Genetic studies of congenital upper limb anomalies

The overall aim of the work reported in this thesis is to improve epidemiological and genetic knowledge of congenital upper limb anomalies (CULA). To accomplish the specific aims of each paper several different methods and approaches have been used such as register studies, array comparative genome hybridization, Sanger sequencing, exome sequencing and functional studies using Lacz enhancer assay, Zebrafish morpholinos and computational transcription factor binding site prediction. By screening all available medical records and X-rays retrospectively at all hospitals treating CULA in Stockholm county between 1997 and 2007 we identified 562 individuals with CULA resulting in an incidence of 21.5 per 10000 live births. In 99 of the 562 individuals (18%) there was a known occurrence of limb anomalies among relatives. One hundred and thirty of the 562 children (23%) had associated non-hand anomalies. A general table with all studied data that provides good counselling information about gender, laterality, associated anomalies and occurrence among relatives for each type of CULA was created. The conserved Zone of polarizing Activity Regulating sequence (ZRS) restricts Sonic hedgehog expression to the posterior limb bud and thereby controls anterioposterior patterning in the upper limb. Sanger sequencing of the ZRS in a family with autosomal dominant inherited triphalangeal thumbs with an extra hypoplastic radial thumb revealed an insertion of 13 base pairs segregating with the phenotype. The insertion was predicted to add binding sites for several limb related transcription factors and in a Lac-Z enhancer assay, the insertion mimics the ectopic anterior expression of Sonic hedgehog in the limb bud previously reported to cause radial polydactyly. A multicentre retrospective study was performed, based on six individuals with overlapping microdeletions of 17q22 including the NOG gene. Phenotypic and genotypic comparison between the six included individuals revealed a novel, previously not described 17q22 microdeletion syndrome with symptoms comprising common facial characteristics, multiple bone and joint problems including symphalangism, urogenital malformations and intellectual disability. In addition, some important differences were noted between the individuals, such as hypogonadotrophic hypogonadism and absence of uterus in one individual with a larger heterozygous deletion including TRIM25, also named EFP (estrogenresponsive finger protein) Mice carrying a loss of function mutation in one of the Efp genes have underdeveloped uterus suggesting that Efp could be involved in the normal estrogen-induced cell proliferation of uterus and the uterine swelling Exome sequencing and Sanger sequencing in three unrelated families with the recently described condition X-linked recessive fusion of the fourth and fifth metacarpals, MF4 (OMIM309630), showed three novel variants in FGF16. In one of the families a truncating FGF16 mutation also segregated with heart disease. The importance of Fgf16 in mouse heart development has previously been shown. We performed zebrafish functional knockdown of fgf16 and showed heart oedema besides the expected recently described reduction of fin size. Taken together, this thesis provides information about incidence and comorbidity of CULA and adds knowledge about phenotype and genetic mechanisms underlying radial polydactyly, X-linked recessive MF4 and the novel 17q22 microdeletion syndrome

A flow equation approach to periodically driven quantum systems

We present a theoretical method to generate a highly accurate {\em time-independent} Hamiltonian governing the finite-time behavior of a time-periodic system. The method exploits infinitesimal unitary transformation steps, from which renormalization group-like flow equations are derived to produce the effective Hamiltonian. Our tractable method has a range of validity reaching into frequency regimes that are usually inaccessible via high frequency $\omega$ expansions in the parameter $h/\omega$, where $h$ is the upper limit for the strength of local interactions. We demonstrate our approach on both interacting and non-interacting many-body Hamiltonians where it offers an improvement over the more well-known Magnus expansion and other high frequency expansions. For the interacting models, we compare our approximate results to those found via exact diagonalization. While the approximation generally performs better globally than other high frequency approximations, the improvement is especially pronounced in the regime of lower frequencies and strong external driving. This regime is of special interest because of its proximity to the resonant regime where the effect of a periodic drive is the most dramatic. Our results open a new route towards identifying novel non-equilibrium regimes and behaviors in driven quantum many-particle systems.Comment: 25 pages, 14 figure

Health Reforms in Mexico City. 2000-2006

Objectives: To describe the reform applied to the health system of Mexico City between 2000 and 2006 and to present their results

Attosecond photoelectron interferometry: from wavepackets to density matrices

Through the advent of high-order harmonic generation and attosecond light pulses, photoionization dynamics has been studied on the attosecond time-scale, the intrinsic time-scale of such dynamics. When the electron leaves the atomic potential a phase shift is imprinted on the electron wavefunction. The measurement of this phase, together with amplitude allows us to determine the dynamics that of the photoionization.In this thesis, attosecond (10−18 s) and femtosecond (10−15 s) photoionization dynamics are studied using the photoelectron interferometry technique, Reconstruction of Attosecond Beating By Interference of two-photon Transitions (RABBIT). In RABBIT, the electron wave-packet is interfered with itself, and through this spectral interference, the spectral amplitude and phase can be retrieved.Attosecond time-delay measurements, are performed in argon and xenon where different aspects of electron correlation are investigated. In argon photoionization is studied in the region of the Cooper minumum, where the ionization cross section rapidly decrease. In xenon photoionization is studied across the 4d giant dipole resonance. Resonant dynamics is stud- ied using energy-resolved RABBIT. The studied resonances are the 1s3p, 1s4p, 1s5p (below threshold) and 2s2p (above threshold) in He and 3s−14p (above threshold) in Ar. Most of the measurements in the thesis are angular-integrated.If the photoelectron is prepared as a mixed state, RABBIT is unsuccessful in characterizing the quantum state of the electron, since it cannot be represented as a wavefunction. Therefore a quantum state tomography protocol for photoelectrons (KRAKEN) was developed and tested experimentally in non-resonant ionization of helium, neon and argon. In the case of neon and argon, due to spin-orbit splitting, the entanglement between the photoelectron and ion leads to decoherence induced by incomplete measurements where the state of the ion is not measured

Journal Staff

This thesis describes the development and rationalization of processes involved in a new methodology developed in our group, minor enantiomer recycling. The first part of the thesis addresses mechanistic studies of one of the reactions involved in minor enantiomer recycling, dual Lewis acid-Lewis base catalyzed acetylcyanation of aldehydes. The methodology uses a combination of a chiral titanium-salen  complex with a tertiary amine as a catalytic  system  in  the enantioselective  synthesis  of  O-acylated  cyanohydrins from aldehydes and ketonitriles. Mechanistic investigations revealed that the rate-determining step in the reaction changes, depending on the nature of the aldehyde that was used. It was also concluded that cyanohydrin is coordinated to the Lewis acid in the acylation step. The second part of the thesis deals with minor enantiomer recycling, a highly selective one-pot recycling system. In a first step the product is formed as a minor and a major enantiomer by asymmetric catalysis. Recycling of the minor enantiomer, by selective kinetic resolution, regenerates the starting material. Continuous addition of a second reagent, also involved in a coupled exergonic process, leads to an increase of both yield and enantiomeric excess. Recycling procedures for the synthesis of O-acylated and O-formylated cyanohydrins have been developed with high yield and high enantiomeric excess of the products. The study includes development of the systems, comparison to other methodologies in asymmetric catalysis, and attempts to understand the processes involved.  QC 20141202</p

Examining the Landscape of Leadership of Charter School Executives in Low-Performing or Priority Schools in North Carolina

Charter Schools in North Carolina have been serving students since 1997 in grades K-12. From their inception, charter schools in North Carolina have operated as their own Local Education Agency (LEA) and were created to serve the fundamental purpose of providing opportunities for teachers, parents, students, and community members to establish and maintain schools that operate independently of existing schools