Milwaukee School Of Engineering Research Articles

Formula Hybrid + Electric: Because it's crazy to try

This column is a change of pace, a report on Formula Hybrid+Electric contest held last May at the New Hampshire Motor Speedway in Loudon, NH. Formula Hybrid was founded by the Thayer School of Engineering at Dartmouth and is sponsored by, among others, IEEE and SAE. Formula Hybrid racers are modeled on scaled down formula race cars, and are single seat, open cockpit, and open wheel. Universities and colleges competing at the May event included Dartmouth, BU, Carnegie Mellon, Illinois Institute of Technology, Indiana and Purdue Universities, Lafayette, Lawrence Tech, MIT, Middlebury, Milwaukee School of Engineering, Princeton, RPI, Tufts, UVM, U. Victoria, U. Waterloo, U. Wyoming, WPI, and Yale.

Establishing an interdisciplinary research team for cardio-oncology artificial intelligence informatics precision and health equity

Study objectiveA multi-institutional interdisciplinary team was created to develop a research group focused on leveraging artificial intelligence and informatics for cardio-oncology patients. Cardio-oncology is an emerging medical field dedicated to prevention, screening, and management of adverse cardiovascular effects of cancer/cancer therapies. Cardiovascular disease is a leading cause of death in cancer survivors. Cardiovascular risk in these patients is higher than in the general population. However, prediction and prevention of adverse cardiovascular events in individuals with a history of cancer/cancer treatment is challenging. Thus, establishing an interdisciplinary team to create cardiovascular risk stratification clinical decision aids for integration into electronic health records for oncology patients was considered crucial. Design/setting/participantsCore team members from the Medical College of Wisconsin (MCW), University of Wisconsin-Milwaukee (UWM), and Milwaukee School of Engineering (MSOE), and additional members from Cleveland Clinic, Mayo Clinic, and other institutions have joined forces to apply high-performance computing in cardio-oncology. ResultsThe team is comprised of clinicians and researchers from relevant complementary and synergistic fields relevant to this work. The team has built an epidemiological cohort of ~5000 cancer survivors that will serve as a database for interdisciplinary multi-institutional artificial intelligence projects. ConclusionLessons learned from establishing this team, as well as initial findings from the epidemiology cohort, are presented. Barriers have been broken down to form a multi-institutional interdisciplinary team for health informatics research in cardio-oncology. A database of cancer survivors has been created collaboratively by the team and provides initial insight into cardiovascular outcomes and comorbidities in this population.

Judge rules against former employee

Case name: Fitzpatrick v. Milwaukee School of Engineering, No. 18‐cv‐0541 (E.D. Wis. 12/02/20).

Judge rules against former employee

Case name: Fitzpatrick v. Milwaukee School of Engineering, No. 18‐cv‐0541 (E.D. Wis. 12/02/20).

July 2021 Placement Ads

July 2021 Placement Ads

A virtual classroom activity for teaching sunlight‐initiated DNA damage and its protection

As a consequence of COVID-19 pandemic, most of classroom teaching went virtual in the academic year 2020-21. We took this opportunity to create a virtual activity for a biochemistry course for undergraduate nursing students at Milwaukee School of Engineering. It is well understood that prolonged exposure to sunlight is one of the major causes of skin cancer due to mutations in the keratinocyte DNA. Skin cancer is one of the most common forms of cancer in the US. UV-B radiation in the region of 290-320 nm is absorbed by skin cells resulting in mutated DNA which can lead to cancer. We developed the virtual activity with a dual purpose in mind. First, the activity would enhance their learning experience about DNA mutations using a 3D-printed model showing the biochemical DNA damage which could lead to skin cancer. Second, the activity could increase general awareness among students about the dangers of UVB-radiation exposure and protection strategies by directly testing everyday products such as sunscreens. We randomly picked nine commercially available sunscreens with various SPF values and tested their ability to protect from UVB radiation. Testing for protection from UVB radiation was performed using an in-house created customized chamber equipped with a UVB light source emitting a single wavelength at 310 nm. A thin, even layer of sunscreen was applied on a thin clear plastic wrap and exposed to UVB light. The sunscreens’ ability to block UVB radiation was quantitated compared to a control sample with no sunscreen.Further, using a 3D model of a DNA segment created by 3D printing at the Center for Biomolecular Modeling, we explained molecular-level changes. We created a two-part video. Part I narrates details of the sunscreen protection experiment. Part II explains the molecular details of DNA damage using 3D-printed model including (i) location of a broken A-T hydrogen bond (ii) location ofa T-T dimer and discussion of possible impact of the change in the DNA structure and (iii) explaining the formation of a ‘kink’ in the DNA strand as a result of the T-T photoproduct. The video will be accompanied by a student survey questionnaire on Canvas LMS. The goal of this study is to quantitatively test students’ understanding of this biochemistry topic before and after watching the virtual activity. Further, it is our hope that the activity will also increase general awareness among nursing students about the harmful effects of ultraviolet radiation exposure.

