Molecular Surface Features in Modeling the HIV-1 RT Inhibitory Activity of 2-(2,6-Disubstituted phenyl)-3-(substituted pyrimidin-2-yl)-thiazolidin-4-ones

The human immunodeficiency virus-1 reverse transcriptase inhibitory activity of 2-(2,6-disubstituted phenyl)-3-(substituted pyrimidin-2-yl)-thiazolidin-4-ones have been analyzed using combinatorial protocol in multiple linear regression (CP-MLR) with several electronic and molecular surface area features of the compounds obtained from Molecular Operating Environment (MOE) software. The study has indicated the role of different charged molecular surface areas in modeling the inhibitory activity of the compounds. The derived models collectively suggested that the compounds should be compact without bulky substitutions on its peripheries for better HIV-1 RT inhibitory activity. It also emphasized the necessity of hydrophobicity and compact structural features for their activity. The scope of the descriptors identified for these analogues have been verified by extending the dataset with different 2-(disubstituted phenyl)-3-(substituted pyridin-2-yl)-thiazolidin-4-ones. The joint analysis of extended dataset highlighted the information content of identified descriptors in modeling the HIV-1 RT inhibitory activity of the compounds.

Hands-Free Navigation in Immersive Environments for the Evaluation of the Effectiveness of Indoor Navigation Systems

While navigation systems for cars are in widespread use, only recently, indoor navigation systems based on smartphone apps became technically feasible. Hence tools in order to plan and evaluate particular designs of information provision are needed. Since tests in real infrastructures are costly and environmental conditions cannot be held constant, one must resort to virtual infrastructures. This paper presents the development of an environment for the support of the design of indoor navigation systems whose center piece consists in a hands-free navigation method using the Microsoft Kinect in the four-sided Definitely Affordable Virtual Environment (DAVE). Navigation controls using the user's gestures and postures as the input to the controls are designed and implemented. The installation of expensive and bulky hardware like treadmills is avoided while still giving the user a good impression of the distance she has traveled in virtual space. An advantage in comparison to approaches using a head mounted display is that the DAVE allows the users to interact with their smartphone. Thus the effects of different indoor navigation systems can be evaluated already in the planning phase using the resulting system

Extracortical plate fixation with new plate inserts and cerclage wires for the treatment of periprosthetic hip fractures

PURPOSE Fixation of periprosthetic hip fractures with intracortical anchorage might not be feasible in cases with bulky implants and/or poor bone stock. METHODS Rotational stability of new plate inserts with extracortical anchorage for cerclage fixation was measured and compared to the stability found using a standard technique in a biomechanical setup using a torsion testing machine. In a synthetic PUR bone model, transverse fractures were fixed distally using screws and proximally by wire cerclages attached to the plates using "new" (extracortical anchorage) or "standard" (intracortical anchorage) plate inserts. Time to fracture consolidation and complications were assessed in a consecutive series of 18 patients (18 female; mean age 81 years, range 55-92) with periprosthetic hip fractures (ten type B1, eight type C-Vancouver) treated with the new device between July 2003 and July 2010. RESULTS The "new" device showed a higher rotational stability than the "standard" technique (p < 0.001). Fractures showed radiographic consolidation after 14 ± 5 weeks (mean ± SD) postoperatively in patients. Revision surgery was necessary in four patients, unrelated to the new technique. CONCLUSION In periprosthetic hip fractures in which fixation with intracortical anchorage using conventional means might be difficult due to bulky revision stems and/or poor bone stock, the new device may be an addition to the range of existing implants.

Energy-Efficient Management Of Heterogeneous Wireless Sensor Networks

Various applications for the purposes of event detection, localization, and monitoring can benefit from the use of wireless sensor networks (WSNs). Wireless sensor networks are generally easy to deploy, with flexible topology and can support diversity of tasks thanks to the large variety of sensors that can be attached to the wireless sensor nodes. To guarantee the efficient operation of such a heterogeneous wireless sensor networks during its lifetime an appropriate management is necessary. Typically, there are three management tasks, namely monitoring, (re) configuration, and code updating. On the one hand, status information, such as battery state and node connectivity, of both the wireless sensor network and the sensor nodes has to be monitored. And on the other hand, sensor nodes have to be (re)configured, e.g., setting the sensing interval. Most importantly, new applications have to be deployed as well as bug fixes have to be applied during the network lifetime. All management tasks have to be performed in a reliable, time- and energy-efficient manner. The ability to disseminate data from one sender to multiple receivers in a reliable, time- and energy-efficient manner is critical for the execution of the management tasks, especially for code updating. Using multicast communication in wireless sensor networks is an efficient way to handle such traffic pattern. Due to the nature of code updates a multicast protocol has to support bulky traffic and endto-end reliability. Further, the limited resources of wireless sensor nodes demand an energy-efficient operation of the multicast protocol. Current data dissemination schemes do not fulfil all of the above requirements. In order to close the gap, we designed the Sensor Node Overlay Multicast (SNOMC) protocol such that to support a reliable, time-efficient and energy-efficient dissemination of data from one sender node to multiple receivers. In contrast to other multicast transport protocols, which do not support reliability mechanisms, SNOMC supports end-to-end reliability using a NACK-based reliability mechanism. The mechanism is simple and easy to implement and can significantly reduce the number of transmissions. It is complemented by a data acknowledgement after successful reception of all data fragments by the receiver nodes. In SNOMC three different caching strategies are integrated for an efficient handling of necessary retransmissions, namely, caching on each intermediate node, caching on branching nodes, or caching only on the sender node. Moreover, an option was included to pro-actively request missing fragments. SNOMC was evaluated both in the OMNeT++ simulator and in our in-house real-world testbed and compared to a number of common data dissemination protocols, such as Flooding, MPR, TinyCubus, PSFQ, and both UDP and TCP. The results showed that SNOMC outperforms the selected protocols in terms of transmission time, number of transmitted packets, and energy-consumption. Moreover, we showed that SNOMC performs well with different underlying MAC protocols, which support different levels of reliability and energy-efficiency. Thus, SNOMC can offer a robust, high-performing solution for the efficient distribution of code updates and management information in a wireless sensor network. To address the three management tasks, in this thesis we developed the Management Architecture for Wireless Sensor Networks (MARWIS). MARWIS is specifically designed for the management of heterogeneous wireless sensor networks. A distinguished feature of its design is the use of wireless mesh nodes as backbone, which enables diverse communication platforms and offloading functionality from the sensor nodes to the mesh nodes. This hierarchical architecture allows for efficient operation of the management tasks, due to the organisation of the sensor nodes into small sub-networks each managed by a mesh node. Furthermore, we developed a intuitive -based graphical user interface, which allows non-expert users to easily perform management tasks in the network. In contrast to other management frameworks, such as Mate, MANNA, TinyCubus, or code dissemination protocols, such as Impala, Trickle, and Deluge, MARWIS offers an integrated solution monitoring, configuration and code updating of sensor nodes. Integration of SNOMC into MARWIS further increases performance efficiency of the management tasks. To our knowledge, our approach is the first one, which offers a combination of a management architecture with an efficient overlay multicast transport protocol. This combination of SNOMC and MARWIS supports reliably, time- and energy-efficient operation of a heterogeneous wireless sensor network.

