Feasibility study for the use of iophenoxic acid as a reference marker for plasma proteins Final report

Equilibrium dialysis experiments of human and bovine albumin with iophenoxic acid - feasibility of acid as reference marker for plasma protein

Excited States of Nucleic Acids Probed by Proton Relaxation Dispersion NMR Spectroscopy

In this work an improved stable isotope labeling protocol for nucleic acids is introduced. The novel building blocks eliminate/minimize homonuclear 13C and 1H scalar couplings thus allowing proton relaxation dispersion (RD) experiments to report accurately on the chemical exchange of nucleic acids. Using site-specific 2H and 13C labeling, spin topologies are introduced into DNA and RNA that make 1H relaxation dispersion experiments applicable in a straightforward manner. The novel RNA/DNA building blocks were successfully incorporated into two nucleic acids. The A-site RNA was previously shown to undergo a two site exchange process in the micro- to millisecond time regime. Using proton relaxation dispersion experiments the exchange parameters determined earlier could be recapitulated, thus validating the proposed approach. We further investigated the dynamics of the cTAR DNA, a DNA transcript that is involved in the viral replication cycle of HIV-1. Again, an exchange process could be characterized and quantified. This shows the general applicablility of the novel labeling scheme for 1H RD experiments of nucleic acids

Strategies and challenges to facilitate situated learning in virtual worlds post-Second Life

Virtual worlds can establish a stimulating environment to support a situated learning approach in which students simulate a task within a safe environment. While in previous years Second Life played a major role in providing such a virtual environment, there are now more and more alternative—often OpenSim-based—solutions deployed within the educational community. By drawing parallels to social networks, we discuss two aspects: how to link individually hosted virtual worlds together in order to implement context for immersion and how to identify and avoid “fake” avatars so people behind these avatars can be held accountable for their actions

Deep learning prediction of proton and photon dose distributions for paediatric abdominal tumours

OBJECTIVE: Dose prediction using deep-learning networks prior to radiotherapy might lead to more efficient modality selections. The study goal was to predict proton and photon dose distributions based on the patient-specific anatomy and to assess their clinical usage for paediatric abdominal tumours. MATERIAL &METHODS: Data from 80 patients with neuroblastoma or Wilms' tumour was included. Pencil beam scanning (PBS) (5mm/3%) and volumetric-modulated arc therapy (VMAT) plans (5mm) were robustly optimized on the internal target volume (ITV). Separate 3-dimensional patch-based U-net networks were trained to predict PBS and VMAT dose distributions. Doses, planning-computed tomography images and relevant optimization masks (ITV, vertebra and organs-at-risk) of 60 patients were used for training with a 5-fold cross validation. The networks' performance was evaluated by computing the relative error between planned and predicted dose-volume histogram (DVH) parameters for 20 inference patients. In addition, the organs-at-risk mean dose difference between modalities was calculated using planned and predicted dose distributions (ΔDmean= DVMAT-DPBS). Two radiation oncologists performed a blind PBS/VMAT modality selection based on either planned or predicted ΔDmean. RESULTS: Average DVH differences between planned and predicted dose distributions were ≤|6%|for both modalities. The networks classified the organs-at-risk difference as a gain (ΔDmean>0) with 98% precision. An identical modality selection based on planned compared to predicted ΔDmean was made for 18/20 patients. CONCLUSION: Deep-learning networks for accurate prediction of proton and photon dose distributions for abdominal paediatric tumours were established. These networks allowing fast dose visualization might aid in identifying the optimal radiotherapy technique when experience and/or resources are unavailable

Heart Rate Variability Analysis Guided by Respiration in Major Depressive Disorder

In this study a Heart Rate Variability (HRV) analysis guided by respiration to evaluate different patterns of Autonomic Nervous System (ANS) in response to a cognitive stressor between Major Depressive Disorder (MDD) and control (CT) subjects is presented. Cardiorespiratory Time Frequency Coherence (TFC) reveals the local coupling of HRV and respiration signal which is essential and usually not included in estimation of ANS measures derived by HRV. Parasympathetic activity of ANS is measured as the power at the frequencies where TFC between HRV and respiration is significant, whereas sympathetic dominance is measured as the normalized power in the low frequency band [0.04,0.15] Hz of HRV excluding the power of those frequencies related to respiration. Results showed significantly lower (p <; 0.05) sympathetic dominance in MDD with respect to CT subjects during stress, suggesting that ANS reactivity as response to stress stimuli is lower in MDD patients. The study of ANS reactivity to a stressor may serve as a biomarker useful for the early diagnosis and monitoring of MDD patients

Autonomic response to walk tests is useful for assessing outcome measures in people with multiple sclerosis

