Understanding how behavior emerges from brain electrical activity is one of the ultimate goals of neuroscience. To achieve this goal we require methods for large-scale recording of the electrical activity of specific neuronal circuits. A very promising approach is to use optical reporting of membrane voltage transients, particularly if the voltage reporter is genetically targeted to specific neuronal populations. Targeting in this way allows population signals to be recorded and interpreted without blindness to neuronal diversity. Here, we evaluated the voltage-sensitive fluorescent protein, VSFP Butterfly 2.1, a genetically encoded voltage indicator (GEVI), for monitoring electrical activity of layer 2/3 cortical pyramidal neurons in mouse brain slices. Standard widefield fluorescence and two-photon imaging revealed robust, high signal-to-noise ratio read-outs of membrane voltage transients that are predominantly synaptic in nature and can be resolved as discrete areas of synaptically connected layer 2/3 neurons. We find that targeted expression of this GEVI in the cortex provides a flexible and promising tool for the analysis of L2/3 cortical network function.
The use of intravesical BCG has improved the survival and outcomes in the treatment of bladder cancer. However, the worldwide shortage of OncoTice BCG has caused disruption and changes in treatment regimes, leading to use of alternative strains. We describe a severe complication as the result of using intravesical SII Onco BCG for the treatment bladder cancer, in an 82 year old man presenting with granulomatous epididymo-orchitis.
A growing demand for cheap, strong, and lightweight structures has resulted in an increasing need for materials incorporating macroscopic structures such as surface textures in the form of dimples or internal non-uniformities such as porosity. This has highlighted the potential for misleading results when applying the current standards for the determination of yield strength to materials incorporating such non-uniformities. In the present study, discontinuous, continuous, and severely continuous (departure from linearity significantly prior to macroscopic yield) yield behaviours during tensile loading have been explored with respect to the determination of yield strength. This has clearly shown the limitations of standard measures as well as the incompatibility of different measures, making the comparison of yield strengths deceptive. Therefore, a novel derivative yield method has been proposed. Based on the second derivative of stress with respect to strain, this method is independent of both yield type and the presence or lack of macroscopic structures, and it correctly identifies the upper yield for discontinuous yield as well as the first significant departure from linearity for continuous yield. Furthermore, the derivative yield method is shown to more accurately characterise the behaviour of dimpled steel, non-arbitrarily quantifying the yield strength for severely continuous yielding. This wide applicability, in many cases, eliminates the need for the comparison of results produced by mutually incompatible yield criteria, e.g., when quantifying strengthening due to dimpling.
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