3.88 A structure of cytoplasmic polyhedrosis virus by cryo-electron microscopy.

Cytoplasmic polyhedrosis virus (CPV) is unique within the Reoviridae family in having a turreted single-layer capsid contained within polyhedrin inclusion bodies, yet being fully capable of cell entry and endogenous RNA transcription. Biochemical data have shown that the amino-terminal 79 residues of the CPV turret protein (TP) is sufficient to bring CPV or engineered proteins into the polyhedrin matrix for micro-encapsulation. Here we report the three-dimensional structure of CPV at 3.88 A resolution using single-particle cryo-electron microscopy. Our map clearly shows the turns and deep grooves of alpha-helices, the strand separation in beta-sheets, and densities for loops and many bulky side chains; thus permitting atomic model-building effort from cryo-electron microscopy maps. We observed a helix-to-beta-hairpin conformational change between the two conformational states of the capsid shell protein in the region directly interacting with genomic RNA. We have also discovered a messenger RNA release hole coupled with the mRNA capping machinery unique to CPV. Furthermore, we have identified the polyhedrin-binding domain, a structure that has potential in nanobiotechnology applications.

Molecular mechanisms of Ca$\sp{2+}$ signal transduction from cardiac troponin C to troponin I

$\rm Ca\sp{2+}$-dependent exposure of an N-terminal hydrophobic region in troponin C (TnC) is thought to be important for the regulation of contraction in striated muscle. To study these conformational changes in cardiac troponin (cTnC), the $\varepsilon$C and $\varepsilon$H chemical shifts for all 10 Met residues in cTnC were sequence-specific assigned on NMR spectra using a combination of two dimensional NMR techniques and site-directed mutagenesis. The assigned methyl-Met chemical shifts were used as structural markers to monitor conformational changes induced by $\rm Ca\sp{2+}.$ The results showed that binding of $\rm Ca\sp{2+}$ to the regulatory site in the N-domain induced large changes in the $\varepsilon$H and $\varepsilon$C chemical shifts of Met 45, Met 80, Met 81 in the predicted N-terminal hydrophobic region, but had no effect on the chemical shifts of Met residues located in the C-domain. These results suggest that the $\rm Ca\sp{2+}$-dependent functions of cTnC are mainly through N-terminal domain of cTnC.^ To further define the molecular mechanism by which TnC regulates muscle contraction, single Cys residues were engineered at positions 45, 81, 84 or 85 in the N-terminal hydrophobic region of cTnC to provide sites for attachment of specific blocking groups. Blocking groups were coupled to these Cys residues in cTnC mutants and the covalent adducts were tested for activity in TnC-extracted myofibrils. Covalent modification of cTnC(C45) had no effect on maximal myofibril ATPase activity. Greatly decreased myofibril ATPase activity resulted when the peptide or biotin was conjugated to residue 81 in cTnC(C81), while less inhibition resulted from covalent modification of cTnC(C84) or cTnC(C85). The results suggest that limited sites of the N-terminal hydrophobic region in cTnC are important for transducing the $\rm Ca\sp{2+}$ signal to troponin I (TnI) and are sensitive to modification, while other regions are less important or can adapt to steric hindrances introduced by bulky blocking groups.^ Although the exposed TnI interaction site in the N-terminal hydrophobic region of TnC is crucial for function of TnC, other regions in the N-domain of TnC may also participate in transducing the $\rm Ca\sp{2+}$ signal and conferring the maximal activation of actomyosin ATPase. The interactions between the B-/C-helices of cTnC and cTnI were characterized using a combination of site-directed mutagenesis, fluorescence and covalent modification. The results suggest that the $\rm Ca\sp{2+}$-dependent interactions of the B-/C-helices of cTnC with TnI may be required for the maximal activation of muscle contraction. ^

Oligodeoxynucleotide Duplexes Containing (5′S)-5′-C-Alkyl-Modified 2′-Deoxynucleosides: Can an Alkyl Zipper across the DNA Minor-Groove Enhance Duplex Stability?

