Rat Elbow Project

Current methods for treating post-traumatic joint stiffness (PTJS), a common clinical problem following elbow surgeries which causes functional impairment of the limb, have proven insufficient.1 The main factors that expose the elbow joint to this complication are a high degree of congruence, the complexity of the joint surfaces and the high tissue sensitivity to trauma, especially the joint capsule.1 As a result, the Lake laboratory is working with elbow tissue to determine how the injury presents itself. With a deeper understanding of the injury, the lab hopes to develop more effective prevention and treatment methods for PTJS. Before the fall of 2016, the lab successfully developed an animal model for the injury which can lead to PTJS. This model utilizes surgically injured elbows of Long-Evans rats. Currently, the lab is using this model to further understand the injury. In order to explore the presentation of the injury, the lab would like to use gait analysis. Gait analysis, or the examination of the steps and stepping patterns of the rats, provides an effective method to test the consequences of physical and drug therapy in a noninvasive manner. This is because walking is a natural behavior and therefore can be used to compare an injured rat to control. Gait analysis quantifies the consequences of injuries and provides useful data which can be used to gain a deeper understanding of the injury. Before the fall of 2016, DigiGait, an automated gait analysis system, was used with minimal success. Thus, the laboratory decided to pursue other methods

Macroscopic Model of a Cilium Appendage

The goal of this project is to develop a macroscopic model of the cilia appendage and a realistic testing environment for the model. The model should be created with materials that effectively replicate the material and mechanical properties of the appendage in the human body. Additionally, the testing environment should mimic the viscous fluid that surrounds cilia in the human body to allow for more accurate testing. The fluid’s flow should be parallel to the model and induce instability in the system. This instability should force the cilia model to oscillate like a flag in the wind. Upon completion of this project, our model should allow testers to gain a deeper understanding of cilia\u27s motion by observing and measuring these oscillations. Ideally, our model and testing environment will be transportable and easy to set up. This project is important because cilia malfunction can lead to many different diseases in the human body

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

Dissolution and Migration of Platinum in PEMFCs Investigated for Start/Stop Cycling and High Potential Degradation

Dissolution and migration of platinum due to start/stop degradation and increased cathode potentials were studied for commercial membrane electrode assemblies (MEA). The chosen conditions closely mimic real situations in automotive operation. In start/stop tests, we observed a strongly enhanced platinum dissolution due to the dynamic interplay of repeated cell start-up and consecutive normal fuel cell operation, which is related to platinum oxidation (start-up) and reduction (normal operation) cycles. Consequently, the performed test protocols distinguish between dynamic and static load profiles. Electrochemical investigations before and after degradation monitor the loss in cell performance. Since electron microscopy offers the unique possibility to unravel and distinguish degradation due to carbon corrosion and agglomeration or platinum dissolution, a focus was set on this method. For the start/stop MEA pronounced platinum dissolution accompanied by the formation of large platinum precipitations in the membrane was found. Carbon corrosion was also observed, but did not lead to a significantly reduced porosity and loss in platinum dispersion. In contrast, the MEA which was exposed to high constant potentials exhibited severe damage to the 3D cathode structure due to carbon corrosion. However, no pronounced platinum dissolution was observed and only few Pt precipitations were found in the membrane itself

Mechanical Endurance of Polymer Electrolyte Membrane and PEM Fuel Cell Durability

The life of proton exchange membrane fuel cells (PEMFC) is currently limited by the mechanical endurance of polymer electrolyte membranes and membrane electrode assemblies (MEAs). In this paper, the authors report recent experimental and modeling work toward understanding the mechanisms of delayed mechanical failures of polymer electrolyte membranes and MEAs under relevant PEMFC operating conditions. Mechanical breach of membranes/MEAs in the form of pinholes and tears has been frequently observed after long-term or accelerated testing of PEMFC cells/stacks. Catastrophic failure of cell/stack due to rapid gas crossover shortly follows the mechanical breach. Ex situmechanical characterizations were performed on MEAs after being subjected to the accelerated chemical aging and relative humidity (RH) cycling tests. The results showed significant reduction of MEA ductility manifested as drastically reduced strain-to-failure of the chemically aged and RH-cycled MEAs. Postmortem analysis revealed the formation and growth of mechanical defects such as cracks and crazing in the membranes and MEAs. A finite element model was used to estimate stress/strain states of an edge-constrained MEA under rapid RH variations. Damage metrics for accelerated testing and life prediction of PEMFCs are discussed