bluuebunny/crossref_metadata_2025 huggingface dataset:
Methods of plant breeding in the genome era
Authors: XU SHIZHONG , HU ZHIQIU
Published: March 2011

Methods of genomic value prediction are reviewed. The majority of the methods are related to mixed model methodology, either explicitly or implicitly, by treating systematic environmental effects as fixed and quantitative trait locus (QTL) effects as random. Six different methods are reviewed, including least squares (LS), ridge regression, Bayesian shrinkage, least absolute shrinkage and selection operator (Lasso), empirical Bayes and partial least squares (PLS). The LS and PLS methods are non-Bayesian because they do not require probability distributions for the data. The PLS method is introduced as a special dimension reduction scheme to handle high-density marker information. Theory and methods of cross-validation are described. The leave-one-out cross-validation approach is recommended for model validation. A working example is used to demonstrate the utility of genome selection (GS) in barley. The data set contained 150 double haploid lines and 495 DNA markers covering the entire barley genome, with an average marker interval of 2·23 cM. Eight quantitative traits were included in the analysis. GS using the empirical Bayesian method showed high predictability of the markers for all eight traits with a mean accuracy of prediction of 0·70. With traditional marker-assisted selection (MAS), the average accuracy of prediction was 0·59, giving an average gain of GS over MAS of 0·11. This study provided strong evidence that GS using marker information alone can be an efficient tool for plant breeding.
Statistical analysis of genetic interactions
Authors: YI NENGJUN
Published: March 2011

Many common human diseases and complex traits are highly heritable and influenced by multiple genetic and environmental factors. Although genome-wide association studies (GWAS) have successfully identified many disease-associated variants, these genetic variants explain only a small proportion of the heritability of most complex diseases. Genetic interactions (gene–gene and gene–environment) substantially contribute to complex traits and diseases and could be one of the main sources of the missing heritability. This paper provides an overview of the available statistical methods and related computer software for identifying genetic interactions in animal and plant experimental crosses and human genetic association studies. The main discussion falls under the three broad issues in statistical analysis of genetic interactions: the definition, detection and interpretation of genetic interactions. Recently developed methods based on modern techniques for high-dimensional data are reviewed, including penalized likelihood approaches and hierarchical models; the relationships between these methods are also discussed. I conclude this review by highlighting some areas of future research.
Genomic selection in livestock populations
Authors: GODDARD MICHAEL E. , HAYES BEN J. , MEUWISSEN THEO H. E.
Published: March 2011

Most traits of economic importance in livestock are either quantitative or complex. Despite considerable efforts, there has been only limited success in identifying the polymorphisms that cause variation in these traits. Nevertheless, selection based on estimated breeding values (BVs), calculated from data on phenotypic performance and pedigree has been very successful. Genomic tools, such as single nucleotide polymorphism (SNP) chips, have led to a new method of selection called ‘genomic selection’ in which dense SNP genotypes covering the genome are used to predict the BV. In this review we consider the statistical methodology for estimating BVs from SNP data, factors affecting the accuracy, the long-term response to genomic selection and the design of breeding programmes including the management of inbreeding.
Characterizing allelic association in the genome era
Authors: WEIR B. S. , LAURIE C. C.
Published: March 2011

Whole genome data are allowing the estimation of population genetic parameters with an accuracy not imagined 50 years ago. Variation in these parameters along the genome is being found empirically where once only approximate theoretical values were available. Along with increased information, however, has come the issue of multiple testing and the realization that high values of the coefficients of variation of quantities such as relatedness measures may make it difficult to draw inferences. This review concentrates on measures of allelic association within and between individuals and within and between populations.
Forum on Universalism and Relativism in Asian Studies Editor's Introduction
Authors: Buck David D.
Published: March 2011

How to establish and transmit understanding across the boundaries of language, geography, culture, and time lies at the very heart of Asian Studies. Ours is a highly refined form of cross-cultural activity, but one that places the highest value on this understanding. To engage in this activity, individuals undergo long periods of training to master other languages, to produce, and then to present their knowledge in certain rigorously defined forms. The scholar works in this way both to establish some particular understanding and then to transmit that understanding to other Asianists, students, various other specialists, and the public at large.
Patterns of Cousin Marriage in Rural Zhejiang and in Dream of the Red Chamber
Authors: Cooper Eugene , Zhang Meng
Published: March 2011

Dream of the red chamber has been analyzed and reanalyzed by thousands of Chinese commentators in the more than two centuries since it was written (e.g., Yu 1923; Hu 1940; Zhou 1953; He 1956; Liu 1956; Jiang 1959; Wu 1961; Wang 1983). Indeed, entire journals are devoted exclusively to the novel's analysis, and strictly original contributions to this vast literature are rare. However, Meng Zhang's comparison of the genealogical relations of the principal characters of the novel with Eugene Cooper's ethnographic data on twentieth-century Zhejiang, and the joint analysis of the results are informed by an anthropological consciousness uncommon to previous commentators. The analysis not only takes note of patterns of cousin marriage recognized by earlier commentators (e.g., Yu 1923; Zhou 1953; Wu 1961), but also discovers instances of several of the more obscure patterns noted by Cooper in his Zhejiang materials (Cooper, in press).
The asymptotic structure of a slender dragged viscous thread
Authors: BLOUNT MAURICE J. , LISTER JOHN R.
Published: March 2011

