Expanding the cerebrospinal fluid endopeptidome

Biomarkers of neurodegenerative disorders are needed to assist in diagnosis, to monitor disease progression and therapeutic interventions, and to provide insight into disease mechanisms. One route to identify such biomarkers is by proteomic and peptidomic analysis of cerebrospinal fluid (CSF). In the current study, we performed an in-depth analysis of the human CSF endopeptidome to establish an inventory that may serve as a basis for future targeted biomarker studies. High-pH RP HPLC was employed for off-line sample prefractionation followed by low-pH nano-LC-MS analysis. Different software programs and scoring algorithms for peptide identification were employed and compared. A total of 18 031 endogenous peptides were identified at a FDR of 1%, increasing the number of known endogenous CSF peptides 10-fold compared to previous studies. The peptides were derived from 2 053 proteins of which more than 60 have been linked to neurodegeneration. Notably, among the findings were six peptides derived from microtubule-associated protein tau, three of which span the diagnostically interesting threonine-181 (Tau-F isoform). Also, 213 peptides from amyloid precursor protein were identified, 58 of which were partially or completely within the sequence of amyloid β 1-40/42, as well as 109 peptides from apolipoprotein E, spanning sequences that discriminate between the E2/E3/E4 isoforms of the protein

Tobacco use and caries risk among adolescents - a longitudinal study in Sweden

Background: Smoking and the use of smokeless tobacco have a detrimental impact on general and oral health. The relationship to dental caries is however still unclear. As caries is a multi-factorial disease with clear life-style, socio-economic and socio-demographic gradients, the tobacco use may be a co-variable in this complex rather than a direct etiological factor. Our aim was to analyze the impact of tobacco use on caries incidence among adolescents, with consideration to socio-economic variables by residency, using epidemiological data from a longitudinal study in the region of Halland, Sweden. Methods: The study population consisted of 10,068 adolescents between 16-19 years of age from whom yearly data on caries and tobacco use (cigarette smoking and use of smokeless tobacco) were obtained during the period 2006-2012. Reported DMFS increment between 16 and 19 years of age (Delta DMFS) for an individual was considered as the primary caries outcome. The outcome data were compared for self-reported never vs. ever users of tobacco, with consideration to neighborhood-level socio-economy (4 strata), baseline (i.e., 16 years of age) DMFS and sex. The region consists of 65 parishes with various socio-economic conditions and each study individual was geo-coded with respect to his/her residence parish. Neighborhood (parish-level) socio-economy was assessed by proportion of residing families with low household purchasing power. Results:Delta DMFS differed evidently between ever and never users of tobacco (mean values: 1.8 vs. 1.2; proportion with Delta DMFS > 0: 54.2% vs. 40.5%; p < 0.0001). Significant differences were observed in each neighborhood-level socio-economic stratum. Even after controlling for baseline DMFS and sex, Delta DMFS differed highly significantly between the ever and never users of tobacco (overall p < 0.0001). Conclusion: Tobacco use was clearly associated with increased caries increment during adolescence. Hence, this factor is relevant to consider in the clinical caries risk assessment of the individual patient as well as for community health plans dealing with oral health

Investigation of how observed methane concentrations in Ny-Ålesund are influenced by atmospheric flow patterns

International audienceLong-range atmospheric transport to Svalbard has been studied with a compilation of 4 years of daily trajectories to determine how the atmospheric flow patterns influence the observed methane (CH4) at Mt. Zeppelin station (475 m.a.s.l.) in Ny-Ålesund (78&deg54' N, 11°53' E). The flow patterns were determined through cluster analysis of 5-day back-trajectories arriving at Ny-Ålesund twice a day (00:00 and 12:00 UTC) for the period 2000?2003. Eight cluster patterns were obtained and used in the analysis of the continuous methane measurements at Mt. Zeppelin station. The analysis shows a shift in frequencies eastward into the Arctic compared to identical studies of transport for 1992?2001. Higher concentrations of methane are mainly seen in clusters with transport from Europe and Russia in contrast to air following transport pathways within the Arctic Basin. The vertical motion of the trajectories has been investigated and shows that it has an effect on the methane concentration at the Mt. Zeppelin station. This is consistent with previous similar studies of CO2 and of other anthropogenic species. Seasonal variation in trajectory frequency can be seen, like for instance more trajectories from Europe and Siberia during winter, and short trajectories from the Arctic region in summer. The identified seasonal and indications of decadal shifts in transport pathways translate into shifts in source areas sampled by a single station. To determine shifts in regional source (and sink) strengths it is necessary to correct for transport pathway shifts when interpreting time series data

