Individual heat map assessments demonstrate vestronidase alfa treatment response in a highly heterogeneous mucopolysaccharidosis VII study population.

Mucopolysaccharidosis (MPS) VII is an ultra-rare, progressively debilitating, life-threatening lysosomal disease caused by deficiency of the enzyme, β-glucuronidase. Vestronidase alfa is an approved enzyme replacement therapy for MPS VII. UX003-CL301 was a phase 3, randomized, placebo-controlled, blind-start study examining the efficacy and safety of vestronidase alfa 4 mg/kg intravenously administered every 2 weeks to 12 patients with MPS VII. Due to the rarity of disease, broad eligibility criteria resulted in a highly heterogeneous population with variable symptoms. For an integrated view of the diverse data, the changes from baseline (or randomization for the placebo period) in clinical endpoints were grouped into three functional domains (mobility, fatigue, and fine motor + self-care) and analyzed post-hoc as subject-level heat maps. Mobility assessments included the 6-minute walk test, 3-minute stair climb test, Bruininks-Oseretsky test (BOT-2) gross motor function subtests, and patient-reported outcome assessments (PROs) related to movement, pain, and ambulation. Fatigue assessments included the Pediatric Quality of Life Multidimensional Fatigue Scale and other fatigue-related PROs. Fine motor + self-care assessments included BOT-2 fine motor function subtests and PROs for eating, dressing, hygiene, and caregiver assistance. Most subjects showed improvement in at least one domain. Two subjects improved in two or more domains and two subjects did not show clear improvement in any domain. Both severely and mildly affected subjects improved with vestronidase alfa in clinical assessments, PRO results, or both. Heat map analysis demonstrates how subjects responded to treatment across multiple domains, providing a useful visual tool for studying rare diseases with variable symptoms

Selective axonal growth of embryonic hippocampal neurons according to topographic features of various sizes and shapes

David Y Fozdar1*, Jae Y Lee2*, Christine E Schmidt2–6, Shaochen Chen1,3–5,7,1Departments of Mechanical Engineering, 2Chemical Engineering, 3Biomedical Engineering; 4Center for Nano Molecular Science and Technology; 5Texas Materials Institute; 6Institute of Neuroscience; 7Microelectronics Research Center, The University of Texas at Austin, Austin, TX, USA *Contributed equally to this workPurpose: Understanding how surface features influence the establishment and outgrowth of the axon of developing neurons at the single cell level may aid in designing implantable scaffolds for the regeneration of damaged nerves. Past studies have shown that micropatterned ridge-groove structures not only instigate axon polarization, alignment, and extension, but are also preferred over smooth surfaces and even neurotrophic ligands.Methods: Here, we performed axonal-outgrowth competition assays using a proprietary four-quadrant topography grid to determine the capacity of various micropatterned topographies to act as stimuli sequestering axon extension. Each topography in the grid consisted of an array of microscale (approximately 2 µm) or submicroscale (approximately 300 nm) holes or lines with variable dimensions. Individual rat embryonic hippocampal cells were positioned either between two juxtaposing topographies or at the borders of individual topographies juxtaposing unpatterned smooth surface, cultured for 24 hours, and analyzed with respect to axonal selection using conventional imaging techniques.Results: Topography was found to influence axon formation and extension relative to smooth surface, and the distance of neurons relative to topography was found to impact whether the topography could serve as an effective cue. Neurons were also found to prefer submicroscale over microscale features and holes over lines for a given feature size.Conclusion: The results suggest that implementing physical cues of various shapes and sizes on nerve guidance conduits and other advanced biomaterial scaffolds could help stimulate axon regeneration.Keywords: axon guidance, micropatterning, polarization, surface topography, tissue engineerin

U-Th Dating of lacustrine carbonates

Submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy in Oceanography and Applied Ocean Science and Engineering at the Massachusetts Institute of Technology and the Woods Hole Oceanographic Institution February 2020.Carbonates are prevalent in many modern and ancient lacustrine settings, but reconstructions of past lake levels or environments from such materials have been hindered by poor chronology. Uranium-thorium (U-Th) dating has the potential to fill a gap in current geochronological tools for such archives, but past attempts have been confounded by poor understanding of the complex makeup of lacustrine carbonates, leading to misguided conclusions on both the utility of certain geochronological tools as well as the age of these deposits. This thesis showcases strategies for the successful application of U-Th geochronology to two types of lacustrine carbonates: lake bottom sediments and tufa deposits. Chapter 2 presents a systematic approach to U-Th dating carbonate-rich lake sediments using the ICDP sediment core from Lake Junín, Peru. Chapters 3–5 seek to demonstrate the descriptive power of combining precise U-Th dates on tufas and other carbonates with geologic observations of their depositional context at all scales—from the outcrop to the microscale. Here, the tufas originate from a transect of closed-basin lakes in the central Andes of northern Chile. With improved sample selection and leveraging of the incontrovertible constraints of stratigraphy and coevality, we are able to test the validity of U-Th data. Combining quality-controlled geochronological constraints with careful characterization of different carbonate facies can yield new insight on the character of lake level changes. These case studies offer frameworks for interpreting scattered geochronologic data of any size or system. By embracing the noise in our data, we now have a richer understanding of the controls on uranium in these deposits. Of all the lessons learned, we hold the following as most important: for the determination of the age of lacustrine carbonates, geologic context—in the form of sedimentological observations, additional geochemical data, and paleoecological descriptions—is of equal importance to the numerical accuracy and precision of geochronological measurements.Funding sources: National Science Foundation, Massachusetts Institute of Technology, Geological Society of America, MIT MISTI, Comer Foundation, American Philosophical Society, National Geographic Society, Explorers Club

