Weather and Random Forest-based Load Profiling Approximation Models and Their Transferability across Climate Zones

This study is to provide predictive understanding of the associations of weather attributes with electricity load profiles across a variety of climate zones and seasons. Firstly, machine learning (ML) approaches were used to identify and quantify the impacts of various weather attributes on residential and commercial electricity demand and its components across the western United States. Performance and transferability of the developed ML models were then evaluated across different temperate zones (e.g., southern, middle, and northern US) and across coastal, mid-continent, and wet zones, with inputs of weather condition data from the National Oceanic and Atmospheric Administration (NOAA) at representative weather stations. The predictive models were developed based on the ranked and screened factors using the regression tree (RT) and random forest (RF) approaches, for five different scenarios (seasons)

The Insulin Resistance Intervention after Stroke trial: a perspective on future practice and research

The prevention of recurrent events after ischaemic stroke and transient ischaemic attack is well established and based on lifestyle changes, antithrombotics, statins, antihypertensives and carotid surgery. The international IRIS trial assessed whether pioglitazone, a glucose-lowering insulin-sensitizing drug, would reduce recurrent vascular events in patients with ischaemic stroke or transient ischaemic attack. After 4.8 years, pioglitazone therapy was associated with reduced vascular events and new diabetes, and an increase in weight, oedema and bone fractures. Pioglitazone may add to the strategies for preventing further events in patients with stroke or transient ischaemic attack

Towards Space-like Photometric Precision from the Ground with Beam-Shaping Diffusers

We demonstrate a path to hitherto unachievable differential photometric precisions from the ground, both in the optical and near-infrared (NIR), using custom-fabricated beam-shaping diffusers produced using specialized nanofabrication techniques. Such diffusers mold the focal plane image of a star into a broad and stable top-hat shape, minimizing photometric errors due to non-uniform pixel response, atmospheric seeing effects, imperfect guiding, and telescope-induced variable aberrations seen in defocusing. This PSF reshaping significantly increases the achievable dynamic range of our observations, increasing our observing efficiency and thus better averages over scintillation. Diffusers work in both collimated and converging beams. We present diffuser-assisted optical observations demonstrating $62^{+26}_{-16}$ppm precision in 30 minute bins on a nearby bright star 16-Cygni A (V=5.95) using the ARC 3.5m telescope---within a factor of $\sim$2 of Kepler's photometric precision on the same star. We also show a transit of WASP-85-Ab (V=11.2) and TRES-3b (V=12.4), where the residuals bin down to $180^{+66}_{-41}$ppm in 30 minute bins for WASP-85-Ab---a factor of $\sim$4 of the precision achieved by the K2 mission on this target---and to 101ppm for TRES-3b. In the NIR, where diffusers may provide even more significant improvements over the current state of the art, our preliminary tests have demonstrated $137^{+64}_{-36}$ppm precision for a $K_S =10.8$ star on the 200" Hale Telescope. These photometric precisions match or surpass the expected photometric precisions of TESS for the same magnitude range. This technology is inexpensive, scalable, easily adaptable, and can have an important and immediate impact on the observations of transits and secondary eclipses of exoplanets.Comment: Accepted for publication in ApJ. 30 pages, 20 figure

Adaptation of Microelectrode Array Technology for the Study of Anesthesia-Induced Neurotoxicity in the Intact Piglet Brain

Every year, millions of children undergo anesthesia for a multitude of procedures. However, studies in both animals and humans have called into question the safety of anesthesia in children, implicating anesthetics as potentially toxic to the brain in development. To date, no studies have successfully elucidated the mechanism(s) by which anesthesia may be neurotoxic. Animal studies allow investigation of such mechanisms, and neonatal piglets represent an excellent model to study these effects due to their striking developmental similarities to the human brain. This protocol adapts the use of enzyme-based microelectrode array (MEA) technology as a novel way to study the mechanism(s) of anesthesia-induced neurotoxicity (AIN). MEAs enable real-time monitoring of in vivo neurotransmitter activity and offer exceptional temporal and spatial resolution. It is hypothesized that anesthetic neurotoxicity is caused in part by glutamate dysregulation and MEAs offer a method to measure glutamate. The novel implementation of MEA technology in a piglet model presents a unique opportunity for the study of AIN

A tunable zinc finger-based framework for Boolean logic computation in mammalian cells

The ability to perform molecular-level computation in mammalian cells has the potential to enable a new wave of sophisticated cell-based therapies and diagnostics. To this end, we developed a Boolean logic framework utilizing artificial Cys2–His2 zinc finger transcription factors (ZF-TFs) as computing elements. Artificial ZFs can be designed to specifically bind different DNA sequences and thus comprise a diverse set of components ideal for the construction of scalable networks. We generate ZF-TF activators and repressors and demonstrate a novel, general method to tune ZF-TF response by fusing ZF-TFs to leucine zipper homodimerization domains. We describe 15 transcriptional activators that display 2- to 463-fold induction and 15 transcriptional repressors that show 1.3- to 16-fold repression. Using these ZF-TFs, we compute OR, NOR, AND and NAND logic, employing hybrid promoters and split intein-mediated protein splicing to integrate signals. The split intein strategy is able to fully reconstitute the ZF-TFs, maintaining them as a uniform set of computing elements. Together, these components comprise a robust platform for building mammalian synthetic gene circuits capable of precisely modulating cellular behavior