The behaviour of a viscous thread as it falls onto a moving belt is analysed in the asymptotic limit of a slender thread. While the bending resistance of a slender thread is small, its effects are dynamically important near the contact point with the belt, where it changes the curvature and orientation of the thread. Steady flows are shown to fall into one of three distinct regimes, depending on whether the belt is moving faster than, slower than or close to the same speed as the free-fall velocity of the thread. The key dynamical balances in each regime are explained and the role of bending stresses is found to be qualitatively different. The asymptotic solutions exhibit the ‘backward-facing heel’ observed experimentally for low belt speeds, and provide the leading-order corrections to the stretching catenary in theory previously developed for high belt speeds. The asymptotic stability of the thread to the onset of meandering is also analysed. It is shown that the entire thread, rather than the bending boundary layer alone, governs the stability. A balance between the destabilising reaction forces near the belt and the restoring force of gravity on the remainder of the thread determines the onset of meandering, and an analytic estimate for the meandering frequency is thereby obtained. At leading order, neutral stability occurs with the belt moving a little more slowly than the free-fall velocity of the thread, not when the lower part of the thread begins to be under compression, but when the horizontal reaction force at the belt begins to be slightly against the direction of belt motion. The onset of meandering is the heel ‘losing its balance’.
The dynamics of a vesicle in simple shear flow
Authors: ZHAO HONG , SHAQFEH ERIC S. G.
Published: March 2011

We have performed direct numerical simulation (DNS) of a lipid vesicle under Stokes flow conditions in simple shear flow. The lipid membrane is modelled as a two-dimensional incompressible fluid with Helfrich surface energy in response to bending deformation. A high-fidelity spectral boundary integral method is used to solve the flow and membrane interaction system; the spectral resolution and convergence of the numerical scheme are demonstrated. The critical viscosity ratios for the transition from tank-treading (TT) to ‘trembling’ (TR, also called VB, i.e. vacillating-breathing, or swinging) and eventually ‘tumbling’ (TU) motions are calculated by linear stability analysis based on this spectral method, and are in good agreement with perturbation theories. The effective shear rheology of a dilute suspension of these vesicles is also calculated over a wide parameter regime. Finally, our DNS reveals a family of time-periodic and off-the-shear-plane motion patterns where the vesicle's configuration follows orbits that resemble but are fundamentally different from the classical Jeffery orbits of rigid particles due to the vesicle's deformability.
Topological analysis of separation phenomena in liquid metal flow in sudden expansions. Part 2. Magnetohydrodynamic flow
Authors: MISTRANGELO C.
Published: March 2011

A numerical study has been carried out to analyse liquid metal flows in a sudden expansion of electrically conducting rectangular ducts under the influence of an imposed uniform magnetic field. Separation phenomena are investigated by selecting a reference Reynolds number and by increasing progressively the applied magnetic field. The magnetic effects leading to the reduction of the size of separation zones that form behind the cross-section enlargement are studied by considering modifications of flow topology, streamline patterns and electric current density distribution. In the range of parameters investigated, the magnetohydrodynamic flow undergoes substantial transitions from a hydrodynamic-like flow to one dominated by electromagnetic forces, where the influence of inertia and viscous forces is confined to thin internal layers aligned with the magnetic field and to boundary layers that form along the walls. Scaling laws describing the reattachment length and the pressure drop in the sudden expansion are derived for intense magnetic fields.
No reliable gender differences in attachment across the lifespan
Authors: Bakermans-Kranenburg Marian J. , van IJzendoorn Marinus H.
Published: March 2011

In middle childhood, boys show more avoidant attachments and girls more ambivalent attachments as a prelude to gender differentiation in reproductive strategies. However, we have failed to find systematic and method-independent gender differences in middle or late childhood attachments, nor in adult attachment representations. We conclude that Del Giudice's model rests on a brittle empirical basis.
Prólogo del presidente del Tribunal Penal International para Ruanda
Authors: Kama Laïty
Published: March 2011

La iniciativa de la Revista Internacional de la Cruz Roja de dedicar un número a una serie de artículos acerca de los dos Tribunales Penales Internacionales ad hoc, establecidos por las Naciones Unidas a fin de enjuiciar a los presuntos responsables de las violaciones graves del derecho internacional humanitario cometidas en ex Yugoslavia y en Ruanda es un símbolo de la creciente importancia que tienen ambas jurisdicciones penales, tanto para el gran público como para los especialistas.
Tribunal para Ruanda: algunos aspectos jurídicos
Authors: Harhoff Frederik
Published: March 2011

Si nos remontamos a los diversos orígenes de las leyes de la guerra, una pregunta elemental parece haber retenido la atención de los primeros legisladores: ¿por qué, de hecho, habría que imponer limitaciones jurídicas a las acciones bélicas, siendo así que su finalidad es destruir al enemigo extranjero? A primera vista, estas restricciones resultan ser incompatibles con el objetivo mismo de la guerra y no tenían valor alguno para quienes estaban obligados a resistir a un ataque armado o deseaban librar batalla contra el enemigo.
El Tribunal Penal Internacional para Ruanda
Authors: Aptel Cécile
Published: March 2011