A Spitzer MIPS Study of 2.5-2.0 M\odot Stars in Scorpius-Centaurus

We have obtained Spitzer Space Telescope Multiband Imaging Photometer for Spitzer (MIPS) 24 {\mu}m and 70 {\mu}m observations of 215 nearby, Hipparcos B- and A-type common proper motion single and binary systems in the nearest OB association, Scorpius-Centaurus. Combining our MIPS observations with those of other ScoCen stars in the literature, we estimate 24 {\mu}m B+A-type disk fractions of 17/67 (25+6%), 36/131 (27+4%), and 23/95 (24+5%) for Upper Scorpius (\sim11 Myr), Upper Centaurus Lupus (\sim15 Myr), and Lower Centaurus Crux (\sim17 Myr), respectively, somewhat smaller disk fractions than previously obtained for F- and G-type members. We confirm previous IRAS excess detections and present new discoveries of 51 protoplanetary and debris disk systems, with fractional infrared luminosities ranging from LIR/L\ast = 1e-6 to 1e-2 and grain temperatures ranging from Tgr = 40 - 300 K. In addition, we confirm that the 24 {\mu}m and 70 {\mu}m excesses (or fractional infrared luminosities) around B+A type stars are smaller than those measured toward F+G type stars and hypothesize that the observed disk property dependence on stellar mass may be the result of a higher stellar companion fraction around B- and A-type stars at 10 - 200 AU and/or the presence of Jupiter-mass companions in the disks around F- and G- type stars. Finally, we note that the majority of the ScoCen 24 {\mu}m excess sources also possess 12 {\mu}m excess, indicating that Earth-like planets may be forming via collisions in the terrestrial planet zone at \sim10 - 100 Myr.Comment: 62 pages, 17 figures including 6 colo

Quantum Hacking: Experimental demonstration of time-shift attack against practical quantum key distribution systems

Quantum key distribution (QKD) systems can send signals over more than 100 km standard optical fiber and are widely believed to be secure. Here, we show experimentally for the first time a technologically feasible attack, namely the time-shift attack, against a commercial QKD system. Our result shows that, contrary to popular belief, an eavesdropper, Eve, has a non-negligible probability (~4%) to break the security of the system. Eve's success is due to the well-known detection efficiency loophole in the experimental testing of Bell inequalities. Therefore, the detection efficiency loophole plays a key role not only in fundamental physics, but also in technological applications such as QKD.Comment: 5 pages, 3 figures. Substantially revised versio

Allelic expression mapping across cellular lineages to establish impact of non-coding SNPs

This is an open access article under the terms of the Creative Commons Attribution 4.0 License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited

HST and Spitzer Observations of the HD 207129 Debris Ring

A debris ring around the star HD 207129 (G0V; d = 16.0 pc) has been imaged in scattered visible light with the ACS coronagraph on the Hubble Space Telescope and in thermal emission using MIPS on the Spitzer Space Telescope at 70 microns (resolved) and 160 microns (unresolved). Spitzer IRS (7-35 microns) and MIPS (55-90 microns) spectrographs measured disk emission at >28 microns. In the HST image the disk appears as a ~30 AU wide ring with a mean radius of ~163 AU and is inclined by 60 degrees from pole-on. At 70 microns it appears partially resolved and is elongated in the same direction and with nearly the same size as seen with HST in scattered light. At 0.6 microns the ring shows no significant brightness asymmetry, implying little or no forward scattering by its constituent dust. With a mean surface brightness of V=23.7 mag per square arcsec, it is the faintest disk imaged to date in scattered light.Comment: 28 pages, 8 figure

Phenolic Impregnated Carbon Ablators (PICA) as Thermal Protection Systems for Discovery Missions

This paper presents the development of the light weight Phenolic Impregnated Carbon Ablators (PICA) and its thermal performance in a simulated heating environment for planetary entry vehicles. The PICA material was developed as a member of the Light Weight Ceramic Ablators (LCA's), and the manufacturing process of this material has since been significantly improved. The density of PICA material ranges from 14 to 20 lbm/ft(exp 3), having uniform resin distribution with and without a densified top surface. The thermal performance of PICA was evaluated in the Ames arc-jet facility at cold wall heat fluxes from 375 to 2,960 BtU/ft(exp 2)-s and surface pressures of 0.1 to 0.43 atm. Heat loads used in these tests varied from 5,500 to 29,600 BtU/ft(exp 2) and are representative of the entry conditions of the proposed Discovery Class Missions. Surface and in-depth temperatures were measured using optical pyrometers and thermocouples. Surface recession was also measured by using a template and a height gage. The ablation characteristics and efficiency of PICA are quantified by using the effective heat of ablation, and the thermal penetration response is evaluated from the thermal soak data. In addition, a comparison of thermal performance of standard and surface densified PICA is also discussed