10.1002/hlca.200390311.abs A series of oligonucleotides containing (5′S)-5′-C-butyl- and (5′S)-5′-C-isopentyl-substituted 2′-deoxyribonucleosides were designed, prepared, and characterized with the intention to explore alkyl-zipper formation between opposing alkyl chains across the minor groove of oligonucleotide duplexes as a means to modulate DNA-duplex stability. From four possible arrangements of the alkyl groups that differ in the density of packing of the alkyl chains across the minor groove, three (duplex types I–III, Fig. 2) could experimentally be realized and their duplex-forming properties analyzed by UV-melting curves, CD spectroscopy, and isothermal titration calorimetry (ITC), as well as by molecular modeling. The results show that all arrangements of alkyl residues within the minor groove of DNA are thermally destabilizing by 1.5–3°/modification in Tm. We found that, within the proposed duplexes with more loosely packed alkyl groups (type-III duplexes), accommodation of alkyl residues without extended distorsion of the helical parameters of B-DNA is possible but does not lead to higher thermodynamic stability. The more densely packed and more unevenly distributed arrangement (type-II duplexes) seems to suffer from ecliptic positioning of opposite alkyl groups, which might account for a systematic negative contribution to stability due to steric interactions. The decreased stability in the type-III duplexes described here may be due either to missing hydrophobic interactions of the alkyl groups (not bulky enough to make close contacts), or to an overcompensation of favorable alkyl-zipper formation presumably by loss of structured H2O in the minor groove.

A clinically applicable laser-based image-guided system for laparoscopic liver procedures

PURPOSE Laser range scanners (LRS) allow performing a surface scan without physical contact with the organ, yielding higher registration accuracy for image-guided surgery (IGS) systems. However, the use of LRS-based registration in laparoscopic liver surgery is still limited because current solutions are composed of expensive and bulky equipment which can hardly be integrated in a surgical scenario. METHODS In this work, we present a novel LRS-based IGS system for laparoscopic liver procedures. A triangulation process is formulated to compute the 3D coordinates of laser points by using the existing IGS system tracking devices. This allows the use of a compact and cost-effective LRS and therefore facilitates the integration into the laparoscopic setup. The 3D laser points are then reconstructed into a surface to register to the preoperative liver model using a multi-level registration process. RESULTS Experimental results show that the proposed system provides submillimeter scanning precision and accuracy comparable to those reported in the literature. Further quantitative analysis shows that the proposed system is able to achieve a patient-to-image registration accuracy, described as target registration error, of [Formula: see text]. CONCLUSIONS We believe that the presented approach will lead to a faster integration of LRS-based registration techniques in the surgical environment. Further studies will focus on optimizing scanning time and on the respiratory motion compensation.

Fray Alonso de la Veracruz : ensayo de síntesis

El artículo presenta una síntesis de la obra escrita de Veracruz y, en parte, también de su acción. De tal modo, se exponen sus escritos filosóficos, en materia de lógica (Recognitio Summularum y Dialectica Resolutio) y de filosofía natural (Physica Speculatio), y las relecciones en las que se ocupó de los títulos de la conquista y la condición de los indios (De dominio infidelium y De decimis). También es propósito del trabajo proporcionar, a quien quiera continuar con el tema, una guía de buena parte de la abundante literatura secundaria que se ha ocupado de Fray Alonso de la Veracruz. Veracruz es un importante representante de la escolástica novohispana del siglo XVI, y simboliza el comienzo del trasplante filosófico que bajo el signo de la escolástica se extendería en Iberoamérica hasta el siglo XVIII y parte del XIX.

FDG-PET Intra-tratamiento como valor pronóstico en el tratamiento del linfoma Hodgkin

Introducción: La utilización de regímenes de tratamiento más individualizados requiere de mejores sistemas de estratificación temprana en Linfoma Hodgkin (LH). El estudio Tomografía por Emisión de Positrones utilizando 2-[18F] fluoro-2-deoxi-Dglucosa (FDG-PET) intra-tratamiento podría jugar un rol muy importante en esta evaluación. Objetivo: Determinar el valor pronóstico del FDG-PET intra-tratamiento en pacientes con LH para predecir sobrevida libre de progresión y sobrevida global. Material y método: El estudio fue llevado a cabo en el Servicio de Hematología del Hospital Central de Mendoza incluyendo pacientes con diagnóstico de LH confirmados por histología. De acuerdo al estadio y sitio de presentación, los pacientes recibieron quimioterapia sola o la combinación de radioterapia y quimioterapia, con el uso del esquema ABVD (adriamicina, bleomicina, vinblastina y dacarbazina) como protocolo estándar. Los estudios FDG-PET fueron practicados como parte de la evaluación intra-tratamiento y a la finalización. Resultados: En total fueron evaluados 8 pacientes, Sexo: F/M: 4/4, Edad: 18-58 años (Mediana: 29 años), Estadios: IIB:1, IIIA:2, IIIB:1, IVA:1, IVB:3, regiones nodales: 2-10 (Mediana:4), compromiso extranodal: 4/8, síntomas B: 5/8, enfermedad bulky 2/8 . Subtipos: Escleronodular: 6/8, Celularidad mixta: 1/8, Depleción linfocítica: 1/8. IPS: 1: 3/8 2: 3/8 3: 1/8 4: 0/8 ≥ 5: 1/8. Tratamientos: ABVD x 6: 6/8, ABVD x 6 + Radioterapia: 2/8. PET intermedio: 8/8 negativos (6/8 PET 3, 2/8 PET 2). PET final: 7/8 PET negativo, 1/8 PET positivo. Recaída: 1/8 (10° mes). Seguimiento: 11-37 meses (mediana de 24 meses). Discusión y Conclusiones: Al momento actual el FDG-PET intra-tratamiento demostró tener un importante valor predictivo negativo dado que todos los pacientes, menos uno, se encuentran en remisión completa sin progresión de enfermedad. Resta aún determinar el rol que esta herramienta pueda tener en el futuro en la terapia adaptada al riesgo de pacientes con LH.

