Statin usage, vascular diagnosis and vascular risk factors in Parkinson's disease

Background and aims: Vascular disease is a common comorbidity in Parkinson’s disease patients. Statins are potentially neuroprotective for Parkinson’s disease through non-vascular mechanisms. We investigated prevailing statin use in a Parkinson’s disease cohort. Methods and results: Data on diagnostic indication for statins, anti-Parkinson therapy, vascular risk factors, and statin prescription, were obtained from electronic medical record review for consecutive Parkinson’s disease patients. The ASsessing cardiac risk using Scottish Intercollegiate Guidelines Network system was used to calculate future cardiovascular risk and identify those warranting statin use. Of 441 patients included, 59.9% were male, with a mean age of 68.9 years (standard deviation 10.3). One hundred and seventy-four (39.5%) patients had at least one diagnostic indication for statin use, of whom 136 (78.2%) were prescribed a statin. In the 267 (60.5%) cases without a diagnostic indication, 54 (20.2%) were excluded owing to age limitations defined in ASsessing cardiac risk using Scottish Intercollegiate Guidelines Network. Of the remaining 213, 62 (29.1%) had an ASsessing cardiac risk using Scottish Intercollegiate Guidelines Network score in the recommended range for statin therapy, of whom 15 (24.1%) were prescribed statins. Conclusion: There is suboptimal implementation of statin therapy in Parkinson’s disease patients. Given the possible neuroprotective effects of statins in Parkinson’s disease in addition to reducing cardiovascular risk, reasons for suboptimal implementation warrant further investigation

Near-Unity Unselective Absorption in Sparse InP Nanowire Arrays

We experimentally demonstrate near-unity, unselective absorption, broadband, angle-insensitive, and polarization-independent absorption, in sparse InP nanowire arrays, embedded in flexible polymer sheets via geometric control of waveguide modes in two wire motifs: (i) arrays of tapered wires and (ii) arrays of nanowires with varying radii. Sparse arrays of these structures exhibit enhanced absorption due to strong coupling into the first order azimuthal waveguide modes of individual nanowires; wire radius thus controls the spectral region of the absorption enhancement. Whereas arrays of cylindrical wires with uniform radius exhibit narrowband absorption, arrays of tapered wires and arrays with multiple wire radii expand this spectral region and achieve broadband absorption enhancement. Herein, we present an economic, top-down lithographic/etch fabrication method that enables fabrication of multiple InP nanowire arrays from a single InP wafer with deliberate control of nanowire radius and taper. Using this method, we create sparse tapered and multiradii InP nanowire arrays and demonstrate optical absorption that is broadband (450–900 nm), angle-insensitive, and near-unity (>90%) in roughly 100 nm planar equivalence of InP. These highly absorbing sparse nanowire arrays represent a promising approach to flexible, high efficiency optoelectronic devices, such as photodetectors, solar cells, and photoelectrochemical devices

Modular and automated synthesis of oligonucleotide-small molecule conjugates for cathepsin B mediated traceless release of payloads † ‡

The reversible attachment of small molecules to oligonucleotides provides versatile tools for the development of improved oligonucleotide therapeutics. However, cleavable linkers in the oligonucleotide field are scarce, particularly with respect to the requirement for traceless release of the payload in vivo. Herein, we describe a cathepsin B-cleavable dipeptide phosphoramidite, Val-Ala(NB) for the automated synthesis of oligonucleotide-small molecule conjugates. Val-Ala(NB) was protected by a photolabile 2-nitrobenzyl group to improve the stability of the peptide linker during DNA synthesis. Intracellular cathepsin B digests the dipeptide efficiently, releasing the payload-phosphate which is converted to the free payload by endogenous phosphatase enzymes. With the advantages of modular synthesis and stimuli-responsive drug release, we believe Val-Ala(NB) will be a potentially valuable cleavable linker for use in oligonucleotide-drug conjugates

Statistical Workflow for Feature Selection in Human Metabolomics Data.

