Dynamics of single biopolymer translocation and sedimentation

In this Thesis the dynamics of translocation and sedimentation of a single biopolymer (typically DNA, RNA or a protein) is studied. A coarse-graining paradigm is invoked to justify the various computational models by use of which the results are obtained. The transport of biopolymers through a nano-scale pore in a membrane is a ubiquitous process in biology. Experimental interest in translocation process focuses on its potential applicability in ultra-fast sequencing of DNA and RNA molecules. Polymer translocation has been under intense study for over a decade. Inspite of the vast theoretical research, the experimental results on the driven case have not been explained. We claim that the reason for this is that the translocation process must be treated as (at least) two dynamically distinct cases, where the dynamics takes place either close to or out of equilibrium. Here, we find that the latter case corresponds to the experiments. We make a comprehensive investigation on how the process can be discriminated based on its dynamics, and define and use some indicators to this end. In addition, we study the role of hydrodynamics, and find it to govern the dynamics when the process takes place out of equilibrium. Sedimentation is a natural process induced by gravity that can be applied experimentally in a quickened form by the use of ultracentrifuges, and which is similar to electrophoresis. Our study on behavior of single polymers under non-equilibrium conditions falls within the rapidly developing field of nano- and microfluidics that has important applications in "lab-on-a-chip" based technologies. In polymer sedimentation, we study the settling of the polymer in a steady-state in the limit of zero Péclet number, i.e. where no thermal fluctuations exist. The hydrodynamic coupling of the polymer beads leads to chaotic time-dependent behavior of the chain conformations that in turn are coupled with the velocity fluctuations of the polymer's center of mass

Sub-classification based specific movement control exercises are superior to general exercise in sub-acute low back pain when both are combined with manual therapy: A randomized controlled trial

Background: Clinical guidelines recommend research on sub-groups of patients with low back pain (LBP) but, to date, only few studies have been published. One sub-group of LBP is movement control impairment (MCI) and clinical tests to identify this sub-group have been developed. Also, exercises appear to be beneficial for the management of chronic LBP (CLBP), but very little is known about the management of sub-acute LBP. Methods: A randomized controlled trial (RCT) was conducted to compare the effects of general exercise versus specific movement control exercise (SMCE) on disability and function in patients with MCI within the recurrent sub-acute LBP group. Participants having a MCI attended five treatment sessions of either specific or general exercises. In both groups a short application of manual therapy was applied. The primary outcome was disability, assessed by the Roland-Morris Disability Questionnaire (RMDQ). The measurements were taken at baseline, immediately after the three months intervention and at twelve-month follow-up. Results: Seventy patients met the inclusion criteria and were eligible for the trial. Measurements of 61 patients (SMCE n = 30 and general exercise n = 31) were completed at twelve months. (Drop-out rate 12.9 %). Patients in both groups reported significantly less disability (RMDQ) at twelve months follow-up. However, the mean Change on the RMDQ between baseline and the twelve-month measurement showed statistically significantly superior improvement for the SMCE group -1.9 points (-3.9 to -0.5) 95 % (CI). The result did not reach the clinically significant three point difference. There was no statistical difference between the groups measured with Oswestry Disability Index (ODI). Conclusion: For subjects with non-specific recurrent sub-acute LBP and MCI an intervention consisting of SMCE and manual therapy combined may be superior to general exercise combined with manual therapy. Trial registration: The study protocol registration number is ISRCTN48684087. It was registered retrospectively 18th Jan 2012

Recognition of Indoor Scenes using 3D Scene Graphs

Scene recognition is a fundamental task in 3-D scene understanding. It answers the question, 'What is this place?' In an indoor environment, the answer can be an office, kitchen, lobby, and so on. As the number of point clouds increases, using embedded point information in scene recognition becomes computationally heavy to process. To achieve computational efficiency and accurate classification, our idea is to use an indoor scene graph that represents the 3-D spatial structures via object instances. The proposed method comprises two parts, namely: 1) construction of indoor scene graphs leveraging object instances and their spatial relationships and 2) classification of these graphs using a deep learning network. Specifically, each indoor scene is represented by a graph, where each node represents either a structural element (like a ceiling, a wall, or a floor) or a piece of furniture (like a chair or a table), and each edge encodes the spatial relationship between these elements. Then, these graphs are used as input for our proposed graph classification network to learn different scene representations. The public indoor dataset, ScanNet v2, with 625.53 million points, is selected to test our method. Experiments yield good results with up to 88.00% accuracy and 82.30% F1 score in the fixed validation dataset and 90.46% accuracy and 81.45% F1 score in the ten-fold cross-validation method; moreover, if some indoor objects cannot be successfully identified, the scene classification accuracy depends sublinearly on the rate of missing objects in the scene.</p

Single Photon Lidar in Mobile Laser Scanning: The Sampling Rate Problem and Initial Solution via Spatial Correlations

