Bistability versus Bimodal Distributions in Gene Regulatory Processes from Population Balance

In recent times, stochastic treatments of gene regulatory processes have appeared in the literature in which a cell exposed to a signaling molecule in its environment triggers the synthesis of a specific protein through a network of intracellular reactions. The stochastic nature of this process leads to a distribution of protein levels in a population of cells as determined by a Fokker-Planck equation. Often instability occurs as a consequence of two (stable) steady state protein levels, one at the low end representing the “off” state, and the other at the high end representing the “on” state for a given concentration of the signaling molecule within a suitable range. A consequence of such bistability has been the appearance of bimodal distributions indicating two different populations, one in the “off” state and the other in the “on” state. The bimodal distribution can come about from stochastic analysis of a single cell. However, the concerted action of the population altering the extracellular concentration in the environment of individual cells and hence their behavior can only be accomplished by an appropriate population balance model which accounts for the reciprocal effects of interaction between the population and its environment. In this study, we show how to formulate a population balance model in which stochastic gene expression in individual cells is incorporated. Interestingly, the simulation of the model shows that bistability is neither sufficient nor necessary for bimodal distributions in a population. The original notion of linking bistability with bimodal distribution from single cell stochastic model is therefore only a special consequence of a population balance model

There is more than one way to turn a spherical cellular monolayer inside out: type B embryo inversion in Volvox globator

Höhn S, Hallmann A. There is more than one way to turn a spherical cellular monolayer inside out: type B embryo inversion in Volvox globator. BMC Biology. 2011;9(1): 89.Background: Epithelial folding is a common morphogenetic process during the development of multicellular organisms. In metazoans, the biological and biomechanical processes that underlie such three-dimensional (3D) developmental events are usually complex and difficult to investigate. Spheroidal green algae of the genus Volvox are uniquely suited as model systems for studying the basic principles of epithelial folding. Volvox embryos begin life inside out and then must turn their spherical cell monolayer outside in to achieve their adult configuration; this process is called 'inversion.' There are two fundamentally different sequences of inversion processes in Volvocaceae: type A and type B. Type A inversion is well studied, but not much is known about type B inversion. How does the embryo of a typical type B inverter, V. globator, turn itself inside out? Results: In this study, we investigated the type B inversion of V. globator embryos and focused on the major movement patterns of the cellular monolayer, cell shape changes and changes in the localization of cytoplasmic bridges (CBs) connecting the cells. Isolated intact, sectioned and fragmented embryos were analyzed throughout the inversion process using light microscopy, confocal laser scanning microscopy, scanning electron microscopy and transmission electron microscopy techniques. We generated 3D models of the identified cell shapes, including the localizations of CBs. We show how concerted cell-shape changes and concerted changes in the position of cells relative to the CB system cause cell layer movements and turn the spherical cell monolayer inside out. The type B inversion of V. globator is compared to the type A inversion in V. carteri. Conclusions: Concerted, spatially and temporally coordinated changes in cellular shapes in conjunction with concerted migration of cells relative to the CB system are the causes of type B inversion in V. globator. Despite significant similarities between type A and type B inverters, differences exist in almost all details of the inversion process, suggesting analogous inversion processes that arose through parallel evolution. Based on our results and due to the cellular biomechanical implications of the involved tensile and compressive forces, we developed a global mechanistic scenario that predicts epithelial folding during embryonic inversion in V. globator

General anaesthetic and airway management practice for obstetric surgery in England: a prospective, multi-centre observational study

There are no current descriptions of general anaesthesia characteristics for obstetric surgery, despite recent changes to patient baseline characteristics and airway management guidelines. This analysis of data from the direct reporting of awareness in maternity patients' (DREAMY) study of accidental awareness during obstetric anaesthesia aimed to describe practice for obstetric general anaesthesia in England and compare with earlier surveys and best-practice recommendations. Consenting patients who received general anaesthesia for obstetric surgery in 72 hospitals from May 2017 to August 2018 were included. Baseline characteristics, airway management, anaesthetic techniques and major complications were collected. Descriptive analysis, binary logistic regression modelling and comparisons with earlier data were conducted. Data were collected from 3117 procedures, including 2554 (81.9%) caesarean deliveries. Thiopental was the induction drug in 1649 (52.9%) patients, compared with propofol in 1419 (45.5%). Suxamethonium was the neuromuscular blocking drug for tracheal intubation in 2631 (86.1%), compared with rocuronium in 367 (11.8%). Difficult tracheal intubation was reported in 1 in 19 (95%CI 1 in 16-22) and failed intubation in 1 in 312 (95%CI 1 in 169-667). Obese patients were over-represented compared with national baselines and associated with difficult, but not failed intubation. There was more evidence of change in practice for induction drugs (increased use of propofol) than neuromuscular blocking drugs (suxamethonium remains the most popular). There was evidence of improvement in practice, with increased monitoring and reversal of neuromuscular blockade (although this remains suboptimal). Despite a high risk of difficult intubation in this population, videolaryngoscopy was rarely used (1.9%)

