Whole-Exome Sequencing in Familial Parkinson Disease

IMPORTANCE: Parkinson disease (PD) is a progressive neurodegenerative disease for which susceptibility is linked to genetic and environmental risk factors. OBJECTIVE: To identify genetic variants contributing to disease risk in familial PD. DESIGN, SETTING, AND PARTICIPANTS: A 2-stage study design that included a discovery cohort of families with PD and a replication cohort of familial probands was used. In the discovery cohort, rare exonic variants that segregated in multiple affected individuals in a family and were predicted to be conserved or damaging were retained. Genes with retained variants were prioritized if expressed in the brain and located within PD-relevant pathways. Genes in which prioritized variants were observed in at least 4 families were selected as candidate genes for replication in the replication cohort. The setting was among individuals with familial PD enrolled from academic movement disorder specialty clinics across the United States. All participants had a family history of PD. MAIN OUTCOMES AND MEASURES: Identification of genes containing rare, likely deleterious, genetic variants in individuals with familial PD using a 2-stage exome sequencing study design. RESULTS: The 93 individuals from 32 families in the discovery cohort (49.5% [46 of 93] female) had a mean (SD) age at onset of 61.8 (10.0) years. The 49 individuals with familial PD in the replication cohort (32.6% [16 of 49] female) had a mean (SD) age at onset of 50.1 (15.7) years. Discovery cohort recruitment dates were 1999 to 2009, and replication cohort recruitment dates were 2003 to 2014. Data analysis dates were 2011 to 2015. Three genes containing a total of 13 rare and potentially damaging variants were prioritized in the discovery cohort. Two of these genes (TNK2 and TNR) also had rare variants that were predicted to be damaging in the replication cohort. All 9 variants identified in the 2 replicated genes in 12 families across the discovery and replication cohorts were confirmed via Sanger sequencing. CONCLUSIONS AND RELEVANCE: TNK2 and TNR harbored rare, likely deleterious, variants in individuals having familial PD, with similar findings in an independent cohort. To our knowledge, these genes have not been previously associated with PD, although they have been linked to critical neuronal functions. Further studies are required to confirm a potential role for these genes in the pathogenesis of PD

Physical and electrochemical analyses of spin coated hexaammineruthenium(III)/ Nafion/ITO electrodes for heavy metal detection

Varying concentrations of hexaammineruthenium (III), [Ru(NH3)6]3+- Nafion®, films were spin coated on indium tin oxide (ITO)-coated glass substrates. The coating solutions were diluted with ethanol, methanol, or isopropanol. The effects of the solvent type, [Ru(NH3)6]3+ or RuHex concentration, and spin rate on the morphology and transport properties of the fabrication electrodes were investigated. Surface micrographs revealed the presence of sub-micron grooves that diminished with increased RuHex concentration. The surface morphology of the electrodes, however, was independent of the spin rate. The viscosity, η, for all 3 solvent types has an inverse power, n = -0.5, proportionality with RuHex concentration, x i.e. {u1D702}={u1D45A}{u1D465}−0.5. Isopropanol diluted solutions were more viscous than ethanol and methanol diluted solutions with the latter being the least viscous. 75mgRuHex/30mL concentrations were prone to become semi-solid gel suspensions. Cyclic voltammetry determined that 50mgRuHex/30mL, isopropanol-diluted solution, spin coated at 2000rpm yielded the best electrode. The optimized electrodes were used to detect lead and cadmium in yellow and pink pigments obtained from commercially available water colors and mask paint

An Investigation on the transport properties of spin coated redox-active nafion® thin films using cyclic voltammetry