El Tribunal Penal International para Ruanda (TPIR), instituido, el 8 de noviembre, por el Consejo de Seguridad, del que es órgano subsidiario, tiene por cometido contribuir al restablecimiento y al mantenimiento de la paz, así como a la reconciliatión national, mediante el enjuiciamiento de los presuntos responsables de actos de genocidio o de otras violaciones graves del derecho international humanitario cometidos en el territorio de Ruanda, así como de ciudadanos ruandeses presuntos responsables de tales actos y de otras violaciones perpetrados, entre el 1 de enero y el 31 de diciembre de 1994 en el territorio de Estados vecinos.
El Tribunal Penal Internacional para Ruanda ¿Se han examinado todas las cuestiones? ¿Puede compararse con la Comisíón de la Verdad y la Reconciliatión de Sudáfrica?
Authors: Erasmus Gerhard , Fourie Nadine
Published: March 2011

La reactión de la comunidad internacional ante la matanza y el genocidio en Ruanda ha sido, a veces, reticente e inadecuada. Esto se debe, en parte, a la cantidad de recursos humanos y materiales que habrían sido necesarios para restaurar la paz y resolver las cuestiones más fundamentales del derrumbamiento del Estado mismo. Sin embargo, la experiencia de Ruanda también plantea serios interrogantes acerca de la adecuación de las estructuras internacionales y regionales encargadas de mantener y restaurar la paz.
La protección a la mujer en el derecho internacional humanitario
Authors: Krill Françoise
Published: March 2011

Antes de la Primera Guerra Mundial, fueron pocas las mujeres que participaron directamente en las guerras y, por lo tanto, hasta entonces no se sintió la necesidad de otorgarles una protectión jurídica especial. Sin embargo, ello no significa que, en el pasado, las mujeres se beneficiaran de toda protección. Tras el nacimiento del derecho internacional humanitario se han beneficiado de la misma protectión jurídica que los hombres. Las mujeres heridas en campaña estaban protegidas, primeramente, por las disposiciones del Convenio de Ginebra de 1864 para mejorar la suerte que corren los militares heridos en los ejércitos en campaña; las prisioneras de guerra se beneficiaban de las disposiciones del Reglamento anexo a los Convenios de La Haya de 1899 y 1907 sobre las leyes y costumbres de la guerra terrestre
Texto de síntesis IV: Identificación—Principio fundamental
Authors: de Preux J.
Published: March 2011

Las familias tienen derecho a conocer la suerte de sus miembros (P. I, art. 32).

Cada Parte en conflicto debe buscar a las personas cuya desaparición haya señalado una Parte adversa y comunicar todas las informaciones pertinentes sobre las personas de que se trate (P.I, art. 33).
La evolución de la idea de paz en el pensamiento de Henry Dunant
Authors: Durand André
Published: March 2011

Fue en Solferino donde Henry Dunant se enfrentó por primera vez con el problema de la guerra. Ello le produjo una conmoción que jamás se borró de su memoria y que decidió su destine Animado por un sentimiento innato de no violencia, emprendió entonces el largo camino que lo llevó a enunciar, primero, los medios para proteger a las víctimas de la guerra; luego, para limitar las circunstancias en las que ésta puede surgir y, finalmente, para abolirla. Esos tres planteamientos: protección, limitación y abolición, se completan sin sustituirse; en la mente de Henry Dunant, constituían un sistema coherente, encaminado a la vez a reprimir los excesos de la guerra, a evitar su aparición y a extirpar sus causas.
Los Protocolos adicionales a los Convenios de Ginebra
Authors: de Preux Jean
Published: March 2011

Nuestro planeta tiene actualmente cinco mil millones de habitantes. En 1863, año de la fundación de la Cruz Roja, y en el que se realizaron los primeros esfuerzos de codificaión del derecho en los conflictos armados, tenía mil millones. Durante casi un siglo, la Cruz Roja ha fijado, sucesivamente, su atención en los militares heridos en combate, en las víctimas de los enfrentamientos navales, en los prisioneros de guerra y en las personas civiles abandonadas —en tiempo de guerra— a la arbitrariedad de una soberanía extranjera.
Los Protocolos adicionales a los Convenios de Ginebra de 1949 y su relación con México
Authors: de la Rosa Antonio López
Published: March 2011

Con motivo de la próxima celebración de los primeros 10 años de los Protocolos adicionales a los Convenios de Ginebra del 12 de agosto de 1949, la Redacción de la Revista International de la Cruz Roja ha invitado, muy gentilmente, a la Cruz Roja Mexicana para que escriba un artículo sobre este acontecimiento resaltando la importancia de esos instrumentos jurídicos para ella, las gestiones que se han hecho acerca de su difusión pero, tal vez mas importante, la labor que esta Sociedad Nacional ha realizado en favor de su ratificatión.
Los Protocolos de 1977 y la Cruz Roja Neerlandesa
Authors: Kalshoven Frits
Published: March 2011

Los Países Bajos contribuyeron en gran medida a la redacción del texto de los Protocolos de 1977 y fue uno de los primeros Estados en firmar esos instrumentos, el 12 de diciembre de 1977, en Berna. Sin embargo, hasta hoy, aún no los ha ratificado. Por qué ese retraso?

