A population‐based temporal logic gate for timing and recording chemical events

Engineered bacterial sensors have potential applications in human health monitoring, environmental chemical detection, and materials biosynthesis. While such bacterial devices have long been engineered to differentiate between combinations of inputs, their potential to process signal timing and duration has been overlooked. In this work, we present a two‐input temporal logic gate that can sense and record the order of the inputs, the timing between inputs, and the duration of input pulses. Our temporal logic gate design relies on unidirectional DNA recombination mediated by bacteriophage integrases to detect and encode sequences of input events. For an E. coli strain engineered to contain our temporal logic gate, we compare predictions of Markov model simulations with laboratory measurements of final population distributions for both step and pulse inputs. Although single cells were engineered to have digital outputs, stochastic noise created heterogeneous single‐cell responses that translated into analog population responses. Furthermore, when single‐cell genetic states were aggregated into population‐level distributions, these distributions contained unique information not encoded in individual cells. Thus, final differentiated sub‐populations could be used to deduce order, timing, and duration of transient chemical events.     

Automated cerebrospinal fluid cytology

OBJECTIVE: To evaluate the Abbott CELL-DYN Sapphire cytometer for cerebrospinal fluid (CSF) cell count and differentiation. METHODS: One hundred three analyses of CSF cells by the CELL-DYN Sapphire were compared with routine cell count and microscopic differentiation and correlation coefficients calculated. RESULTS: The total cell count of both methods correlated well. The detection of erythrocytes was good (0.898), and a higher content of erythrocytes >100/microL had little effect on total leukocyte count. The correlation between both methods was best with higher leukocyte counts >25/microL (r=0.987), whereas at cell counts <25/microL, the correlation was considerably less precise (r=0.613). For the differentiation of cells, lymphocytes and neutrophils showed moderate correlation. The results for monocytes and eosinophils did not correlate. CONCLUSION: The results for the total cell count in this study are comparable with those achieved with the Bayer Advia 120. While the Abbott CELL-DYN Sapphire yielded slightly better results for erythrocytes and total cell count with a higher erythrocyte content, the Advia 120 achieved slightly better results of lymphocyte and neutrophil count in a previous study.     

An innovative approach for testing bioinformatics programs using metamorphic testing

Background  

Recent advances in experimental and computational technologies have fueled the development of many sophisticated bioinformatics programs. The correctness of such programs is crucial as incorrectly computed results may lead to wrong biological conclusion or misguide downstream experimentation. Common software testing procedures involve executing the target program with a set of test inputs and then verifying the correctness of the test outputs. However, due to the complexity of many bioinformatics programs, it is often difficult to verify the correctness of the test outputs. Therefore our ability to perform systematic software testing is greatly hindered.