Analysis and design of multirate synchronous sampling schemes for sparse multiband signals

We consider the problem of developing efficient sampling schemes for multiband sparse signals. Previous results on multicoset sampling implementations that lead to universal sampling patterns (which guarantee perfect reconstruction), are based on a set of appropriate interleaved analog to digital converters, all of them operating at the same sampling frequency. In this paper we propose an alternative multirate synchronous implementation of multicoset codes, that is, all the analog to digital converters in the sampling scheme operate at different sampling frequencies, without need of introducing any delay. The interleaving is achieved through the usage of different rates, whose sum is significantly lower than the Nyquist rate of the multiband signal. To obtain universal patterns the sampling matrix is formulated and analyzed. Appropriate choices of the parameters, that is the block length and the sampling rates, are also proposed.

Comparison of existing formulae for estimating the overtopping rate in harbour breakwaters

The research that is summarized in this article, resultant of diverse studies realized in the CEDEX, has for object a comparative analysis of methods of overtopping rates developed by different authors. For that, the summary was realized first and the analysis of the existing formulations to estimate the rate of overtopping on rubble mound and vertical breakwaters. Later, there was carried out the contrast of the above mentioned formulations by the results obtained in a serie of hydraulic model tests of the Hydraulic Research Laboratory (the Center of Studies of Ports and Coasts of the CEDEX, Madrid, Spain).

Integration of congestion pricing and intertemporal preferences rate integration in social welfare function

Many researchers have used theoretical or empirical measures to assess social benefits in transport policy implementation. However, few have measured social benefits by using discount rates, including the intertemporal preference rate of users, the private investment discount rate, and the intertemporal preference rate of the government. In general, the social discount rate used is the same for all social actors. This paper aims to assess a new method by integrating different types of discount rates belonging to different social actors to measure the real benefits of each actor in the short term, medium term, and long term. A dynamic simulation is provided by a strategic land use and transport interaction model. The method was tested by optimizing a cordon toll scheme in Madrid, Spain. Socioeconomic efficiency and environmental criteria were considered. On the basis of the modified social welfare function, the effects on the measure of social benefits were estimated and compared with the classical welfare function measures. The results show that the use of more suitable discount rates for each social actor had an effect on the selection and definition of optimal strategy of congestion pricing. The usefulness of the measure of congestion toll declines more quickly over time. This result could be the key to understanding the relationship between transport system policies and the distribution of social actors? benefits in a metropolitan context.

Contraction speed of the actomyosin cytoskeleton in the absence of the cell membrane

The contraction of the actomyosin cytoskeleton, which is produced by the sliding of myosin II along actin filaments, drives important cellular activities such as cytokinesis and cell migration. To explain the contraction velocities observed in such physiological processes, we have studied the contraction of intact cytoskeletons of Dictyostelium discoideum cells after removing the plasma membrane using Triton X-100. The technique developed in this work allows for the quantitative measurement of contraction rates of individual cytoskeletons. The relationship of the contraction rates with forces was analyzed using three different myosins with different in vitro sliding velocities. The cytoskeletons containing these myosins were always contractile and the contraction rate was correlated with the sliding velocity of the myosins. However, the values of the contraction rate were two to three orders of magnitude slower than expected from the in vitro sliding velocities of the myosins, presumably due to internal and external resistive forces. The contraction process also depended on actin cross-linking proteins. The lack of α-actinin increased the contraction rate 2-fold and reduced the capacity of the cytoskeleton to retain internal materials, while the lack of filamin resulted in the ATP-dependent disruption of the cytoskeleton. Interestingly, the myosin-dependent contraction rate of intact contractile rings is also reportedly much slower than the in vitro sliding velocity of myosin, and is similar to the contraction rates of cytoskeletons (different by only 2–3 fold), suggesting that the contraction of intact cells and cytoskeletons is limited by common mechanisms.

