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The imaging software used to create the figures also may account for the difference in many factors of both the original and the replicate. The original figure was created through Inkscape and the replicate figure may have been created through microsoft word. Imaging size differences could be explained by this software as well as Word limits the margin sizes to one inch by default, whereas in Inkscape, the images are not bound to any range. This could also explain the letter label sizing, as font size 70 in Inkscape may appear differently than font size 70 in Word. Word also does not have the same centering functions of the letter labels as Inkscape, also accounting for this difference between the original and replicate. Discrepancies in arrow shape and size may also be explained by this software difference. In Word, arrows appear blue and naturally thick. In Inkscape, one can edit the arrow color and width. The arrowheads are also different as Inkscape offers a wide range of heads to choose from while Word has the singular arrowhead of 90 degrees. The black line in the interaction image and green backgrounds of images in the replicate figure may also be fragments of Word imaging that Inkscape does not possess.

Many differences in the two figures may have resulted from lack of specifications in the original methods. Although the proportions between the two figures match, the individual image sizes may have not been specified enough in the methods, accounting for this difference. The arrow shape and size may not have been specified enough in the methods as well, resulting in a shape and thickness difference. The white square background of the letter labels may have also not been specified clearly enough in the methods. Dimensions should have been included to minimize this discrepancy.

The image quality also differs between the two figures and images are clearer in the original figure than the replicate. The images in the original figure also take up most of the frame whereas in the replicate, there is more background space. The background setting of the images in each figure also differs slightly. In the original figure, the individual goose is standing on snow, the individual duck is standing on ice, and the interaction shows both species half swimming on water and half standing on ice. In the replicate figure, the individual goose is standing on snow, but there is a tree and other geese in the background. The individual duck is standing in a muddy terrain, and the interaction depicts both species swimming in the water and standing on snow with two benches in the foreground.

There are also subtle differences between the two compilations that become apparent upon closer examination. In the replicated figure, the letter labels are not centered within each white square like in the original. There is also a black line running in the center portion close to the top edge of the interaction image in the replicate figure, a marking that the original figure does not have. A third quality the replicated figure possesses that the original figure does not have includes green borders around each white square label.

Although the original and replicated figures (shown in the appendix) are similar, there are many noticeable differences. The overall size of 1200 pixels is consistent across both figures, but the sizing of each image differs despite the correct orientation. The images of individual species in the original figure are slightly larger than the ones in the replicate, making the interaction image in the original slightly smaller in comparison to that of the replicate. The letter labels also differ between each figure with lowercase letters in the original and uppercase letters in the replicate. The white squares behind each letter also differ in size between the two figures and are smaller in the original than the replicate. Another smaller detail that differs between the original and replicated figures is the arrow width, location, and color. In the original figure, the arrows are black and narrow, depicted closer to the middle of the interspecific interaction. In the replicate, the arrows are blue and wide, depicted closer to the edges of the interspecific interaction. The shapes of the arrowheads also differ, in the replicate figure, the wings are approximately 90 degrees in relation to the body whereas in the original figure, the wings are approximately 30 degrees in relation to the body.

The researchers would like to assess dosage efficiency through repeated titrations for a standard therapeutic threshold of 50% or greater based on liposomal binding and delivery of its interior components. If a certain percentage of tumor cells are sensitized with each dose, it will allow the researchers to further assess binding efficiencies of the liposome to its targets as well as therapeutic efficiency. Due to its phospholipid bilayer and biochemical interactions with water that hold its structure together, this liposome will be delivered intravenously to the patient suspended in an aqueous or hydrophilic solution. Hydrophilic drugs (ONC201, ABT263, and Cbl) will be located in the interior, while antibodies for pancreatic adenocarcinoma-specific antigens (CA 19-9, MUC-1, and NT5E) will be dispersed among the exterior.

Apoptosis is a crucial cellular function that can become misregulated in cancers, along with cell growth and proliferation. It can be activated in multiple ways throughout the cell, but is mainly characterized by two pathways: intrinsic and extrinsic. The intrinsic pathway is activated in response to cellular stress, which then affects the mitochondria either by swelling through pores or increasing permeability of the membranes (Kroemer et al. 2007). Second mitochondria-derived activator of caspases (SMAC) proteins are then released into the cytoplasm, which deactivate inhibitor of apoptosis proteins (IAPs), allowing the caspases involved in apoptosis to become active (Fesik and Shi, 2001). The extrinsic pathway of apoptosis is activated in response to external signals, which bind to receptors of the tumor necrosis factor (TNF) families. The binding of these ligands to their receptors can activate caspases and indirectly activate transcription factors involved in the inflammatory response and cell death (Adler 2007).

