Cal Poly Supermileage Electric Vehicle Drivetrain and Motor Control Design

The Cal Poly Supermileage Vehicle team is a multidisciplinary club that designs and builds high efficiency vehicles to compete internationally at Shell Eco-Marathon (SEM). Cal Poly Supermileage Club has been competing in the internal combustion engine (ICE) category of the competition since 2007. The club has decided it is time to expand their competition goals and enter their first battery electric prototype vehicle. To this end, a yearlong senior design project was presented to this team of engineers giving us the opportunity to design an electric powertrain with a custom motor controller. This system has been integrated into Ventus, the 2017 Supermileage competition car, bringing it back to life as E-Ventus for future competitions. The scope of this project includes sizing a motor, designing the drivetrain, programing the motor driver, building a custom motor controller, and finally mounting all these components into the chassis. The main considerations in this design are the energy efficiency measured in distance per power used (mi/kWh) and the whole system reliability. Driven train system reliability has been defined as the car starts the first time every time and can complete two competition runs of 6.3 miles each without mechanical or electrical failure. Drivetrain weight target was less than 25 pounds, and the finished system came in at 20 lbs 4 oz. Due to the design difficulties of the custom controller, three iterations were able to be produced by the end of this project, but there will need to be further iterations to complete the controller. Because of these difficulties our sponsor, Will Sirski, and club advisor, Dr. Mello, have agreed that providing the club with a working mechanical powertrain, powertrain data from the club chassis dynamometer using the programmed TI evaluation motor controller board, and providing board layout for the third iteration design for the custom controller satisfy their requirements for this project

Defective Osteogenic Differentiation in the Development of Osteosarcoma

Osteosarcoma (OS) is associated with poor prognosis due to its high incidence of metastasis and chemoresistance. It often arises in areas of rapid bone growth in long bones during the adolescent growth spurt. Although certain genetic conditions and alterations increase the risk of developing OS, the molecular pathogenesis is poorly understood. Recently, defects in differentiation have been linked to cancers, as they are associated with high cell proliferation. Treatments overcoming these defects enable terminal differentiation and subsequent tumor inhibition. OS development may be associated with defects in osteogenic differentiation. While early regulators of osteogenesis are unable to bypass these defects, late osteogenic regulators, including Runx2 and Osterix, are able to overcome some of the defects and inhibit tumor propagation through promoting osteogenic differentiation. Further understanding of the relationship between defects in osteogenic differentiation and tumor development holds tremendous potential in treating OS

Mesenchymal Progenitor Cells and Their Orthopedic Applications: Forging a Path towards Clinical Trials

Mesenchymal progenitor cells (MPCs) are nonhematopoietic multipotent cells capable of differentiating into mesenchymal and nonmesenchymal lineages. While they can be isolated from various tissues, MPCs isolated from the bone marrow are best characterized. These cells represent a subset of bone marrow stromal cells (BMSCs) which, in addition to their differentiation potential, are critical in supporting proliferation and differentiation of hematopoietic cells. They are of clinical interest because they can be easily isolated from bone marrow aspirates and expanded in vitro with minimal donor site morbidity. The BMSCs are also capable of altering disease pathophysiology by secreting modulating factors in a paracrine manner. Thus, engineering such cells to maximize therapeutic potential has been the focus of cell/gene therapy to date. Here, we discuss the path towards the development of clinical trials utilizing BMSCs for orthopaedic applications. Specifically, we will review the use of BMSCs in repairing critical-sized defects, fracture nonunions, cartilage and tendon injuries, as well as in metabolic bone diseases and osteonecrosis. A review of www.ClinicalTrials.gov of the United States National Institute of Health was performed, and ongoing clinical trials will be discussed in addition to the sentinel preclinical studies that paved the way for human investigations

Retinoic Acids Potentiate BMP9-Induced Osteogenic Differentiation of Mesenchymal Progenitor Cells

As one of the least studied bone morphogenetic proteins (BMPs), BMP9 is one of the most osteogenic BMPs. Retinoic acid (RA) signaling is known to play an important role in development, differentiation and bone metabolism. In this study, we investigate the effect of RA signaling on BMP9-induced osteogenic differentiation of mesenchymal progenitor cells (MPCs).Both primary MPCs and MPC line are used for BMP9 and RA stimulation. Recombinant adenoviruses are used to deliver BMP9, RARalpha and RXRalpha into MPCs. The in vitro osteogenic differentiation is monitored by determining the early and late osteogenic markers and matrix mineralization. Mouse perinatal limb explants and in vivo MPC implantation experiments are carried out to assess bone formation. We find that both 9CRA and ATRA effectively induce early osteogenic marker, such as alkaline phosphatase (ALP), and late osteogenic markers, such as osteopontin (OPN) and osteocalcin (OC). BMP9-induced osteogenic differentiation and mineralization is synergistically enhanced by 9CRA and ATRA in vitro. 9CRA and ATRA are shown to induce BMP9 expression and activate BMPR Smad-mediated transcription activity. Using mouse perinatal limb explants, we find that BMP9 and RAs act together to promote the expansion of hypertrophic chondrocyte zone at growth plate. Progenitor cell implantation studies reveal that co-expression of BMP9 and RXRalpha or RARalpha significantly increases trabecular bone and osteoid matrix formation.Our results strongly suggest that retinoid signaling may synergize with BMP9 activity in promoting osteogenic differentiation of MPCs. This knowledge should expand our understanding about how BMP9 cross-talks with other signaling pathways. Furthermore, a combination of BMP9 and retinoic acid (or its agonists) may be explored as effective bone regeneration therapeutics to treat large segmental bony defects, non-union fracture, and/or osteoporotic fracture