Chemiluminescence determination of surfactant Triton X-100 in environmental water with luminol-hydrogen peroxide system

<p>Abstract</p> <p>Background</p> <p>The rapid, simple determination of surfactants in environmental samples is essential because of the extensive use and its potential as contaminants. We describe a simple, rapid chemiluminescence method for the direct determination of the non-ionic surfactant Triton X-100 (polyethylene glycol tert-octylphenyl ether) in environmental water samples. The optimized experimental conditions were selected, and the mechanism of the Luminol-H₂O₂-Triton X-100 chemiluminesence system was also studied.</p> <p>Results</p> <p>The novel chemiluminescence method for the determination of non-ionic surfactant Triton X-100 was based on the phenomenon that Triton X-100 greatly enhanced the CL signal of the luminol-H₂O₂system. The alkaline medium of luminol and the pH value obviously affected the results. Luminol concentration and hydrogen peroxide concentration also affected the results. The optimal conditions were: Na₂CO₃being the medium, pH value 12.5, luminol concentration 1.0 × 10^-4mol L^-1, H₂O₂concentration 0.4 mol L^-1. The possible mechanism was studied and proposed.</p> <p>Conclusion</p> <p>Under the optimal conditions, the standard curve was drawn up and quotas were evaluated. The linear range was 2 × 10^-4g·mL^-1-4 × 10^-2g·mL^-1(w/v), and the detection limit was 3.97 × 10^-5g·mL^-1Triton X-100 (w/v). The relative standard deviation was less than 4.73% for 2 × 10^-2g·mL^-1(w/v) Triton X-100 (n = 7). This method has been applied to the determination of Triton X-100 in environmental water samples. The desirable recovery ratio was between 96%–102% and the relative standard deviation was 2.5%–3.3%. The luminescence mechanism was also discussed in detail based on the fluorescence spectrum and the kinetic curve, and demonstrated that Triton X-100-luminol-H₂O₂was a rapid reaction.</p

The Effect of CoPt Crystallinity and Grain Texturing on Properties of Exchange-Coupled Fe/CoPt Systems

The effect of the crystallinity and the grain texturing of CoPt hard layers on exchange coupled Fe/CoPt soft/hard magnetic systems was studied using gradient thickness multilayer thin films. We have studied the hard layer structures by transmission electron microscopy and x-ray diffraction, and characterized the exchange coupling interaction through magnetization loops obtained by the magneto-optical Kerr effect measurement. We found that exchange coupling strongly depends on the crystalline characteristics of the CoPt hard layer. There is correlation between the mixture of different grain orientations of the CoPt hard layer and coupling efficiency. In particular, interlayer coupling is enhanced when there is only one orientation, namely, the L10 CoPt structure with its c-axis inclined at 45° with respect to the substrate plane. An increased degree of mixture of the latter with the in-plane-c-axis L10 CoPt structure is detrimental to obtaining one-phase-like magnetization loops. The present work points to the importance of controlling the crystalline properties of the hard layer in order to enhance the maximum energy product (BH)max in hard/soft nanocomposite magnets

One-carbon metabolism in cancer

Cells require one-carbon units for nucleotide synthesis, methylation and reductive metabolism, and these pathways support the high proliferative rate of cancer cells. As such, anti-folates, drugs that target one-carbon metabolism, have long been used in the treatment of cancer. Amino acids, such as serine are a major one-carbon source, and cancer cells are particularly susceptible to deprivation of one-carbon units by serine restriction or inhibition of de novo serine synthesis. Recent work has also begun to decipher the specific pathways and sub-cellular compartments that are important for one-carbon metabolism in cancer cells. In this review we summarise the historical understanding of one-carbon metabolism in cancer, describe the recent findings regarding the generation and usage of one-carbon units and explore possible future therapeutics that could exploit the dependency of cancer cells on one-carbon metabolism

Inhibition of the Integrin/FAK Signaling Axis and c-Myc Synergistically Disrupts Ovarian Cancer Malignancy

Integrins, a family of heterodimeric receptors for extracellular matrix, are promising therapeutic targets for ovarian cancer, particularly high-grade serous-type (HGSOC), as they drive tumor cell attachment, migration, proliferation and survival by activating focal adhesion kinase (FAK)-dependent signaling. Owing to the potential off-target effects of FAK inhibitors, disruption of the integrin signaling axis remains to be a challenge. Here, we tackled this barrier by screening for inhibitors being functionally cooperative with small-molecule VS-6063, a phase II FAK inhibitor. From this screening, JQ1, a potent inhibitor of Myc oncogenic network, emerged as the most robust collaborator. Treatment with a combination of VS-6063 and JQ1 synergistically caused an arrest of tumor cells at the G2/M phase and a decrease in the XIAP-linked cell survival. Our subsequent mechanistic analyses indicate that this functional cooperation was strongly associated with the concomitant disruption of activation or expression of FAK and c-Myc as well as their downstream signaling through the PI3K/Akt pathway. In line with these observations, we detected a strong co-amplification or upregulation at genomic or protein level for FAK and c-Myc in a large portion of primary tumors in the TCGA or a local HGSOC patient cohort. Taken together, our results suggest that the integrin–FAK signaling axis and c-Myc synergistically drive cell proliferation, survival and oncogenic potential in HGSOC. As such, our study provides key genetic, functional and signaling bases for the small-molecule-based co-targeting of these two distinct oncogenic drivers as a new line of targeted therapy against human ovarian cancer