Influencia de un nuevo marco jurídico en la competitividad del sistema portuario español

El sistema portuario español movió en el año 2013 aproximadamente 458,54 millones de toneladas, 13,8 millones de TEUs, con un total de 131.128 buques que accedieron a puerto para el conjunto de las 28 Autoridades Portuarias. Con el 62% de las exportaciones y el 86% de las importaciones realizadas por vía marítima, una rentabilidad del 2,34 %, muy cerca del objetivo del 2,5 % de rentabilidad media annual establecida legalmente, y una cifra de negocios aproximada de 1.028 millones de euros equivalentes al 1,1 % del PIB que genera un empleo directo e indirecto vinculado de 145.000 personas, concluimos que estamos hablando de un sector estratégico para la economía del país. Desde hace décadas, en muchos puertos del mundo se han venido desarrollando terminales “hub” o de concentración y distribución de cargas. Las navieras concentran entre este tipo de terminales sus líneas transoceánicas con buques de enormes dimensiones y capacidad de carga para producir los tránsitos de contenedores desde estas líneas a otras líneas llamadas “feeder”, con buques de menor tamaño que enlazan el “hub” con los puertos de su área marítima de influencia. La excepcional ubicación geoestratégica de España, con aproximadamente ocho mil kilómetros de costa, ha originado que los puertos españoles de mayor dimensión aspiren a incorporarse a esta red marítima internacional de contenedores y determina que en nuestro sistema portuario los movimientos de contenedores de tránsito tengan gran importancia. Sin embargo, la crisis económica ha tenido un efecto decisivo en el sector marítimo, determinando una lucha feroz entre todos los puertos, nacionales e internacionales, por captar este tipo de tráficos, lo que origina una búsqueda de las compañías navieras de puertos cada vez más eficientes en términos calidad/coste del servicio. La entrada en vigor del Texto Refundido de la Ley de Puertos y la piedra angular de su reforma, la Ley 33/2010, plantea como objetivo principal la mejora de la competitividad del sistema portuario español y liderar su recuperación, ofreciendo unas condiciones de entorno favorables a los puertos españoles que acaben por incentivar la captación de tráficos e inversión privada a través de una oferta de servicios e infraestructura de calidad y a precios competitivos que consoliden su posición dentro del tráfico marítimo mundial. Surge, por tanto, la conveniencia de investigar la influencia de las medidas propuestas por dicha norma legal y las soluciones ofrecidas a las demandas de un sector considerado estratégico para la economía del país, y cuya resolución se considera imprescindible para consolidar su recuperación. Por eso, se han analizado los aspectos más importantes de la reforma mediante la realización de un resumen ejecutivo y se ha estudiado la influencia de las medidas que incorpora desde el punto de vista de tres factores, que previamente se han considerado como fundamentales para la recuperación del sistema portuario español, y que históricamente habían sido demandados por el mismo, como son, en primer lugar, un progresivo sistema de flexibilización tributaria que permitiera a los puertos españoles ganar en términos de competitividad respecto a otros modelos portuarios mucho más flexibles en materia tarifaria, en segundo lugar, una necesaria liberalización del régimen de prestación de los servicios portuarios que posibilite el libre acceso a cualquier interesado en su prestación y, en último lugar, el progresivo abaratamiento de los costes inherentes a dichos servicios, fundamentalmente la manipulación de mercancías. Con posterioridad se ha investigado el trámite parlamentario al que se ha sometido la ley, fruto del enorme consenso alcanzado entre las dos principales fuerzas políticas del país, que determinó que se presentaran más de 700 enmiendas al proyecto original, y en algunos casos, se ha prestado especial atención a determinadas enmiendas que se consideran, en opinión de este investigador, novedosas y aventuradas, razón por la cual quizás no fueron incorporadas definitivamente al texto legal. Y se han analizado las principales demandas y aportaciones extraídas de la Sesión Informativa sobre la tramitación del entonces proyecto de ley ofrecida por la Comisión de Fomento del Congreso de los Diputados a los principales representantes del sector, comunidad portuaria, universidad y sindicatos. Siendo conscientes de la incidencia que tiene el servicio portuario de manipulación de mercancías en el paso de la mercancía por el puerto, se ha hecho una referencia concreta al peculiar régimen jurídico y laboral del personal vinculado al servicio. Avanzamos que las características de la relación laboral especial, y su peculiar régimen jurídico, con una dualidad de relaciones laborales, tiene una influencia decisiva en la nómina del trabajador que se repercute en los usuarios del servicio, fundamentalmente el naviero y el operador de la terminal, que en definitiva, incide en la competitividad del puerto. Y se ha constatado el auge