Hay numerosas razones para ello. Por una parte, los Países Bajos son miembros de la Organizatión del Tratado del Atlántico Norte (OTAN), la cual necesitó mucho tiempo para evaluar los Protocolos a la luz de sus planes de defensa militar. Por otra, según las normas y la práctica constitucionales, siempre que el Gobierno holandés desea ratificar un tratado, debe obtener primero la autorización de ambas Cámaras del Parlamento.
Hacia una prohibición mundial de las minas terrestres
Authors: Parlow Anita
Published: March 2011

En el marco conceptual del Convenio de La Hay a de 1907 (IV) y del Protocolo de Ginebra de 1925 se prohibió la utilizatión de armas, en particular de armas tóxicas (armas químicas y biológicas), proyectiles o de materias destinadas a causar sufrimientos innecesarios. En los debates previos a la prohibitión del uso de las armas químicas, diplomáticos de todo el mundo calificaron su uso de «bárbaro y deshonroso», a causa de sus efectos en los soldados y las probables repercusiones indiscriminadas para la población civil. Es un logro universal el hecho de que actualmente sea inconcebible que la opinion publica mundial permanezca indiferente ante la suerte de la población civil atrapada por la guerra. A la vez que aumenta la atención internacional a la protección de la población civil en los conflictos armados internos, se reanuda el debate sobre la reglamentación de la conducta de las partes beligerantes mediante el derecho humanitario y el derecho de los derechos humanos.
«Convención sobre la Seguridad del Personal de las Naciones Unidas y del Personal Asociado»: presentación y análisis
Authors: Bouvier Antoine
Published: March 2011

El día 9 de diciembre de 1994, la Asamblea General de la Organización de las Naciones Unidas (ONU) aprobó, por consenso, una «Convención sobre la Seguridad del Personal de las Naciones Unidas y el Personal Asociado». Con este convenio concluía un proceso de codificación y de desarrollo progresivo del derecho internacional, realizado a un ritmo excepcional, si se tiene en cuenta que el Comité Especial al que la cuadragésima octava Asamblea General (1993) había encomendado la elaboración de la Convención cumplió su cometido en menos de nueve meses.
Tendencias en la aplicación del derecho internacional humanitario por los mecanismos de derechos humanos de las Naciones Unidas
Authors: O'Donnell Daniel
Published: March 2011

Los mecanismos de derechos humanos de las Naciones Unidas no han cesado de proliferar, dando lugar a numerosas decisiones y voluminosos informes. En el presente artículo, se reseña cómo tales mecanismos se utilizan para aplicar el derecho internacional humanitario, entre otros el derecho de Ginebra y el derecho de La Haya. Para ello, se hace resaltar principalmente la práctica de los relatores designados por la Comisión de Derechos Humanos de las Naciones Unidas, a fin de investigar la situación de los derechos humanos en determinados países, así como la de los relatores y grupos de trabajo temáticos, a los que la Comisión ha encargado vigilar tipos específicos de violaciones graves de los derechos humanos dondequiera que se perpetren, en particular la experiencia del relator especial sobre ejecuciones extrajudiciales, sumarias o arbitrarias y la del representante del secretario general encargado de la cuestión de las personas internamente desplazadas, cuyo cometido es, a menudo, examinar los abusos cometidos en el contexto de los conflictos armados. Se hace referencia, asimismo, a dos innovadores mecanismos que funcionaron en El Salvador, a saber: la primera «comisión de la verdad», patrocinada por las Naciones Unidas, y el primer órgano de vigilancia de derechos humanos instituido como parte de un dispositivo global para supervisar la aplicación de un acuerdo de paz, auspiciado por las Naciones Unidas. Se mencionan igualmente algunas observaciones formuladas por los órganos de vigilancia de los tratados.
Las organizaciones no gubernamentales de derechos humanos y el derecho international humanitario
Authors: Brett Rachel
Published: March 2011

En el fondo de la labor en favor de los derechos humanos yace el afán de proteger a las personas contra los abusos de poder o la negligencia de sus propios Gobiernos. A escala internacional, esto transfiere al Estado la responsabilidad del trato que el Gobierno da a sus ciudadanos, complementando el derecho internacional—más antiguo—relativo al trato debido a los extranjeros y el derecho de la guerra, que (en su origen) sólo se refería también al trato debido a los extranjeros.
Protección del agua en período de conflicto armado
Authors: Zemmali Ameur
Published: March 2011

Fuente de vida y de bien, símbolo de fecundidad y de pureza, el agua es también portadora de temores, de riesgos y de peligros y es motivo de codicias y de conflictos. Sus múltiples funciones, tan necesarias las unas como las otras, la convierten en un recurso vital, cuyos uso y gestión el hombre siempre ha tratado de reglamentar. Pero, contrariamente al derecho aplicable en tiempo de paz, como evidencian los usos y las costumbres de las sociedades más antiguas o incluso los instrumentos jurídicos internos e internacionales de los tiempos modernos, en el derecho de los conflictos armados sobre el agua —expresa y tardíamente— solo versan algunas disposiciones. Esto es menos un reproche que una comprobación y podría explicarse por el hecho de que el agua es indispensable en todas las circunstancias. Abstracción hecha de las consecuencias de las catástrofes naturales en las que el agua puede ser amenazante y amenazada, algunas actividades humanas pueden surtir efectos nefastos y perjudiciales para el medio ambiente y los medios de supervivencia de la población, de los cuales el agua es el elemento básico. Basta evocar los efectos de la contaminación o de los conflictos armados. La experiencia de las guerras contemporáneas nos enseña, por desgracia, que la población civil y los bienes civiles están expuestos a las operaciones militares y que, en ciertos casos, la sed puede resultar más mortífera que las armas.
Classification of periodic and chaotic passive limit cycles for a compass-gait biped with gait asymmetries
Authors: Moon Jae-Sung , Spong Mark W.
Published: March 2011

