Papers by Nicholas Rodriguez

Frontiers in aging neuroscience, Mar 8, 2024
The differential expression of emotional reactivity from early to late adulthood may involve matu... more The differential expression of emotional reactivity from early to late adulthood may involve maturation of prefrontal cortical responses to negative valence stimuli. In mice, age-related changes in affective behaviors have been reported, but the functional neural circuitry warrants further investigation. We assessed age variations in affective behaviors and functional connectivity in male and female C57BL6/J mice. Mice aged 10, 30 and 60 weeks (wo) were tested over 8 weeks for open field activity, sucrose preference, social interactions, fear conditioning, and functional neuroimaging. Prefrontal cortical and hippocampal tissues were excised for metabolomics. Results: Our results indicate that young and old mice differ significantly in affective behavioral, functional connectome and prefrontal corticalhippocampal metabolome. Young mice show a greater responsivity to novel environmental and social stimuli compared to older mice. Conversely, late middle-aged mice (60wo group) display variable patterns of fear conditioning and during re-testing in a modified context. Functional connectivity between a temporal cortical/auditory cortex network and subregions of the anterior cingulate cortex and ventral hippocampus, and a greater network modularity and assortative mixing of nodes was stronger in young versus older adult mice. Metabolome analyses identified differences in several essential amino acids between 10wo mice and the other age groups. Discussion: The results support differential expression of 'emotionality' across distinct stages of the mouse lifespan involving greater prefrontal-hippocampal connectivity and neurochemistry.

Differences in affective behavioral expression from early to late adulthood is thought to involve... more Differences in affective behavioral expression from early to late adulthood is thought to involve changes in frontal cortical responsiveness to negative valence stimuli. In mice, similar maturational changes in affective behaviors have also been reported but the functional neural circuitry remains unclear. In the present study we investigated age variations in affective behaviors and functional connectivity in male and female C57BL6/J mice. Mice aged 10, 30 and 60 weeks (wo) were tested over 8 weeks for open field activity, sucrose reward preference, social interactions and fear conditioning and functional neuroimaging. Frontal cortical and hippocampal tissues were excised for metabolomics analysis. Our results indicate that young 10wo mice display greater levels of anxiety-like locomotor behavior and develop robust fear conditioning compared to older adult and late middle-aged mice (30-60wo). This was accompanied by greater functional connectivity between a temporal cortical/audito...
Large-Volume, High-Viscosity Additive Manufacturing Through Vat Photopolymerization: Printing High-Viscosity and Low-Reactivity Silicones
OSTI OAI (U.S. Department of Energy Office of Scientific and Technical Information), Jun 14, 2022
Aging of UV curable PDMS developed for large-scale, high viscosity stereolithography
Polymer Degradation and Stability

Latent Variable Representations for Interactive Structural Design Exploration
Volume 3A: 48th Design Automation Conference (DAC)
Additive manufacturing and topology optimization are complementary technologies that enable unpre... more Additive manufacturing and topology optimization are complementary technologies that enable unprecedented levels of design freedom for realizing complex structures. This increasing design freedom is accompanied by increasing complexity, such that it can become difficult for either computational algorithms or human designers alone to search these expansive design spaces effectively. Our previous work laid the foundation for an interactive design framework that enables human designers to use their expertise and intuition to guide computational algorithms quickly towards promising solutions. The framework established a latent representation of a library of designs by combining classical topology optimization techniques with a conditional generative adversarial network (cGAN). Our goal is to expand on this framework by creating interactive functionalities that allow users to more efficiently visualize and search an expansive structural design space by manipulating its latent variable re...

