Poblamiento americano y otras hipótesis del Abate Molina

MEMORIA Sobre la propagación sucesiva del género humano1por el Abate Juan Ignacio Molina  

Bovine polledness

The persistent horns are an important trait of speciation for the family Bovidae with complex morphogenesis taking place briefly after birth. The polledness is highly favourable in modern cattle breeding systems but serious animal welfare issues urge for a solution in the production of hornless cattle other than dehorning. Although the dominant inhibition of horn morphogenesis was discovered more than 70 years ago, and the causative mutation was mapped almost 20 years ago, its molecular nature remained unknown. Here, we report allelic heterogeneity of the POLLED locus. First, we mapped the POLLED locus to a ∼381-kb interval in a multi-breed case-control design. Targeted re-sequencing of an enlarged candidate interval (547 kb) in 16 sires with known POLLED genotype did not detect a common allele associated with polled status. In eight sires of Alpine and Scottish origin (four polled versus four horned), we identified a single candidate mutation, a complex 202 bp insertion-deletion event that showed perfect association to the polled phenotype in various European cattle breeds, except Holstein-Friesian. The analysis of the same candidate interval in eight Holsteins identified five candidate variants which segregate as a 260 kb haplotype also perfectly associated with the POLLED gene without recombination or interference with the 202 bp insertion-deletion. We further identified bulls which are progeny tested as homozygous polled but bearing both, 202 bp insertion-deletion and Friesian haplotype. The distribution of genotypes of the two putative POLLED alleles in large semi-random sample (1,261 animals) supports the hypothesis of two independent mutations

Modeling, Observing and Controlling a Cable-Suspended Aerial Manipulator as a Constrained System

The cable-suspended aerial manipulator is a robot consisting of a platform that is fully actuated with a system of 8 propellers, to which a 7-degrees of freedom manipulator is attached. It can be used for manipulation tasks at locations that are in great height or otherwise difficult to access from the ground. The system can be modeled in different ways, four of which are sketched in this thesis, before their equivalence is demonstrated. In particular, modeling it as a collection of rigid bodies subject to Pfaffian constraints is further developed. Different models of the cable-suspended aerial manipulator providing a variety in complexity and accuracy is presented. Subsequently, experimental data is used to validate two selected models and show their respective benefits and drawbacks. Furthermore, the data is used to identify some parameters defining the system's behavior. The full state of the system can not be measured using proprioceptive sensors. Therefore, an observer is extended to be applicable to the system. It runs on exterioceptive sensors' pose and velocity measurements and provides estimate of the full absolute pose. In addition to the observer, a position controller is proposed. The observer and the controller are extensively analyzed using simulations. Finally, the observers is applied to experimental data to show their applicability to the cable- suspended aerial manipulator

Geschlechtsspezifische Unterschiede in der Lebensqualität von Patienten mit Lungenkarzinom: Die ambulante und stationäre Betreuung im Vergleich