Figure 1 Geomorphological map of proglacial area of Yala (Dakpatsen) Glacier, Langtang Himal, Nepal (pdf 500 kB)

A series of minor moraine ridges are observed on the till surface in the proglacial area of Yala Glacier, Nepal Himalaya. The till surface, which is often fluted, consists ofsix different till sheets. It lies present glacial margin and the bulky terminal moraine ridges. These till sheets correspond to six re-advance stages during the general retreat which followed Little Ice Age ad- vance which formed the bulky terminal moraine ridges. Field observations and till fabric analysis suggest that the minor moraine ridges of Yala Glacier seem to be formed annually, by ice push. On the assumption that their annual character was maintained for a long time, and that the time span needed for each re-advance was proportional to the height of terminal moraine of each till sheet, the dating of Little fee Age moraines was attempted. The results indicate that Little Ice Age advances occurred in 1815 and in 1843, roughly simultanously with those in Europe.

Multiple Input-Output Bidirectional Solid State Transformer Based on a Series Resonant Converter

Las fuentes de alimentación de modo conmutado (SMPS en sus siglas en inglés) se utilizan ampliamente en una gran variedad de aplicaciones. La tarea más difícil para los diseñadores de SMPS consiste en lograr simultáneamente la operación del convertidor con alto rendimiento y alta densidad de energía. El tamaño y el peso de un convertidor de potencia está dominado por los componentes pasivos, ya que estos elementos son normalmente más grandes y más pesados que otros elementos en el circuito. Para una potencia de salida dada, la cantidad de energía almacenada en el convertidor que ha de ser entregada a la carga en cada ciclo de conmutación, es inversamente proporcional a la frecuencia de conmutación del convertidor. Por lo tanto, el aumento de la frecuencia de conmutación se considera un medio para lograr soluciones más compactas con los niveles de densidad de potencia más altos. La importancia de investigar en el rango de alta frecuencia de conmutación radica en todos los beneficios que se pueden lograr: además de la reducción en el tamaño de los componentes pasivos, el aumento de la frecuencia de conmutación puede mejorar significativamente prestaciones dinámicas de convertidores de potencia. Almacenamiento de energía pequeña y el período de conmutación corto conducen a una respuesta transitoria del convertidor más rápida en presencia de las variaciones de la tensión de entrada o de la carga. Las limitaciones más importantes del incremento de la frecuencia de conmutación se relacionan con mayores pérdidas del núcleo magnético convencional, así como las pérdidas de los devanados debido a los efectos pelicular y proximidad. También, un problema potencial es el aumento de los efectos de los elementos parásitos de los componentes magnéticos - inductancia de dispersión y la capacidad entre los devanados - que causan pérdidas adicionales debido a las corrientes no deseadas. Otro factor limitante supone el incremento de las pérdidas de conmutación y el aumento de la influencia de los elementos parásitos (pistas de circuitos impresos, interconexiones y empaquetado) en el comportamiento del circuito. El uso de topologías resonantes puede abordar estos problemas mediante el uso de las técnicas de conmutaciones suaves para reducir las pérdidas de conmutación incorporando los parásitos en los elementos del circuito. Sin embargo, las mejoras de rendimiento se reducen significativamente debido a las corrientes circulantes cuando el convertidor opera fuera de las condiciones de funcionamiento nominales. A medida que la tensión de entrada o la carga cambian las corrientes circulantes incrementan en comparación con aquellos en condiciones de funcionamiento nominales. Se pueden obtener muchos beneficios potenciales de la operación de convertidores resonantes a más alta frecuencia si se emplean en aplicaciones con condiciones de tensión de entrada favorables como las que se encuentran en las arquitecturas de potencia distribuidas. La regulación de la carga y en particular la regulación de la tensión de entrada reducen tanto la densidad de potencia del convertidor como el rendimiento. Debido a la relativamente constante tensión de bus que se encuentra en arquitecturas de potencia distribuidas los convertidores resonantes son adecuados para el uso en convertidores de tipo bus (transformadores cc/cc de estado sólido). En el mercado ya están disponibles productos comerciales de transformadores cc/cc de dos puertos que tienen muy alta densidad de potencia y alto rendimiento se basan en convertidor resonante serie que opera justo en la frecuencia de resonancia y en el orden de los megahercios. Sin embargo, las mejoras futuras en el rendimiento de las arquitecturas de potencia se esperan que vengan del uso de dos o más buses de distribución de baja tensión en vez de una sola. Teniendo eso en cuenta, el objetivo principal de esta tesis es aplicar el concepto del convertidor resonante serie que funciona en su punto óptimo en un nuevo transformador cc/cc bidireccional de puertos múltiples para atender las necesidades futuras de las arquitecturas de potencia. El nuevo transformador cc/cc bidireccional de puertos múltiples se basa en la topología de convertidor resonante serie y reduce a sólo uno el número de componentes magnéticos. Conmutaciones suaves de los interruptores hacen que sea posible la operación en las altas frecuencias de conmutación para alcanzar altas densidades de potencia. Los problemas posibles con respecto a inductancias parásitas se eliminan, ya que se absorben en los Resumen elementos del circuito. El convertidor se caracteriza con una muy buena regulación de la carga propia y cruzada debido a sus pequeñas impedancias de salida intrínsecas. El transformador cc/cc de puertos múltiples opera a una frecuencia de conmutación fija y sin regulación de la tensión de entrada. En esta tesis se analiza de forma teórica y en profundidad el funcionamiento y el diseño de la topología y del transformador, modelándolos en detalle para poder optimizar su diseño. Los resultados experimentales obtenidos se corresponden con gran exactitud a aquellos proporcionados por los modelos. El efecto de los elementos parásitos son críticos y afectan a diferentes aspectos del convertidor, regulación de la tensión de salida, pérdidas de conducción, regulación cruzada, etc. También se obtienen los criterios de diseño para seleccionar los valores de los condensadores de resonancia para lograr diferentes objetivos de diseño, tales como pérdidas de conducción mínimas, la eliminación de la regulación cruzada o