Development of a variable tensioning system to reduce separation force in large scale stereolithography
Additive Manufacturing
Abstract Projection micro stereolithography (PµSL) is an additive manufacturing tool that offers ... more Abstract Projection micro stereolithography (PµSL) is an additive manufacturing tool that offers multiple advantages, including unparalleled resolution and throughput, but the ability to print high viscosity resin for large-scale parts is limited. One of the key challenges in PµSL is to separate a newly polymerized layer from the vat floor without damaging the part. Since the separation force scales with the printing area, the risk of damaging the part increases significantly with larger-scale systems and must be addressed. In this paper, a novel roll-to-roll, variable tensioning system is proposed to reduce the separation force during printing. A mathematical model is proposed to predict the separation force for different 2D geometries, and a set of experiments is conducted on an experimental prototype to validate the model. The effects of different separation parameters including peel rate and peel angle are discussed in detail. The results show that the proposed tensioning system reduces the separation force significantly.
Discovering Content through Text Mining for a Synthetic Biology Knowledge System
ACS Synthetic Biology

Effects of data and entity ablation on multitask learning models for biomedical entity recognition
Journal of Biomedical Informatics
MOTIVATION Training domain-specific named entity recognition (NER) models requires high quality h... more MOTIVATION Training domain-specific named entity recognition (NER) models requires high quality hand curated gold standard datasets which are time-consuming and expensive to create. Furthermore, the storage and memory required to deploy NLP models can be prohibitive when the number of tasks is large. In this work, we explore utilizing multi-task learning to reduce the amount of training data needed to train new domain-specific models. We evaluate our system across 22 distinct biomedical NER datasets and evaluate the extent to which transfer learning helps task performance using two forms of ablation. RESULTS We found that multitasking models generally do not improve performance, but in many cases perform on par compared to single-task models. However, we show that in some cases, new unseen tasks can be trained as a single model using less data by starting with weights from a multitask model and improve performance. AVAILABILITY The software underlying this article are available in: https://github.com/NLPatVCU/multitasking_bert-1 CONTACT: btmcinnes@vcu.edu.
Use of wire grid polarizers with liquid crystal display for large-volume stereolithography
Additive Manufacturing, 2022

Translational Psychiatry, 2021
Post-traumatic stress disorder (PTSD) leads to impairments in both cognitive and affective functi... more Post-traumatic stress disorder (PTSD) leads to impairments in both cognitive and affective functioning. Animal work suggests that chronic stress reduces dopamine tone, and both animal and human studies argue that changes in dopamine tone influence working memory, a core executive function. These findings give rise to the hypothesis that increasing cortical dopamine tone in individuals with greater PTSD symptomatology should improve working memory performance. In this pharmacological functional magnetic resonance imaging (fMRI) study, 30 US military veterans exhibiting a range of PTSD severity completed an emotional working memory task. Each subject received both placebo and the catechol-O-methyl transferase inhibitor tolcapone, which increases cortical dopamine tone, in randomized, double-blind, counterbalanced fashion. Mnemonic discriminability (calculated with d′, an index of the detectability of working memory signals) and response bias were evaluated in the context of task-relat...

New filament deposition technique for high strength ductile 3D printed parts
Amputees across the world are often left with inadequate solutions to their needs due to a lack o... more Amputees across the world are often left with inadequate solutions to their needs due to a lack of financial resources or access to proper infrastructure and expertise. Current methods of lower limb prosthetic socket fitting and fabrication are too expensive, labor intensive, and dependent on highly skilled technicians, and thus are not suitable to properly serve patients in rural, impoverished areas, particularly in developing countries. Additive manufacturing techniques, and in particular Fused Deposition Modeling (FDM), have already been widely utilized to fabricate products designed specifically for an individual customer and therefore, they show promise in use for manufacturing customizable prosthetic sockets. Current additive manufacturing methods are either too expensive for use in developing countries or result in parts that are not fit to bear the load of a patient, and thus, their use in socket manufacturing for developing countries has been limited. The goal of this research is to develop a technique that enables an off-the-shelf FDM printer with minimal modifications to manufacture durable, reliable, and inexpensive prosthetic sockets. This is accomplished through the development of a new deposition technique to increase the strength and ductility of FDM printed parts without changing their geometry or significantly increasing their expense to print. This novel technique has been simulated through a Finite Element Model and subjected to mechanical testing to validate its proposed enhancements to a printed part’s material properties and its feasibility for use in manufacturing prosthetic sockets.Mechanical Engineerin

