JME 4110 Senior Design Project - C.H.E.T.

C.H.E.T. is designed to be a educational tool for children of ages 6-12 that are interested in mechanical equipment and mechanical concepts. C.H.E.T. provides a simple hydraulic system that incorporates linkages, cylinders, springs, pins and other mechanical features to operate the excavator assembly. We wanted to design and build an educational toy that is fun, reliable. educational, hands-on and yet still affordable for typical families

IMPACT OF PASSIVE LEG MOVEMENT ON LOWER LIMB VASCULAR FUNCTION IN PATIENTS WITH A SPINAL CORD INJURY

Background: Individuals with spinal cord injuries (SCI) are at a greater risk for developing cardiovascular diseases. Of note, post injury mediated increases in physical inactivity leads to muscle atrophy, which also results in vascular dysfunction in this population. Although a growing body of evidence suggests that passive leg movement (PLM) may be a useful exercise modality to improve peripheral blood flow and skeletal muscle activation in individuals with limited mobility, few studies have examined the impact of PLM on local skeletal muscle blood flow. Therefore, there is a need to examine the impact of PLM on lower limb vascular function and skeletal muscle oxygen utilization capacity in patients with SCI. Methods: Individuals with SCI (n=2) and healthy age-matched controls (CON, n=5) were recruited for this study. Participants were fitted with a standard knee brace and were instructed to rest in the seated position for 20 minutes with their legs bent at 90. PLM was performed by flexion and extension of the lower leg (90-180) at a rate of 1 Hz (60 bpm) for 5 minutes. A Doppler ultrasound was located on the superficial femoral artery, and blood flow and diameter were measured for 5 minutes at rest and during the PLM protocol. Following the PLM protocol, the leg was held in the extended position (180) for 5 minutes of recovery. Results: We found that the SCI group had a significantly lower blood flow response to PLM compared to the CON group (p=0.004). Furthermore, post-PLM femoral artery blood velocity and shear rate significantly increased in both SCI and CON compared to pre-PLM (p=0.014, and p=0.016, respectively) but no differences were found between groups. Finally, the SCI group had significantly smaller vessel diameters compared with CON (pConclusion: We found that PLM could efficiently increase blood flow and blood velocity in SCI. Although the magnitude of this increase was significantly lower in SCI compared to healthy age-matched control, PLM produced shear rates in the leg arteries that were similar between SCI and CON, which indicates that PLM may potentially be an efficient exercise modality to improve leg vascular function in individuals with SCI

Solar Powered Multipurpose Remotely Powered Aircraft

Increase in energy demands coupled with rapid depletion of natural energy resources have deemed solar energy as an attractive alternative source of power. The focus was to design and construct a solar powered, remotely piloted vehicle to demonstrate the feasibility of solar energy as an effective, alternate source of power. The final design included minimizing the power requirements and maximizing the strength-to-weight and lift-to-drag ratios. Given the design constraints, Surya (the code-name given to the aircraft), is a lightweight aircraft primarily built using composite materials and capable of achieving level flight powered entirely by solar energy

Endothelial cell Nrf2-KO attenuates endothelial function and skeletal muscle antioxidant capacity

INTRODUCTION: Endothelial cells line the inner surface of blood vessels and play a major role in modulating blood flow and gas exchange. Endothelial dysfunction is thought to be a contributor to cardiovascular disease development, and it is well-accepted that excessive reactive oxygen species (harmful molecules) likely contribute to endothelial dysfunction. The transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2) is considered the master regulator of cellular protection in response to elevated reactive oxygen species. Therefore, Nrf2 may be a potential therapeutic target to protect against endothelial dysfunction. However, the roles of endothelial cell-specific Nrf2 on endothelial function are not known. The purpose of this study was to investigate the impacts of endothelial cell-specific Nrf2 deletion on vascular function (endothelium-dependent and endothelium-independent vasodilation) and skeletal muscle antioxidant status. METHODS: Leg arteries were harvested from 6-mo old C57BL/6 mice (WT, n = 6) and endothelial cell-specific Nrf2-knockout mice (Tie2-Cre-Nrf2 floxed-KO, n = 6). Endothelium-dependent vasodilation was assessed in response to flow (30 uL·min-1) and acetylcholine (ACh, 10-7-10-3 M) with and without Nω-Nitro-L-arginine methyl ester (L-NAME), and endothelium-independent vasodilation was assessed with sodium nitroprusside (SNP, 10-9-10-4 M) using videomicroscopy. Skeletal muscle antioxidant protein expression for glutathione peroxidase-1 (GPX-1) and catalase (CAT) was assessed by immunoblotting. RESULTS: Endothelium-dependent vasodilation was lower in Nrf2-KO compared to WT induced by flow (WT: 34.8±2.9%, Nrf2-KO: 20.7±3.7%, P-3M, WT: 68.3±8.2%, Nrf2-KO: 44.5±7.1%, PP-3 M, 19.1±4.4%, PP=0.28) or ACh (10-3 M, 37.7±7.0%, P = 0.16). Endothelium-independent vasodilation was not different (SNP 10-4 M, WT: 92.7±3.6%, Nrf2-KO: 81.9± 0.2%, P=0.157). In addition, GPX-1 was lower in Nrf2-KO mice (WT: 0.47±0.06, Nrf2-KO: 0.001±0.003, PP=0.08). CONCLUSIONS: Endothelial cell Nrf2 may play a key role in endothelial-mediated vasodilatory function. The nitric oxide synthase inhibitor L-NAME attenuated endothelial-mediated vasodilation in WT but not in endothelial cell Nrf2-KO. Furthermore, endothelial cell Nrf2 may play a role in skeletal muscle antioxidant homeostasis, which suggests potential systemic implications of endothelial cell Nrf2 deletion. These results collectively suggest that the endothelial cell Nrf2 system is linked to endothelial dysfunction and changes in the skeletal muscle redox environment, likely through nitric oxide- and oxidative stress-related mechanisms