Lysophosphatidic Acid Acyltransferase β (LPAATβ) Promotes the Tumor Growth of Human Osteosarcoma

Osteosarcoma is the most common primary malignancy of bone with poorly characterized molecular pathways important in its pathogenesis. Increasing evidence indicates that elevated lipid biosynthesis is a characteristic feature of cancer. We sought to investigate the role of lysophosphatidic acid acyltransferase β (LPAATβ, aka, AGPAT2) in regulating the proliferation and growth of human osteosarcoma cells. LPAATβ can generate phosphatidic acid, which plays a key role in lipid biosynthesis as well as in cell proliferation and survival. Although elevated expression of LPAATβ has been reported in several types of human tumors, the role of LPAATβ in osteosarcoma progression has yet to be elucidated.Endogenous expression of LPAATβ in osteosarcoma cell lines is analyzed by using semi-quantitative PCR and immunohistochemical staining. Adenovirus-mediated overexpression of LPAATβ and silencing LPAATβ expression is employed to determine the effect of LPAATβ on osteosarcoma cell proliferation and migration in vitro and osteosarcoma tumor growth in vivo. We have found that expression of LPAATβ is readily detected in 8 of the 10 analyzed human osteosarcoma lines. Exogenous expression of LPAATβ promotes osteosarcoma cell proliferation and migration, while silencing LPAATβ expression inhibits these cellular characteristics. We further demonstrate that exogenous expression of LPAATβ effectively promotes tumor growth, while knockdown of LPAATβ expression inhibits tumor growth in an orthotopic xenograft model of human osteosarcoma.Our results strongly suggest that LPAATβ expression may be associated with the aggressive phenotypes of human osteosarcoma and that LPAATβ may play an important role in regulating osteosarcoma cell proliferation and tumor growth. Thus, targeting LPAATβ may be exploited as a novel therapeutic strategy for the clinical management of osteosarcoma. This is especially attractive given the availability of selective pharmacological inhibitors

The Efficacy of Plant-Based Ionizers in Removing Aerosol for COVID-19 Mitigation

Small-sized droplets/aerosol transmission is one of the factors responsible for the spread of COVID-19, in addition to large droplets and surface contamination (fomites). While large droplets and surface contamination can be relatively easier to deal with (i.e., using mask and proper hygiene measures), aerosol presents a different challenge due to their ability to remain airborne for a long time. This calls for mitigation solutions that can rapidly eliminate the airborne aerosol. Pre-COVID-19, air ionizers have been touted as effective tools to eliminate small particulates. In this work, we sought to evaluate the efficacy of a novel plant-based ionizer in eliminating aerosol. It was found that factors such as the ion concentration, humidity, and ventilation can drastically affect the efficacy of aerosol removal. The aerosol removal rate was quantified in terms of ACH (air changes per hour) and CADR- (clean air delivery rate-) equivalent unit, with ACH as high as 12 and CADR as high as 141 ft3/minute being achieved by a plant-based ionizer in a small isolated room. This work provides an important and timely guidance on the effective deployment of ionizers in minimizing the risk of COVID-19 spread via airborne aerosol, especially in a poorly-ventilated environment

Mesenchymal stem cells: Molecular characteristics and clinical applications

Mesenchymal stem cells (MSCs) are non-hematopoietic stem cells with the capacity to differentiate into tissues of both mesenchymal and non-mesenchymal origin. MSCs can differentiate into osteoblastic, chondrogenic, and adipogenic lineages, although recent studies have demonstrated that MSCs are also able to differentiate into other lineages, including neuronal and cardiomyogenic lineages. Since their original isolation from the bone marrow, MSCs have been successfully harvested from many other tissues. Their ease of isolation and ex vivo expansion combined with their immunoprivileged nature has made these cells popular candidates for stem cell therapies. These cells have the potential to alter disease pathophysiology through many modalities including cytokine secretion, capacity to differentiate along various lineages, immune modulation and direct cell-cell interaction with diseased tissue. Here we first review basic features of MSC biology including MSC characteristics in culture, homing mechanisms, differentiation capabilities and immune modulation. We then highlight some in vivo and clinical evidence supporting the therapeutic roles of MSCs and their uses in orthopedic, autoimmune, and ischemic disorders

Effect of LPAATβ on osteosarcoma cell proliferation.

<p><b>A</b>. Crystal violet staining assay for cell viability. 143B cells were seeded in 12-well plates and infected with an optimal titer of AdR-LPAATβ, AdR-LPAATβ, or AdRFP control. Viable cells were subjected to crystal violet staining at 5 days after infection. Representative duplicate staining is shown. <b>B</b>. Quantitative analysis of the crystal violent staining assay. Relative staining intensities were measured by using ImageJ software. “*” <i>p-value <0.05</i>. <b>C</b>. MTT cell proliferation. 143B cells were seeded in 96-well plates and infected with an optimal titer of AdR-LPAATβ, AdR-LPAATβ, or AdRFP control (in triplicate). At the indicated time points after infection, cells were subjected to MTT assay to determine relative proliferative activity. “*” <i>p-value <0.01</i>.</p

Histological evaluation of xenograft osteosarcoma tumors.

<p>Tumors were retrieved from animals and subjected to paraffin-embedded. Sections were subjected to Hemotoxylin & Eosin staining (top panel) and PCNA antibody immunohistochemical staining (bottom panel). Representative results are shown.</p