Co-Clustering Network-Constrained Trajectory Data

Recently, clustering moving object trajectories kept gaining interest from both the data mining and machine learning communities. This problem, however, was studied mainly and extensively in the setting where moving objects can move freely on the euclidean space. In this paper, we study the problem of clustering trajectories of vehicles whose movement is restricted by the underlying road network. We model relations between these trajectories and road segments as a bipartite graph and we try to cluster its vertices. We demonstrate our approaches on synthetic data and show how it could be useful in inferring knowledge about the flow dynamics and the behavior of the drivers using the road network

Improving your target-template alignment with MODalign

Summary: MODalign is an interactive web-based tool aimed at helping protein structure modelers to inspect and manually modify the alignment between the sequences of a target protein and of its template(s). It interactively computes, displays and, upon modification of the target-template alignment, updates the multiple sequence alignments of the two protein families, their conservation score, secondary structure and solvent accessibility values, and local quality scores of the implied three-dimensional model(s). Although it has been designed to simplify the target-template alignment step in modeling, it is suitable for all cases where a sequence alignment needs to be inspected in the context of other biological information

The ModFOLD4 server for the quality assessment of 3D protein models

Once you have generated a 3D model of a protein, how do you know whether it bears any resemblance to the actual structure? To determine the usefulness of 3D models of proteins, they must be assessed in terms of their quality by methods that predict their similarity to the native structure. The ModFOLD4 server is the latest version of our leading independent server for the estimation of both the global and local (per-residue) quality of 3D protein models. The server produces both machine readable and graphical output, providing users with intuitive visual reports on the quality of predicted protein tertiary structures. The ModFOLD4 server is freely available to all at: http://www.reading.ac.uk/bioinf/ModFOLD/

Ultrafast time-resolved spectroscopy of 1D metal-dielectric photonic crystals

We study the all-optical switching behavior of one-dimensional metal-dielectric photonic crystals due to the nonlinearity of the free metal electrons. A polychromatic pump-probe setup is used to determine the wavelength and pump intensity dependence of the ultrafast transmission suppression as well as the dynamics of the process on a subpicosecond timescale. We find ultrafast (sub-picosecond) as well as a slow (millisecond) behavior. We present a model of the ultrafast dynamics and nonlinear response which can fit the measured data well and allows us to separate the thermal and the electronic response of the system.Comment: 7 pages, 5 figure

FunFOLDQA: a quality assessment tool for protein-ligand binding site residue predictions

The estimation of prediction quality is important because without quality measures, it is difficult to determine the usefulness of a prediction. Currently, methods for ligand binding site residue predictions are assessed in the function prediction category of the biennial Critical Assessment of Techniques for Protein Structure Prediction (CASP) experiment, utilizing the Matthews Correlation Coefficient (MCC) and Binding-site Distance Test (BDT) metrics. However, the assessment of ligand binding site predictions using such metrics requires the availability of solved structures with bound ligands. Thus, we have developed a ligand binding site quality assessment tool, FunFOLDQA, which utilizes protein feature analysis to predict ligand binding site quality prior to the experimental solution of the protein structures and their ligand interactions. The FunFOLDQA feature scores were combined using: simple linear combinations, multiple linear regression and a neural network. The neural network produced significantly better results for correlations to both the MCC and BDT scores, according to Kendall’s τ, Spearman’s ρ and Pearson’s r correlation coefficients, when tested on both the CASP8 and CASP9 datasets. The neural network also produced the largest Area Under the Curve score (AUC) when Receiver Operator Characteristic (ROC) analysis was undertaken for the CASP8 dataset. Furthermore, the FunFOLDQA algorithm incorporating the neural network, is shown to add value to FunFOLD, when both methods are employed in combination. This results in a statistically significant improvement over all of the best server methods, the FunFOLD method (6.43%), and one of the top manual groups (FN293) tested on the CASP8 dataset. The FunFOLDQA method was also found to be competitive with the top server methods when tested on the CASP9 dataset. To the best of our knowledge, FunFOLDQA is the first attempt to develop a method that can be used to assess ligand binding site prediction quality, in the absence of experimental data

High-Throughput NMR Assessment of the Tertiary Structure of Food Allergens

In vitro component-resolved diagnosis of food allergy requires purified allergens that have to meet high standards of quality. These include the authentication of their conformation, which is relevant for the recognition by specific IgE antibodies from allergic patients. Therefore, highly sensitive and reliable screening methods for the analysis of proteins/allergens are required to assess their structural integrity. In the present study one-dimensional 1H Nuclear Magnetic Resonance (1D 1H-NMR) analysis was adopted for the assessment of overall structural and dynamic properties and authentication of a set of relevant food allergens, including non-specific lipid transfer proteins from apple, peach and hazelnut, 7/8S seed storage globulins from hazelnut and peanut, 11S seed storage globulins from hazelnut and peanut, caseins from cows' and goats' milk and tropomyosin from shrimp.Two sets of 1D 1H-NMR experiments, using 700 MHz and 600 MHz instruments at 298 K were carried out to determine the presence and the extent of tertiary structure. Structural similarity among members of the individual allergen families was also assessed and changes under thermal stress investigated. The nuclear magnetic resonance (NMR) results were compared with structural information available either from the literature, Protein Data Bank entries, or derived from molecular models.1D (1)H-NMR analysis of food allergens allowed their classification into molecules with rigid, extended and ordered tertiary structures, molecules without a rigid tertiary structure and molecules which displayed both features. Differences in thermal stability were also detected. In summary, 1D (1)H-NMR gives insights into molecular fold of proteins and offers an independent method for assessing structural properties of proteins

The Swiss Multiple Sclerosis Cohort-Study (SMSC): A Prospective Swiss Wide Investigation of Key Phases in Disease Evolution and New Treatment Options.

