Bio-inspired friction switches: adaptive pulley systems

Frictional influences in tendon-driven robotic systems are generally unwanted, with efforts towards minimizing them where possible. In the human hand however, the tendon-pulley system is found to be frictional with a difference between high-loaded static post-eccentric and post-concentric force production of 9-12% of the total output force. This difference can be directly attributed to tendon-pulley friction. Exploiting this phenomenon for robotic and prosthetic applications we can achieve a reduction of actuator size, weight and consequently energy consumption. In this study, we present the design of a bio-inspired friction switch. The adaptive pulley is designed to minimize the influence of frictional forces under low and medium-loading conditions and maximize it under high-loading conditions. This is achieved with a dual-material system that consists of a high-friction silicone substrate and low-friction polished steel pins. The system, designed to switch its frictional properties between the low-loaded and high-loaded conditions, is described and its behavior experimentally validated with respect to the number and spacing of pins. The results validate its intended behavior, making it a viable choice for robotic tendon-driven systems.Comment: Conference. First submission, before review

Evolutionary history of regulatory variation in human populations

Genetic variation in the regulation of gene expression is likely to be a major contributor to phenotypic variation in humans, and it also constitutes an important target of recent natural selection in human populations and plays a major role in morphological evolution. The increasing amount of data of genome and transcriptome variation is now leading to a better annotation of regulatory elements and a growing understanding of how the evolution of gene regulation has shaped human diversity. In this review, we discuss the evolutionary history of the variation in the expression of protein-coding genes in humans. We outline the current methodology for mapping regulatory variants and their distribution in human populations. General mechanisms of regulatory evolution are discussed with a special emphasis on different selective processes targeting gene regulation in human

Genetic and epigenetic contribution to complex traits

Much of the recent advances in functional genomics owe to developments in next-generation sequencing technology, which has contributed to the exponential increase of genomic data available for different human disease and population samples. With functional sequencing assays available to query both the transcriptome and the epigenome, annotation of the non-coding, regulatory genome is steadily improving and providing means to interpret the functional consequences of genetic variants associated with human complex traits. This has highlighted the need to better understand the normal variation in various cellular phenotypes, such as epigenetic modifications, and their transgenerational inheritance. In this review, we discuss different aspects of epigenetic variation in the context of DNA sequence variation and its contribution to complex phenotype

Genomic Selective Constraints in Murid Noncoding DNA

Recent work has suggested that there are many more selectively constrained, functional noncoding than coding sites in mammalian genomes. However, little is known about how selective constraint varies amongst different classes of noncoding DNA. We estimated the magnitude of selective constraint on a large dataset of mouse-rat gene orthologs and their surrounding noncoding DNA. Our analysis indicates that there are more than three times as many selectively constrained, nonrepetitive sites within noncoding DNA as in coding DNA in murids. The majority of these constrained noncoding sites appear to be located within intergenic regions, at distances greater than 5 kilobases from known genes. Our study also shows that in murids, intron length and mean intronic selective constraint are negatively correlated with intron ordinal number. Our results therefore suggest that functional intronic sites tend to accumulate toward the 5' end of murid genes. Our analysis also reveals that mean number of selectively constrained noncoding sites varies substantially with the function of the adjacent gene. We find that, among others, developmental and neuronal genes are associated with the greatest numbers of putatively functional noncoding sites compared with genes involved in electron transport and a variety of metabolic processes. Combining our estimates of the total number of constrained coding and noncoding bases we calculate that over twice as many deleterious mutations have occurred in intergenic regions as in known genic sequence and that the total genomic deleterious point mutation rate is 0.91 per diploid genome, per generation. This estimated rate is over twice as large as a previous estimate in murids

The resolution of the genetics of gene expression

Understanding the influence of genetics on the molecular mechanisms underpinning human phenotypic diversity is fundamental to being able to predict health outcomes and treat disease. To interrogate the role of genetics on cellular state and function, gene expression has been extensively used. Past and present studies have highlighted important patterns of heritability, population differentiation and tissue-specificity in gene expression. Current and future studies are taking advantage of systems biology-based approaches and advances in sequencing technology: new methodology aims to translate regulatory networks to enrich pathways responsible for disease etiology and 2nd generation sequencing now offers single-molecular resolution of the transcriptome providing unprecedented information on the structural and genetic characteristics of gene expression. Such advances are leading to a future where rich cellular phenotypes will facilitate understanding of the transmission of genetic effect from the gene to organis