High-throughput metabolomics investigations, when conducted in large human cohorts, represent a potentially powerful tool for elucidating the biochemical diversity underlying human health and disease. Large-scale metabolomics data sources, generated using either targeted or nontargeted platforms, are becoming more common. Appropriate statistical analysis of these complex high-dimensional data will be critical for extracting meaningful results from such large-scale human metabolomics studies. Therefore, we consider the statistical analytical approaches that have been employed in prior human metabolomics studies. Based on the lessons learned and collective experience to date in the field, we offer a step-by-step framework for pursuing statistical analyses of cohort-based human metabolomics data, with a focus on feature selection. We discuss the range of options and approaches that may be employed at each stage of data management, analysis, and interpretation and offer guidance on the analytical decisions that need to be considered over the course of implementing a data analysis workflow. Certain pervasive analytical challenges facing the field warrant ongoing focused research. Addressing these challenges, particularly those related to analyzing human metabolomics data, will allow for more standardization of as well as advances in how research in the field is practiced. In turn, such major analytical advances will lead to substantial improvements in the overall contributions of human metabolomics investigations

Interstellar and Circumstellar Optical & Ultraviolet Lines Towards SN1998S

We have observed SN1998S which exploded in NGC3877, with the UES at the WHT and with the E230M echelle of STIS aboard HST. Both data sets were obtained at two seperate epochs. From our own Galaxy we detect interstellar absorption lines of CaII, FeII, MgI, and probably MnII from the edge of the HVC Complex M. We derive gas-phase abundances which are very similar to warm disk clouds in the local ISM, which we believe argues against the HVC material having an extragalactic origin. At the velocity of NGC3877 we detect interstellar MgI, MgII, MnII, CaII, & NaI. Surprisingly, one component is seen to increase by a factor of ~1 dex in N(NaI) and N(MgI) between the two epochs over which the data were taken. Unusually, our data also show narrow Balmer, HeI, and metastable FeII P-Cygni profiles, with a narrow absorption component superimposed on the bottom of the profile's absorption trough. Both the broad and narrow components of the optical lines are seen to increase substantially in strength between the two epochs. Most of the low-ionization absorption can be understood in terms of gas co-rotating with the disk of NGC 3877, providing the SN is at the back of an HI disk with a similar thickness to that of our own Galaxy. However, the variable absorption components, and the classic P-Cygni emission profiles, most likely arise in slow-moving circumstellar outflows originating from the red supergiant progenitor of SN1998S. [Abridged.]Comment: Accepted by ApJ, 26 pages including 9 figure

High Broadband Light Transmission for Solar Fuels Production Using Dielectric Optical Waveguides in TiO₂ Nanocone Arrays

We describe the fabrication and use of arrays of TiO₂ nanocones to yield high optical transmission into semiconductor photoelectrodes covered with high surface loadings of light-absorbing electrocatalysts. Covering over 50% of the surface of a light absorber with an array of high-refractive-index TiO₂ nanocones imparted antireflective behavior ( 85% transmission of broadband light to the underlying Si, even when thick metal contacts or opaque catalyst coatings were deposited on areas of the light-facing surface that were not directly beneath a nanocone. Three-dimensional full-field electromagnetic simulations for the 400 – 1100 nm spectral range showed that incident broadband illumination couples to multiple waveguide modes in the TiO₂ nanocones, reducing interactions of the light with the metal layer. A proof-of-concept experimental demonstration of light-driven water oxidation was performed using a p⁺n-Si photoanode decorated with an array of TiO₂ nanocones additionally having a Ni catalyst layer electrodeposited onto the areas of the p⁺n-Si surface left uncovered by the TiO₂ nanocones. This photoanode produced a light-limited photocurrent density of ~ 28 mA cm⁻² under 100 mW cm⁻² of simulated Air Mass 1.5 illumination, equivalent to the photocurrent density expected for a bare planar Si surface even though 54% of the front surface of the Si was covered by an ~ 70 nm thick Ni metal layer

Double Field Inflation

We present an inflationary universe model which utilizes two coupled real scalar fields. The inflation field $\phi$ experiences a first order phase transition and its potential dominates the energy density of the Universe during the inflationary epoch. This field $\phi$ is initially trapped in its metastable minimum and must tunnel through a potential barrier to reach the true vacuum. The second auxiliary field $\psi$ couples to the inflaton field and serves as a catalyst to provide an abrupt end to the inflationary epoch; i.e., the $\psi$ field produces a time-dependent nucleation rate for bubbles of true $\phi$ vacuum. In this model, we find that bubbles of true vacuum can indeed percolate and we argue that thermalization of the interiors can more easily take place. The required degree of flatness (i.e., the fine tuning) in the potential of the $\psi$ field is comparable to that of other models which invoke slowly rolling fields. Pseudo Nambu-Goldstone bosons may naturally provide the flat potential for the rolling field.Comment: 18 pages, 2 figures, This early paper is being placed on the archive to make it more easily accessible in light of recent interest in reviving tunneling inflationary models and as its results are used in an accompanying submissio