conmutación en apagado con corriente cero en plena carga de todos los puentes secundarios. Las conmutaciones en encendido con tensión cero en todos los interruptores se consiguen ajustando el entrehierro para obtener una inductancia magnetizante finita en el transformador. Se propone, además, un cambio en los señales de disparo para conseguir que la operación con conmutaciones en apagado con corriente cero de todos los puentes secundarios sea independiente de la variación de la carga y de las tolerancias de los condensadores resonantes. La viabilidad de la topología propuesta se verifica a través una extensa tarea de simulación y el trabajo experimental. La optimización del diseño del transformador de alta frecuencia también se aborda en este trabajo, ya que es el componente más voluminoso en el convertidor. El impacto de de la duración del tiempo muerto y el tamaño del entrehierro en el rendimiento del convertidor se analizan en un ejemplo de diseño de transformador cc/cc de tres puertos y cientos de vatios de potencia. En la parte final de esta investigación se considera la implementación y el análisis de las prestaciones de un transformador cc/cc de cuatro puertos para una aplicación de muy baja tensión y de decenas de vatios de potencia, y sin requisitos de aislamiento. Abstract Recently, switch mode power supplies (SMPS) have been used in a great variety of applications. The most challenging issue for designers of SMPS is to achieve simultaneously high efficiency operation at high power density. The size and weight of a power converter is dominated by the passive components since these elements are normally larger and heavier than other elements in the circuit. If the output power is constant, the stored amount of energy in the converter which is to be delivered to the load in each switching cycle is inversely proportional to the converter’s switching frequency. Therefore, increasing the switching frequency is considered a mean to achieve more compact solutions at higher power density levels. The importance of investigation in high switching frequency range comes from all the benefits that can be achieved. Besides the reduction in size of passive components, increasing switching frequency can significantly improve dynamic performances of power converters. Small energy storage and short switching period lead to faster transient response of the converter against the input voltage and load variations. The most important limitations for pushing up the switching frequency are related to increased conventional magnetic core loss as well as the winding loss due to the skin and proximity effect. A potential problem is also increased magnetic parasitics – leakage inductance and capacitance between the windings – that cause additional loss due to unwanted currents. Higher switching loss and the increased influence of printed circuit boards, interconnections and packaging on circuit behavior is another limiting factor. Resonant power conversion can address these problems by using soft switching techniques to reduce switching loss incorporating the parasitics into the circuit elements. However the performance gains are significantly reduced due to the circulating currents when the converter operates out of the nominal operating conditions. As the input voltage or the load change the circulating currents become higher comparing to those ones at nominal operating conditions. Multiple Input-Output Many potential gains from operating resonant converters at higher switching frequency can be obtained if they are employed in applications with favorable input voltage conditions such as those found in distributed power architectures. Load and particularly input voltage regulation reduce a converter’s power density and efficiency. Due to a relatively constant bus voltage in distributed power architectures the resonant converters are suitable for bus voltage conversion (dc/dc or solid state transformation). Unregulated two port dc/dc transformer products achieving very high power density and efficiency figures are based on series resonant converter operating just at the resonant frequency and operating in the megahertz range are already available in the market. However, further efficiency improvements of power architectures are expected to come from using two or more separate low voltage distribution buses instead of a single one. The principal objective of this dissertation is to implement the concept of the series resonant converter operating at its optimum point into a novel bidirectional multiple port dc/dc transformer to address the future needs of power architectures. The new multiple port dc/dc transformer is based on a series resonant converter topology and reduces to only one the number of magnetic components. Soft switching commutations make possible high switching frequencies to be adopted and high power densities to be achieved. Possible problems regarding stray inductances are eliminated since they are absorbed into the circuit elements. The converter features very good inherent load and cross regulation due to the small output impedances. The proposed multiple port dc/dc transformer operates at fixed switching frequency without line regulation. Extensive theoretical analysis of the topology and modeling in details are provided in order to compare with the experimental results. The relationships that show how the output voltage regulation and conduction losses are affected by the circuit parasitics are derived. The methods to select the resonant capacitor values to achieve different design goals such as minimum conduction losses, elimination of cross regulation or ZCS operation at full load of all the secondary side bridges are discussed. ZVS turn-on of all the switches is achieved by relying on the finite magnetizing inductance of the Abstract transformer. A change of the driving pattern is proposed to achieve ZCS operation of all the secondary side bridges independent on load variations or resonant capacitor tolerances. The feasibility of the proposed topology is verified through extensive simulation and experimental work. The optimization of the high frequency transformer design is also addressed in this work since it is the most bulky component in the converter. The impact of dead time interval and the gap size on the overall converter efficiency is analyzed on the design example of the three port dc/dc transformer of several hundreds of watts of the output power for high voltage applications. The final part of this research considers the implementation and performance analysis of the four port dc/dc transformer in a low voltage application of tens of watts of the output power and without isolation requirements.