In this paper we study the problem of passive walking for a compass-gait biped with gait asymmetries. In particular, we identify and classify bifurcations leading to chaos caused by the gait asymmetries because of unequal leg masses. We present bifurcation diagrams showing step period versus the ratio of leg masses at various walking slopes. The cell mapping method is used to find stable limit cycles as the parameters are varied. It is found that a variety of bifurcation diagrams can be grouped into six stages that consist of three expanding and three contracting stages. The analysis of each stage shows that marginally stable limit cycles exhibit period-doubling, period-remerging, and saddle-node bifurcations. We also show qualitative changes regarding chaos, i.e., generation and extinction of chaos follow cyclic patterns in passive dynamic walking.
The integration of local chromatic motion signals is sensitive to contrast polarity
Authors: WUERGER SOPHIE M. , RUPPERTSBERG ALEXA , MALEK STEPHANIE , BERTAMINI MARCO , MARTINOVIC JASNA
Published: March 2011

Global motion integration mechanisms can utilize signals defined by purely chromatic information. Is global motion integration sensitive to the polarity of such color signals? To answer this question, we employed isoluminant random dot kinematograms (RDKs) that contain a single chromatic contrast polarity or two different polarities. Single-polarity RDKs consisted of local motion signals with either a positive or a negative S or L–M component, while in the different-polarity RDKs, half the dots had a positive S or L–M component, and the other half had a negative S or L–M component. In all RDKs, the polarity and the motion direction of the local signals were uncorrelated. Observers discriminated between 50% coherent motion and random motion, and contrast thresholds were obtained for 81% correct responses. Contrast thresholds were obtained for three different dot densities (50, 100, and 200 dots). We report two main findings: (1) dependence on dot density is similar for both contrast polarities (+S vs. −S, +LM vs. −LM) but slightly steeper for S in comparison to LM and (2) thresholds for different-polarity RDKs are significantly higher than for single-polarity RDKs, which is inconsistent with a polarity-blind integration mechanism. We conclude that early motion integration mechanisms are sensitive to the polarity of the local motion signals and do not automatically integrate information across different polarities.
From spatial frequency contrast to edge preponderance: the differential modulation of early visual evoked potentials by natural scene stimuli
Authors: HANSEN BRUCE C. , JACQUES THEODORE , JOHNSON AARON P. , ELLEMBERG DAVE
Published: March 2011

The contrast response function of early visual evoked potentials elicited by sinusoidal gratings is known to exhibit characteristic potentials closely associated with the processes of parvocellular and magnocellular pathways. Specifically, the N1 component has been linked with parvocellular processes, while the P1 component has been linked with magnocellular processes. However, little is known regarding the response properties of the N1 and P1 components during the processing and encoding of complex (i.e., broadband) stimuli such as natural scenes. Here, we examine how established physical characteristics of natural scene imagery modulate the N1 and P1 components in humans by providing a systematic investigation of component modulation as visual stimuli are gradually built up from simple sinusoidal gratings to highly complex natural scene imagery. The results suggest that the relative dominance in signal output of the N1 and P1 components is dependent on spatial frequency (SF) luminance contrast for simple stimuli up to natural scene imagery possessing few edges. However, such a dependency shifts to a dominant N1 signal for natural scenes possessing abundant edge content and operates independently of SF luminance contrast.
SEIZURES IN WOMEN WITH PREECLAMPSIA: MECHANISMS AND MANAGEMENT
Authors: CIPOLLA MARILYN J , KRAIG RICHARD P
Published: March 2011

Eclampsia is defined in the obstetrical literature as the occurrence of unexplained seizure during pregnancy in a woman with preeclampsia. In the Western world, the incidence of eclampsia is ~1 per 2000 to 1 per 3000 pregnancies, but the incidence is 10-fold higher in tertiary referral centers and undeveloped countries where there is poor prenatal care, and in multi-fetal gestations. Nearly 1 in 50 women with eclampsia die as do 1 in 14 of their offspring, and mortality rates are considerably higher in undeveloped countries. Eclampsia is also associated with significant life-threatening complications, including neurological events. Seizure acutely can cause stroke, haemorrhage, oedema and brain herniation and thus lead to epilepsy and cognitive impairment later in life.
The new Amplatzer duct occluder II: when is its use advantageous?
Authors: Venczelova Zuzana , Tittel Peter , Masura Jozef
Published: March 2011

Objectives

To determine the safety and efficacy of the Amplatzer duct occluder and the Amplatzer duct occluder II in different types of arterial ducts, and to determine in which types of ducts the use of this new device can be advantageous.

Methods

All children with a device-based ductal closure between September, 2005 and February, 2010 were included. We retrospectively analysed the catheterisation and follow-up data.

Results

Between September, 2005 and February, 2010, 44 ducts were closed with the Amplatzer duct occluder – group Amplatzer duct occluder – and 52 ducts were closed with the Amplatzer duct occluder II – group Amplatzer duct occluder II. In the Amplatzer duct occluder group, the mean age was 3 years and 4 months, and the mean weight was 14.7 kilograms. Closure was successfully performed in all children. Complete closure at 24 hours was attained in 42 of 44 children (95.45%). No major complications occurred. In the Amplatzer duct occluder II group, the mean age was 6 years and 2 months, and the mean weight was 25.4 kilograms. Closure was successfully performed in all children, except in two children in whom the occluder protruded into the aortic isthmus and was replaced by the Amplatzer duct occluder. Complete closure at 24 hours was attained in 51 of 52 children (98.08%). No major complications occurred.