Novel Anti-bacterial Activities of β-defensin 1 in Human Platelets: Suppression of Pathogen Growth and Signaling of Neutrophil Extracellular Trap Formation

Human β-defensins (hBD) are antimicrobial peptides that curb microbial activity. Although hBD's are primarily expressed by epithelial cells, we show that human platelets express hBD-1 that has both predicted and novel antibacterial activities. We observed that activated platelets surround Staphylococcus aureus (S. aureus), forcing the pathogens into clusters that have a reduced growth rate compared to S. aureus alone. Given the microbicidal activity of β-defensins, we determined whether hBD family members were present in platelets and found mRNA and protein for hBD-1. We also established that hBD-1 protein resided in extragranular cytoplasmic compartments of platelets. Consistent with this localization pattern, agonists that elicit granular secretion by platelets did not readily induce hBD-1 release. Nevertheless, platelets released hBD-1 when they were stimulated by α-toxin, a S. aureus product that permeabilizes target cells. Platelet-derived hBD-1 significantly impaired the growth of clinical strains of S. aureus. hBD-1 also induced robust neutrophil extracellular trap (NET) formation by target polymorphonuclear leukocytes (PMNs), which is a novel antimicrobial function of β-defensins that was not previously identified. Taken together, these data demonstrate that hBD-1 is a previously-unrecognized component of platelets that displays classic antimicrobial activity and, in addition, signals PMNs to extrude DNA lattices that capture and kill bacteria

AI is a viable alternative to high throughput screening: a 318-target study

: High throughput screening (HTS) is routinely used to identify bioactive small molecules. This requires physical compounds, which limits coverage of accessible chemical space. Computational approaches combined with vast on-demand chemical libraries can access far greater chemical space, provided that the predictive accuracy is sufficient to identify useful molecules. Through the largest and most diverse virtual HTS campaign reported to date, comprising 318 individual projects, we demonstrate that our AtomNet® convolutional neural network successfully finds novel hits across every major therapeutic area and protein class. We address historical limitations of computational screening by demonstrating success for target proteins without known binders, high-quality X-ray crystal structures, or manual cherry-picking of compounds. We show that the molecules selected by the AtomNet® model are novel drug-like scaffolds rather than minor modifications to known bioactive compounds. Our empirical results suggest that computational methods can substantially replace HTS as the first step of small-molecule drug discovery

Using the Light Microscopy Module (LMM) on the International Space Station (ISS), The Advanced Colloids Experiment (ACE) and MacroMolecular Biophysics (MMB)

The Light Microscopy Module (LMM) was launched to the International Space Station (ISS) in 2009 and began science operations in 2010. It continues to support Physical and Biological scientific research on ISS. During 2016, if all goes as planned, three experiments will be completed: [1] Advanced Colloids Experiments with Heated base-2 (ACE-H2) and [2] Advanced Colloids Experiments with Temperature control (ACE-T1). Preliminary results, along with an overview of present and future LMM capabilities will be presented; this includes details on the planned data imaging processing and storage system, along with the confocal upgrade to the core microscope. [1] a consortium of universities from the State of Kentucky working through the Experimental Program to Stimulate Competitive Research (EPSCoR): Stuart Williams, Gerold Willing, Hemali Rathnayake, et al. and [2] from Chungnam National University, Daejeon, S. Korea: Chang-Soo Lee, et al