A STUDY OF THE NASCENT POLYPEPTIDES SYNTHESIZED ON THE FREE POLYRIBOSOMES OF RAT BRAIN IN VIVO 1

The free polyribosomes of the cerebral cortex of the immature rat (12-14 days old) were exposed to very low concentrations of trypsin at 0°C and for very brief periods of time and the conditions under which their breakdown to smaller aggregates occurs were determined. Trypsin also caused the release of nascent, radioactive polypeptides from polyribosomes prelabelled with [ 14 C]amino acids in vivo. An examination of the kinetics of release of the nascent chains by trypsin revealed that it was dependent on the concentration of trypsin as well as on the duration of incubation in the presence of trypsin. The influence of the nature of the [ 14 C]amino acid used as precursor of the nascent polypeptides and of the duration of the radioactive pulse in vivo was also determined. The radioactivity associated with polyribosomes as a result of the brief radioactive pulses administered (2 to 10 minutes) was incompletely removed even after the ribosomes were dissociated into subunits by EDTA. These findings suggest that the assembly of the cerebral ribosome in vivo must be a very rapid process, particularly in the immature animal. The nature of the nascent, radioactive polypeptides was studied by disc gel and high voltage electrophoresis and by thin-layer and column chromatography. Evidence was obtained that a rather limited number of qualitatively different molecules resides on the polyribosomes at any given moment.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65454/1/j.1471-4159.1971.tb00223.x.pd

Machine learning based estimation of axonal permeability: validation on cuprizone treated in-vivo mouse model of axonal demyelination

Estimating axonal permeability reliably is extremely important, however not yet achieved because mathematical models that express its relationship to the MR signal accurately are intractable. Recently introduced machine learning based computational model showed to outperforms previous approximate mathematical models. Here we apply and validate this novel method experimentally on a highly controlled in-vivo mouse model of axonal demyelination, and demonstrate for the first time in practice the power of machine learning as a mechanism to construct complex biophysical models for quantitative MRI

Deep neural network based framework for in-vivo axonal permeability estimation

This study introduces a novel framework for estimating permeability from diffusion-weighted MRI data using deep learning. Recent work introduced a random forest (RF) regressor model that outperforms approximate mathematical models (Kärger model). Motivated by recent developments in machine learning, we propose a deep neural network (NN) approach to estimate the permeability associated with the water residence time. We show in simulations and in in-vivo mouse brain data that the NN outperforms the RF method. We further show that the performance of either ML method is unaffected by the choice of training data, i.e. raw diffusion signals or signal-derived features yield the same results

The Digital Fish Library: Using MRI to Digitize, Database, and Document the Morphological Diversity of Fish

Museum fish collections possess a wealth of anatomical and morphological data that are essential for documenting and understanding biodiversity. Obtaining access to specimens for research, however, is not always practical and frequently conflicts with the need to maintain the physical integrity of specimens and the collection as a whole. Non-invasive three-dimensional (3D) digital imaging therefore serves a critical role in facilitating the digitization of these specimens for anatomical and morphological analysis as well as facilitating an efficient method for online storage and sharing of this imaging data. Here we describe the development of the Digital Fish Library (DFL, http://www.digitalfishlibrary.org), an online digital archive of high-resolution, high-contrast, magnetic resonance imaging (MRI) scans of the soft tissue anatomy of an array of fishes preserved in the Marine Vertebrate Collection of Scripps Institution of Oceanography. We have imaged and uploaded MRI data for over 300 marine and freshwater species, developed a data archival and retrieval system with a web-based image analysis and visualization tool, and integrated these into the public DFL website to disseminate data and associated metadata freely over the web. We show that MRI is a rapid and powerful method for accurately depicting the in-situ soft-tissue anatomy of preserved fishes in sufficient detail for large-scale comparative digital morphology. However these 3D volumetric data require a sophisticated computational and archival infrastructure in order to be broadly accessible to researchers and educators

Positive airway pressure (PAP) treatment reduces glycated hemoglobin (HbA1c) levels in obstructive sleep apnea patients with concomitant weight loss: Longitudinal data from the ESADA