Development of a hands‐on learning activity on potential DNA damage and skin cancer for a nursing biochemistry class

Skin cancer (basal cell carcinoma) is one of the most common forms of cancer in the US (about 4.3 million cases/year). Prolonged exposure to sunlight is one of the major causes of skin cancer due to mutations in the DNA. Ultraviolet‐B (UV‐B) radiations in the region of 290–320 nm of the solar spectrum are absorbed by basal keratinocyte cells resulting in mutated DNA leading to cancer. We developed a two‐part active learning experience for the nursing biochemistry class. Part I: In this activity, the relative intensity of UV radiation at 308 nm in the absence and presence of sunscreen was measured using a UVX Digital Radiometer‐UVX31 Sensor by first‐year nursing students in a biochemistry course at the Milwaukee School of Engineering (MSOE). A class of 20 students brought in their own commercially available sunscreens to class. Students tested the sunscreens’ ability to block the UVB light. A thin layer of sunscreen was applied to a plastic wrap sheet and placed between the UV source and the sensor. Students compared the intensity of the UV light (in mW/cm2) transmitted through an uncoated and coated plastic wrap. They then observed that different commercial sunscreens have different abilities to block UV light.DNA damage by UVB causes mutations due to the development of cyclobutane‐pyridine photodimers commonly recognized as thymine‐thymine (T‐T) dimers. Part II: Students made connections between the real‐life classroom activity performed in Part I and a three‐dimensional physical model of DNA segment (crystal structure source entries: ndb UD0053 or PDB 1SM5) showing the formation of the T‐T dimer using a hand‐held model and images. The model was constructed by 3D‐printing. Students were challenged to locate the T‐T dimers in the model and discuss the possible impact of the change in the DNA structure.The activity motivated the nursing biochemistry students and enhanced their learning experience with DNA mutations by directly relating it to everyday products such as sunscreens and a 3‐D model showing the biochemical DNA damage which could lead to skin cancer. Additionally, the two‐part activity enhanced one‐on‐one student‐faculty interactions in the classroom. In the future we plan to conduct an in‐depth quantitative educational study to understand the benefits of this active learning exercise as compared to traditional classroom instruction.Support or Funding InformationSummer professional development grant, Milwaukee School of Engineering, Milwaukee, WI. Center for BioMolecular Modeling (CBM), Milwaukee School of Engineering, Milwaukee, WI.

Fatty Acid Regulation of Virulence in Vibrio cholerae: A Structural Analysis of Unbound, Ligand‐Bound, and DNA‐Bound ToxT

Vibrio cholerae is an infectious bacterium that causes activation of transmembrane ion channels responsible for mediating the tonicity of cells in the small intestine. Activation of these ion channels results in osmotic movement into the small intestine, thus dehydrating cells and the infected individual. The transcription factor, ToxT, upregulates production of cholera toxin (CT) and the toxin coregulated pilus (TCP), key virulence factors in the progression of cholera. ToxT, a member of the AraC family of transcriptional regulators, has been crystallized in the presence of an unsaturated fatty acid (UFA) revealing a repressed form of the transcription factor in a conformation that prevents DNA binding. Two □‐helices in the DNA binding domain (DBD), □6 and □9, must be parallel to bind consecutive major grooves in the DNA. In the UFA‐bound structure, these helices are non‐parallel, supporting the model that ligand binding to ToxT prevents DNA binding. ToxT has been shown biochemically to be homodimeric when bound to DNA. However, crystallization of the DNA bound form of ToxT has been challenging due to instability of the complex. Recently, a natural variant of ToxT with increased solubility has been crystallized in the presence and absence of UFA. Crystallization of the apo form of ToxT required a lysine to alanine substitution at position 231 in the ligand‐binding pocket of the protein to prevent UFA binding. Although the structure of apo‐ToxT is highly similar to the UFA‐bound structure, the apo version was shown to be more flexible than ligand‐bound ToxT, supporting a model in which □6 and □9 in each subunit of dimeric ToxT are parallel and capable of binding to DNA. Using the structures described in this study, The Pingry School SMART (Students Modeling A Research Topic) Team used a 3D‐printer from the Milwaukee School of Engineering (MSOE) to model the apo structure and the dimeric DNA‐bound model of ToxT. These models support an in‐depth analysis of ToxT structural conformations in support of the proposed mechanism of regulation. A detailed structural understanding of ToxT may support future development of vaccines and therapeutics for cholera and other pathogens whose toxicity is regulated by AraC family members.

