Analysis of EMG and acceleration signals for quantifying the effects of deep brain stimulation in Parkinson's disease

Deep brain stimulation (DBS) is effective in reducing motor symptoms in Parkinson's disease (PD). However, objective methods for quantifying its efficacy are lacking. We present a principal component (PC)-based tracking method for quantifying the effects of DBS in PD by using electromyography (EMG) and acceleration measurements. Ten parameters capturing PD characteristic signal features were initially extracted from isometric EMG and acceleration recordings. Using a PC approach, the original parameters were transformed into a smaller number of PCs. Finally, the effects of DBS were quantified by examining the PCs in a low-dimensional feature space. The EMG and acceleration data from 13 PD patients with DBS ON and OFF, and 13 healthy age-matched controls were used for analysis. Clinical evaluation of patients showed that their motor symptoms were effectively reduced with DBS. The analysis results showed that the signal characteristics of 12 patients were more similar to those of the healthy controls with DBS ON than with DBS OFF. These observations indicate that the PC-based tracking method can be used to objectively quantify the effects of DBS on the neuromuscular function of PD patients. Further studies are suggested to estimate the clinical sensitivity of the method to different types of PD.     

A fast O(N) multiresolution polygonal approximation algorithm for GPS trajectory simplification

Recent advances in geopositioning mobile phones have made it possible for users to collect a large number of GPS trajectories by recording their location information. However, these mobile phones with built-in GPS devices usually record far more data than needed, which brings about both heavy data storage and a computationally expensive burden in the rendering process for a Web browser. To address this practical problem, we present a fast polygonal approximation algorithm in 2-D space for the GPS trajectory simplification under the so-called integral square synchronous distance error criterion in a linear time complexity. The underlying algorithm is designed and implemented using a bottom-up multiresolution method, where the input of polygonal approximation in the coarser resolution is the polygonal curve achieved in the finer resolution. For each resolution (map scale), priority-queue structure is exploited in graph construction to construct the initialized approximated curve. Once the polygonal curve is initialized, two fine-tune algorithms are employed in order to achieve the desirable quality level. Experimental results validated that the proposed algorithm is fast and achieves a better approximation result than the existing competitive methods.     

On-Line Characterization of Morphology and Water Adsorption on Fumed Silica Nanoparticles

The first wetting layer on solid nanoparticles has direct implications on the roles these particles play in industrial processes and technological applications as well as in the atmosphere. We present a technique for online measurements of the adsorption of the first few water layers onto insoluble aerosol nanoparticles. Atomized fumed silica nanoparticles were dispersed from aqueous suspension and their hygroscopic growth factors (HGF) and number of the adsorbed water layers at subsaturated conditions were measured using a nanometer hygroscopic tandem differential mobility analyzer (HTDMA). Particle morphology was characterized by electron microscopy and particle density was determined by mobility analysis. The HGFs of the size-selected particles at mobility diameters from 10 to 50 nm at 90% relative humidity (RH) varied from 1.05 to 1.24, corresponding to 2–6 layers of adsorbed water. The morphology of the generated fumed silica nanoparticles varied from spheres at 8–10 nm to agglomerates at larger diameters with effective density from 1.7 to 0.8 g/cm³ and fractal dimension of 2.6. The smallest spheres and agglomerates had the highest HGFs. The smallest particles with diameters of 8 and 10 nm adsorbed two to three water layers in subsaturated conditions, which agreed well with the Frenkel, Halsey, and Hill (FHH) isotherm fitting. In comparison to the small spheres or large agglomerates, the compact agglomerate structure containing a few primary particles increased the number of adsorbed water layers by a factor of ～1.5. This was probably caused by the capillary effect on the small cavities between the primary particles in the agglomerate.     

Effects of Ospemifene on Drug Metabolism Mediated by Cytochrome P450 Enzymes in Humans in Vitro and in Vivo

The objective of these investigations was to determine the possible effects of the novel selective estrogen receptor modulator, ospemifene, on cytochrome P450 (CYP)-mediated drug metabolism. Ospemifene underwent testing for possible effects on CYP enzyme activity in human liver microsomes and in isolated human hepatocytes. Based on the results obtained in vitro, three Phase 1 crossover pharmacokinetic studies were conducted in healthy postmenopausal women to assess the in vivo effects of ospemifene on CYP-mediated drug metabolism. Ospemifene and its main metabolites 4-hydroxyospemifene and 4′-hydroxyospemifene weakly inhibited a number of CYPs (CYP2B6, CYP2C9, CYP2C19, CYP2C8, and CYP2D6) in vitro. However, only CYP2C9 activity was inhibited by 4-hydroxyospemifene at clinically relevant concentrations. Induction of CYPs by ospemifene in cultured human hepatocytes was 2.4-fold or less. The in vivo studies showed that ospemifene did not have significant effects on the areas under the plasma concentration-time curves of the tested CYP substrates warfarin (CYP2C9), bupropion (CYP2B6) and omeprazole (CYP2C19), demonstrating that pretreatment with ospemifene did not alter their metabolism. Therefore, the risk that ospemifene will affect the pharmacokinetics of drugs that are substrates for CYP enzymes is low.     