aperturista de numerosas legislaciones portuarias europeas, prestando especial atención al proyecto frustrado de liberalización de los servicios portuarios en la Unión Europea de la conocida como Directiva Loyola de Palacio del año 2003 y al Libro Blanco de Transportes del año 2011. Así como a las deficiencias advertidas por el Dictamen de la Comisión Europea de fecha 27/09/2012 en relación al régimen jurídico del servicio portuario de manipulación de mercancías, que lo considera disconforme y contrario con las normas de libertad de establecimiento en Europa y que amenaza con una previsible reforma unilateral de la legislación portuaria española, a instancias europeas. Bajo este planteamiento, se ha procedido a analizar el marco de prestación de dichos servicios desde el punto de vista de la propia comunidad portuaria. Inicialmente, a través de un estudio de fuerzas de la competitividad del sector de los servicios portuarios en el sistema portuario español que nos permitirá trazar un mapa estratégico del mismo a través del “Modelo de las Cinco Fuerzas de Porter” concluyendo, que el poder de los prestadores de servicios portuarios como proveedores de los mismos, fundamentalmente en la manipulación de mercancías, es máximo, con un único colectivo, los estibadores portuarios, que al amparo de la normativa legal vigente tienen la exclusividad de su prestación. Dichas circunstancias restan competitividad al sistema frente a alternativas portuarias más flexibles y desincentivan la inversión privada. Y, en segundo lugar, mediante un proceso participativo en distintas encuestas sobre el modelo legislativo y sobre el marco formativo del sector con los propios agentes afectados dentro de la comunidad portuaria, desde la triple perspectiva de la vertiente pública que representan las Autoridades Portuarias, como gestores de las infraestructuras, la vertiente privada que representan los usuarios y prestadores de servicios, como principal cliente del puerto y desde el punto de vista de la propia mano de obra portuaria materializada en la representación sindical de dichos trabajadores. Los resultados nos permitirán concluir, respectivamente, la incidencia del servicio portuario mercancía por el puerto, por representar más de la mitad de los costes. Así como la aspiración de los trabajadores adscritos a dicho servicio de consolidar un título formativo que unifique y potencie su capacitación profesional, circunstancia esta última, también demandada por toda comunidad portuaria. Analizadas las conclusiones extraídas en cada una de las líneas de investigación se han detectado una serie de ineficiencias dentro del mismo que dicho marco regulador no ha sabido resolver, por lo que se ha considerado la conveniencia de formular, como herramienta de ayuda a gestores del sistema portuario español, una relación de medidas que, en opinión de este investigador, se consideran necesarias para mejorar el régimen de prestación de los servicios portuarios y se ha propuesto un borrador de modificación del actual Texto Refundido que pueda servir de base para materializar una futura reforma legal. Las conclusiones obtenidas en la investigación deben sentar las bases de una profunda reflexión sobre la necesidad de encaminar, como alternativa a una previsible modificación a instancias europeas, una reforma legal que decididamente apueste por la competitividad del sistema portuario español desde el punto de vista de la liberalización de servicios, el abaratamiento de los costes de la estiba y la necesaria profesionalización de los trabajadores adscritos al servicio portuario de manipulación de mercancías. During 2013 the Spanish Port System moved nearly 458,54 million tons of freight, 13,8 million TEUs, involving a total of 131.128 ships for the 28 existing Port Authorities. With 62% of exports and 86% of imports made through sea transportation, a 2,34% profit, close to the 2,5% average annual profit goal legally established, revenues of 1.028 million € equivalent to a 1.1% of Spain’s GDP and a figure of 145.000 people a directly or indirectly employed we can conclude that maritime industry is undoubtedly one of the strategic and key sectors for the country’s economy. Since several decades many ports in the world have been increasingly developing “Hub” terminals, those which concentrate and distribute freight. Shipping companies place among these type of terminals their transoceanic sea liners along with huge dimension & capacity ships to make the container transit from these liners to other called “feeder” which are smaller freight ships that connect the “hub” with the ports within its maritime area of influence. Spain’s exceptional geostrategic location with over 8.000 km of coastline has originated that those big dimension Spanish ports aspire to become a part of a container international maritime network which also determines that transit container move is key within our port system. Nevertheless the economic crisis has had a decisive impact on the maritime sector originating a fierce battle between all ports, national and international ones, all of them