Barreling Forward: Advancements in De Novo Protein Design

Natural evolution and protein redesign have only explored a tiny fraction of theoretically possible protein structures. However, de novo protein design will prove powerful in engineering novel proteins with specific functions by comprehensively sampling the protein space using computational methods guided by protein folding principles. De novo protein design involves working backwards from a desired protein with special structure and function to derive an amino acid sequence capable of folding into such a conformation—a challenging approach due to the vast number of protein conformations to evaluate. Here, we present a review of the latest advancements in de novo protein design methods and applications in conjunction with a physical model of a de novo fluorescence‐activating β‐barrel protein. Approaches to de novo protein design include: (1) simulating the folding of a fixed amino acid sequence to determine each residue’s most stable conformation, (2) determining the amino acid sequence that folds into a desired protein conformation, and (3) performing comprehensive rapid evaluations of each possible conformation. This novel protein is then synthesized and validated through in vitro or in vivo assays. In one recent breakthrough by Baker et. al., a de novo approach was used to design a β‐barrel protein comprised of a cylindrical pleated β‐sheet which binds the fluorogenic compound DFHBI. This study is the first instance of a de novo protein designed to bind to a small molecule of interest, with applications in visualizing cell movement, gene expression, DNA replication, protein translation, and tumor progression. In designing this fluorescence activating β‐barrel protein, structural irregularities were introduced to stabilize the structure and enlarge the β‐barrel cavity. Subsequently, the optimal sequences for β‐barrels with reasonable binding site and affinity for DFHBI were designed by computationally adjusting individual residue conformations. Finally, this optimized protein was synthesized, which had greater affinity with DFHBI and increased fluorescence in in vitro and in vivo experiments.Support or Funding InformationThis is a SMART Team project supported through the contributions of Dr. Jinan Wang of the University of Kansas Center for Computational Biology, the Milwaukee School of Engineering, and the Olathe Medical Professions 21st Century Academy.

The Structure and Function of Estrogen Receptor β: Essential Roles in Gene Regulation

The Olathe North MSOE Center for BioMolecular Modeling SMART Team used 3‐D modeling and printing technology to examine the structure‐function relationships and regulatory roles of ERβ. Estrogens are steroid hormones synthesized from cholesterol in cells of the ovary and other tissues expressing the enzyme aromatase. These hormones are secreted into the bloodstream and modulate numerous physiological functions through gene regulation. To achieve this, estrogens pass through cell and nuclear membranes, facilitated by their lipophilic and miniscule nature. In target cells, estrogens bind to nuclear transcription factors called estrogen receptors (ERs), the two primary types being estrogen receptor alpha (ERα) and beta (ERβ). ERs typically form either homodimers with an identical molecule or heterodimers of ERα with ERβ. Estrogen binding occurs at ER's ligand binding domain (LBD), activating the ER's DNA binding domain (DBD). The ER dimer then binds to DNA at estrogen response elements (EREs) located in the promoter regions of estrogen‐responsive genes, allowing the ER to regulate the transcription of target genes. However, this process is only one of four mechanisms by which ERs function. In addition to this genomic mechanism, ERs can also function through tethered, nongenomic, and ligand‐independent mechanisms. In all these processes, ERs' role as a gene regulator is determined by the physical change in the structure of various ER domains, making it essential to analyze the ERs' protein structure. In this review, we focus on the structure and function of ERβ because of its largely unexplored physiological significance and clinical potential. ERβ is most highly expressed in the ovaries, mammary glands, prostate, testes, gastrointestinal tract, and immune system. Transcriptional regulation by ERβ is essential for ovarian follicle maturation and ovulation. Additionally, ERβ is involved in neurogenesis, vascular function modulation, cardiac myocyte maintenance, and metabolism regulation, among other physiological functions. In a pathological context, recent studies suggest ERβ is tumor suppressing while ERα increases tumor growth. Specifically, ERβ can inhibit proliferation while inducing differentiation and apoptosis in tumor cells. Thus, activation of ERβ by synthetic agonists, known as selective estrogen receptor modulators (SERM), has clinical significance concerning the treatment of breast, prostate, colon, and ovarian cancers. Here, we present a review of the latest research on ERβ in conjunction with its physical model, emphasizing ERβ's regulatory roles in human health.Support or Funding InformationThis is a SMART Team project supported through the contributions of Dr. M.A. Karim Rumi of the University of Kansas Medical Center, the Milwaukee School of Engineering, and the Olathe Medical Professions 21st Century Academy.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Preliminary Results of Assessing the Impact of a High School Science Outreach Program on the Confidence, Attitudes, and Skills of the Participants