The mechanisms leading to disability and the long-term efficacy and safety of disease modifying drugs (DMDs) in multiple sclerosis (MS) are unclear. We aimed at building a prospective cohort of MS patients with standardized collection of demographic, clinical, MRI data and body fluids that can be used to develop prognostic indicators and biomarkers of disease evolution and therapeutic response. The Swiss MS Cohort (SMSC) is a prospective observational study performed across seven Swiss MS centers including patients with MS, clinically isolated syndrome (CIS), radiologically isolated syndrome or neuromyelitis optica. Neurological and radiological assessments and biological samples are collected every 6-12 months. We recruited 872 patients (clinically isolated syndrome [CIS] 5.5%, relapsing-remitting MS [RRMS] 85.8%, primary progressive MS [PPMS] 3.5%, secondary progressive MS [SPMS] 5.2%) between June 2012 and July 2015. We performed 2,286 visits (median follow-up 398 days) and collected 2,274 serum, plasma and blood samples, 152 cerebrospinal fluid samples and 1,276 brain MRI scans. 158 relapses occurred and expanded disability status scale (EDSS) scores increased in PPMS, SPMS and RRMS patients experiencing relapses. Most RRMS patients were treated with fingolimod (33.4%), natalizumab (24.5%) or injectable DMDs (13.6%). The SMSC will provide relevant information regarding DMDs efficacy and safety and will serve as a comprehensive infrastructure available for nested research projects

Renal Function and Body Mass Index Contribute to Serum Neurofilament Light Chain Levels in Elderly Patients With Atrial Fibrillation.

Objective: Serum neurofilament light chain (sNfL) is increasingly used as a neuroaxonal injury biomarker in the elderly. Besides age, little is known about how other physiological factors like renal function and body mass index (BMI) alter its levels. Here, we investigated the association of estimated glomerular filtration rate (eGFR) and BMI with sNfL in a large sample of elderly patients with atrial fibrillation (AF). Methods: This is a cross-sectional analysis from the Swiss-AF Cohort (NCT02105844). We measured sNfL using an ultrasensitive single-molecule array assay. We calculated eGFR using the chronic kidney disease epidemiology collaboration (CKD-EPI) creatinine (eGFRcrea) and creatinine–cystatin C (eGFRcrea–cys) formulas, and BMI from weight and height measurements. We evaluated the role of eGFR and BMI as determinants of sNfL levels using multivariable linear regression and the adjusted R2 (R2adj). Results: Among 2,277 Swiss-AF participants (mean age 73.3 years), eGFRcrea showed an inverse curvilinear association with sNfL after adjustment for age and cardiovascular comorbidities. BMI also showed an independent, inverse linear association with sNfL. The R2adj of models with age, eGFRcrea, and BMI alone was 0.26, 0.35, and 0.02, respectively. A model with age and eGFRcrea combined explained 45% of the sNfL variance. Sensitivity analyses (i) further adjusting for vascular brain lesions (N = 1,402 participants with MRI) and (ii) using eGFRcrea–cys yielded consistent results. Interpretation: In an elderly AF cohort, both renal function and BMI were associated with sNfL, but only renal function explained a substantial proportion of the sNfL variance. This should be taken into account when using sNfL in elderly patients or patients with cardiovascular disease

Attitudes to antipsychotic drugs and their side effects: a comparison between general practitioners and the general population

BACKGROUND: Attitudes towards antipsychotic medication play an important part in the treatment for schizophrenia and related disorders. We aimed measuring general practitioners' attitudes to antipsychotic drugs and their adverse side effects and comparing these with the attitudes of the general population. METHODS: Analysis and comparison of two representative samples, one comprising 100 General Practitioners (GPs), the other 791 individuals randomly selected from the general population. The setting was the German speaking cantons of Switzerland. RESULTS: General practitioners have significantly more positive attitudes towards anti-psychotic drugs than the general public. They reject widespread prejudices about the use of anti-psychotic medication significantly more than the general population. In particular the risk of dependency was assessed as 'low' by GP's (80%), in contrast to only 18% of the general population sample. In no instance did a majority of the GPs advise not tolerating any of the 10 possible adverse effects presented in this study. This is in marked contrast to the general population sample, where a majority recommended discontinuation for movement disorder (63%), strong tremor (59%), risk of dependency (55%) and feelings of unrest (54%). CONCLUSION: As well as effective management of side-effects being a vital aspect of patient and carer education, prescribing doctors need to be aware that their mentally ill patients are likely to be confronted with extremely negative public attitudes towards antipsychotic medication and with strong pressures to stop taking their medication in the event of side-effects

TRH: Pathophysiologic and clinical implications

Thyrotropin releasing hormone is thought to be a tonic stimulator of the pituitary TSH secretion regulating the setpoint of the thyrotrophs to the suppressive effect of thyroid hormones. The peptide stimulates the release of normal and elevated prolactin. ACTH and GH may increase in response to exogenous TRH in pituitary ACTH and GH hypersecretion syndromes and in some extrapituitary diseases. The pathophysiological implications of extrahypothalamic TRH in humans are essentially unknown. The TSH response to TRH is nowadays widely used as a diganostic amplifier in thyroid diseases being suppressed in borderline and overt hyperthyroid states and increased in primary thyroid failure. In hypothyroid states of hypothalamic origin, TSH increases in response to exogenous TRH often with a delayed and/or exaggerated time course. But in patients with pituitary tumors and suprasellar extension TSH may also respond to TRH despite secondary hypothyroidism. This TSH increase may indicate a suprasellar cause for the secondary hypothyroidism, probably due to portal vessel occlusion. The TSH released in these cases is shown to be biologically inactive