Objective: The aim of this study was to evaluate the association between changes in the autonomic control of cardiorespiratory system induced by walk tests and outcome measures in people with Multiple Sclerosis (pwMS). Methods: Electrocardiogram (ECG) recordings of 148 people with Relapsing-Remitting MS (RRMS) and 58 with Secondary Progressive MS (SPMS) were acquired using a wearable device before, during, and after walk test performance from a total of 386 periodical clinical visits. A subset of 90 participants repeated a walk test at home. Various MS-related symptoms, including fatigue, disability, and walking capacity were evaluated at each clinical visit, while heart rate variability (HRV) and ECG-derived respiration (EDR) were analyzed to assess autonomic nervous system (ANS) function. Statistical tests were conducted to assess differences in ANS control between pwMS grouped based on the phenotype or the severity of MS-related symptoms. Furthermore, correlation coefficients (r) were calculated to assess the association between the most significant ANS parameters and MS-outcome measures. Results: People with SPMS, compared to RRMS, reached higher mean heart rate (HRM) values during walk test, and larger sympathovagal balance after test performance. Furthermore, pwMS who were able to adjust their HRM and ventilatory values, such as respiratory rate and standard deviation of the ECG-derived respiration, were associated with better clinical outcomes. Correlation analyses showed weak associations between ANS parameters and clinical outcomes when the Multiple Sclerosis phenotype is not taken into account. Blunted autonomic response, in particular HRM reactivity, was related with worse walking capacity, yielding r = 0.36 r = 0.29 (RRMS) and r > 0.5 (SPMS). A positive strong correlation r > 0.7 r > 0.65 between cardiorespiratory parameters derived at hospital and at home was also found. Conclusion: Autonomic function, as measured by HRV, differs according to MS phenotype. Autonomic response to walk tests may be useful for assessing clinical outcomes, mainly in the progressive stage of MS. Participants with larger changes in HRM are able to walk longer distance, while reduced ventilatory function during and after walk test performance is associated with higher fatigue and disability severity scores. Monitoring of disorder severity could also be feasible using ECG-derived cardiac and respiratory parameters recorded with a wearable device at home

Prosthetic overhang is the most effective way to prevent scapular conflict in a reverse total shoulder prosthesis

Methods An average and a "worst case scenario" shape in A-P view in a 2-D computer model of a scapula was created, using data from 200 "normal" scapulae, so that the position of the glenoid and humeral component could be changed as well as design features such as depth of the polyethylene insert, the size of glenosphere, the position of the center of rotation, and downward glenoid inclination. The model calculated the maximum adduction (notch angle) in the scapular plane when the cup of the humeral component was in conflict with the scapula. Results A change in humeral neck shaft inclination from 155 degrees to 145 degrees gave a 10 degrees gain in notch angle. A change in cup depth from 8 mm to 5 mm gave a gain of 12 degrees. With no inferior prosthetic overhang, a lateralization of the center of rotation from 0 mm to 5 mm gained 16 degrees. With an inferior overhang of only 1 mm, no effect of lateralizing the center of rotation was noted. Downward glenoid inclination of 0 boolean OR to 10 boolean OR gained 10 degrees. A change in glenosphere radius from 18 mm to 21 mm gained 31 degrees due to the inferior overhang created by the increase in glenosphere. A prosthetic overhang to the bone from 0 mm to 5 mm gained 39 degrees. Interpretation Of all 6 solutions tested, the prosthetic overhang created the biggest gain in notch angle and this should be considered when designing the reverse arthroplasty and defining optimal surgical technique

Preparation of selective and segmentally labeled single-stranded DNA for NMR by self-primed PCR and asymmetrical endonuclease double digestion

We demonstrate a new, efficient and easy-to-use method for enzymatic synthesis of (stereo-)specific and segmental 13C/15N/2H isotope-labeled single-stranded DNA in amounts sufficient for NMR, based on the highly efficient self-primed PCR. To achieve this, new approaches are introduced and combined. (i) Asymmetric endonuclease double digestion of tandem-repeated PCR product. (ii) T4 DNA ligase mediated ligation of two ssDNA segments. (iii) In vitro dNTP synthesis, consisting of in vitro rNTP synthesis followed by enzymatic stereo-selective reduction of the C2′ of the rNTP, and a one-pot add-up synthesis of dTTP from dUTP. The method is demonstrated on two ssDNAs: (i) a 36-nt three-way junction, selectively 13C9/15N3/2H(1′,2″,3′,4′,5′,5″)-dC labeled and (ii) a 39-nt triple-repeat three-way junction, selectively 13C9/15N3/2H(1′,2″,3′,4′,5′,5″)-dC and 13C9/15N2/2H(1′,2″,3′,4′,5′,5″)-dT labeled in segment C20-C39. Their NMR spectra show the spectral simplification, while the stereo-selective 2H-labeling in the deoxyribose of the dC-residues, straightforwardly provided assignment of their C1′–H2′ and C2′–H2′ resonances. The labeling protocols can be extended to larger ssDNA molecules and to more than two segments