Science outreach has been shown to enhance science education and cultivate students' interest in science. The Summit Country Day School, an independent Cincinnati‐based co‐educational K‐12 school, established a Milwaukee School of Engineering (MSOE) Center for Biomolecular Modeling Modeling a Protein Story (MAPS) team this school year, with the overall goal of increasing the scientific and technical skills of its participants. Through this 22 week program, the participants studied the structure‐function relationship of an assigned protein (Aquaporin) by researching relevant scientific articles and using software (Jmol) for molecular modeling to 3D print the protein structure. Seven underclassmen participated; two science faculty members facilitated and mentored. A Likert survey was developed to assess and compare the confidence, attitudes, and skills of the participants. Specifically, the tool evaluated these learning goals: 1) selecting relevant scientific articles, 2) assessing important points in the selected articles, 3) presenting the summary of the articles and their ideas to the group, 4) writing a scientific abstract, and 5) managing computer software for molecular modeling for 3D printing. The tool was administered at the beginning and halfway through the program, with planned administration at its conclusion. Wilcoxon signed‐rank test was performed to assess statistically significant differences between the survey responses at the two time periods. The survey findings demonstrated no statistically significant differences between the responses at the beginning of the program and at the halfway through the program. However, there were overall trends for improvement in the confidence, attitudes, and skills of the participants, especially regarding understanding scientific articles (Fig. 1). In conclusion, participating in a MAPS team generally increases the confidence, attitudes, and skills of the participants in regard to scientific activities. The lack of statistical significance may be because of the short duration of the program and small sample size.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Protein E6 in High Risk Human Papillomaviruses

Human Papillomavirus (HPV) refers to a group of more than one hundred HPV high risk or low risk strains associated with a variety of conditions. Over fifty strains lead to genital infections, while others influence the development of various cancers, such as cervical, skin, etc. The combination of HPV E6/E7, hTERT, and Ki67 mRNA expression levels complement each other to diagnose lesions of the aforementioned cancers, specifically dealing with the cervix. All HPV strains share a common structure: circular, double stranded DNA encoding for eight open reading frames (ORF) surrounded by a non‐enveloped capsid. ORFs function to produce the E1‐E7 proteins needed for HPV replication (early region), L1‐L2 proteins that make up the capsid (late region), and replicate and transcribe viral DNA with the help of cis components (long control region). The E6, in particular, is an oncoprotein composed of polypeptides made up of 150 amino acids and a Cys‐X‐X‐Cys motif that allow for the formation of two zinc fingers. E6 and E7 recognize a number of host proteins by hijacking their cellular domain‐motif interaction networks. In the HPV‐16 and HPV‐18 strains, the E6 protein binds its amino and carboxyl terminal regions to a leucine‐rich sequence (LxxLL) within the cellular ubiquitin ligase, E6AP. This heterodimer degrades p53, a proapoptotic tumor suppressor, although the exact mode of assembly is unknown. Complete degradation potentially leads to oncogenesis in high‐risk HPV strains, as these transformed cells have lost their ability to arrest at the G1 checkpoint within their cell cycle and perform apoptosis. Aside from the E6‐E6AP heterodimer binding directly to p53, the E6 protein has other oncogenic functions, allowing it to bind to four general classes of other proteins, providing indirect pathways to degrade p53. Binding options include proteins involved in cell polarity and motility, tumor suppressors and inducers of apoptosis, transcriptional coactivators and DNA replication/repair factors. Regarding transcription coactivators, degradation of p53 transcriptional activity is possible, as seen by the targeting of p53 coactivator p300/CBP or yADA3. Given the mechanism of E6‐E6AP complex hindering p53's from carrying out normal function, E6 is an attractive target for therapies against cervical cancers. The Olathe North High School MSOE Center for BioMolecular Modeling SMART Team used 3‐D modeling and printing technology to examine structure‐function relationships of E6.Support or Funding InformationSMART team is a joint venture between the Milwaukee School of Engineering and the Olathe School District's 21st century program Medical Professions Academy.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