Criterios técnicos del proyecto con módulos tridimensionales ligeros: las casas del Solar Decathlon 2005 y 2007

Este trabajo se ocupa de la construcción modular ligera de viviendas unifamiliares, más concretamente aborda el problema de la definición constructiva de las mismas, habida cuenta de lo poco conocido y publicado de este aspecto en particular. Dado que la construcción es fruto de la evolución, resulta de gran importancia el estudio de los antecedentes para comprender la situación actual, por ello para documentar como corresponde el estado de la técnica y de la investigación se estudiaron los antecedentes desde sus primeras manifestaciones a finales del siglo XIX hasta nuestros días. Contrariamente a las profecías de Le Corbusier y otros, la industrialización no ha llegado a la construcción ni en la forma ni en la medida que era de esperar a principios del siglo XX. Sin embargo y a pesar del relativo “fracaso” de la industrialización en convertirse en la forma mayoritaria de producir edificios, lo cierto es que algunos sistemas altamente industrializados, como lo es la construcción modular ligera, han logrado un lugar en el mercado, que en algunos países resulta cuanto menos significativo. Delimitar el estado de la técnica y la situación actual es crucial en este trabajo, toda vez que la construcción industrializada la realizan empresas, y situarse al margen de las mismas y de su producción, nos guste o no, resulta contrario al sentido común. De este modo se han identificado y documentado ejemplos como el de EE.UU. y Japón, entre otros, que resultan muy ilustrativos tanto desde la evolución como del estado actual. Del estado de la técnica y la investigación también resulta la escasez de publicación de detalles constructivos específicos de la construcción modular ligera. Es obvio que los fabricantes intentan blindarse mediante el secreto industrial, logrando que las soluciones constructivas más interesantes queden fuertemente protegidas dentro del conocimiento reservado de la empresa. De este modo un sistema que alcanza grados de prefabricación del 95%, tan atractivo e interesante para el arquitecto queda reservado al conocimiento de unos pocos dentro de las empresas. La búsqueda de mayor información sobre estos sistemas encuentra un filón indiscutible en los proyectos de las casas del concurso Solar Decathlon. En efecto, debido a las condiciones particulares de este concurso, las casas que compiten deben ser instaladas en un plazo corto, por lo que en su mayoría recurren al método de construcción modular ligera, para lograr correctamente este objetivo. Adicionalmente todos los planos de proyecto incluidos los de detalle, así como memorias de especificaciones técnicas, quedan colgadas en la Web, a libre disposición del público. De este modo se ha considerado interesante, conveniente y útil, aprovechar como fuente documental de este trabajo, aparte de lo obtenido en el estado de la técnica y la investigación, los proyectos de las casas de los concursos 2005 y 2007, que fueron las dos últimas ediciones celebradas cuando se inició esta tesis. De modo similar a esta carencia de detalles publicados se observa igualmente una falta de investigación y de metodologías adecuadas a la misma sobre soluciones y detalles constructivos propios de la construcción modular ligera. Por eso y ante la dificultad de manejar adecuadamente una información disponible pero farragosa, este trabajo ha dedicado una parte importante de su esfuerzo a la creación de una metodología adecuada a este tipo de situación. Hay que destacar que cada proyecto puede constar fácilmente de 60 a casi 200 planos, sin contar las memorias técnicas y otros documentos, tales como galerías de imágenes, etc. Por otra parte resulta útil establecer esta metodología, no solo para esta tesis, sino para futuros trabajos de investigación sobre el tema, toda vez que con posterioridad a 2007 se han celebrado nuevas ediciones del concurso con su correspondiente volumen de información disponible. La metodología del análisis de los proyectos se basa en el diseño y creación de siete fichas tipo que resumen los aspectos fundamentales del proyecto desde el punto de vista constructivo, permitiendo de este modo su rápida visualización y comprensión sin pretender exhaustividad, ya que en caso de querer profundizar en el detalle de la información siempre está el proyecto original para ello. Tras estudiar la información obtenida de los proyectos de las casas de concurso, se contrastan y discuten los resultados para obtener conocimientos de interés para el objetivo propuesto en la tesis. Se comparan los resultados procedentes del estado de la técnica y de la investigación y se obtienen las conclusiones correspondientes. De este modo ha sido posible identificar una serie de criterios técnicos de proyecto de viviendas unifamiliares realizadas mediante construcción modular ligera, que además se organizan en varios niveles, por lo que el resultado es un conjunto de criterios como germen de una futura guía o manual. Como conclusiones fundamentales de la tesis hay que destacar las metodológicas, que habilitan la extensión de este estudio a otros trabajos y la aportación original al conocimiento con la definición de una serie de criterios técnicos de proyecto de viviendas realizadas mediante construcción modular ligera, que además de mejorar esta parte del saber constructivo serán de gran ayuda a los arquitectos de cara a la reducción de errores, que a menudo derivan en mayores costes y plazos, cuando no directamente al abandono del sistema constructivo. El trabajo de la tesis se estructura en siete capítulos a saber: Capítulo 1: Introducción, donde se explica el tema de la tesis, el objetivo principal, las limitaciones y se aportan algunas definiciones. Capítulo 2: Estado de la técnica y la investigación, dentro del cual se presentan los antecedentes desde sus inicios pasando por la primera y segunda mitad del siglo XX y finalizando con el estado actual que recorre los sistemas de EE.UU, Japón, Europa, Escandinavia, centro Europa, Francia, España y algunos ejemplos de Latinoamérica. En el estado de la investigación se presentan las publicaciones tanto en revistas científicas indexadas en el JCR, como publicaciones no indexadas en las que se muestran artículos científicos, comunicaciones a congresos, documentación sobre el concurso Solar Decathlon, libros específicos y libros genéricos sobre construcción modular ligera, tesis doctorales tanto generales como específicas sobre el concurso Solar Decathlon, documentos de idoneidad técnica, páginas Web del concurso Solar Decathlon y finalmente páginas Web de empresas de construcción modular ligera y patentes. También se expresan las conclusiones parciales del capítulo así también como la justificación y los objetivos particulares. Capítulo 3: Metodología, se expone en primer lugar el planteamiento del problema, para luego desarrollar los métodos utilizados para el estudio y clasificación del transporte y de la organización modular, la relación entre la organización modular y distribución espacial, el diseño y contenido de las fichas resumen de los 38 proyectos presentados al SD2005 y SD2007, así también como la información consultada para su realización. Se explica asimismo como se realizaron las tablas comparativas partiendo de la información de las fichas. Finalmente se expresa la manera en que se trató el estudio particular de la junta entre módulos. Capítulo 4: Discusión de resultados, dónde en primer lugar se presenta la clasificación y las estrategias del transporte así también como una clasificación de la organización modular, en segundo lugar se estudian las relaciones que existen entre el sistema modular y la organización espacial. A partir de aquí se muestra el estudio de la estructura de todas las casas del SD2005 y SD2007, según el tipo y material de las zapatas, mostrando tanto tablas cuantitativas como tablas gráficas con fotos. De la misma manera se tratan los forjados, los pilares y las vigas y las cubiertas. Se estudia además el cerramiento opaco y acristalado, la cubierta y el forjado según las capas que lo componen. En el caso de las instalaciones se estudian las que son especiales, descartando las normales en este tipo de casas, como son los paneles fotovoltaicos, placas térmicas o tubos de vacío y los sistemas de almacenamiento de energía, como las baterías, presentando tablas numéricas y gráficas con fotos. El transporte se analiza según corresponda al traslado de la vivienda o al transporte de apoyo, según el tipo y la cantidad utilizado. Con respecto al montaje se diferencia en si se usó grúa o no, y en el caso de no utilizarse se muestran los métodos alternativos. Con respecto a la exploración de la organización modular se presentan la cantidad de módulos que utilizó cada casa, así como también la cuantificación de los sistemas híbridos como son elementos lineales 1D, paneles 2D. Por último se muestra el estudio detallado de la junta entre módulos 3D. Finalmente se realiza la propuesta de un conjunto de criterios técnicos de proyecto organizado en cuatro niveles: 1º nivel de criterios generales, 2º nivel sobre sistemas constructivos, 3º nivel de detalles constructivos y el 4º nivel llamado logística obras previas, transporte y montaje. Capítulo 5: Conclusiones y líneas futuras de investigación, se exponen las conclusiones generales, metodológicas, documentales y por último las de construcción modular. Finalmente se realiza una propuesta