Bei zunehmend längeren Überlebensraten von Patienten mit Lungenkarzinom und einer stetig wachsenden Bedeutung der ambulanten Behandlung rückt die Lebensqualität von Patienten mit Lungenkarzinom weiter in den Mittelpunkt der Forschung. Die große Relevanz der Lebensqualität im klinischen und therapeutischen Verlauf des Lungenkarzinoms macht den diesbezüglichen Vergleich der ambulanten und stationären Behandlung interessant. Das Ziel dieser prospektiven Querschnittstudie war es, die Lebensqualität von Patienten mit Lungenkrebs im Hinblick auf Genderaspekte zu untersuchen. Um die bisherigen Erkenntnisse dahingehend weiter zu spezifizieren, wurde neben dem Geschlecht das Behandlungssetting herausgegriffen. Es werden Unterschiede in der Lebensqualität von Erkrankten mit ambulant und stationär erfolgter Therapie betrachtet sowie Frauen und Männer innerhalb der ambulanten und stationären Behandlung auf genderspezifische Aspekte in der Lebensqualität untersucht. Die Datenerhebung erfolgte mittels der Fragebögen EORTC QLQ-C30 sowie QLQ-LC29. Das Studienkollektiv umfasst 198 Patienten (weiblich/ambulant: 40, weiblich/stationär: 33, männlich/ambulant: 45, männlich/stationär 80; medianes Alter: 64,5 Jahre). Im Vergleich von ambulant und stationär behandelten Patienten ergeben sich für den Summenscore (geschätzter Randmittelwert: ambulant 74,6 und stationär 65,4, p = 0,002) des QLQ-C30 sowie auf den Skalen physische Funktion (geschätzter Randmittelwert: ambulant 76,9 und stationär 62,3, p < 0,001), Rollenfunktion (geschätzter Randmittelwert: ambulant 66,8 und stationär 51,9, p = 0,004), Global Health Score (geschätzter Randmittelwert: ambulant 65,3 und stationär 51,8, p < 0,001), Fatigue (geschätzter Randmittelwert: ambulant 41,1 und stationär 51,1, p = 0,023), Schmerz (geschätzter Randmittelwert: ambulant 21,0 und stationär 32,3, p = 0,027), Appetitverlust (geschätzter Randmittelwert: ambulant 17,4 und stationär 33,7, p = 0,004), Diarrhoe (geschätzter Randmittelwert: ambulant 7,8 und stationär 16,5, p = 0,034), Husten (geschätzter Randmittelwert: ambulant 28,4 und stationär 37,5, p = 0,050), Sprechprobleme (geschätzter Randmittelwert: ambulant -0,5 und stationär 12,1, p = 0,002) und Gewichtsverlust (geschätzter Randmittelwert: ambulant 17,2 und stationär 32,8, p = 0,008) signifikante Resultate. Auf den Skalen Haarverlust (geschätzter Randmittelwert: ambulant 41,0 und stationär 30,9, p = 0,054) sowie entzündete Augen (geschätzter Randmittelwert: ambulant 22,7 und stationär 14,2, p= 0,040) ergeben sich signifikant schlechtere Ergebnisse für die ambulanten Patienten. Innerhalb der ambulanten Patienten resultiert aus erhobenen Daten nur auf der Skala wunder Mund (geschätzter Randmittelwert: männlich/ambulant 13,5 und weiblich/ambulant 1,2, p= 0,012) eine signifikant höhere Symptomlast des männlichen Geschlechts. Stationär ergibt sich eine signifikant höhere Symptomlast des weiblichen Geschlechts auf den Skalen Übelkeit/Erbrechen (geschätzter Randmittelwert: männlich/stationär 9,3 und weiblich/stationär 17,6, p= 0,037), Haarverlust (geschätzter Randmittelwert: männlich/stationär 21,7 und weiblich/stationär 40,0, p= 0,010) sowie Schwindel (geschätzter Randmittelwert: männlich/stationär 17,5 und weiblich/stationär 32,4, P = 0,014). Dem gegenüber liegt im stationären Bereich zwischen Frauen und Männern ein signifikanter Unterschied des Global Health Scores (geschätzter Randmittelwert: männlich/stationär 46,1 und weiblich/stationär 57,5, p= 0,016) vor, der für Männer deutlich ungünstiger ausfällt als für Frauen. Der Unterschied der Lebensqualität von ambulanten und stationären Patienten lässt sich anhand der Ergebnisse eindeutig belegen. Es zeigt sich homogen, dass ambulante Patienten auf den Funktions- sowie Symptomskalen eine günstigere Lebensqualität und eine geringere Symptomlast aufweisen. Im ambulanten Bereich ergeben sich auf den Skalen für die Subgruppen der Geschlechter weitgehend ähnliche Werte oder lediglich Tendenzen für eine größere Symptomlast des weiblichen Geschlechts. Damit werden Beschwerden durch unterschiedliche Copingstrategien weniger konkret und machen genderspezifische Unterschiede im ambulanten Bereich weniger präsent. Mit Blick auf die stationären Subgruppen ist die Symptomlast der Männer geringer und die Lebensqualität besser als bei Frauen, was aber im Vergleich nicht derart beurteilt wird. Die subjektive Lebensqualität wird von Männern schlechter eingeschätzt als von Frauen. Die Daten dieser Studie zeigen, dass die Therapie bei Frauen im stationären Alltag ausgeprägteren Symptomen als bei Männern begegnen muss. Die Diskrepanz zwischen der Symptomlast der Männer und der männlichen Einschätzung gibt Anlass das männliche Selbstbild, einen psychosozialen Betreuungsbedarf sowie eine geringere Akzeptanz des stationären Aufenthalts zu diskutieren. Dagegen kann das weibliche Geschlecht eine stationäre Behandlung in diesem Kontext subjektiv besser kompensieren

Novel Insights into the Bovine Polled Phenotype and Horn Ontogenesis in Bovidae

Despite massive research efforts, the molecular etiology of bovine polledness and the developmental pathways involved in horn ontogenesis are still poorly understood. In a recent article, we provided evidence for the existence of at least two different alleles at the Polled locus and identified candidate mutations for each of them. None of these mutations was located in known coding or regulatory regions, thus adding to the complexity of understanding the molecular basis of polledness. We confirm previous results here and exhaustively identify the causative mutation for the Celtic allele (PC) and four candidate mutations for the Friesian allele (PF). We describe a previously unreported eyelash-and-eyelid phenotype associated with regular polledness, and present unique histological and gene expression data on bovine horn bud differentiation in fetuses affected by three different horn defect syndromes, as well as in wild-type controls. We propose the ectopic expression of a lincRNA in PC/p horn buds as a probable cause of horn bud agenesis. In addition, we provide evidence for an involvement of OLIG2, FOXL2 and RXFP2 in horn bud differentiation, and draw a first link between bovine, ovine and caprine Polled loci. Our results represent a first and important step in understanding the genetic pathways and key process involved in horn bud differentiation in Bovidae

