Biochemical and clinical response after umbilical cord blood transplant in a boy with early childhood-onset beta-mannosidosis.

BACKGROUND: Deficiency in the enzyme β-mannosidase was described over three decades ago. Although rare in occurrence, the presentation of childhood-onset β-mannosidase deficiency consists of hypotonia in the newborn period followed by global development delay, behavior problems, and intellectual disability. No effective pharmacologic treatments have been available. METHODS: We report 2-year outcomes following the first umbilical cord blood transplant in a 4-year-old boy with early childhood-onset disease. RESULTS: We show restoration of leukocyte β-mannosidase activity which remained normal at 2 years posttransplant, and a simultaneous increase in plasma β-mannosidase activity and dramatic decrease in urine-free oligosaccharides were also observed. MRI of the brain remained stable. Neurocognitive evaluation revealed test point gains, although the magnitude of improvement was less than expected for age, causing lower IQ scores that represent a wider developmental gap between the patient and unaffected peers. CONCLUSION: Our findings suggest that hematopoietic cell transplant can correct the biochemical defect in β-mannosidosis, although preservation of the neurocognitive trajectory may be a challenge

Radon--Nikodym representations of Cuntz--Krieger algebras and Lyapunov spectra for KMS states

We study relations between $(H,\beta)$--KMS states on Cuntz--Krieger algebras and the dual of the Perron--Frobenius operator $\mathcal{L}_{-\beta H}^{*}$. Generalising the well--studied purely hyperbolic situation, we obtain under mild conditions that for an expansive dynamical system there is a one--one correspondence between $(H,\beta)$--KMS states and eigenmeasures of $\mathcal{L}_{-\beta H}^{*}$ for the eigenvalue 1. We then consider representations of Cuntz--Krieger algebras which are induced by Markov fibred systems, and show that if the associated incidence matrix is irreducible then these are $\ast$--isomorphic to the given Cuntz--Krieger algebra. Finally, we apply these general results to study multifractal decompositions of limit sets of essentially free Kleinian groups $G$ which may have parabolic elements. We show that for the Cuntz--Krieger algebra arising from $G$ there exists an analytic family of KMS states induced by the Lyapunov spectrum of the analogue of the Bowen--Series map associated with $G$. Furthermore, we obtain a formula for the Hausdorff dimensions of the restrictions of these KMS states to the set of continuous functions on the limit set of $G$. If $G$ has no parabolic elements, then this formula can be interpreted as the singularity spectrum of the measure of maximal entropy associated with $G$.Comment: 30 pages, minor changes in the proofs of Theorem 3.9 and Fact

Superhumps in Cataclysmic Binaries. XXV. q_crit, epsilon(q), and Mass-Radius

We report on successes and failures in searching for positive superhumps in cataclysmic variables, and show the superhumping fraction as a function of orbital period. Basically, all short-period systems do, all long-period systems don't, and a 50% success rate is found at P_orb=3.1+-0.2 hr. We can use this to measure the critical mass ratio for the creation of superhumps. With a mass-radius relation appropriate for cataclysmic variables, and an assumed mean white-dwarf mass of 0.75 M_sol, we find a mass ratio q_crit=0.35+-0.02. We also report superhump studies of several stars of independently known mass ratio: OU Virginis, XZ Eridani, UU Aquarii, and KV UMa (= XTE J1118+480). The latter two are of special interest, because they represent the most extreme mass ratios for which accurate superhump measurements have been made. We use these to improve the epsilon(q) calibration, by which we can infer the elusive q from the easy-to-measure epsilon (the fractional period excess of P_superhump over P_orb). This relation allows mass and radius estimates for the secondary star in any CV showing superhumps. The consequent mass-radius law shows an apparent discontinuity in radius near 0.2 M_sol, as predicted by the disrupted magnetic braking model for the 2.1-2.7 hour period gap. This is effectively the "empirical main sequence" for CV secondaries.Comment: PDF, 45 pages, 9 tables, 12 figures; accepted, in press, to appear November 2005, PASP; more info at http://cba.phys.columbia.edu

Establishing nonlinearity thresholds with ultraintense X-ray pulses

X-ray techniques have evolved over decades to become highly refined tools for a broad range of investigations. Importantly, these approaches rely on X-ray measurements that depend linearly on the number of incident X-ray photons. The advent of X-ray free electron lasers (XFELs) is opening the ability to reach extremely high photon numbers within ultrashort X-ray pulse durations and is leading to a paradigm shift in our ability to explore nonlinear X-ray signals. However, the enormous increase in X-ray peak power is a double-edged sword with new and exciting methods being developed but at the same time well-established techniques proving unreliable. Consequently, accurate knowledge about the threshold for nonlinear X-ray signals is essential. Herein we report an X-ray spectroscopic study that reveals important details on the thresholds for nonlinear X-ray interactions. By varying both the incident X-ray intensity and photon energy, we establish the regimes at which the simplest nonlinear process, two-photon X-ray absorption (TPA), can be observed. From these measurements we can extract the probability of this process as a function of photon energy and confirm both the nature and sub-femtosecond lifetime of the virtual intermediate electronic state

Isolation of DNA sequences on human chromosome 21 by application of a recombination-based assay to DNA from flow-sorted chromosomes

By merging two efficient technologies, bivariate flow sorting of human metaphase chromosomes and a recombination-based assay for sequence complexity, we isolated 28 cloned DNA segments homologous to loci on human chromosome 21. Subregional mapping of these DNA segments with a somatic cell hybrid panel showed that 26 of the 28 cloned DNA sequences are distributed along the long arm of chromosome 21, while the other 2 hybridize with sequences on the short arm of both chromosome 21 and other chromosomes. This new collection of probes homologous to chromosome 21 should facilitate molecular analyses of trisomy 21 by providing DNA probes for the linkage map of chromosome 21, for studies of nondisjunction, for chromosome walking in clinically relevant subregions of chromosome 21, and for the isolation of genes on chromosome 21 following the screening of cDNA libraries.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/47623/1/439_2004_Article_BF00366237.pd

Antiretroviral activity and safety of once-daily etravirine in treatment-naive HIV-infected adults: 48-week results

Etravirine (ETR), an NNRTI approved for 200 mg BID dosing in conjunction with other antiretrovirals (ARVs), has pharmacokinetic properties which support once-daily dosing

Mosaicism of the UDP-Galactose Transporter SLC35A2 Causes a Congenital Disorder of Glycosylation

Biochemical analysis and whole-exome sequencing identified mutations in the Golgi-localized UDP-galactose transporter SLC35A2 that define an undiagnosed X-linked congenital disorder of glycosylation (CDG) in three unrelated families. Each mutation reduced UDP-galactose transport, leading to galactose-deficient glycoproteins. Two affected males were somatic mosaics, suggesting that a wild-type SLC35A2 allele may be required for survival. In infancy, the commonly used biomarker transferrin showed abnormal glycosylation, but its appearance became normal later in childhood, without any corresponding clinical improvement. This may indicate selection against cells carrying the mutant allele. To detect other individuals with such mutations, we suggest transferrin testing in infancy. Here, we report somatic mosaicism in CDG, and our work stresses the importance of combining both genetic and biochemical diagnoses