The goal of this project is to develop a dynamically evolving connectionist model that more closely resembles the brain through its information-processing. Over the years, AI has shifted from the first generation of feedforward systems to the use of recurrent or convolutional Neural Networks. The third and newest generation of AI models, the brain-based models, and the Spiking Neural Network (SNN), attempts to bridge the gap between Neuroscience and ML using biologically realistic models like Θ-model, LIF, Izhikevich, HR, HH. These models, however, are still a black box leaving very little control or understanding on the learning process within the system without the access to the inner structure of the network. In addition, these systems are highly inefficient, slow, and very complex due to the limitations imposed by the hardware and explicit simulation of partial differential equations. Real world problems require “flexible learning and dynamically adaptive connectionist systems” that are capable to adapt and accommodate new input in real time. Current solutions have focused on varying the weights within a system rather than focusing on how connections within the system are formed. Based on our understanding from organismal brain structures, our approach, called biomimetic information codec, .bic, is a morphologically-adaptive coding hierarchical network that form in accordance with energy minimization - driven by dissipation of "heat" generated by the training data - constructing cortices and connectome for processing of information. My first objective herein is to quantitatively compare detailed structures between biological (fly brain) and .bic. networks using a random matrix approach.

Midfacial hypoplasia (MFH) is a disorder characterized by underdevelopment of the upper jaw, nose, and cheek bones which can impede feeding and breathing. The causes of MFH are not yet fully understood, but a novel pig model suggests that the posterior nasal septal cartilage is ossified, or converted to bone, prematurely in pigs with MFH. Thus, we predict that there is an increase in the amount of ossified septum in pigs with MFH. To test the hypothesis that pigs with MFH have increased septal ossification, we measured the area of the entire septum and the fraction occupied by bone on CT scans taken from 20 pigs with MFH and 10 normal pigs ages 3-10 months using ImageJ. All measurements were standardized for size by dividing by skull length. We compared MFH and normal pigs with t-tests using excel. As predicted, the fraction of ossified septum was greater in MFH pigs (0.39 ± 0.08) than normal pigs (0.25 ± 0.06, p<0.0001). The nasal septal cartilage is thought to be the primary driver of facial growth. A decrease in septal cartilage due to increased ossification may hamper normal growth and lead to MFH. Premature ossification of the nasal septal cartilage may also be a cause of MFH in humans and this finding could be used to develop better treatments for this disorder.

Periodontal disease stands to be the leading cause of tooth loss in older adults and is characterized by inflammation of tissues supporting the teeth and periodontal bone loss. This oral disease also occurs during normative aging in mice models. Thus, targeting the biological aging process may provide an innovative approach to reduce the impact of this disease in the elderly population. Rapamycin is a specific mTOR inhibitor shown to delay age-related decline and significantly extend the lifespan of mice models. Our lab has demonstrated that an 8 week treatment with rapamycin in aged animals reversed age-related periodontal disease. However, whether this improvement persists even after the treatment ends is still unknown. To determine whether reversal of periodontal disease persists even after stopping rapamycin treatment, cohorts of aged mice were either started with 8 week treatment with control (eudragit) food or rapamycin (42ppm) food, and then switched to either rapamycin (42ppm) food or control (eudragit) food for another 8 weeks, respectively. High resolution microCT imaging was completed to measure the amount of periodontal bone, and western blot was performed on total alveolar bone extracts and probed for the osteoclast marker RANKL. Our microCT analysis showed there was less periodontal bone loss in aged mice treated with rapamycin, and this result persisted even after 8 weeks on the control diet. Additionally, the age-related increase in RANKL expression was decreased in both treatment groups. In conclusion, the regain of lost periodontal bone in aged mice persisted even after cessation of rapamycin treatment, and the age-related increase in the osteoclast marker RANKL was decreased after rapamycin treatment and such decrease persisted. Overall, our studies indicate that short term treatment with rapamycin is sufficient to rejuvenate oral health and the benefits are maintained even after stopping the treatment.

The purpose of this project is to determine if there are compensatory changes to the height and width of the skull as a result of midfacial hypoplasia (MFH) in pigs. Secondarily, this research aims to determine if the ability to respirate may be impacted because of changes in the anatomy of the airway. MFH is a malformation of the face in which the upper jaw, cheekbones, and eye sockets grow less than the rest of the face, often resulting in a “bug-eyed” appearance and/or an “underbite”. In severe cases, MFH can cause dental crowding and airway obstruction. By gaining a better understanding of the causes and consequences of midfacial hypoplasia, there can be better progress in the prevention and treatment of this sometimes life-threatening malformation. Methods: This project utilized 158 skulls, including 132 dry skulls which were hand measured using a metric ruler, and the remaining 26 skulls are in CT scan format. These skulls are being measured using the program AVIZO. Out of the 158 skulls, 68 have MFH. Each pig skull provides a series of 6 measurements. To determine if there are changes to the height and width of the skull, I measured the snout height and width, and calvarial height and width. To determine if the airway is affected, I measured the choanal height and width. Using the measurements from the total of 158 skulls, I plan to compare normal pigs to pigs with MFH by using t-tests and by correlating the measurements based on the severity of MFH using Excel. The results from this project will render insight to the causes and consequences of this malformation.

Dental implantation is a common clinical procedure used to replace missing teeth and maintain bone structure and facial aesthetics. However, it leads to unexpected side effects, including bone loss or peri-implantitis in 1 out of 10 cases due to failure of osseointegration, defined as improper integration of the implant into the mineralized bone. To enhance osseointegration, the present study aimed to form a layer of hydroxyapatite that could facilitate the integration of the implant (Titanium or Zirconia) with the alveolar bone that lead, while also having antimicrobial property to prevent local infection. Our previous study demonstrated that titanium-binding peptides (TiBPs) are able to bind specifically to the surface of Ti and that amelogenin-derived peptide (ADPs) can be used for direct remineralization on the bone surface. We also identified antimicrobial peptides (AMPs) that can inhibit common oral bacterial growth. These results imply that there is an opportunity to design two of heterofunctional peptides, both binding to Ti with one has the function of directing biomimetic remineralization process, while the other providing antimicrobial activity. The Ti-surface is modified by chimerizing the TiBPs and the ADPs, and TiBPs and AMPs, with short amino acid sequences. The overall process is separated into two main steps: 1. Designing and synthesizing the chimeric peptide; 2. Characterizing (a) binding, (b) mineralization and (c) antimicrobial efficacy of chimeric peptides on the implant surface. We predict that the chimeric peptides will have high binding affinity to the titanium surface while simultaneously enabling mineralization on the implant surface and inhibiting the growth of bacteria. The present aims to contribute to the foundation of finding a long-term novel dental implant treatment via the molecular biomimetic approach towards a clinical strategy to enhance the long-term durability of dental implants. The research is supported by Mary Gates Scholarship (YL), Spencer Funds from School of Dentistry, and CoMotion.