Interrogation of modern and ancient genomes reveals the complex domestic history of cattle

The analysis of mitochondrial and nuclear DNA sequence polymorphisms from modern cattle populations has had a profound impact on our understanding of the events surrounding the domestication of cattle. From these studies, it has been possible to distinguish between pre- and post-domestic genetic differentiation, supporting previous assertions from archaeological studies and, in some cases, revealing novel aspects of the demographic history of cattle. Analyses of genetic material retrieved from the remains of extinct ancestral wild cattle have also added valuable layers of information pertaining to cattle domestic origins; however, information from these investigations have, in general, been limited to small, variable portions of the mitochondrial genome owing to technical challenges associated with the retrieval and amplification of ancient DNA. In recent years, however, new high-throughput, massively parallel genomics technology platforms, such as single-nucleotide polymorphism (SNP) genotyping arrays and next-generation sequencing (NGS), have provided a new impetus to the studies of genetic variation in extant and ancient cattle. Arrays of SNP have facilitated high-resolution genetic surveys of global cattle populations and detection of ancient and recent genomic selective sweeps. Next-generation sequencing analyses of modern and ancient cattle hold great promise for identifying and cataloging of pre- and post-domestication patterns of genomic variation and correlating this with natural and artificial selection processes

Initiator-free photo-crosslinkable cellulose-based resists for fabricating submicron patterns via direct laser writing

Novel bifunctional cellulose diacetate derivatives were synthesized in order to achieve bio-based photoresists, which can be structured by two-photon absorption via direct laser writing (DLW) without the need to use a photoinitiator. Therefore, cellulose diacetate is functionalized with thiol moieties and olefinic or methacrylic side groups enabling thiol-conjugated crosslinking. These cellulose derivatives are also photo-crosslinkable via UV irradiation ($\lambda$ = 254 nm and 365 nm) without using an initiator

The 80-kb DNA duplication on BTA1 is the only remaining candidate mutation for the polled phenotype of Friesian origin

Background: The absence of horns, called polled phenotype, is the favored trait in modern cattle husbandry. To date, polled cattle are obtained primarily by dehorning calves. Dehorning is a practice that raises animal welfare issues, which can be addressed by selecting for genetically hornless cattle. In the past 20 years, there have been many studies worldwide to identify unique genetic markers in complete association with the polled trait in cattle and recently, two different alleles at the POLLED locus, both resulting in the absence of horns, were reported: (1) the Celtic allele, which is responsible for the polled phenotype in most breeds and for which a single candidate mutation was detected and (2) the Friesian allele, which is responsible for the polled phenotype predominantly in the Holstein-Friesian breed and in a few other breeds, but for which five candidate mutations were identified in a 260-kb haplotype. Further studies based on genome-wide sequencing and high-density SNP (single nucleotide polymorphism) genotyping confirmed the existence of the Celtic and Friesian variants and narrowed down the causal Friesian haplotype to an interval of 145 kb. Results: Almost 6000 animals were genetically tested for the polled trait and we detected a recombinant animal which enabled us to reduce the Friesian POLLED haplotype to a single causal mutation, namely a 80 kb duplication. Moreover, our results clearly disagree with the recently reported perfect co-segregation of the POLLED mutation and a SNP at position 1 390 292 bp on bovine chromosome 1 in the Holstein-Friesian population. Conclusion: We conclude that the 80-kb duplication, as the only remaining variant within the shortened Friesian haplotype, represents the most likely causal mutation for the polled phenotype of Friesian origin

Utilizing the sensitization effect for direct laser writing in a novel photoresist based on the chitin monomer N-acetyl-D-glucosamine

The great flexibility of direct laser writing arises from the possibility to fabricate precise three-dimensional structures on very small scales as well as the broad range of applicable materials. However, there is still a vast number of promising materials which are currently inaccessible requiring the continuous development of novel photoresists. Here, a new bio-sourced resist is reported which relies on the monomeric unit of chitin, N-acetyl-D-glucosamine, expanding the existing plant-based biopolymer resists by a bio-based monomer from the animal kingdom. In addition it is shown that combined use of two photoinitiators is advantageous over the use of a single one. In our approach, the first photoinitator is a good two-photon absorber at the applied wavelength, while the second photoinitiator exhibits poor two-photon absorbtion abilities, but is better suited for crosslinking of the monomer. The first photoinitiator absorbs the light acting as a sensitizer and transfers the energy to the second initiator, which subsequently forms a radical and initializes the polymerization. This sensitization effect enables a new route to utilize reactive photointiators with a small two-photon absorption cross-section for direct laser writing without changing their chemical structure