Conclusion

In our experience, duct closure with the Amplatzer duct occluder II is a safe and effective method. The advantages of using it are the smaller sheath sizes and softer shape.
Donated breast milk substitutes and incidence of diarrhoea among infants and young children after the May 2006 earthquake in Yogyakarta and Central Java
Authors: Hipgrave David B , Assefa Fitsum , Winoto Anna , Sukotjo Sri
Published: March 2011

Objective

Distribution of breast milk substitutes (BMS) after the 2006 Yogyakarta earthquake was uncontrolled and widespread. We assessed the magnitude of BMS distribution after the earthquake, its impact on feeding practices and the association between consumption of infant formula and diarrhoea among infants and young children.

Design

One month after the earthquake, caregivers of 831 children aged 0–23 months were surveyed regarding receipt of unsolicited donations of BMS, and on recent child-feeding practices and diarrhoeal illness.

Setting

Community-level survey in an earthquake-affected district.

Subjects

Primary caregivers of surveyed children.

Results

In all, 75 % of households with an infant aged 0–5 months and 80 % of all households surveyed received donated infant formula; 76 % of all households received commercial porridge and 49 % received powdered milk. Only 32 % of 0–5-month-old infants had consumed formula before the earthquake, but 43 % had in the 24 h preceding the survey (P< 0·001). Consumption of all types of BMS was significantly higher among those who received donated commodities, regardless of age (P< 0·01). One-week diarrhoea incidence among those who received donated infant formula (25·4 %) was higher than among those who did not (11·5 %; relative risk = 2·12, 95 % CI = 1·34, 3·35). The rate of diarrhoea among those aged 12–23 months was around five times the pre-earthquake rate.

Conclusions

There were strong associations between receipt of BMS and changes in feeding practices, and between receipt of infant formula and diarrhoea. Uncontrolled distribution of infant formula exacerbates the risk of diarrhoea among infants and young children in emergencies.
Where has all the chocolate gone? A national survey assesses the effects of recent legislation to improve the nutritional quality of English secondary-school vending
Authors: Matthews Anne , Nelson Michael , Kaur Asha , Rayner Mike , Kelly Paul , Cowburn Gill
Published: March 2011

Objective

Obesity levels are rising in almost all parts of the world, including the UK. School food offers children in Great Britain between 25 % and 33 % of their total daily energy, with vending typically offering products high in fat, salt or sugar. Government legislation of 2007 to improve the quality of school food now restricts what English schools can vend. In assessing the effect of this legislation on the quality of English secondary-school vending provision, the response of schools to these effects is explored through qualitative data.

Design

A longitudinal postal and visit-based inventory survey of schools collected vending data during the academic year 2006–2007 (pre-legislation), 2007–2008 and 2008–2009 (both post-legislation). Interviews with school staff explored issues of compliance. Product categorisation and analysis were carried out by product type, nutrient profiling and by categories of foods allowed or prohibited by the legislation.

Setting

English secondary schools.

Subjects

A representative sample of 279 schools including sixty-two researcher-visited inventory schools participated in the research.

Results

School vending seems to have moved towards compliance with the new standards – now drinks vending predominates and is largely compliant, whereas food vending is significantly reduced and is mostly non-compliant. Sixth form vending takes a disproportionate share of non-compliance. Vending has declined overall, as some schools now perceive food vending as uneconomic. Schools adopting a ‘whole-school’ approach appeared the most successful in implementing the new standards.

Conclusions

Government legislation has achieved significant change towards improving the quality of English school vending, with the unintended consequence of reducing provision.
Response to ‘Comment on Recent Modeling Studies of Astrocyte—Neuron Metabolic Interactions’: Much ado about Nothing
Authors: Mangia Silvia , DiNuzzo Mauro , Giove Federico , Carruthers Anthony , Simpson Ian A , Vannucci Susan J
Published: March 2011

For many years, a tenet of cerebral metabolism held that glucose was the obligate energy substrate of the mammalian brain and that neuronal oxidative metabolism represented the majority of this glucose utilization. In 1994, Pellerin and Magistretti formulated the astrocyte-neuron lactate shuttle (ANLS) hypothesis, in which astrocytes, not neurons, metabolized glucose, with subsequent transport of the glycolytically derived lactate to fuel the energy needs of the neuron during neurotransmission. By considering the concentrations and kinetic characteristics of the nutrient transporter proteins, Simpson et al later supported the opposite view, in which lactate flows from neurons to astrocytes, thus leading to the neuron-astrocyte lactate shuttle (NALS). Most recently, a commentary was published in this journal attempting to discredit the NALS. This challenge has stimulated the present response in which we detail the inaccuracies of the commentary and further model several different possibilities. Although our simulations continue to support the predominance of neuronal glucose utilization during activation and neuronal to astrocytic lactate flow, the most important result is that, regardless of the direction of the flow, the overall contribution of lactate to cerebral glucose metabolism is found to be so small as to make this ongoing debate ‘much ado about nothing'.
The tuberous sclerosis complex: balancing proliferation and survival
Authors: Tomasoni Romana , Mondino Anna
Published: March 2011