Single photon lidars (in solid state form) offer several benefits over pulsed lidars, such as independence of micro-mechanical moving parts or rotating joints, lower power consumption, faster acquisition rate, and reduced size. When mass produced, they will be cheaper and smaller and thus very attractive for mobile laser scanning applications. However, as these lidars operate by receiving single photons, they are very susceptible to background illumination such as sunlight. In other words, the observations contain a significant amount of noise, or to be specific, outliers. This causes trouble for measurements done in motion, as the sampling rate (i.e. the measurement frequency) should be low and high at the same time. It should be low enough so that target detection is robust, meaning that the targets can be distinguished from the single-photon avalanche diode (SPAD) triggings caused by the background photons. On the other hand, the sampling rate should be high enough to allow for measurements to be done from motion. Quick sampling reduces the probability that a sample gathered during motion would contain data from more than a single target at a specific range. Here, we study the exploitation of spatial correlations that exist between the observations as a mean to overcome this sampling rate paradox. We propose computational methods for short and long range. Our results indicate that the spatial correlations do indeed allow for faster and more robust sampling of measurements, which makes single photon lidars more attractive in (daylight) mobile laser scanning

Surgery versus non-operative treatment for ER-stress unstable Weber-B unimalleolar fractures : A study protocol for a prospective randomized non-inferiority (Super-Fin) trial

Publisher Copyright: ©Roughly two-thirds of ankle fractures are unimalleolar injuries, the Weber B-type fibula fracture being by far the most common type. Depending on the trauma and the accompanying soft-tissue injury, these fractures are either stable or unstable. Current clinical practice guidelines recommend surgical treatment for unstable Weber B-type fibula fractures. An ongoing randomized, parallel group, non-inferiority trial comparing surgery and non-operative treatment for unstable Weber B-type ankle fractures with allocation ratio 1:1. The rationale for non-inferiority design is as follows: By being able to prove non-inferiority of non-operative treatment, we would be able to avoid complications related to surgery. However, the primary concern related to non-operative treatment is increased risks of ankle mortise incongruency, leading to secondary surgery, early post-traumatic osteoarthritis and poor function. After providing informed consent, 126 patients aged 16 years or older with an unimalleolar Weber B-type unstable fibula fracture were randomly assigned to surgery (open reduction and internal fixation) or non-operative treatment (6-week cast immobilization). We have completed the patient enrolment and are currently in the final stages of the 2-year follow-up. The primary, non-inferiority outcome is the Olerud-Molander Ankle Score (OMAS) at 2 years (primary time point). The predefined non-inferiority margin is set at 8 OMAS points. Secondary outcomes include the Foot and Ankle Score, a 100 mm Visual Analogue Scale for function and pain, the RAND-36-Item Health Survey for health-related quality-of-life, the range-of-motion of the injured ankle, malunion (ankle joint incongruity) and fracture union. Treatment-related complications and harms; symptomatic non-unions, loss of congruity of the ankle joint, reoperations and wound infections will also be recorded. We hypothesize that non-operative treatment yields non-inferior functional outcome to surgery, the current standard treatment, with no increased risk of harms.Peer reviewe

Computer-based Eye-tracking Analysis of King-Devick Test Differentiates Persons with Idiopathic Normal Pressure Hydrocephalus from Cognitively Unimpaired

Publisher Copyright: © 2022 Lippincott Williams and Wilkins. All rights reserved.Background: Functional defects in eye movements and reduced reading speed in neurodegenerative diseases represent a potential new biomarker to support clinical diagnosis. We investigated whether computer-based eye-tracking (ET) analysis of the King-Devick (KD) test differentiates persons with idiopathic normal pressure hydrocephalus (iNPH) from cognitively unimpaired [control (CO)] and persons with Alzheimer's disease (AD). Methods: We recruited 68 participants (37 CO, 10 iNPH, and 21 AD) who underwent neurological examination, the Consortium to Establish a Registry for Alzheimer's Disease neuropsychological test battery (CERAD-NB), and a Clinical Dementia Rating interview. The KD reading test was performed using computer-based ET. We analyzed the total time used for the reading test, number of errors, durations of fixation and saccade, and saccade amplitudes. Results: The iNPH group significantly differed from the CO group in the KD test mean total time (CO 69.3 s, iNPH 87.3 s; P≤0.009) and eye-tracking recording of the mean saccade amplitude (CO 3.6 degree, iNPH 3.2 degree; P≤0.001). The AD group significantly differed from the CO group in each tested parameter. No significant differences were detected between the iNPH and AD groups. Conclusion: For the first time, we demonstrated altered reading ability and saccade amplitudes in patients with iNPH.Peer reviewe

Shortening of Saccades as a Possible Easy-to-Use Biomarker to Detect Risk of Alzheimer's Disease