On Quality Control Measures in Genome-wide Association Studies: A Test to Assess the Genotyping Quality of Individual Probands in Family-based Association Studies and an Application to the HapMap Data

Allele transmissions in pedigrees provide a natural way of evaluating the genotyping quality of a particular proband in a family-based, genome-wide association study. We propose a transmission test that is based on this feature and that can be used for quality control filtering of genome-wide genotype data for individual probands. The test has one degree of freedom and assesses the average genotyping error rate of the genotyped SNPs for a particular proband. As we show in simulation studies, the test is sufficiently powerful to identify probands with an unreliable genotyping quality that cannot be detected with standard quality control filters. This feature of the test is further exemplified by an application to the third release of the HapMap data. The test is ideally suited as the final layer of quality control filters in the cleaning process of genome-wide association studies. It identifies probands with insufficient genotyping quality that were not removed by standard quality control filtering

Needed for completion of the human genome: hypothesis driven experiments and biologically realistic mathematical models

With the sponsorship of ``Fundacio La Caixa'' we met in Barcelona, November 21st and 22nd, to analyze the reasons why, after the completion of the human genome sequence, the identification all protein coding genes and their variants remains a distant goal. Here we report on our discussions and summarize some of the major challenges that need to be overcome in order to complete the human gene catalog.Comment: Report and discussion resulting from the `Fundacio La Caixa' gene finding meeting held November 21 and 22 2003 in Barcelon

Contact mechanics for soft robotic fingers: modeling and experimentation

Human fingers possess mechanical characteristics, which enable them to manipulate objects. In robotics, the study of soft fingertip materials for manipulation has been going on for a while; however, almost all previous researches have been carried on hemispherical shapes whereas this study concentrates on the use of hemicylindrical shapes. These shapes were found to be more resistant to elastic deformations for the same materials. The purpose of this work is to generate a modified nonlinear contact-mechanics theory for modeling soft fingertips, which is proposed as a power-law equation. The contact area of a hemicylindrical soft fingertip is proportional to the normal force raised to the power of γcy, which ranges from 0 to 1/2. Subsuming the Timoshenko and Goodier (S. P. Timoshenko and J. N. Goodier, Theory of Elasticity, 3rd ed. (McGraw-Hill, New York, 1970) pp. 414-420) linear contact theory for cylinders confirms the proposed power equation. We applied a weighted least-squares curve fitting to analyze the experimental data for different types of silicone (RTV 23, RTV 1701, and RTV 240). Our experimental results supported the proposed theoretical prediction. Results for human fingers and hemispherical soft fingers were also compare

The mounting of a skeleton of the fossil species Candiaceruus sp. II from Liko Cave, Crete, Greece