Redox-active hexaammineruthenium(III) [Ru(NH3)6]3+ incorporated Nafion® thin films (\u3c600 \u3enm) were fabricated using spin-coating technique on indium tin oxide (ITO) coated glass substrate. The deposition of the films onto the substrates was verified using energy dispersive x-ray (EDX), surface morphology characterized using scanning electron microscopy (SEM), and electrochemical characteristic through cyclic voltammetry. The concentration of the ruthenium complex, and thinning rate were chosen as the parameters for the study. EDX results confirm the presence of the films on the substrate. Surface morphological results determine that the film is smooth at 10,000x magnification but exhibit lumps at high concentrations but were smoothened out at increasing thinning rates. Voltammetry results show that peak currents decrease at increasing thinning rates and at decreasing concentrations. Moreover, the diffusion coefficients decrease at increasing concentration and decrease at increasing thinning rates. Calculated values of the diffusion coefficients indicate that the ruthenium complex is immobilized in the film

Morphological, thickness and electrochemical analyses of spin-coated [Ru(NH3)6]\u3csup\u3e3+\u3c/sup\u3e /Nafion films

Nafion thin films were fabricated using the spin coating method. Hexaammineruthenium(III) [Ru(NH3)6]3+ was used as the redox mediator and was incorporated in the film. The amount of [Ru(NH3)6]3+ was varied and three different solvents were used. The morphology of the films was investigated and the film thickness was measured using scanning electron microscopy (SEM). The effects of varying the amount of the redox mediator and the solvent type on the viscosity of the coating solution, film thickness and morphology were investigated. The electrochemical properties of the fabricated films were studied using cyclic voltammetry. © 2015, National Institute of Optoelectronics. All rights reserved

CELL-TO-CELL SPREAD BY

This manuscript has been repmbced fFDm the microfilm master. UMI films the text diredly hwn the Original or copy submitted. Thus, sane and dissertation copies are in typemiter face, while others may be from any type of computer printer. The quality of thk reproduction is depedmt upon the quality of the copy submitted. Woken or indistinct cdomd or poor qualii illustratiorrs and photographs. pfint Meedthrough, shtawbd margins, and impmpew alignment can adversely affect reproduction. In the unlikety event that iha author did not send UMI a complete manutaipt and there am missing pages. these will be noted. Also, if unauthoriteed copyrioht material had to be removed, a will indii the de(etion. Oversize ma&riaIs (eg.. maps, dWngs, charts) am mpmdmd by sectioning the original, beginning at UUB upper le(t4mnd comer and eontiwing from left to right in equal sections with small ov-s, Photographs induded in the original mawalpt have been reQrodUCBd xerographically in this copy. Highew quality 6 " x Q bbdc and white photographic prints are available for any photographs or illusbations appearing in this copy fw an additional charge. Confact UMI directly to order

FPGA-based automated forced-air device for body temperature regulation

Hypothermia is known as the drop in a person\u27s core body temperature. Patients experience a range of mild to severe hypothermia after general anesthetics are applied for surgery. Forced-air devices are used to increase and maintain body temperature in order to prevent damage to the patient\u27s body due to hypothermia. This device forces heated air into a blanket, which in turn becomes a medium to apply heat to the patient. However, today\u27s existing forced-air devices are manually operated. This project aims to create an automated forced-air device using a Field Programmable Gate Array (FPGA) development board. Through automation, the patient\u27s temperature readings are read constantly and heater levels are changed as soon as the patient\u27s body requires it. The temperature accuracy of heater outputs are increased by manipulating them based on feedback from the blanket itself. Also, this device periodically logs and displays temperature readings in order for doctors to analyze the patient\u27s body temperature response. These factors enable the device to require less human operation and less human error

A point-of-care test for measles diagnosis: detection of measles-specific IgM antibodies and viral nucleic acid