Mutations in genes encoding either hamartin [TSC1 (tuberous sclerosis complex 1)] or tuberin (TSC2) result in a multisystem disorder characterized by the development of benign tumours and hamartomas in several organs. The TSC1 and TSC2 proteins form a complex that lies at the crossroad of many signalling pathways integrating the energy status of the cell with signals induced by nutrients and growth factors. The TSC1/2 complex is a critical negative regulator of mTORC1 [mTOR (mammalian target of rapamycin) complex 1], and by that controls anabolic processes to promote cell growth, proliferation and survival. In the present paper, we review recent evidence highlighting the notion that the TSC1/2 complex simultaneously controls mTOR-dependent and mTOR-independent signals critical for the balancing of cell proliferation and cell death.
Occupational hazards: allosteric regulation of protein kinases through the nucleotide-binding pocket
Authors: Cameron Angus J.M.
Published: March 2011

Targeting the protein kinase ATP-binding pocket provides a significant opportunity for the treatment of disease. Recent studies have revealed a central activity-independent role for nucleotide pocket occupation in the allosteric behaviour of diverse kinases. Regulation of nucleotide pocket conformation with either nucleotides or ATP competitive inhibitors has revealed an added dimension to the targeting of kinases. In the present paper, using PKC (protein kinase C) as a paradigm, the liabilities and opportunities associated with the occupation of the nucleotide pocket are explored.
A critical role for non-coding RNA GAS5 in growth arrest and rapamycin inhibition in human T-lymphocytes
Authors: Williams Gwyn T. , Mourtada-Maarabouni Mirna , Farzaneh Farzin
Published: March 2011

Non-coding RNA GAS5 (growth arrest-specific transcript 5) is a 5′-TOP (5′-terminal oligopyrimidine tract) RNA, whose translation, and consequently also stability, is controlled by the mTOR (mammalian target of rapamycin) pathway. GAS5 was identified by functional expression cloning and is necessary and sufficient for normal growth arrest in both leukaemic and untransformed human T-lymphocytes. GAS5 is also required for the inhibitory effects of rapamycin and its analogues on T-cells. The striking functional effects of GAS5 may be mediated through the snoRNAs (small nucleolar RNAs) encoded in its introns and/or through the unusual folding of the mRNA itself, which sequesters, and therefore inhibits, the glucocorticoid receptor.
MAF1: a new target of mTORC1
Authors: Michels Annemieke A.
Published: March 2011

Yeast and mammalian MAF1 are both regulated by the TOR (target of rapamycin) pathway. However, the exact mechanisms of regulation diverge at TOR, with yeast Maf1 phosphorylated mainly by the TORC1 (TOR complex 1) substrate Sch9 kinase and mammalian MAF1 by mTORC1 (mammalian target of rapamycin complex 1) itself. Sch9 phosphorylation of yeast Maf1 regulates Maf1 localization, but it is less clear whether phosphorylation of human MAF1 regulates its localization. Replacement of phosphosites with alanine decreases Pol III (RNA polymerase III) transcription, but the effect is much more pronounced for human MAF1 than for the yeast protein. In both cases, Pol III repression can be further increased by rapamycin treatment or, in mammalian cells, serum starvation, suggesting that the TOR pathway controls another aspect of Pol III transcription that is closely linked to MAF1, as it depends on the presence of MAF1.
Regulation of the SREBP transcription factors by mTORC1
Authors: Lewis Caroline A. , Griffiths Beatrice , Santos Claudio R. , Pende Mario , Schulze Almut
Published: March 2011

In recent years several reports have linked mTORC1 (mammalian target of rapamycin complex 1) to lipogenesis via the SREBPs (sterol-regulatory-element-binding proteins). SREBPs regulate the expression of genes encoding enzymes required for fatty acid and cholesterol biosynthesis. Lipid metabolism is perturbed in some diseases and SREBP target genes, such as FASN (fatty acid synthase), have been shown to be up-regulated in some cancers. We have previously shown that mTORC1 plays a role in SREBP activation and Akt/PKB (protein kinase B)-dependent de novo lipogenesis. Our findings suggest that mTORC1 plays a crucial role in the activation of SREBP and that the activation of lipid biosynthesis through the induction of SREBP could be part of a regulatory pathway that co-ordinates protein and lipid biosynthesis during cell growth. In the present paper, we discuss the increasing amount of data supporting the potential mechanisms of mTORC1-dependent activation of SREBP as well as the implications of this signalling pathway in cancer.
The role of tetraspanins in fusion
Authors: Fanaei Marzieh , Monk Peter N. , Partridge Lynda J.
Published: March 2011

Membrane fusion underlies such important biological processes as virus entry into host cells, intracellular protein trafficking, fertilization, formation of muscle fibres and bone resorption. In addition, pathologies such as osteoporosis and implant rejection have been attributed to aberrant fusion. Members of the tetraspanin protein superfamily have been ascribed multiple roles in membrane biology, forming extensive lateral associations and regulating the function of effector molecules by clustering them in specific areas of the membrane. The present review aims to summarize the experimental evidence for tetraspanin function in different fusion events and highlight common themes.
Tetraspanin functions during HIV-1 and influenza virus replication
Authors: Thali Markus
Published: March 2011

By virtue of their multiple interactions with partner proteins and due to their strong propensity to multimerize, tetraspanins create scaffolds in membranes, recruiting or excluding specific proteins needed for particular cellular processes. We and others have shown that (i) HIV-1 assembles at, and buds through, membrane areas that are enriched in tetraspanins CD9, CD63, CD81 and CD82, and (ii) the presence of these proteins at exit sites and in viral particles inhibits virus-induced membrane fusion. In the present paper, I review these findings and briefly discuss the results of our ongoing investigations that are aimed at elucidating when and how tetraspanins regulate this fusion process and how such control affects virus spreading. Finally, I give a preview of studies that we have initiated more recently and which aim to delineate exactly when CD81 functions during the replication of another enveloped RNA virus: influenza virus.
Hepatitis C virus entry and the tetraspanin CD81
Authors: Farquhar Michelle J. , Harris Helen J. , McKeating Jane A.
Published: March 2011