Cobalt‐Catalysed Addition of Allylidene Dipivalate to Aldehydes. A Formal Homoaldol Condensation

A Co(I)‐catalysed condensation of allylidene dipivalate with aldehydes to give (Z)‐4‐hydroxybut‐1‐enyl pivalates in 62 to 87% isolated yields, is reported. Reactions are run in acetonitrile at 0 or 25 °C depending on the nature of the aldehyde, and exploiting the Co(II)/Zn(0) redox couple for the preparation of the catalytic Co(I) species.     

Toxicological characterization of particulate emissions from straw,Miscanthus, and poplar pellet combustion in residential boilers

Wood pellets have been used in domestic heating appliances for three decades. However, because the share of renewable energy for heating will likely rise over the next several years, alternative biomass fuels, such as short-rotation coppice or energy crops, will be utilized. We tested particulate emissions from the combustion of standard softwood pellets and three alternative pellets (poplar, Miscanthus sp., and wheat straw) for their ability to induce inflammatory, cytotoxic, and genotoxic responses in a mouse macrophage cell line. Our results showed clear differences in the chemical composition of the emissions, which was reflected in the toxicological effects. Standard softwood and straw pellet combustion resulted in the lowest PM₁ mass emissions. Miscanthus sp. and poplar combustion emissions were approximately three times higher. Emissions from the herbaceous biomass pellets contained higher amounts of chloride and organic carbon than the emissions from standard softwood pellet combustion. Additionally, the emissions of the poplar pellet combustion contained the highest concentration of metals. The emissions from the biomass alternatives caused significantly higher genotoxicity than the emissions from the standard softwood pellets. Moreover, straw pellet emissions caused higher inflammation than the other samples. Regarding cytotoxicity, the differences between the samples were smaller. Relative toxicity was generally highest for the poplar and Miscanthus sp. samples, as their emission factors were much higher. Thus, in addition to possible technical problems, alternative pellet materials may cause higher emissions and toxicity. The long-term use of alternative fuels in residential-scale appliances will require technological developments in both burners and filtration.

Copyright © 2016 American Association for Aerosol Research     

If Virchow and Ehrlich Had Dreamt Together: What the Future Holds for KRAS-Mutant Lung Cancer

Non-small-cell lung cancer (NSCLC) with Kirsten rat sarcoma (KRAS) mutations has notoriously challenged oncologists and researchers for three notable reasons: (1) the historical assumption that KRAS is “undruggable”, (2) the disease heterogeneity and (3) the shaping of the tumor microenvironment by KRAS downstream effector functions. Better insights into KRAS structural biochemistry allowed researchers to develop direct KRAS(G12C) inhibitors, which have shown early signs of clinical activity in NSCLC patients and have recently led to an FDA breakthrough designation for AMG-510. Following the approval of immune checkpoint inhibitors for PDL1-positive NSCLC, this could fuel yet another major paradigm shift in the treatment of advanced lung cancer. Here, we review advances in our understanding of the biology of direct KRAS inhibition and project future opportunities and challenges of dual KRAS and immune checkpoint inhibition. This strategy is supported by preclinical models which show that KRAS(G12C) inhibitors can turn some immunologically “cold” tumors into “hot” ones and therefore could benefit patients whose tumors harbor subtype-defining STK11/LKB1 co-mutations. Forty years after the discovery of KRAS as a transforming oncogene, we are on the verge of approval of the first KRAS-targeted drug combinations, thus therapeutically unifying Paul Ehrlich’s century-old “magic bullet” vision with Rudolf Virchow’s cancer inflammation theory.     

Exit pupil expander with a large field of view based on diffractive optics

Abstract— The field of view is an important parameter of a near‐to‐eye display. To achieve an immersive viewing experience, the field of view should be as high as possible. Presently, in most of the commercially available devices the field of view is between 15° and 30°. In this paper, a large‐field‐of‐view exit pupil expander that is based on diffractive optics was demonstrated. Usually these types of diffractive expanders cannot have a field of view much more than 25°. Here, an exit pupil expander with an extended field of view, based on two stacked plates, was demonstrated. The expander is designed for green light and it achieves a field of view of more than 40°.