FXYD3: A Promising Biomarker for Urothelial Carcinoma

Objective Urothelial carcinoma (UC) of the kidney is a relatively rare but aggressive form of kidney cancer. Differential diagnosis of renal UC from renal cell carcinoma (RCC) can be difficult, but is critical for correct patient management. We aimed to use global gene expression profiling to identify genes specifically expressed in urothelial carcinoma (UC) of the kidney, with purpose of finding new biomarkers for differential diagnosis of UC of both upper and lower tract from normal tissues. Materials and Methods Microarray gene expression profiling was performed on a variety of human kidney tumor samples, including clear cell, papillary, chromophobe, oncocytoma, renal UC and normal kidney controls. Differentially expressed mRNAs in various kidney tumor subtypes were thus identified. Protein expression in human UC tumor samples from both upper and lower urinary tract was evaluated by immunohistochemistry. Results FXYD3 (MAT-8) mRNA was specifically expressed in UC of the kidney and not in normal kidney tissue or in any RCC tumor subtypes. FXYD3 mRNA levels displayed equal or better prediction rate for the detection of renal UC than the mRNA levels of selected known UC markers as p63, vimentin, S100P, KRT20 and KRT7. Finally, immunohistochemical staining of clinical UC samples showed that FXYD3 protein is overexpressed in majority of UC of the upper genitourinary tract (encompassing the kidney, ~90%) and in majority of high grade bladder UC (~84%, it's < 40% in low grade tumors, P < 0.001) compared to normal kidney and bladder tissues. Conclusion FXYD3 may be a promising novel biomarker for the differential diagnosis of renal UC and a promising prognosis marker of UC from bladder. Because it was identified genome-widely, FXYD3 may have important biological ramifications for the genetic study of UC

Modeling Perennial Bioenergy Crops in the E3SM Land Model (ELMv2)

Perennial bioenergy crops are increasingly important for the production of ethanol and other renewable fuels, and as part of an agricultural system that alters the climate through its impact on biogeophysical and biogeochemical properties of the terrestrial ecosystem. Few Earth System Models (ESMs) represent such crops, however. In this study, we expand the Energy Exascale Earth System Land Model to include perennial bioenergy crops with a high potential for mitigating climate change. We focus on high-productivity miscanthus and switchgrass, estimating various parameters associated with their different growth stages and performing a global sensitivity analysis to identify and optimize these parameters. The sensitivity analysis identifies five parameters associated with phenology, carbon/nitrogen allocation, stomatal conductance, and maintenance respiration as the most sensitive parameters for carbon and energy fluxes. We calibrated and validated the model against observations and found that the model closely captures the observed seasonality and the magnitude of carbon fluxes. The validated model represents the latent heat flux fairly well, but sensible heat flux for miscanthus is not well captured. Finally, we validated the model against observed leaf area index (LAI) and harvest amount and found modeled LAI captured observed seasonality, although the model underestimates LAI and harvest amount. This work provides a foundation for future ESM analyses of the interactions between perennial bioenergy crops and carbon, water, and energy dynamics in the larger Earth system, and sets the stage for studying the impact of future biofuel expansion on climate and terrestrial systems

Opening the Box: Survey of High Power Density Inverter Techniques From the Little Box Challenge

The Little Box Challenge (LBC) was a competition sponsored by Google and the IEEE Power Electronics Society in 2014-2015, where participants were challenged to design a high power-density single-phase 2 kVA inverter. This paper surveys the designs from eight different participating teams, including academic grant awardees, finalists, and the winners. Inverter topologies, power decoupling circuits, and thermal management strategies are overviewed for each team. Wide bandgap switches were heavily utilized in both the inverter and power decoupling circuits, particularly GaN switches. Most teams utilized a full-bridge inverter with some variations and the most common power decoupling strategy was the use of a synchronous buck converter and a power buffering capacitor. One team used a multi-level inverter approach and a number of teams proposed innovative power decoupling topologies. Heat sinks and active cooling systems, many of which were custom made, were crucial for teams to stay within the 50 ??C case temperature limit. The resulting power density of the surveyed teams ranged from 55.8 to 216 W/in3, all of which exceed the 50 W/in3 LBC requirement. This paper surveys the approaches for various teams, shares experimental results from the Taiwan Tech team, and highlights some innovations from the teams that participated in the LBC