Efficient computation of matched solutions of the Kapchinskij-Vladimirskij envelope equations for periodic focusing lattices

A new iterative method is developed to numerically calculate the periodic, matched beam envelope solution of the coupled Kapchinskij-Vladimirskij (KV) equations describing the transverse evolution of a beam in a periodic, linear focusing lattice of arbitrary complexity. Implementation of the method is straightforward. It is highly convergent and can be applied to all usual parameterizations of the matched envelope solutions. The method is applicable to all classes of linear focusing lattices without skew couplings, and also applies to all physically achievable system parameters -- including where the matched beam envelope is strongly unstable. Example applications are presented for periodic solenoidal and quadrupole focusing lattices. Convergence properties are summarized over a wide range of system parameters.Comment: 20 pages, 5 figures, Mathematica source code provide

Fostering collaborative research for rare genetic disease: The example of Niemann-Pick type C disease

Rare disease represents one of the most significant issues facing the medical community and health care providers worldwide, yet the majority of these disorders never emerge from their obscurity, drawing little attention from the medical community or the pharmaceutical industry. The challenge therefore is how best to mobilize rare disease stakeholders to enhance basic, translational and clinical research to advance understanding of pathogenesis and accelerate therapy development. Here we describe a rare, fatal brain disorder known as Niemann-Pick type C (NPC) and an innovative research collaborative known as Support of Accelerated Research for NPC (SOAR-NPC) which illustrates one pathway through which knowledge of a rare disease and its possible treatments are being successfully advanced. Use of the “SOAR” mechanism, we believe, offers a blueprint for similar advancement for many other rare disorders

Genomic characterization of Gli-activator targets in sonic hedgehog-mediated neural patterning

Sonic hedgehog (Shh) acts as a morphogen to mediate the specification of distinct cell identities in the ventral neural tube through a Gli-mediated (Gli1-3) transcriptional network. Identifying Gli targets in a systematic fashion is central to the understanding of the action of Shh. We examined this issue in differentiating neural progenitors in mouse. An epitope-tagged Gli-activator protein was used to directly isolate cis-regulatory sequences by chromatin immunoprecipitation (ChIP). ChIP products were then used to screen custom genomic tiling arrays of putative Hedgehog (Hh) targets predicted from transcriptional profiling studies, surveying 50-150 kb of non-transcribed sequence for each candidate. In addition to identifying expected Gli-target sites, the data predicted a number of unreported direct targets of Shh action. Transgenic analysis of binding regions in Nkx2.2, Nkx2.1 (Titf1) and Rab34 established these as direct Hh targets. These data also facilitated the generation of an algorithm that improved in silico predictions of Hh target genes. Together, these approaches provide significant new insights into both tissue-specific and general transcriptional targets in a crucial Shh-mediated patterning process

Ultrathin Oxide Films by Atomic Layer Deposition on Graphene

In this paper, a method is presented to create and characterize mechanically robust, free standing, ultrathin, oxide films with controlled, nanometer-scale thickness using Atomic Layer Deposition (ALD) on graphene. Aluminum oxide films were deposited onto suspended graphene membranes using ALD. Subsequent etching of the graphene left pure aluminum oxide films only a few atoms in thickness. A pressurized blister test was used to determine that these ultrathin films have a Young's modulus of 154 \pm 13 GPa. This Young's modulus is comparable to much thicker alumina ALD films. This behavior indicates that these ultrathin two-dimensional films have excellent mechanical integrity. The films are also impermeable to standard gases suggesting they are pinhole-free. These continuous ultrathin films are expected to enable new applications in fields such as thin film coatings, membranes and flexible electronics.Comment: Nano Letters (just accepted

Characterization of LP-Z Lipoprotein Particles and Quantification in Subjects with Liver Disease Using a Newly Developed NMR-Based Assay

Background: Lipoprotein particles with abnormal compositions, such as lipoprotein X (LP-X) and lipoprotein Z (LP-Z), have been described in cases of obstructive jaundice and cholestasis. The study objectives were to: (1) develop an NMR-based assay for quantification of plasma/serum LP-Z particles, (2) evaluate the assay performance, (3) isolate LP-Z particles and characterize them by lipidomic and proteomic analysis, and (4) quantify LP-Z in subjects with various liver diseases. Methods: Assay performance was assessed for linearity, sensitivity, and precision. Mass spectroscopy was used to characterize the protein and lipid content of isolated LP-Z particles. Results: The assay showed good linearity and precision (2.5-6.3%). Lipid analyses revealed that LP-Z particles exhibit lower cholesteryl esters and higher free cholesterol, bile acids, acylcarnitines, diacylglycerides, dihexosylceramides, lysophosphatidylcholines, phosphatidylcholines, triacylglycerides, and fatty acids than low-density lipoprotein (LDL) particles. A proteomic analysis revealed that LP-Z have one copy of apolipoprotein B per particle such as LDL, but less apolipoprotein (apo)A-I, apoC3, apoA-IV and apoC2 and more complement C3. LP-Z were not detected in healthy volunteers or subjects with primary biliary cholangitis, primary sclerosing cholangitis, autoimmune hepatitis, or type 2 diabetes. LP-Z were detected in some, but not all, subjects with hypertriglyceridemia, and were high in some subjects with alcoholic liver disease. Conclusions: LP-Z differ significantly in their lipid and protein content from LDL. Further studies are needed to fully understand the pathophysiological reason for the enhanced presence of LP-Z particles in patients with cholestasis and alcoholic liver disease