fight against each other to catch this type of maritime traffic which triggers an ongoing shipping companies search in cost/service quality efficient ports. The cornerstone of the Restated Text of Port Law is Law 33/2010, which lays out as main goal the Spanish Port System competitiveness improvement and lead its recovery offering favorable environment conditions to Spanish ports which help encourage maritime traffic attraction and private investment through a wide offer of services, quality of infrastructure and competitive prices which can consolidate its positioning within the world’s maritime traffic. It is therefore key to investigate the influence of the measures proposed by the above mentioned law and also the solutions offered to the demands of a sector which is considered strategic for the country’s economy and which solution is essential to consolidate the recovery. It is because of this that the most important aspects of the reform have been analyzed through the making of an executive summary and it has also been studied the influence of the measures it includes from the point of view of three factors which have previously been considered as key for the Spanish port system recovery. The system has historically demanded a progressive tax flexibility, which would permit Spanish ports be more competitive compared to other port models much more flexible in rates, a necessary liberalization of the port service provision regime and last but not least, to cut the price of costs related to those services, mainly freight handling. Following this, the parliamentary process of the law has also been studied as a consequence of the vast consensus reached by the main political forces in the country which clearly determined that more than 700 amendments to the original project were presented. In some cases the focus has been on amendments which are adventurous and new, reason why they were finally not included to the final legal text. Being well aware of the importance that freight handling procedure has, I have made a specific reference to the legal and working framework of those employees related to this service. We conclude that the special working relationship, its different legal regime, along with the working relationship dualism has a big impact and decisive influence over the worker’s salary which also affects service users, mainly shipowners and terminal operators, having a bad effect on the port’s competitiveness. The above confirms the new opening trend of main European port laws with special attention to the frustrated European Union port services liberalization project, also known as Directive Loyola de Palacio (2003) and the White Paper on Transports (2011). It is important to highlight that the European Commission has also observed several deficiencies with regard to the freight handling port service Law Regime being in disagreement with it, considering it is against the free establishment rules in Europe. The Commission is likely to present a unilateral reform to the Spanish Port Law. Under this approach the service provision framework is being analyzed from the Port Community point of view. Initially the analysis will focus on the study of the competition forces within the port services industry in Spain, this will allow us to draw up an strategic map through “Porter’s Five Forces Model” concluding that the power of port services providers as freight handlers is maximum, with an only collective, stevedores, which has the exclusivity for their services. All these circumstances not only decrease the system’s competitiveness versus other more flexible but also restrain private investments. Secondly, through a participating procedure in different surveys about the legislative model and about the training framework with the affected agents within the port community, there is a triple perspective: Public point of view represented by Port Authorities as infrastructure managers, Private point of view represented by users and service suppliers as main Port’s customer and finally, port workforce, represented by union leaders. Results will let us conclude that freight handling service is the most critical port service and represents more than half of the costs. This service related workers aspire to obtain a training certificate that unifies and boosts their professional role which is also chased by the entire port community. Once conclusions have been analyzed for all research lines, several deficiencies have been found and the regulatory framework hasn’t yet been able to solve them, it has therefore been a series of necessary measures that help improve the port services provision regime. A new proposal to the Restated Law Text has been drafted as the first step to embrace a future legal reform. Conclusions obtained on the research should set the new basis of a deep reflection about the need to bent on a new legal reform which firmly bets on Spanish port system competitiveness from three key points of view, service liberalization, ship load cost reduction and professionalization of freight handling related workers.