CD81, a member of the tetraspanin integral membrane protein family, has been identified as an essential receptor for HCV (hepatitis C virus). The present review highlights recent published data on the role that CD81 plays in HCV entry, including the importance of actin-dependent lateral diffusion of CD81 within the cell membrane, CD81 endocytosis and the CD81–Claudin-1 receptor complex in HCV internalization. Additional functions for CD81 in the viral life cycle and the role of HCV–CD81 interactions in HCV-induced B-cell and CNS (central nervous system) abnormalities are discussed.
Tetraspanin protein contributions to cancer
Authors: Wang Hong-Xing , Li Qinglin , Sharma Chandan , Knoblich Konstantin , Hemler Martin E.
Published: March 2011

Among the 33 human tetraspanin proteins, CD151, CD9 and Tspan12 play particularly important roles in cancer. Tetraspanin CD151, in partnership with integrins α6β1 and α6β4, modulates tumour cell growth, invasion, migration, metastasis, signalling and drug sensitivity. Tetraspanin CD9 has suppressor functions in multiple tumour cell types. Major CD9 partner proteins, such as EWI-2 and EWI-F, may modulate these tumour-suppressor functions. Tetraspanin Tspan12 mutations are linked to a human disease called familial exudative vitreoretinopathy. In addition, as a regulator of the metalloprotease ADAM10 (a disintegrin and metalloprotease 10) maturation and function, Tspan12 probably contributes to the pro-tumorigenic functions of ADAM10.
Tetraspanin CD151 as a target for antibody-based cancer immunotherapy
Authors: Haeuw Jean-François , Goetsch Liliane , Bailly Christian , Corvaia Nathalie
Published: March 2011

CD151 is a plasma membrane protein belonging to the tetraspanin superfamily which is expressed on normal cells such as endothelial cells and platelets and frequently overexpressed on cancer cells. It is known to be functionally linked to cancer metastasis. In humans, increased expression of CD151 is indicative of a poor prognosis in different cancer types. Whereas its mechanism of action remains obscure, CD151 was shown to regulate cell motility and adhesion through association with laminin-binding integrins such as α3β1 or α6β4. Several anti-CD151 mAbs (monoclonal antibodies) have been shown to display anti-metastatic activity in vivo. Inhibition of metastasis was not attributed to any effect of these mAbs on tumour cell growth, but was essentially attributed to inhibition of cell motility. We have generated anti-CD151 mAbs which can inhibit the tumoral growth in different xenograft cancer models. As expected, these mAbs were also able to inhibit metastasis in orthotopic cancer models. These data suggest that CD151 could function at multiple cancer stages, including not only metastasis cascade steps, but also earlier steps of primary tumour growth, thus reinforcing the interest of this innovative target in oncology. mAbs targeting CD151 may be of significant interest for cancer biotherapy.
A brief review of DNA and RNA chemical synthesis
Authors: Caruthers Marvin H.
Published: March 2011

Current methodologies used to synthesize DNA and RNA are reviewed. These focus on using controlled pore glass and microarrays on glass slides.
The reaction mechanism of FokI excludes the possibility of targeting zinc finger nucleases to unique DNA sites
Authors: Halford Stephen E. , Catto Lucy E. , Pernstich Christian , Rusling David A. , Sanders Kelly L.
Published: March 2011

The FokI endonuclease is a monomeric protein with discrete DNA-recognition and catalytic domains. The latter has only one active site so, to cut both strands, the catalytic domains from two monomers associate to form a dimer. The dimer involving a monomer at the recognition site and another from free solution is less stable than that from two proteins tethered to the same DNA. FokI thus cleaves DNA with two sites better than one-site DNA. The two sites can be immediately adjacent, but they can alternatively be many hundreds of base pairs apart, in either inverted or repeated orientations. The catalytic domain of FokI is often a component of zinc finger nucleases. Typically, the zinc finger domains of two such nucleases are designed to recognize two neighbouring DNA sequences, with the objective of cutting the DNA exclusively between the target sequences. However, this strategy fails to take account of the fact that the catalytic domains of FokI can dimerize across distant sites or even at a solitary site. Additional copies of either target sequence elsewhere in the chromosome must elicit off-target cleavages.
DNA polymerase activity at the single-molecule level
Authors: Gill Joshua P. , Wang Jun , Millar David P.
Published: March 2011

DNA polymerases are essential enzymes responsible for replication and repair of DNA in all organisms. To replicate DNA with high fidelity, DNA polymerases must select the correct incoming nucleotide substrate during each cycle of nucleotide incorporation, in accordance with the templating base. When an incorrect nucleotide is sometimes inserted, the polymerase uses a separate 3′→5′ exonuclease to remove the misincorporated base (proofreading). Large conformational rearrangements of the polymerase–DNA complex occur during both the nucleotide incorporation and proofreading steps. Single-molecule fluorescence spectroscopy provides a unique tool for observation of these dynamic conformational changes in real-time, without the need to synchronize a population of DNA–protein complexes.