Search

Mucopolysaccharidosis type VI (MPS VI), or Maroteaux-Lamy syndrome, is a lysosomal storage disorder caused by a deficiency of N-acetylgalactosamine-4-sulfatase (ARSB). Seven MPS VI patients were chosen for the initial clinical trial of enzyme replacement therapy. Direct sequencing of genomic DNA from these patients was used to identify ARSB mutations. Each individual exon of the ARSB gene was amplified by PCR and subsequently sequenced. Nine substitutions (c.289C>T [p.Q97X], c.629A>G [p.Y210C], c.707T>C [p.L236P], c.936G>T [p.W312C], c.944G>A [p.R315Q], c.962T>C [p.L321P], c.979C>T [p.R327X], c.1151G>A [p.S384N], and c.1450A>G [p.R484G]), two deletions (c.356underscore;358delTAC [p.Y86del] and c.427delG), and one intronic mutation (c.1336+2T>G) were identified. A total of 7 out of the 12 mutations identified were novel (p.Y86del, p.Q97X, p.W312C, p.R327X, c.427delG, p.R484G, and c.1336+2T>G). Two of these novel mutations (p.Y86del and p.W312C) were expressed in Chinese hamster ovary cells and analyzed for residual ARSB activity and mutant ARSB protein. The two common polymorphisms c.1072G>A [p.V358M] and c.1126G>A [p.V376M] were identified among the patients, along with the silent mutation c.1191A>G. Cultured fibroblast ARSB mutant protein and residual activity were determined for each patient, and, together with genotype information, were used to predict the expected clinical severity of each MPS VI patient. Hum Mutat 23:229–233, 2004. © 2004 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

The need to characterize ices coating dust grains in dense interstellar clouds arises from the importance of ice morphology in facilitating the diffusion and storage of radicals and reaction products in ices, a well-known place for the formation of complex molecules. Yet, there is considerable uncertainty about the structure of interstellar medium ices, their ability to store volatiles, and under what conditions. We measured the infrared absorption spectra of CO on the pore surface of porous amorphous solid water (ASW), and quantified the effective pore surface area of ASW. Additionally, we present results obtained from a Monte Carlo model of ASW in which the morphology of the ice is directly visualized and quantified. We found that 200 ML of ASW annealed to 20 K has a total pore surface area that is equivalent to 46 ML. This surface area decreases linearly with temperature to about 120 K. We also found that (1) dangling OH bonds only exist on the surface of pores; (2) almost all of the pores in the ASW are connected to the vacuum–ice interface, and are accessible for adsorption of volatiles from the gas phase; there are few closed cavities inside ASW at least up to a thickness of 200 ML; (3) the total pore surface area is proportional to the total three-coordinated water molecules in the ASW in the temperature range 60–120 K. We also discuss the implications on the structure of ASW and surface reactions in the ice mantle in dense clouds. [ABSTRACT FROM AUTHOR]

We study the impact of experimental imperfections on a recently proposed protocol for performing quantum simulations of vibronic spectroscopy. Specifically, we propose a method for quantifying the impact of these imperfections, optimizing an experiment to account for them, and benchmarking the results against a classical simulation method. We illustrate our findings using a proof of principle experimental simulation of part of the vibronic spectrum of tropolone. Our findings will inform the design of future experiments aiming to simulate the spectra of large molecules beyond the reach of current classical computers. [ABSTRACT FROM AUTHOR]

We present new radio-frequency interferometric maps of emission from the 14NH3, 15NH3, and NH2D isotopologues of ammonia and the 12CH3OH and 13CH3OH isotopologues of methanol toward Sgr B2(N). With a resolution of ∼3″ (0.1 pc), we are able to spatially resolve emission from two hot cores in this source and separate it from absorption against the compact H ii regions in this area. The first (N1) is the well-known v = 64 km s−1 core, and the second (N2) is a core 6″ to the north at v = 73 km s−1. Using emission from 15NH3 and hyperfine satellites of 14NH3 metastable transitions, we estimate the 14NH3 column densities of these sources and compare them to those of NH2D. We find that the ammonia deuteration fraction of N2 is roughly 10–20 times higher than that in N1. We also measure an [15NH3/14NH3] abundance ratio that is apparently 2–3 times higher in N2 than in N1, which could indicate a correspondingly higher degree of nitrogen fractionation in N2. In addition, we find that N2 has a factor of 7 higher methanol abundance than N1. Together, these abundance signatures suggest that N2 is a younger source, for which species characteristic of grain chemistry at low temperatures are currently being actively liberated from ice mantles and have not yet reached chemical equilibrium in the warm gas phase. The high D abundance and possible high 15N abundance in NH3 found in N2 are interesting for studying the potential interstellar origin of abundances in primitive solar system material. [ABSTRACT FROM AUTHOR]

Oncolytic viruses selectively target and kill cancer cells in an immunogenic fashion, thus supporting the establishment of therapeutically relevant tumor-specific immune responses. In 2015, the US Food and Drug Administration (FDA) approved the oncolytic herpes simplex virus T-VEC for use in advanced melanoma patients. Since then, a plethora of trials has been initiated to assess the safety and efficacy of multiple oncolytic viruses in patients affected with various malignancies. Here, we summarize recent preclinical and clinical progress in the field of oncolytic virotherapy. [ABSTRACT FROM AUTHOR]