Modeling of GRBAS perceptual evaluation using spectral features obtained from an auditory-based filterbank.

Perceptual voice evaluation according to the GRBAS scale is modelled using a linear combination of acoustic parameters calculated after a filter-bank analysis of the recorded voice signals. Modelling results indicate that for breathiness and asthenia more than 55% of the variance of perceptual rates can be explained by such a model, with only 4 latent variables. Moreover, the greatest part of the explained variance can be attributed to only one or two latent variables similarly weighted by all 5 listeners involved in the experiment. Correlation factors between actual rates and model predictions around 0.6 are obtained.

Pulsatile blood flow interaction with arterial walls of aorta : autoregulation and impedance pressure boundary condition and its biomedical applications

Para las decisiones urgentes sobre intervenciones quirúrgicas en el sistema cardiovascular se necesitan simulaciones computacionales con resultados fiables y que consuman un tiempo de cálculo razonable. Durante años los investigadores han trabajado en diversos métodos numéricos de cálculo que resulten atractivos para los cirujanos. Estos métodos, precisos pero costosos desde el punto de vista del coste computacional, crean un desajuste entre la oferta de los ingenieros que realizan las simulaciones y los médicos que operan en el quirófano. Por otra parte, los métodos de cálculo más simplificados reducen el tiempo de cálculo pero pueden proporcionar resultados no realistas. El objetivo de esta tesis es combinar los conceptos de autorregulación e impedancia del sistema circulatorio, la interacción flujo sanguíneo-pared arterial y modelos geométricos idealizados tridimensionales de las arterias pero sin pérdida de realismo, con objeto de proponer una metodología de simulación que proporcione resultados correctos y completos, con tiempos de cálculo moderados. En las simulaciones numéricas, las condiciones de contorno basadas en historias de presión presentan inconvenientes por ser difícil conocerlas con detalle, y porque los resultados son muy sensibles ante pequeñas variaciones de dichas historias. La metodología propuesta se basa en los conceptos de autorregulación, para imponer la demanda de flujo aguas abajo del modelo en el ciclo cardiaco, y la impedancia, para representar el efecto que ejerce el flujo en el resto del sistema circulatorio sobre las arterias modeladas. De este modo las historias de presión en el contorno son resultados del cálculo, que se obtienen de manera iterativa. El método propuesto se aplica en una geometría idealizada del arco aórtico sin patologías y en otra geometría correspondiente a una disección Stanford de tipo A, considerando la interacción del flujo pulsátil con las paredes arteriales. El efecto de los tejidos circundantes también se incorpora en los modelos. También se hacen aplicaciones considerando la interacción en una geometría especifica de un paciente anciano que proviene de una tomografía computarizada. Finalmente se analiza una disección Stanford tipo B con tres modelos que incluyen la fenestración del saco. Clinicians demand fast and reliable numerical results of cardiovascular biomechanic simulations for their urgent pre-surgery decissions. Researchers during many years have work on different numerical methods in order to attract the clinicians' confidence to their colorful contours. Though precise but expensive and time-consuming methodologies create a gap between numerical biomechanics and hospital personnel. On the other hand, simulation simplifications with the aim of reduction in computational time may cause in production of unrealistic outcomes. The main objective of the current investigation is to combine ideas such as autoregulation, impedance, fluid-solid interaction and idealized geometries in order to propose a computationally cheap methodology without excessive or unrealistic simplifications. The pressure boundary conditions are critical and polemic in numerical simulations of cardiovascular system, in which a specific arterial site is of interest and the rest of the netwrok is neglected but represented by a boundary condition. The proposed methodology is a pressure boundary condition which takes advantage of numerical simplicity of application of an imposed pressure boundary condition on outlets, while it includes more sophisticated concepts such as autoregulation and impedance to gain more realistic results. Incorporation of autoregulation and impedance converts the pressure boundary conditions to an active and dynamic boundary conditions, receiving feedback from the results during the numerical calculations and comparing them with the physiological requirements. On the other hand, the impedance boundary condition defines the shapes of the pressure history curves applied at outlets. The applications of the proposed method are seen on idealized geometry of the healthy arotic arch as well as idealized Stanford type A dissection, considering the interaction of the arterial walls with the pulsatile blood flow. The effect of surrounding tissues is incorporated and studied in the models. The simulations continue with FSI analysis of a patient-specific CT scanned geometry of an old individual. Finally, inspiring of the statistic results of mortality rates in Stanford type B dissection, three models of fenestrated dissection sac is studied and discussed. Applying the developed boundary condition, an alternative hypothesis is proposed by the author with respect to the decrease in mortality rates in patients with fenestrations.