Short intense ion pulses for materials and warm dense matter research

We have commenced experiments with intense short pulses of ion beams on the Neutralized Drift Compression Experiment-II at Lawrence Berkeley National Laboratory, by generating beam spots size with radius r < 1 mm within 2 ns FWHM and approximately 10^10 ions/pulse. To enable the short pulse durations and mm-scale focal spot radii, the 1.2 MeV Li+ ion beam is neutralized in a 1.6-meter drift compression section located after the last accelerator magnet. An 8-Tesla short focal length solenoid compresses the beam in the presence of the large volume plasma near the end of this section before the target. The scientific topics to be explored are warm dense matter, the dynamics of radiation damage in materials, and intense beam and beam-plasma physics including selected topics of relevance to the development of heavy-ion drivers for inertial fusion energy. Here we describe the accelerator commissioning and time-resolved ionoluminescence measurements of yttrium aluminium perovskite using the fully integrated accelerator and neutralized drift compression components.Comment: 7 pages, 9 figure

Low-temperature and purification-free stereocontrolled ring-opening polymerisation of lactide in supercritical carbon dioxide

A stereoselective, solvent-free ring-opening polymerisation (ROP) of lactide (LA) in supercritical carbon dioxide (scCO2) is reported for the first time. The key aim is to exploit scCO2 to lower the temperature of traditional melt polymerisations, lowering the energy requirement and leading to cleaner polymeric materials. We have utilised a zirconium amine-trisphenolate initiator-stereoselective catalyst [(iPrO)Zr(OPh(tBu)2-CH2)3N] to yield highly heterotactic poly(lactide) (PLA) homopolymer (Pr = 0.74–0.84) from rac-LA, demonstrating control of the PLA microstructure in scCO2. In addition, high monomer conversion (86–93%) was achieved in short reaction time (1 h), affording poly(lactide) with a very low degree of transesterification and narrow molecular weight distribution. Most importantly, all the reactions were performed at only 80 °C, almost 100 °C lower than the conventional melt process (typically performed at 130–180 °C), representing a very significant potential energy saving

Abnormalities in autonomic function in obese boys at-risk for insulin resistance and obstructive sleep apnea.

Study objectivesCurrent evidence in adults suggests that, independent of obesity, obstructive sleep apnea (OSA) can lead to autonomic dysfunction and impaired glucose metabolism, but these relationships are less clear in children. The purpose of this study was to investigate the associations among OSA, glucose metabolism, and daytime autonomic function in obese pediatric subjects.MethodsTwenty-three obese boys participated in: overnight polysomnography; a frequently sampled intravenous glucose tolerance test; and recordings of spontaneous cardiorespiratory data in both the supine (baseline) and standing (sympathetic stimulus) postures.ResultsBaseline systolic blood pressure and reactivity of low-frequency heart rate variability to postural stress correlated with insulin resistance, increased fasting glucose, and reduced beta-cell function, but not OSA severity. Baroreflex sensitivity reactivity was reduced with sleep fragmentation, but only for subjects with low insulin sensitivity and/or low first-phase insulin response to glucose.ConclusionsThese findings suggest that vascular sympathetic activity impairment is more strongly affected by metabolic dysfunction than by OSA severity, while blunted vagal autonomic function associated with sleep fragmentation in OSA is enhanced when metabolic dysfunction is also present

Soil Respiration in a Northeastern US Temperate Forest: A 22-Year Synthesis

To better understand how forest management, phenology, vegetation type, and actual and simulated climatic change affect seasonal and inter-annual variations in soil respiration (R$_{s}$), we analyzed more than 100,000 individual measurements of soil respiration from 23 studies conducted over 22 years at the Harvard Forest in Petersham, Massachusetts, USA. We also used 24 site-years of eddy-covariance measurements from two Harvard Forest sites to examine the relationship between soil and ecosystem respiration (R$_{e}$). R$_{s}$ was highly variable at all spatial (respiration collar to forest stand) and temporal (minutes to years) scales of measurement. The response of R$_{s}$ to experimental manipulations mimicking aspects of global change or aimed at partitioning R$_{s}$ into component fluxes ranged from −70% to +52%. The response appears to arise from variations in substrate availability induced by changes in the size of soil C pools and of belowground C fluxes or in environmental conditions. In some cases (e.g., logging, warming), the effect of experimental manipulations on R$_{s}$ was transient, but in other cases the time series were not long enough to rule out long-term changes in respiration rates. Inter-annual variations in weather and phenology induced variation among annual R$_{s}$ estimates of a magnitude similar to that of other drivers of global change (i.e., invasive insects, forest management practices, N deposition). At both eddy-covariance sites, aboveground respiration dominated R$_{e}$ early in the growing season, whereas belowground respiration dominated later. Unusual aboveground respiration patterns—high apparent rates of respiration during winter and very low rates in mid-to-late summer—at the Environmental Measurement Site suggest either bias in R$_{s}$ and R$_{e}$ estimates caused by differences in the spatial scale of processes influencing fluxes, or that additional research on the hard-to-measure fluxes (e.g., wintertime R$_{s}$, unaccounted losses of CO$_{2}$ from eddy covariance sites), daytime and nighttime canopy respiration and its impacts on estimates of R$_{e}$, and independent measurements of flux partitioning (e.g., aboveground plant respiration, isotopic partitioning) may yield insight into the unusually high and low fluxes. Overall, however, this data-rich analysis identifies important seasonal and experimental variations in R$_{s}$ and R$_{e}$ and in the partitioning of R$_{e}$ above- vs. belowground.Organismic and Evolutionary Biolog