It is crucial for the selected antibodies on the liposome to work in conjunction with each other to bind to only pancreatic adenocarcinoma tumor cells. Although their respective antigens are overexpressed in tumors, they may be still present in lower concentrations in healthy cells. Therefore, the liposome would be best engineered for the antibodies to only bind to antigens when the displayed antigens are present in high enough concentrations. This threshold could be determined through titration experiments until the effective concentrations of antigens are achieved. The use of liposomal therapy also appeals to the researchers due to its adaptability and lower toxicity. In a study involving paclitaxel, the liposomal form induced fewer cardiovascular and hematologic complications than the standard form (Huang et al. 2018). Encapsulation efficiency has also been measured by injection of a doxorubicin liposomal solution into liquid chromatography (Yamamoto et al. 2018). The researchers would like to use this method to further assess liposomal drug delivery.

The methods section of a scientific article allows researchers to determine the validity of a study based off of replicability. When developing an experiment, certain factors that may affect the replicability of a study should be controlled in an effort to minimize discrepancies between iterations. The methods project attempts to practice and develop these skills, as well as distinguish between observation and inference through the examination and replication of a multi-panel figure illustrating an interspecific interaction.

    The interspecific interaction between mallard ducks (Anas platyrhynchos) and canada geese (Branta canadensis) will be examined in this project. At UMass, mallard ducks and canada geese are commonly found around or near the campus pond during the winter months. As a result, both species often interact with each other in multiple ways. The most commonly observed interaction between these two species is the sharing of space on the campus pond. These two species are easily photographable together since they are typically not shy, in the same general region, and quite prevalent. Therefore, images of them in this environment would be feasibly replicable.

Elements of this process to take into account for replicability include photography, location, weather, time, and levels of specificity. The location of the ducks and geese are on the campus pond, which is in the center of campus, making it easy to find. Due to its vast size and the mobility of these two organisms, a camera with zooming capabilities should be chosen to document their interaction as well as the organisms individually. The ducks and geese are typically observed near the end of the campus pond closest to the Fine Arts Center, either swimming or along the shore. It may take a while for the ducks and geese to trust a human enough to get close for pictures. If it is raining or snowing outside, the ducks and geese are away from the campus pond, so photography should be performed on a day with fairer weather. Pictures of the geese, ducks, and their interaction should be made as broadly as possible to maximize the chances of successful replication. Out of these three images, the interaction especially should not be particular about exact location on the campus pond due to the mobility of these organisms and the size of their environment.

An estimated 10-15% of pancreatic adenocarcinomas are attributed to genetic causes (Klein 2012). Germline mutations in the BRCA1 and BRCA2 genes are the most common, occurring in 13-19% of families (Lal et al. 2000). The PALB2 and ATM genes are also some that are commonly mutated in hereditary pancreatic adenocarcinomas (Jones et al. 2009). These mutations could be further examined in an effort to detect pancreatic adenocarcinoma earlier in those that are at higher risk. An early screening mechanism of detecting pancreatic adenocarcinoma in patients, regardless of family history, would be significantly beneficial in increasing survivability.

In terms of resistance to the developed ONC201 liposome treatment, a fluorinated-ONC201 analogue, ONC212, has been developed and has shown preclinical efficacy in melanomas and hepatocellular models. A study demonstrated ONC212’s efficacy in in vivo models with ONC201-resistant tumors (Lev et al. 2017). The researchers found an effective combination of ONC212 with the inhibitor AG1024 in vivo for pancreatic adenocarcinoma. ONC212 is effective in pancreatic adenocarcinomas alone and in combination with other drugs such as 5-fluorouracil, irinotecan, oxaliplatin, and RTK inhibitor crizotinib (Lev et al. 2017). This may serve as a backup treatment if resistance to ONC201 develops, and another synergistic combination may be developed from these drugs.