The fungal cell-wall integrity signaling (CWIS) pathway regulates cellular response to environmental stress to enable wall repair and resumption of normal growth.  This complex, interconnected, pathway has been only partially characterized in filamentous fungi.  To better understand the dynamic cellular response to wall perturbation, a β-glucan synthase inhibitor (micafungin) was added to a growing A. nidulans shake-flask culture.  From this flask, transcriptomic and phosphoproteomic data were acquired over 10 and 120 minutes, respectively.  To differentiate statistically-significant dynamic behavior from noise, a multivariate adaptive regression splines (MARS) model was applied to both data sets.  Over 1800 genes were dynamically expressed and 430 phosphorylation sites had changing phosphorylation levels upon micafungin exposure. Twelve kinases had altered phosphorylation and phenotypic profiling of all non-essential kinase deletion mutants revealed putative connections between PrkA, Hk-8-4, and Stk19 and the CWIS pathway. Our collective data implicate actin regulation, endocytosis, and septum formation as critical cellular processes responding to activation of the CWIS pathway, and connections between CWIS and calcium, HOG, and SIN signaling pathways.

The presentation of neoantigens on the cell membrane is the foundation for most cancer immunotherapies. Due to their extremely low abundance, analyzing neoantigens in clinical samples is technically difficult, hindering the development of neoantigen-based therapeutics for more general use in the treatment of diverse cancers worldwide. Here, we describe an integrated system, “Valid-NEO”, which reveals patient-specific cancer neoantigen therapeutic targets from minute amounts of clinical samples through direct observation, without computer-based prediction, in a sensitive, rapid, and reproducible manner. The overall four-hour procedure involves mass spectrometry analysis of neoantigens purified from tumor samples through recovery of HLA molecules with HLA antibodies. Valid-NEO could be applicable to the identification and quantification of presented neoantigens in cancer patients, particularly when only limited amounts of sample are available.

The world’s first automobile built by Karl Benz was powered by a single-cylinder four-stroke engine which was placed at the rear part of the three-wheeled chassis. Since then, the automobile industry has drastically evolved, especially four wheelers. Nowadays, three-wheelers are gaining popularity as they are more fuel efficient than four-wheelers while being more stable than twowheelers. The inherent cost advantages of a threewheeler also make them more affordable. Autorickshaws, having delta configuration, are extensively utilized in several Asian countries like India, Indonesia, Pakistan and others. But they are risky during braking in a turn due to a single front wheel. Alternatively, a tadpole type three-wheeler is safer in braking in a turn and provides better steering control. This three-wheeler configuration also provides better aerodynamic design. They have been recently adopted in European countries for personal mobility and logistics. Therefore, the paper analyses the stability of a Tadpole type three-wheeler based on various standard simulation tests such as Constant Radius test, Acceleration test and Double Lane Change test. These tests provide various results such as Steering Angle, Understeer behaviour and Longitudinal Acceleration where information regarding handling characteristics can be studied. A comparison between Front Wheel Drive and Rear Wheel Drive configuration is carried out to arrive at a conclusion for selecting the right drivetrain configuration. In order to achieve this, a Multibody Dynamics model is created using MSC Adams Car by assembling the various subsystems namely Front Suspension, Rear Suspension, Steering, Brakes, Body, Powertrain and Tires. Simulation results have been compared with existing literature for the verification of the model.

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