S'ha muntat un esquelet del cérvol pleistocènic endèmic de Creta per a la nova exhibició del Museu de Geologia de la Universitat d'Atenes. Aquest cérvol difereix de tots els cérvols continentals vivents i extingits, principalment en les seves proporcions. Les mesures i comparacions confirmen aquesta observació, però això no és prou com per a que el públic general se n'adoni del seu impacte. Per contra, un esquelet muntat deixa clar que aquest cérvol tertia uns membres considerablement escurçats, especialment els metàpodes, mentre que la llargària del cos, a la llargària de la columna vertebral, eren més aviat normals. La impressió global és més propera a la d'un bòvid nan insular, com ara Myotragus, que a la d'un cérvol petit, tal com Axis axis. El primer problema a resoldre fou la selecció de material. Ja que mai s'ha trobat un esquelet articulat complet, se n'ha de fer un de compost. Amb aquest motiu, només es varen seleccionar ossos de la classe de talla II (de Vos, 1979 ; Dermitzakis & de Vos, 1987) provinents d'un nivell d'una cova (cova de Liko, estrat B). D'aquesta manera es garanteix un interval geològic estret. Tot seguit, es varen mesurar tots els espècimens disponibles, i es va calcular el promig per a tots els elements. D'acord amb això, es va triar l'exemplar de cada element que més s'apropava a la mitjana calculada. Les peces dretes i esquerres havien de ser de la mateixa mida i robustesa, i els elements contigus havien de casar anatòmicament. Només en alguns casos s'ha hagut de recórrer a triar algun element que faltava a partir d'un llivell diferent, però mai a partir d'una cova diferent i mai a partir d'una classe de talla diferent. S'ha prioritzat la mida, la robustesa i l'ajustament anatòmic, i després que els ossos fossin complets i el color. Hi havia alguns peus articulats disponibles, encara que de mida i robustesa diferents, que s'han emprat per determinar les proporcions correctes i la posició correcta entre les falanges individuals, i els ossos carpians i tarsians. La mateixa cosa fou vàlida per a la columna vertebral. Per a l'establiment de la postura es van fer servir cérvols vivents com a comparació; per a l'extrapolació dels teixits tous (discos intervertebrals, cartílags de les articulacions) també es va recórrer al model dels cérvols vivents. De cara a amagar els bastiments de suport, es va inserir dins els ossos una armadura metàl-lica interna fent forats i fitxant-la amb goma de poliuretà. S'ha fabricat l'esquelet complet en parts modulars bones d'ajuntar pel seu transport fàcil a la mostra. Parts absents petites (principalment processos vertebrals, parts costals i les ales pèlviques) s'han reconstruït amb apoxy, en base a altres elements disponibles de Candiacervus de la cova de Liko a per interpolació del millor ajustament entre dues parts absents. Les traces de la matriu original han estat estretes, per a una impressió millor del material fòssil. Per completar l'esquelet s'ha fet una rèplica del crani de l'espècimen tipus de la classe de talla II de de Vos (1979) i una rèplica de l'espècimen tipus del banyam tipus I de de Vos (1984).For the new exhibition in the Museum of Palaeontology and Geology of the University of Athens a skeleton of the endemic Pleistocene Cretan deer was mounted. This deer differs from all known recent and extinct mainland deer, mainly in its proportions. Measurements and comparisons confirm this observation, but are not enough to make the public realize its impact. A mounted skeleton on the contrary makes it at once clear that this deer had considerably shortened limbs, especially the metapodals, whereas the body length and the vertebral column length are rather normal. The overall impression is closer to that of an insular dwarf bovid like Myotragus than to that of a small deer such as the spotted deer (Axis axis). The first problem to be tackled was the selection of the material. Since a complete articulated skeleton has never been found, a composite had to be made. For this purpose, only bones of size class II (de Vas, 1979; Dermitzakis & de Vas, 1987) coming from one layer of one cave (Liko Cave, layer El were selected. In this way a narrow geological range was assured. Subsequently, tile available specimens were measured, and of all elements the average size was calculated. Accordingly, of each element tile specimen that came tile most close to tile calculated average was selected. Left and right had to be of exactly the same size and robustness, and adjoining elements had to fit anatornically. Only in some cases a missing element had to be chosen from a different layer (layers C and Dl. but never from a different cave, and never from a different size class. Priority was first given to size, robustness and anatomical fitting, and next to completeness and colour. Several articulated feet were available, although of tile wrong size or robustness, which were used in determining the right proportions and right stance between individual phalanges, tarsal and carpal bones. The same was valid for tile vertebral column. For postural aspects, living deer were used as comparison; for extrapolation of soft tissue (intervertebral disks, articulation cartilage) also living deer stood model. In order to keep the supporting fabrication as hidden as possible, an internal metal armature was inserted in tile bones through drilled holes and fixed with polyurethane glue. The complete skeleton is fabricated in ready-to-assemble modular parts for easy transportation and reassembly on the spot. Minor missing parts (mainly vertebral processes, costal parts and tile pelvic wings) have been reconst: ructed in epoxy putty, based on other Candiaceruus elements from Liko or by interpolating the best fit between two existing parts. For a better impression of the fossil material, traces of tile original matrix were left on the bones. A cast of the skull of the type specimen of size II of de Vas (1979) and a cast of tile type specimen of antler type 1 of de Vas (1984) were made to complete the skeleton