The Anthrax Toxin: A Molecular Trojan Horse

Anthrax is a three protein component exotoxin released by the virulent bacterium Bacillus anthracis that causes cell lethality in its host. In humans and many animals, Bacillus anthracis can enter the body through the lungs, skin, intestines, or bloodstream. Symptoms of Anthrax poisoning are commonly displayed between one day to two months after initial contact. Once the bacterium spores enter the host organism, the spores germinate and the bacterium synthesizes and releases the anthrax endotoxin protein molecules in response to elevated CO2 levels. Anthrax toxin is composed of three protein molecules: protective antigen, edema factor, and the lethal factor. The protective antigen is released by the bacterium as an 83 kDa protein single chain, and then binds to the host cell receptors. It is then cleaved by proteases on the host cell into a smaller 63 kDa assembly competent monomer which assembles on the cell surface as a heptamer. This heptameric ring binds to edema factor and lethal factor. The pre pore three component complex is then endocytosed into the host cell. As the endosome acidifies to pH 5.0, the prepore protective antigen changes shape, and inserts into the endosomal lipid membrane. The bound edema factor and the lethal factor are gradually unfolded and threaded through the protective antigen pore translocon injection system. The translocated edema and lethal factors then refold in the cytoplasm. This threading is facilitated by a pH gradient. During the threading of the lethal and edema factors, the acidic residues of these proteins are first protonated, resulting in a positive charged state. As these enzymatic proteins are threaded through the pore, the proton is lost after crossing a critical phenylalanine clamp loop region and the protein continues to thread in a unidirectional manner into the cytoplasm. Once the translocated enzymes refold in the cytoplasm, the lethal factor disrupts cell signaling and the edema factor disrupts cell homeostasis. To study this translocation mechanism, one can use the 20 kDa N terminal portion of the lethal factor (called LFN) that binds to the pore and removes the enzymatic portion of the protein. Research is progressing where this translocation system is used to deliver drugs that are attached onto the LFN and be transported into cells in a very specific manner. Thus the understanding of this transport mechanism may be important for engineered drug delivery systems. The Olathe North MSOE Center for BioMolecular Modeling SMART Team used 3‐D modeling and printing technology to examine structure‐function relationships of anthrax.Support or Funding InformationThe Olathe North SMART Team is joint venture between the Medical Professions Academy and the Milwaukee School of Engineering.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