Measurement of community metabolism and significance in the coral reef CO2 source-sink debate

Two methods are commonly used to measure the community metabolism (primary production, respiration, and calcification) of shallow-water marine communities and infer air–sea CO2 fluxes: the pH-total alkalinity and pH-O2 techniques. The underlying assumptions of each technique are examined to assess the recent claim that the most widely used technique in coral reefs (pH-total alkalinity), may have provided spurious results in the past because of high rates of nitrification and release of phosphoric acid in the water column [Chisholm, J. R. M. & Barnes, D. J. (1998) Proc. Natl. Acad. Sci. USA 95, 6566–6569]. At least three lines of evidence suggest that this claim is not founded. First, the rate of nitrification required to explain the discrepancy between the two methods recently reported is not realistic as it is much higher than the rates measured in another reef system and greater than the highest rate measured in a marine environment. Second, fluxes of ammonium, nitrate, and phosphorus are not consistent with high rates of nitrification and release of phosphoric acid. Third, the consistency of the metabolic parameters obtained by using the two techniques is in good agreement in two sites recently investigated. The pH-total alkalinity technique therefore appears to be applicable in most coral reef systems. Consequently, the conclusion that most coral reef flats are sources of CO2 to the atmosphere does not need revision. Furthermore, we provide geochemical evidence that calcification in coral reefs, as well as in other calcifying ecosystems, is a long-term source of CO2 for the atmosphere.

The kinetic mechanism of myosin V

Myosin V is an unconventional myosin proposed to be processive on actin filaments, analogous to kinesin on a microtubule [Mehta, A. D., et al. (1999) Nature (London) 400, 590–593]. To ascertain the unique properties of myosin V that permit processivity, we undertook a detailed kinetic analysis of the myosin V motor. We expressed a truncated, single-headed myosin V construct that bound a single light chain to study its innate kinetics, free from constraints imposed by other regions of the molecule. The data demonstrate that unlike any previously characterized myosin a single-headed myosin V spends most of its kinetic cycle (>70%) strongly bound to actin in the presence of ATP. This kinetic tuning is accomplished by increasing several of the rates preceding strong binding to actin and concomitantly prolonging the duration of the strongly bound state by slowing the rate of ADP release. The net result is a myosin unlike any previously characterized, in that ADP release is the rate-limiting step for the actin-activated ATPase cycle. Thus, because of a number of kinetic adaptations, myosin V is tuned for processive movement on actin and will be capable of transporting cargo at lower motor densities than any other characterized myosin.

Mutation rates among RNA viruses

The rate of spontaneous mutation is a key parameter in modeling the genetic structure and evolution of populations. The impact of the accumulated load of mutations and the consequences of increasing the mutation rate are important in assessing the genetic health of populations. Mutation frequencies are among the more directly measurable population parameters, although the information needed to convert them into mutation rates is often lacking. A previous analysis of mutation rates in RNA viruses (specifically in riboviruses rather than retroviruses) was constrained by the quality and quantity of available measurements and by the lack of a specific theoretical framework for converting mutation frequencies into mutation rates in this group of organisms. Here, we describe a simple relation between ribovirus mutation frequencies and mutation rates, apply it to the best (albeit far from satisfactory) available data, and observe a central value for the mutation rate per genome per replication of μg ≈ 0.76. (The rate per round of cell infection is twice this value or about 1.5.) This value is so large, and ribovirus genomes are so informationally dense, that even a modest increase extinguishes the population.

A first-generation X-inactivation profile of the human X chromosome

In females, most genes on the X chromosome are generally assumed to be transcriptionally silenced on the inactive X as a result of X inactivation. However, particularly in humans, an increasing number of genes are known to “escape” X inactivation and are expressed from both the active (Xa) and inactive (Xi) X chromosomes; such genes reflect different molecular and epigenetic responses to X inactivation and are candidates for phenotypes associated with X aneuploidy. To identify genes that escape X inactivation and to generate a first-generation X-inactivation profile of the X, we have evaluated the expression of 224 X-linked genes and expressed sequence tags by reverse-transcription–PCR analysis of a panel of multiple independent mouse/human somatic cell hybrids containing a normal human Xi but no Xa. The resulting survey yields an initial X-inactivation profile that is estimated to represent ≈10% of all X-linked transcripts. Of the 224 transcripts tested here, 34 (three of which are pseudoautosomal) were expressed in as many as nine Xi hybrids and thus appear to escape inactivation. The genes that escape inactivation are distributed nonrandomly along the X; 31 of 34 such transcripts map to Xp, implying that the two arms of the X are epigenetically and/or evolutionarily distinct and suggesting that genetic imbalance of Xp may be more severe clinically than imbalance of Xq. A complete X-inactivation profile will provide information relevant to clinical genetics and genetic counseling and should yield insight into the genomic and epigenetic organization of the X chromosome.