A systematic and reliable approach to pattern classification

A systematic and reliable approach to classify patterns is proposed when no a priori information except a set of pre-classified data is provided. A classifier is selected from a number of state of the art pattern classification schemes which are diverse in approach as well as the assumptions employed in their design. The selected schemes include the k-nearest neighbour classifier (kNNC), the minimum Mahalanobis distance classifier (MMDC), and the artificial neural network classifier (ANNC). In order to ensure that the selected classification scheme is properly designed and correctly implemented, the given pre-classified data is analysed, and the relative performance of the classifiers are cross validated as well as compared with a benchmark performance measure. The given data set is subjected to data validation, data visualization and feature quality analysis with a view to detect bad data, to obtain a qualitative picture of the class separability, and to derive a benchmark performance measure called the Bhattacharyya distance measure. In the design phase, the classifiers are executed in the order of increasing accuracy and increasing complexity so that a classifier at one level in the hierarchy sets the performance goal (e.g. classification accuracy) for the task at the next level. Further, to ensure a peak performance, the classifier accuracy is compared with the Bhattacharyya distance measure. The proposed scheme is evaluated on both simulated as well as actual data obtained from the images of the biological cells

SST time-series for Eastern Arabian Sea recostructed from paired measurement of δ¹⁸O and Mg/Ca of planktonic foraminifera

The deglacial transition from the last glacial maximum at ∼20 kiloyears before present (ka) to the Holocene (11.7 ka to Present) was interrupted by millennial-scale cold reversals, viz., Antarctic Cold Reversal (∼14.5–12.8 ka) and Greenland Younger Dryas (∼12.8–11.8 ka) which had different timings and extent of cooling in each hemisphere. The cause of this synchronously initiated, but different hemispheric cooling during these cold reversals (Antarctic Cold Reversal ∼3∘C and Younger Dryas ∼10∘C) is elusive because CO2, the fundamental forcing for deglaciation, and Atlantic meridional overturning circulation, the driver of antiphased bipolar climate response, both fail to explain this asymmetry. We use centennial-resolution records of the local surface water 18O of the Eastern Arabian Sea, which constitutes a proxy for the precipitation associated with the Indian Summer Monsoon, and other tropical precipitation records to deduce the role of tropical forcing in the polar cold reversals. We hypothesize a mechanism for tropical forcing, via the Indian Summer Monsoons, of the polar cold reversals by migration of the Inter-Tropical Convergence Zone and the associated cross-equatorial heat transport

Unsupervised and uncued segmentation of the fundamental heart sounds in phonocardiograms using a time-scale representation

A methodology is proposed to segment and label the fundamental activities, namely the first and second heart sounds, S1 and S2, of the phonocardiogram (PCG). Information supplementary to the PCG, such as a cue from a synchronously acquired electrocardiogram (ECG), subject-specific prior information, or training examples regarding the activities, is not required by the proposed methodology. A bank of Morlet wavelet correlators is used to obtain a time-scale representation of the PCG. An energy profile of the time-scale representation and a singular value decomposition (SVD) technique are used to identify segments of the PCG that contain the fundamental activities. The robustness of the methodology is demonstrated by the correct segmentation of over 90% of 1068 fundamental activities in a challenging set of PCGs which were recorded from patients with normally functioning and abnormally functioning bioprosthetic valves. The PCGs included highly varying fundamental activities that overlapped in time and frequency with other aberrant non-fundamental activities such as murmurs and noise-like artifacts

Reliable composite classification strategy

A composite classification scheme is proposed by combining several classifiers with distinctly different design methodologies. The classifiers are selected from a number of state of the art pattern classification schemes with a view to obtain superior performance. In this scheme, no a priori information except a set of pre-classified data is assumed to be available. By using distinctly different classifiers, the common mode data misclassification is reduced. Traditionally, after the design and evaluation phase, the pre-classified data is discarded. In this scheme, however, the misclassified data from each classifier in the training set is tagged and stored with a view to weight the decisions of the classifiers. If a given test sample is close to a misclassified data cluster of a particular classifier, then the decision made by this classifier is given a lower weighting. The final decision is made by analyzing the weighted combination of individual classifier decisions. The proposed algorithm is evaluated on both simulated data and a biological cell classification problem and it is shown that improved accuracy is obtained when compared to that of the most accurate classifier