Designing an Awareness Display for Senior Home Care Professionals

Abstract. Home care professionals play a central role in supporting elderly people when they need help to continue living in their own homes. Using awareness systems, caregivers might better be able to consider the actual and changing needs of individual clients, and better be prepared for the home visits. In the present situation, the functional requirements on a awareness systems for professional caregivers are unknown, and caregivers tend to be unaware of the potential use of these sensor-based systems. This paper presents a case study in which the user needs are studied using a working prototype; the prototype is used to make target users experience an awareness system in their everyday work practice, and thereby enable them to better reflect upon the user needs and the potential use of these systemsWhereas caregivers were skeptical at first, they did value the prototype in the evaluation phase. In the exit interviews, the caregivers came up with an interesting list of requirements and design directions for a future awareness display

Instantaneous Hybridization Factor (IHF) Development for HEV Energy-Emissions Analyses Using Real-World, On-Board Data

Past research has shown on-road emissions patterns unique to HEVs, indicating the need to account for them in emissions models. The main objective of this work is to outline a framework for development of new HEV emissions models based on current knowledge of CV emissions. The premise is that accurate knowledge of the instantaneous (1 Hz) power split between the HEV combustion and electric propulsion sources can be used to modify existing CV emission models for HEV emission predictions that are currently lacking in regulatory models. The HEV power split metric, instantaneous hybridization factor (IHF), was developed and quantified with on-road data collected from a 2010 Toyota Camry HEV operating on a fixed route in hilly Vermont over all seasons. IHF is the second-by-second ratio of electric system power to total system power and accounts for energy storage in the high voltage battery. IHF ranges from -1 to +1 and varies widely with vehicle speed and VSP. Different road types on the driving route were associated with different proportions of binned IHF activity, which represent the three key HEV operating states defined in this study: electric-drive only (EDO), power recovery and electric-drive assist. A more detailed analysis of IHF relationships to tailpipe emissions and road grade is found in a recently published article (Ref 1).View the NCST Project Webpag

Excited States of the Phthalimide Chromophore and Their Exciton Couplings: A Tool for Stereochemical Assignments

The electronically excited states of the phthalimide chromophore have been studied by means of linear dichroism (LD) of samples partially oriented in poly(vinyl alcohol) films, magnetic circular dichroism (MCD), and circular dichroism (CD) spectroscopy. On the basis of the LD measurements, the low-energy tail (340-320 nm) of the first absorption band is assigned to an out-of-plane polarized pi-->pi* transition (I). At higher energy, the electronic spectrum is resolved into contributions from five pi-->pi* transitions: II(300 nm, long-axis polarized), III (275 nm, short-axis polarized), IV (235 nm, short-axis polarized), V (220 nm, long-axis polarized), and VI (similar to 210 nm, short-axis polarized). The results from semiempirical (INDO/S-CI) and ab initio (CIS/6-31+G(d)) MO calculations compare well with the proposed assignments of the excited states. Degenerate exciton interaction between electric-dipole-allowed transitions of two phthalimide chromophores is observed in the electronic absorption spectra of the achiral bis-phthalimides 2a-c and in the CD spectrum of the chiral bis-phthalimide 3a. For the latter compound, the solid-state geometry has been determined by X-ray diffraction analysis. Good agreement between experimental and computed CD spectra confirms that the coupled-oscillator exciton model provides the basis for a reliable nonempirical method for the assignment of absolute configuration for this class of compounds. Nondegenerate exciton coupling between phthalimide and benzoate or phenyl chromophores is born out in the CD spectra of homochiral molecules 3c and 3d with the rigid cyclohexane skeleton. Finally, the exciton coupling method is used to make stereochemical assignments for the acyclic, conformationally flexible derivatives 4a-c and 5b