Background: Wide-ranging functional defects in eye movements have been reported in Alzheimer's disease (AD) dementia. The detection of abnormal eye movements and reading problems may identify persons at risk of AD when clear clinical symptoms are lacking. Objective: To examine whether computer-based eye-tracking (ET) analysis of King-Devick (KD) test results differentiates cognitively healthy persons from persons with minor problems in cognitive testing or diagnosed mild AD. Methods: We recruited 78 participants (57 non-demented, 21 with mild AD) who underwent neurological examination, the Consortium to Establish a Registry for Alzheimer's Disease neuropsychological test battery (CERAD-NB), and a Clinical Dementia Rating (CDR) interview. The non-demented participants were further divided into control (normal CERAD subtests, mean MMSE= 28) and objective mild cognitive impairment (MCI; decline in at least one CERAD memory score, mean MMSE= 27) groups. The KD reading test was performed using computer-based ET. The total time used for the reading test, errors made, fixation and saccade durations, and saccade amplitudes were analyzed. Results: We found significant differences between the control, objective MCI, and AD groups in regard to the mean saccade amplitude (3.58, 3.33, and 3.21 ms, respectively, p < 0.03) and duration (27.1, 25.3, and 24.8 ms, respectively, p < 0.05). The KD error scores in the AD group differed significantly (p < 0.01) from the other groups. Conclusion: Computed ET analysis of the KD test may help detect persons with objective MCI early when clear clinical symptoms are lacking. The portable device for ET is easy to use in primary health care memory clinics.Peer reviewe

Kohti digitaalista ja älykästä rautatieliikennettä : Digirata-valmisteluvaiheen loppuraportti

VALMISTELUVAIHE Suomen rautatieliikenteen kasvun ja kilpailukyvyn mahdollistaa, Digirata-selvityksessä linjattu, radioverkkoteknologiaan perustuva ETCS. ETCS korvaa nykyiset junien kulkua turvaavat järjestelmät sekä mahdollistaa rautateiden digitalisaation. Digiradan valmisteluvaiheessa matka kohti modernia rautatieliikennettä on alkanut. Vaikka eurooppalaisen sääntelyn kehitys voi tuoda matkalle haasteita, tulee Suomi Digirata-hankkeen myötä olemaan merkittävä tekijä kehityskulussa kohti digitalisaatiota ja toimimaan sunnannäyttäjänä esimerkiksi rautateiden radioverkkokehityksessä. Tavoiteltava teknologia on vielä osittain kehityksessä, minkä vuoksi Digiradan seuraavat vaiheet ovat kriittisen tärkeitä onnistumisen varmistamiseksi. Tavoite on asetettu kunnianhimoiseksi kansainvälisestikin tarkasteltuna. Rautateiltä vaaditaan tulevaisuudessa entistä enemmän ketteryyttä ja joustavuutta – Digiradan mahdollistama kuljetusmäärien merkittävä lisääminen ja matkaketjujen tehostaminen rautateillä parantaisi myös Suomen kansainvälistä kilpailukykyä. Turvallisuus on myös erittäin tärkeä osa rautatieliikennettä ja se on keskeinen tekijä Digiradan ytimessä. Matka kohti muutosta on aloitettu ja osa kipupisteistä on jo tunnistettu. Haasteeseen vastaa yhtenäinen rautatiesektori, joka rakentaa tehokkaan vastauksen tulevaisuuden kuljetustarpeisiin. Yhteyshenkilöt liikenne- ja viestintäministeriössä: Suvi Kankare, puh. 0295 34 2105, [email protected] Katariina Säynäjärvi, puh. 0295 34 2029, [email protected] Janne Hauta, puh. 0295 34 2322, [email protected]

Copy number loss in SFMBT1 is common among Finnish and Norwegian patients with iNPH

Objective To evaluate the role of the copy number loss in SFMBT1 in a Caucasian population. Methods Five hundred sixty-seven Finnish and 377 Norwegian patients with idiopathic normal pressure hydrocephalus (iNPH) were genotyped and compared with 508 Finnish elderly, neurologically healthy controls. The copy number loss in intron 2 of SFMBT1 was determined using quantitative PCR. Results The copy number loss in intron 2 of SFMBT1 was detected in 10% of Finnish (odds ratio [OR] = 1.9, p = 0.0078) and in 21% of Norwegian (OR = 4.7, p <0.0001) patients with iNPH compared with 5.4% in Finnish controls. No copy number gains in SFMBT1 were detected in patients with iNPH or healthy controls. The carrier status did not provide any prognostic value for the effect of shunt surgery in either population. Moreover, no difference was detected in the prevalence of hypertension or T2DM between SFMBT1 copy number loss carriers and noncarriers. Conclusions This is the largest and the first multinational study reporting the increased prevalence of the copy number loss in intron 2 of SFMBT1 among patients with iNPH, providing further evidence of its role in iNPH. The pathogenic role still remains unclear, requiring further study.Peer reviewe