PrPc: The Normal Prion

PrPc is a normal cell‐surface glycoprotein that is conformationally characterized by two alpha helices and two complex‐type N‐linked oligosaccharide chains. This protein is unique in its propensity to misfold into a neurodegenerative disease‐causing proteinaceous infectious particle, known as a prion. PrPc can undergo conversion into PrPSc through spontaneous misfolding, a genetic mutation of the human PRNP gene, or exposure to a prion from an external source. When this happens, its composition shifts from an alpha‐helical, soluble protein low in beta pleated sheets to an insoluble, protease‐resistant particle with a high percentage of beta sheets. This resulting misfolded form, known formally as PrPSc, is pathogenic and aggregates in neural tissue by recruiting and converting more PrPc to PrPSc, ultimately causing neuronal cell dysfunction followed by cell death. The prion's form of “self‐replication” without utilizing genetic material is particularly fascinating, as it appears to defy the central dogma of biology and differs from all other pathogenic particle infection mechanisms. It is notable that some prions have evolved to act as transmissible infectious agents, similar to viruses, despite the absence of genetic material. This distinguishes some prion diseases, such as chronic wasting disease (CWD) and scrapie, from their inherited disease counterparts. The biosynthesis pathway of PrPc is similar to other cellular proteins, with replication occurring on the ribosomes on the endoplasmic reticulum. However, whereas malfunctioning proteins are normally tagged by ubiquitin and then degraded in a proteasome, the ubiquitin‐proteasome complex is inhibited during prion formation, allowing PrPSc to form and survive degradation, leading to its buildup in cytosol and subsequent neurotoxicity. Human and animal prion diseases have been classified into three broad categories‐‐genetic, sporadic, and acquired‐‐based on properties of the PrP proteins and prion infection morphology. Physical symptoms of prion infection include deviant behavior, dementia, ataxia, insomnia, paraplegia, and paresthesias. Commonly discussed prion‐induced diseases (differentiated via host type and slight conformational discrepancies between misfolded proteins) include scrapie, kuru, CJD, bovine spongiform encephalopathy (mad cow disease), and CWD. Here, we present current research on prions, with a focus on CWD, which was first found in Colorado and affects deer and other cervids.The Olathe North High School Team 1 MSOE Center for BioMolecular Modeling SMART Team used 3‐D modeling and printing technology to examine the structure‐function relationships and histology of PrPc, or the normal cellular prion.Support or Funding InformationThis project is a joint venture between the Milwaukee School of Engineering and the Medical Professions Academy.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

2017 Elijah High-Altitude Balloon Launch Team Summer Proceedings Report

The 2017 Wisconsin Space Grant Consortium Elijah High-Altitude Balloon Launch Team was comprised of one student from Lawrence University, two students from the Milwaukee School of Engineering, and one student from the University of Wisconsin – Fox Valley. This year, three members of the team had experience with high altitude balloon launches due to previous participation on either the Elijah Payload or Launch Team, or both. A training session was hosted by Dr. Farrow to familiarize or refresh the team with the physical setup of a launch train as well as how to run track predictions and how to read the jet stream charts. Launches were planned and carried out for the Elijah High-Altitude Balloon Payload Team. This launch was successful, reaching a peak altitude of over 115,000 ft (35 km) above mean sea level.

The Systems and Design Philosophy of Mosquito 2.0

The MSOE Underwater Robotics Team is a fifth year student organization at the Milwaukee School of Engineering. Last year, the team attended the international competition at NASA’s Neutral Buoyancy Laboratory and placed fifth attracting the attention of the new students and faculty members. This year’s ROV, Mosquito 2.0, was designed specifically to be compact, practical and modular, focusing on adaptability and stability to be able to complete any scheduled task, while being able to change critical systems for future endeavors. A subsystem approach to design allowed a lot of collaboration to happen since each part of the ROV could be worked on separately and brought together with ease.

Role of Bcl‐2 in Hematological Cancer Formation

B cell leukemia/lymphoma 2 (BCL‐2) is a 26 kilodalton, amphipathic, anti‐apoptotic protein located on the outer mitochondrial membrane. BCL‐2 interacts with other anti‐apoptotic and pro‐apoptotic factors in order to regulate apoptosis. If a structural change occurs on the BCL‐2 gene, overexpression of the BCL‐2 protein can result. This causes a change in the ratio of BCL‐2 to its BCL‐2 Homologous 3 (BH3) ligands, preventing the release of the apoptotic signal. The primary change associated with BCL‐2 overexpression in lymphomas is a t(14;18) chromosomal translocation, which causes an increase in BCL‐2 transcription. The upregulation of the oncogene allows for the survival of the mutated B cells by raising the apoptotic threshold, which then dislodges regular lymphocytes in the bone marrow or lymph nodes. Lack of cell death due to overexpression of BCL‐2 has been linked to hematological malignancies, specifically lymphomas and myelomas. Both B‐lymphocytic cancers can result from alterations of the immunoglobulin heavy chain locus on chromosome 14. While BCL2 translocation can cause Follicular Lymphoma, BCL2 over‐expression is observed in many other tumor types and likely contributes to cancer progression and drug resistance in these tumors. Treatments to inhibit BCL‐2 include attempts at activation and overexpression of the pro apoptotic BH3 proteins, BCL‐2 Associated X Protein (BAX) and BCL‐2 Associated K protein (BAK), and creation of BH3 mimetics. Indeed, the FDA approved the BCL2 inhibitor Venetoclax (ABT‐199) earlier this year for the treatment of Chronic Lymphocytic Leukemia. These treatments could help cause cancer cell death by binding to targeted anti‐apoptotic proteins and causing the signal for apoptosis to be released. This could neutralize the cancerous effects of the BCL‐2 oncogene upregulation. Walton High School SMART (Students Modeling A Research Topic) Team used the computer program Jmol to create a 3D printed model of BCL‐2 and composed a review poster of our secondary research to investigate and demonstrate the relationship between the structure and function of this molecule.Support or Funding InformationDiane Munzenmaier, Ph.D., Center for Biomolecular Modeling, Milwaukee School of Engineering