de líneas futuras de investigación. Capítulo 6: Bibliografía. Capítulo 7: Anexos, en el que se presentan todas las fichas resumen de las casas realizadas por el autor de esta tesis. Además se incluyen los casos concretos de Voisin en Francia y la TVA (Tennessee Valley Authority) en EE.UU., así como referencias de manuales genéricos de construcción ligera, medidas de transporte en España e información sobre estadísticas de viviendas en la Unión Europea. ABSTRACT This paper deals with Light Modular Construction of houses, and specifically addresses the problem of the constructive definition of the same, given how little known and published this subject has been. Since building construction is the result of evolution, it is of great importance to study its background for understanding the current situation, therefore to document the state of the art and research, its history was studied from its origins dating to the end nineteenth century to our days. Contrary to the prophecies of Le Corbusier and others, industrialization has not reached the construction neither in the form nor to the extent that it was expected in the early twentieth century. However, despite the relative "failure" of industrialization to become the major form of production for buildings, the fact is that some highly industrialized systems, such as the so called Lightweight Modular Construction, have achieved a place in the market, which in some countries is at least significant. To outline the state of the art and the current situation is crucial in this work, since industrialized construction is carried out by companies, and to step away from them and their production, whether we like it or not, it is contrary to common sense. So that, several cases have been identified and documented, such as the US and Japan examples, among others, which are very illustrative both from evolution and the current status. The state of the art and research shows also a shortage of publication of specific construction details of light modular construction. Obviously, manufacturers try to shield themselves by trade secret, making the most interesting constructive solutions remain heavily protected within the reserved knowledge of the company, so a system that reaches levels of 95% prefabrication, so attractive and interesting for the architect It is reserved to the knowledge of a few people inside the companies. The search for more information on these systems finds an invaluable reef in the projects of the Solar Decathlon houses. Indeed, due to the particular conditions of this contest, houses competing must be installed in a short time, so mostly turn to modular construction methods for this purpose to achieve properly this goal. Additionally all levels of project, including detailed and technical specifications reports are published on the Web, freely available to the general public. Thus it was considered interesting, convenient and useful to take advantage as a documentary source of this work, apart from what it were obtained in the state of the art and research, the projects of the houses of the 2005 and 2007 contests, which were the last two editions already held before this thesis was started. Similar to this lack of published details it is also observed a lack of research and methodologies adapted to the solutions and construction details of lightweight modular construction. So that, and facing the difficulty of adequately manage the available but bulky information, this work has devoted a significant part of its effort to create an appropriate methodology for this type of situation. It is noteworthy that each project can easily consist of 60 to almost 200 blueprints, not including technical reports and other documents, such as photo galleries, etc. The methodology of the analysis of the projects is based on the design and creation of seven record sheets that summarize key aspects of the project from a construction point of view, thus allowing quick watching and understanding of the project, without claiming completeness, always keeping for further information the blueprints themselves. After studying the information obtained from the projects of the competition houses, the results are compared and discussed to obtain relevant knowledge according to the objective proposed in the thesis. The results from the state of the art and research are also compared and the conclusions so obtained make possible to identify a number of technical design criteria for single family homes made using lightweight modular construction, which also have been organized at various levels, so the result is a set of criteria as a seed for a future guide or manual. Among the main conclusions of the thesis must be noted the methodological ones, that enable the extension of this study to other works and are an original contribution to knowledge with the definition of a number of technical criteria for housing projects made by light modular construction, what in addition to improving this part of the constructive knowledge will be of great help for the architects to reduce errors that often result in higher costs and delays, if not in abandonment of the construction system itself. The work of the thesis is divided into seven chapters as follows: Chapter 1: Introduction, where the topic of the thesis, the main objective, limitations and the provided definitions is explained. Chapter 2: State of the art and research, within which history is presented from the beginning through the first and second half of the twentieth century and ending with the current systems, that spans from the USA to Japan, Europe, Scandinavia, Central Europe, France, Spain and some Latin American examples. In the state of research publications are presented both on scientific journals indexed in the JCR, and non-indexed publications in which scientific articles, conference papers, information about the Solar Decathlon competition, generic and specific books on light modular construction, articles both general and specific on the Solar Decathlon competition, technical approval documents, dissertations, the Solar Decathlon Web pages and finally lightweight modular construction companies Web pages and patents. The partial conclusions of the chapter as well as the rationale and specific objectives are also expressed. Chapter 3: Methodology first of all exposes the problem statement and then develops the methods used for the study and classification of transportation and modular organization, the relationship between the modular organization and spatial distribution, design and content summary records of the 38 projects submitted to the SD2005 and SD2007, as well as information consulted for its realization. It explains equally how the comparative tables based on information from the chips were made. Finally, the way the particular study of the joint between modules is carried out is also treated. Chapter 4: Discussion, first sorting a classification of transport strategies as well as of modular organization, secondly the relationship between the modular system and the spatial organization studied is presented. From then on, the study of the structure of every house Moreover, to establish this methodology is useful not only for this thesis, but for future research on the subject, since after 2007 there have been held new editions of the contest with a corresponding volume of information available. shown in the SD2005 and SD2007 contests, depending on the type and material of the shoe, showing both quantitative tables as graphic boards with pictures is carried out. Similarly slabs, columns and beams and roofs are treated. Furthermore, the opaque and transparent façades, as well as roof and floor enclosure, according to the layers that compose them are studied. In the case of facilities there have been only addressed that which are of a special type, discarding that considered usual in this type of houses such as photovoltaic panels, thermal panels or vacuum tubes and energy storage systems such as batteries, presenting numerical and graphical tables with photos .The transportation is analyzed depending on it is used to move the house or for additional support, depending on the type and quantity of items used. Regarding assembly it has been made a difference if crane is or not used and if not, what the alternative methods are. With respect to the exploration of the modular organization, the amount of modules used in each house is presented, as well as the quantification of hybrid systems such as linear members as well as 1D, 2D panels. Finally, it has been carried out the detailed study of the joint between 3D modules. Finally it is proposed a set of technical criteria organized into four levels, 1st level of general criteria, 2nd level on building systems, 3rd level construction details and 4th level called previous works and logistics, transportation and assembly. Chapter 5: Conclusions and future research, where general, methodological, documentary and finally modular construction findings are presented. A proposal for further research is done. Chapter 6: Bibliography. Chapter 7: Annexes, in which all the record sheets of houses made by the author of this thesis are presented. Besides the specific cases of Voisin in France and TVA (Tennessee Valley Authority) in the USA, as well as general reference manuals on lightweight construction, transportation dimensions in Spain, and information on housing statistics in the European Union are included.