Dynamics of a Chemoattractant Receptor in Living Neutrophils during ChemotaxisV⃞

Persistent directional movement of neutrophils in shallow chemotactic gradients raises the possibility that cells can increase their sensitivity to the chemotactic signal at the front, relative to the back. Redistribution of chemoattractant receptors to the anterior pole of a polarized neutrophil could impose asymmetric sensitivity by increasing the relative strength of detected signals at the cell’s leading edge. Previous experiments have produced contradictory observations with respect to receptor location in moving neutrophils. To visualize a chemoattractant receptor directly during chemotaxis, we expressed a green fluorescent protein (GFP)-tagged receptor for a complement component, C5a, in a leukemia cell line, PLB-985. Differentiated PLB-985 cells, like neutrophils, adhere, spread, and polarize in response to a uniform concentration of chemoattractant, and orient and crawl toward a micropipette containing chemoattractant. Recorded in living cells, fluorescence of the tagged receptor, C5aR–GFP, shows no apparent increase anywhere on the plasma membrane of polarized and moving cells, even at the leading edge. During chemotaxis, however, some cells do exhibit increased amounts of highly folded plasma membrane at the leading edge, as detected by a fluorescent probe for membrane lipids; this is accompanied by an apparent increase of C5aR–GFP fluorescence, which is directly proportional to the accumulation of plasma membrane. Thus neutrophils do not actively concentrate chemoattractant receptors at the leading edge during chemotaxis, although asymmetrical distribution of membrane may enrich receptor number, relative to adjacent cytoplasmic volume, at the anterior pole of some polarized cells. This enrichment could help to maintain persistent migration in a shallow gradient of chemoattractant.

Equilibrium distributions of microsatellite repeat length resulting from a balance between slippage events and point mutations

We describe and test a Markov chain model of microsatellite evolution that can explain the different distributions of microsatellite lengths across different organisms and repeat motifs. Two key features of this model are the dependence of mutation rates on microsatellite length and a mutation process that includes both strand slippage and point mutation events. We compute the stationary distribution of allele lengths under this model and use it to fit DNA data for di-, tri-, and tetranucleotide repeats in humans, mice, fruit flies, and yeast. The best fit results lead to slippage rate estimates that are highest in mice, followed by humans, then yeast, and then fruit flies. Within each organism, the estimates are highest in di-, then tri-, and then tetranucleotide repeats. Our estimates are consistent with experimentally determined mutation rates from other studies. The results suggest that the different length distributions among organisms and repeat motifs can be explained by a simple difference in slippage rates and that selective constraints on length need not be imposed.

Ecological study of reasons for sharp decline in mortality from ischaemic heart disease in Poland since 1991

Objective: To investigate the reasons for the decline in deaths attributed to ischaemic heart disease in Poland since 1991 after two decades of rising rates.

Trichostatin A reverses skewed expression of CD154, interleukin-10, and interferon-γ gene and protein expression in lupus T cells

In systemic lupus erythematosus (SLE), T helper cells exhibit increased and prolonged expression of cell-surface CD40 ligand (CD154), spontaneously overproduce interleukin-10 (IL-10), but underproduce interferon-gamma (IFN-γ). We tested the hypothesis that the imbalance of these gene products reflects skewed expression of CD154, IL-10, and IFN-γ genes. Here, we demonstrate that the histone deacetylase inhibitor, trichostatin A, significantly down-regulated CD154 and IL-10 and up-regulated IFN-γ gene expression in SLE T cells. This reversal corrected the aberrant expression of these gene products, thereby enhancing IFN-γ production and inhibiting IL-10 and CD154 expression. That trichostatin A can simultaneously reverse the skewed expression of multiple genes implicated in the immunopathogenesis of SLE suggests that this pharmacologic agent may be a candidate for the treatment of this autoimmune disease.