Connections between NF‐κB Misregulation and Carcinogenesis

In this review poster, we researched the function, regulation, and structure of NF‐κB as it relates to carcinogenesis. Found in almost all animal cells, nuclear factor kappa‐light‐chain‐enhancer of activated B cells (NF‐κB) is a transcription factor that plays various roles in cellular proliferation, cell survival, inflammation, and T cell activation. There are two different NF‐κB signaling pathways: the canonical pathway and the non‐canonical pathway. NF‐κB forms a p50/Rel A heterodimer in the canonical pathway and a p52/Rel B heterodimer in the non‐canonical pathway. NF‐κB protein is normally sequestered in the cytoplasm as an inactive complex with a κB inhibitor (IκB) protein. Outside stimuli such as reactive oxygen species (ROS) and tumor necrosis factor alpha (TNF‐α) activate cell surface receptors such as Toll‐Like Receptors (TLRs) and Receptor Activators of NF‐κB (RANK). These surface receptors, in turn, activate IκB kinase (IKK). IKK phosphorylates IκB, which causes ubiquitination of IκB, signaling proteasomes to degrade it. NF‐κB then enters the nucleus through a nuclear pore and forms a transcription complex with coactivators and RNA polymerase. NF‐κB binds to specific DNA‐binding sites to induce transcription. One of the target genes of NF‐κB encodes IκBs, so NF‐κB regulates its own activity through a negative feedback loop. Because the cell maintains storage of the signaling protein NF‐κB in the cytoplasm, NF‐κB allows the cell to respond to sudden stimuli by activating quick changes in gene expression. Because proteins that promote cellular proliferation and cell survival are mainly transcribed through NF‐κB activation, uncontrolled overactivation of this transcription factor has major implications in carcinogenesis. Many types of cancer cells have high levels of constitutively active NF‐κB. Mutations in the genes for NF‐κB itself or its inhibitors such as IκBs often found in cancer cells can cause cells to accelerate their proliferation or confer resistance to apoptosis. Some types of cancer cells secrete signaling molecules, inducing improper NF‐κB activity. Because of the tumor promoting characteristics of NF‐κB activation, a focus of current research is to find methods of suppressing NF‐κB to kill cancer cells or slow their growth. We designed a 3D‐printed model of the p50/RelA NF‐κB protein using Jmol to highlight the relationship between its structure and function.Support or Funding InformationDiane Munzenmaier, Ph.D., Center for Biomolecular Modeling, Milwaukee School ofEngineering

2016 Elijah High Altitude Balloon Launch Team Summer Proceedings Report

The 2016 Wisconsin Space Grant Consortium Elijah High Altitude Balloon Launch Team was comprised of two students from Milwaukee School of Engineering, one student from University of Wisconsin – Fox Valley, and one student from Carthage College. This year, the majority of the students involved were discovering the balloon launch experience for the first time. The 2016 Elijah Balloon Launch Team held a meeting for the new members to learn how all of the equipment worked through a practice run using the tools in a trial.The first launch planned was cancelled, and was postponed to the next weekend. This launch was successful, reaching a peak altitude of 31,021m.Â

MSOE Underwater Robotics: The Mosquito

The MSOE ROV team is a fourth year student organization at the Milwaukee School of Engineering that competed at an international ROV competition that took place at the NASA Neutral Buoyancy Lab. The goal was to create an ROV that could complete tasks that simulate bringing the ROV into space and exploring one of Jupiter’s moons, Europa. Named Mosquito for its appearance, the ROV was designed specifically to be compact and light to allow for easy transportation to remote parts of the world. The system is broken down into subsystems that could easily interface and synergize with each other to accomplish all of the needed tasks related to the mission to Europa, including collecting cube sats and oil samples, studying coral, and converting oil rigs to reefs, all while diving deep.Â