OBJECTIVE: To evaluate the performance of a newly developed point-of-care test (POCT) for the detection of measles-specific IgM antibodies in serum and oral fluid specimens and to assess if measles virus nucleic acid could be recovered from used POCT strips. METHODS: The POCT was used to test 170 serum specimens collected through measles surveillance or vaccination programmes in Ethiopia, Malaysia and the Russian Federation: 69 were positive for measles immunoglobulin M (IgM) antibodies, 74 were positive for rubella IgM antibodies and 7 were positive for both. Also tested were 282 oral fluid specimens from the measles, mumps and rubella (MMR) surveillance programme of the United Kingdom of Great Britain and Northern Ireland. The Microimmune measles IgM capture enzyme immunoassay was the gold standard for comparison. A panel of 24 oral fluids was used to investigate if measles virus haemagglutinin (H) and nucleocapsid (N) genes could be amplified by polymerase chain reaction directly from used POCT strips. FINDINGS: With serum POCT showed a sensitivity and specificity of 90.8% (69/76) and 93.6% (88/94), respectively; with oral fluids, sensitivity and specificity were 90.0% (63/70) and 96.2% (200/208), respectively. Both H and N genes were reliably detected in POCT strips and the N genes could be sequenced for genotyping. Measles virus genes could be recovered from POCT strips after storage for 5 weeks at 20–25 °C. CONCLUSION: The POCT has the sensitivity and specificity required of a field-based test for measles diagnosis. However, its role in global measles control programmes requires further evaluation

A point-of-care test for measles diagnosis: detection of measles-specific IgM antibodies and viral nucleic acid

OBJECTIVE: To evaluate the performance of a newly developed point-of-care test (POCT) for the detection of measles-specific IgM antibodies in serum and oral fluid specimens and to assess if measles virus nucleic acid could be recovered from used POCT strips. METHODS: The POCT was used to test 170 serum specimens collected through measles surveillance or vaccination programmes in Ethiopia, Malaysia and the Russian Federation: 69 were positive for measles immunoglobulin M (IgM) antibodies, 74 were positive for rubella IgM antibodies and 7 were positive for both. Also tested were 282 oral fluid specimens from the measles, mumps and rubella (MMR) surveillance programme of the United Kingdom of Great Britain and Northern Ireland. The Microimmune measles IgM capture enzyme immunoassay was the gold standard for comparison. A panel of 24 oral fluids was used to investigate if measles virus haemagglutinin (H) and nucleocapsid (N) genes could be amplified by polymerase chain reaction directly from used POCT strips. FINDINGS: With serum POCT showed a sensitivity and specificity of 90.8% (69/76) and 93.6% (88/94), respectively; with oral fluids, sensitivity and specificity were 90.0% (63/70) and 96.2% (200/208), respectively. Both H and N genes were reliably detected in POCT strips and the N genes could be sequenced for genotyping. Measles virus genes could be recovered from POCT strips after storage for 5 weeks at 20-25 ºC. CONCLUSION: The POCT has the sensitivity and specificity required of a field-based test for measles diagnosis. However, its role in global measles control programmes requires further evaluation

Fabrication and electrochemical study of [Ru(NH3)6]\u3csup\u3e3+\u3c/sup\u3e/Nafion modified electrodes for the determination of trace amounts of Pb\u3csup\u3e2+\u3c/sup\u3e, Cd\u3csup\u3e2+\u3c/sup\u3e, and Zn\u3csup\u3e2+\u3c/sup\u3e via anodic stripping voltammetry

[Ru(NH3)6]3+/Nafion modified indium tin oxide (ITO) electrodes were fabricated via the drop coating technique and were used for the simultaneous determination of lead (Pb2+), cadmium (Cd2+), and zinc (Zn2+) in trace amounts using anodic stripping voltammetry (ASV). The amount of [Ru(NH3)6]3+ in the coating solution was varied at 5 mg, 10 mg, and 15 mg. The fabricated electrodes were used to detect varying concentrations of Pb, Cd and Zn. ASV results showed that as the amount of [Ru(NH3)6]3+ was increased, the reduction current of the heavy metals increased as well. The Pearson correlation values obtained for Pb and Cd were close to 1.0, indicating a strong positive linear relationship between the variables. The minimum heavy metal concentration that can be simultaneously detected by the fabricated electrodes is 0.5 ppm. © 2016 by De Gruyter