral lateral glide mobilization technique (experimental group) and therapeutic ultrasound (control group). Results: On the involved side, the shoulder-girdle elevation force occur-red earlier, and the amount of force at the end of the test was substantially, though not significantly, greater than that on the uninvolved side at the corresponding range of motion. Together with a significant reduction in pain perception after cervical mobilization, a clear tendency toward normalization of the force curve could be observed, namely, a significant decrease in force generation and a delayed onset. The control group demonstrated no differences. Conclusions: Aberrations in force generation during neural, provocation testing are present in patients with neurogenic pain and can be normalized with appropriate treatment modalities.