Patients with obstructive sleep apnea (OSA) are at increased risk of developing metabolic disease such as diabetes. The effects of positive airway pressure on glycemic control are contradictory. We therefore evaluated the change in glycated hemoglobin (HbA1c) in a large cohort of OSA patients after long-term treatment with positive airway pressure. HbA1c levels were assessed in a subsample of the European Sleep Apnea Database [n=1608] at baseline and at long-term follow up with positive airway pressure therapy (mean 378.9±423.0 days). In a regression analysis, treatment response was controlled for important confounders. Overall, HbA1c decreased from 5.98±1.01% to 5.93±0.98% (p=0.001). Patient subgroups with a more pronounced HbA1c response included patients with diabetes (−0.15±1.02, p=0.019), those with severe OSA baseline (−0.10±0.68, p=0.005), those with morbid obesity (−0.20±0.81, p<0.001). The strongest HbA1c reduction was observed in patients with a concomitant weight reduction >5 kilos (−0.38±0.99, p<0.001). In robust regression analysis, severe OSA (p=0.038) and morbid obesity (p=0.005) at baseline, and weight reduction >5 kilos (p<0.001) during follow up were independently associated with a reduction of HbA1c following PAP treatment. In contrast, PAP treatment alone without weight reduction was not associated with significant Hb1Ac reduction. In conclusion, positive airway pressure therapy is associated with HbA1c reduction in patients with severe OSA, in morbidly obese patients. and most obviously in those with significant weight lost during the follow-up. Our study underlines the importance to combine positive airway pressure use with adjustments in lifestyle to substantially modify metabolic complications in OSA

Arterial bicarbonate is associated with hypoxic burden and uncontrolled hypertension in obstructive sleep apnea - The ESADA cohort

Objective: Blood bicarbonate concentration plays an important role for obstructive sleep apnea (OSA) patients to maintain acid-base balance. We investigated the association between arterial standard bicarbonate ([HCO3-]) and nocturnal hypoxia as well as comorbid hypertension in OSA. Methods: A cross-sectional analysis of 3329 patients in the European Sleep Apnea Database (ESADA) was performed. Arterial blood gas analysis and lung function test were performed in conjunction with polysomnographic sleep studies. The 4% oxygen desaturation index (ODI), mean and minimum oxygen saturation (SpO2), and percentage of time with SpO2 below 90% (T90%) were used to reflect nocturnal hypoxic burden. Arterial hypertension was defined as a physician diagnosis of hypertension with ongoing antihypertensive medication. Hypertensive patients with SBP/DBP below or above 140/90 mmHg were classified as controlled-, uncontrolled hypertension, respectively. Results: The [HCO3-] level was normal in most patients (average 24.0 ± 2.5 mmol/L). ODI, T90% increased whereas mean and minimum SpO2 decreased across [HCO3-] tertiles (ANOVA, p = 0.030, <0.001, <0.001, and <0.001, respectively). [HCO3-] was independently associated with ODI, mean SpO2, minimum SpO2, and T90% after adjusting for confounders (β value [95%CI]: 1.21 [0.88–1.54], −0.16 [-0.20 to −0.11], −0.51 [-0.64 to −0.37], 1.76 [1.48–2.04], respectively, all p < 0.001). 1 mmol/L elevation of [HCO3-] was associated with a 4% increased odds of uncontrolled hypertension (OR: 1.04 [1.01–1.08], p = 0.013). Conclusion: We first demonstrated an independent association between [HCO3-] and nocturnal hypoxic burden as well as uncontrolled hypertension in OSA patients. Bicarbonate levels as an adjunctive measure provide insight into the pathophysiology of hypertension in OSA

Improving Wargames using Complex System Practices

This paper describes our ongoing efforts to improve current military wargame as used by the Dutch defence. In a typical wargame scenario military commanders and Intelligence officers are playing the game of blue and red forces, drawing their course of actions in order to outplay one and the other. Most of these games, as far as they don’t require fully scripted scenarios, are based upon regular, symmetric, and large scale military operations. These core models are usually based upon mutual attrition and require a lot of personnel. In this study, we focus on two particular issues. First of all, the configuration of a typical wargame scenario which is a complicated and time consuming process. Second, most wargames lack the incorporation of active non-combatants like civilians which are of utmost importance for the shape and dynamics of today’s battlefield. For both these issues we explore the usefulness of complex (adaptive) system knowledge and tools. Our aim is to use simple models of selforganization, both to simplify scenario configuration and to generate complex human behaviours. To do so, we study the use of various agent-based modelling approaches; in particular the well-known work of Axtell and Epstein on socio-cultural modelling called “Sugarscape”. We believe that, although these kinds of models are a very coarse and simplified representation of reality, they are useful in generating behavioural effects that mimic real-life patterns. Incorporating these models into a wargame context will confront military decision makers with the possible unforeseen higher order effects of their actions. Moreover, such an extended wargame would provide an interesting tool that could support evolutionary approaches to current military challenges