Localization of the C terminus of the assembly domain of hepatitis B virus capsid protein: Implications for morphogenesis and organization of encapsidated RNA

The capsid protein of hepatitis B virus, consisting of an “assembly” domain (residues 1–149) and an RNA-binding “protamine” domain (residues 150–183), assembles from dimers into icosahedral capsids of two different sizes. The C terminus of the assembly domain (residues 140–149) functions as a morphogenetic switch, longer C termini favoring a higher proportion of the larger capsids, it also connects the protamine domain to the capsid shell. We now have defined the location of this peptide in capsids assembled in vitro by engineering a mutant assembly domain with a single cysteine at its C terminus (residue 150), labeling it with a gold cluster and visualizing the cluster by cryo-electron microscopy. The labeled protein is unimpaired in its ability to form capsids. Our density map reveals a single undecagold cluster under each fivefold and quasi-sixfold vertex, connected to sites at either end of the undersides of the dimers. Considering the geometry of the vertices, the C termini must be more crowded at the fivefolds. Thus, a bulky C terminus would be expected to favor formation of the larger (T = 4) capsids, which have a greater proportion of quasi-sixfolds. Capsids assembled by expressing the full-length protein in Escherichia coli package bacterial RNAs in amounts equivalent to the viral pregenome. Our density map of these capsids reveals a distinct inner shell of density—the RNA. The RNA is connected to the protein shell via the C-terminal linkers and also makes contact around the dimer axes.

In vitro repair of oxidative DNA damage by human nucleotide excision repair system: Possible explanation for neurodegeneration in Xeroderma pigmentosum patients

Xeroderma pigmentosum (XP) patients fail to remove pyrimidine dimers caused by sunlight and, as a consequence, develop multiple cancers in areas exposed to light. The second most common sign, present in 20–30% of XP patients, is a set of neurological abnormalities caused by neuronal death in the central and peripheral nervous systems. Neural tissue is shielded from sunlight-induced DNA damage, so the cause of neurodegeneration in XP patients remains unexplained. In this study, we show that two major oxidative DNA lesions, 8-oxoguanine and thymine glycol, are excised from DNA in vitro by the same enzyme system responsible for removing pyrimidine dimers and other bulky DNA adducts. Our results suggest that XP neurological disease may be caused by defective repair of lesions that are produced in nerve cells by reactive oxygen species generated as by-products of an active oxidative metabolism.