Using mechatronics to teach mechanical design and technical communication

It is commonly accepted that hands-on experiences increase both learning and enjoyment during coursework. Mechatronics projects provide both interesting and relevant hands-on experiences for a wide range of topics including design processes, basic mechatronics concepts, technical communication, and working in a group environment. ME2110: Creative Decisions and Design at Georgia Tech integrates mechatronics and technical communication into a sophomore level mechanical design class. This paper describes the course in detail, highlighting the course goals and layout, tools provided to the students, industry involvement, and the main challenges of administering such a course.     

Enclosing all solutions of two-point boundary value problems for ODEs

The two-point boundary value problem (TPBVP) occurs in a wide variety of problems in engineering and science, including the modeling of chemical reactions, heat transfer, and diffusion, and the solution of optimal control problems. A TPBVP may have no solution, a single solution, or multiple solutions. A new strategy is presented for reliably locating all solutions of a TPBVP. The method determines narrow enclosures of all solutions that occur within a specified search interval. Key features of the method are the use of a new solver for parametric ODEs, which is used to produce guaranteed bounds on the solutions of nonlinear dynamic systems with interval-valued parameters and initial states, and the use of a constraint propagation strategy on the Taylor models used to represent the solutions of the dynamic system. Numerical experiments demonstrate the use and computational efficiency of the method.     

Pilot proteomic analysis of cerebrospinal fluid in Alzheimer's disease

Proteomic analysis of cerebrospinal fluid (CSF) holds great promise in understanding the progression of neurodegenerative diseases, including Alzheimer's disease (AD). As one of the primary reservoirs of neuronal biomolecules, CSF provides a window into the biochemical and cellular aspects of the neurological environment. CSF can be drawn from living participants allowing the potential alignment of clinical changes with these biochemical markers. Using cutting-edge mass spectrometry technologies, we perform a streamlined proteomic analysis of CSF. We quantify greater than 700 proteins across 10 pairs of age- and sex-matched participants in approximately one hour of analysis time each. Using the paired participant study structure, we identify a small group of biologically relevant proteins that show substantial changes in abundance between cognitive normal and AD participants, which were then analyzed at the peptide level using parallel reaction monitoring experiments. Our findings suggest the utility of fractionating a single sample and using matching to increase proteomic depth in cerebrospinal fluid, as well as the potential power of an expanded study.     

Podcasting in education: Are students as ready and eager as we think they are?

Instructors in higher education are disseminating instructional content via podcasting, as many rally behind the technology’s potential benefits. Others have expressed concern about the risks of deleterious effects that might accompany the adoption of podcasting, such as lower class attendance. Yet, relatively few studies have investigated students’ perceptions of podcasting for educational purposes, especially in relation to different podcasting forms: repetitive and supplemental. The present study explored students’ readiness and attitudes towards these two forms of podcasting to provide fundamental information for future researchers and educators. The results indicated that students may not be as ready or eager to use podcasting for repetitive or supplemental educational purposes as much as we think they are, but they could be persuaded.     

Simple Penning ion source for laboratory research and development applications

A simple Penning ion generator (PIG) that can be easily fabricated with simple machining skills and standard laboratory accessories is described. The PIG source uses an iron cathode body, samarium cobalt permanent magnet, stainless steel anode, and iron cathode faceplate to generate a plasma discharge that yields a continuous 1 mA beam of positively charged hydrogen ions at 1 mTorr of pressure. This operating condition requires 5.4 kV and 32.4 W of power. Operation with helium is similar to hydrogen. The ion source is being designed and investigated for use in a sealed-tube neutron generator; however, this ion source is thoroughly described so that it can be easily implemented by other researchers for other laboratory research and development applications.     

CX3CL1 Action on Microglia Protects from Diet-Induced Obesity by Restoring POMC Neuronal Excitability and Melanocortin System Activity Impaired by High-Fat Diet Feeding

Both hypothalamic microglial inflammation and melanocortin pathway dysfunction contribute to diet-induced obesity (DIO) pathogenesis. Previous studies involving models of altered microglial signaling demonstrate altered DIO susceptibility with corresponding POMC neuron cytological changes, suggesting a link between microglia and the melanocortin system. We addressed this hypothesis using the specific microglial silencing molecule, CX3CL1 (fractalkine), to determine whether reducing hypothalamic microglial activation can restore POMC/melanocortin signaling to protect against DIO. We performed metabolic analyses in high fat diet (HFD)-fed mice with targeted viral overexpression of CX3CL1 in the hypothalamus. Electrophysiologic recording in hypothalamic slices from POMC-MAPT-GFP mice was used to determine the effects of HFD feeding and microglial silencing via minocycline or CX3CL1 on GFP-labeled POMC neurons. Finally, mice with hypothalamic overexpression of CX3CL1 received central treatment with the melanocortin receptor antagonist SHU9119 to determine whether melanocortin signaling is required for the metabolic benefits of CX3CL1. Hypothalamic overexpression of CX3CL1 increased leptin sensitivity and POMC gene expression, while reducing weight gain in animals fed an HFD. In electrophysiological recordings from hypothalamic slice preparations, HFD feeding was associated with reduced POMC neuron excitability and increased amplitude of inhibitory postsynaptic currents. Microglial silencing using minocycline or CX3CL1 treatment reversed these HFD-induced changes in POMC neuron electrophysiologic properties. Correspondingly, blockade of melanocortin receptor signaling in vivo prevented both the acute and chronic reduction in food intake and body weight mediated by CX3CL1. Our results show that suppressing microglial activation during HFD feeding reduces DIO susceptibility via a mechanism involving increased POMC neuron excitability and melanocortin signaling.     

Generalized Approach towards Secretion-Based Protein Production via Neutralization of Secretion-Preventing Cationic Substrate Residues

Many heterologous proteins can be secreted by bacterial ATP-binding cassette (ABC) transporters, provided that they are fused with the C-terminal signal sequence, but some proteins are not secretable even though they carry the right signal sequence. The invention of a method to secrete these non-secretable proteins would be valuable both for understanding the secretory physiology of ABC transporters and for industrial applications. Herein, we postulate that cationic “supercharged” regions within the target substrate protein block the secretion by ABC transporters. We also suggest that the secretion of such substrate proteins can be rescued by neutralizing those cationic supercharged regions via structure-preserving point mutageneses. Surface-protruding, non-structural cationic amino acids within the cationic supercharged regions were replaced by anionic or neutral hydrophilic amino acids, reducing the cationic charge density. The examples of rescued secretions we provide include the spike protein of SARS-CoV-2, glutathione-S-transferase, streptavidin, lipase, tyrosinase, cutinase, growth factors, etc. In summary, our study provides a method to predict the secretability and a tool to rescue the secretion by correcting the secretion-blocking regions, making a significant step in understanding the physiological properties of ABC transporter-dependent protein secretion and laying the foundation for the development of a secretion-based protein-producing platform.