Polymers, 2021
Recent advances in additive manufacturing, specifically direct ink writing (DIW) and ink-jetting,... more Recent advances in additive manufacturing, specifically direct ink writing (DIW) and ink-jetting, have enabled the production of elastomeric silicone parts with deterministic control over the structure, shape, and mechanical properties. These new technologies offer rapid prototyping advantages and find applications in various fields, including biomedical devices, prosthetics, metamaterials, and soft robotics. Stereolithography (SLA) is a complementary approach with the ability to print with finer features and potentially higher throughput. However, all high-performance silicone elastomers are composites of polysiloxane networks reinforced with particulate filler, and consequently, silicone resins tend to have high viscosities (gel- or paste-like), which complicates or completely inhibits the layer-by-layer recoating process central to most SLA technologies. Herein, the design and build of a digital light projection SLA printer suitable for handling high-viscosity resins is demonstra...

Synthetic Biology Knowledge System
ACS Synthetic Biology, 2021
The Synthetic Biology Knowledge System (SBKS) is an instance of the SynBioHub repository that inc... more The Synthetic Biology Knowledge System (SBKS) is an instance of the SynBioHub repository that includes text and data information that has been mined from papers published in ACS Synthetic Biology. This paper describes the SBKS curation framework that is being developed to construct the knowledge stored in this repository. The text mining pipeline performs automatic annotation of the articles using natural language processing techniques to identify salient content such as key terms, relationships between terms, and main topics. The data mining pipeline performs automatic annotation of the sequences extracted from the supplemental documents with the genetic parts used in them. Together these two pipelines link genetic parts to papers describing the context in which they are used. Ultimately, SBKS will reduce the time necessary for synthetic biologists to find the information necessary to complete their designs.

Isolation design considerations for power supply of medium voltage silicon carbide gate drivers
2017 IEEE Energy Conversion Congress and Exposition (ECCE), 2017
Single switch capable of blocking 10 kV and higher voltages are presently being developed and dem... more Single switch capable of blocking 10 kV and higher voltages are presently being developed and demand improved gate drivers for their functioning. Induction based gate drivers have been the foremost solutions in this regard. Design challenges that have been outlined for these drivers are low coupling capacitance, strong magnetic coupling and smaller dimensions with isolation not considered in depth. In this paper, first isolation requirements and its physical realization guidelines are provided from IEC 61800-5-1 for electric drives application. Based on study, two system insulation designs: single and double PCB are derived for lower MV and higher MV system respectively. Current loop gate driver with double PCB design is found to be practical and economical solution for higher MV power electronics systems. Afterwards, shortcomings of three state of art induction solutions at both system and magnetic link level is discussed. Improved transformers with primary MV cable providing mandatory solid insulation are fabricated. It is shown through impedance measurements that the cable has negative effect on the magnetizing inductance and coupling capacitance compared to state of art transformer solution. At the end, both set of transformers are tested with 64 kV impulse and 32 kV overvoltage with only improved transformers showing positive results.
Materials & Design, 2021
A feedstock compatible with direct ink write and projection microstereolithography is developed t... more A feedstock compatible with direct ink write and projection microstereolithography is developed to produce nanoporous ceramics with 250-500 μm features. • Pore sizes ranging from 0.10-500 μm are achieved through the introduction of designed structural porosity and partial sintering. • Printing by both techniques is enabled by modifying solids loading in the range from 55 to 70 wt% to tailor feedstock viscosity.

Journal of the American Academy of Child & Adolescent Psychiatry, 2020
Dermal fibroblasts (dFBs) are an essential component of skin; they not only produce and organize ... more Dermal fibroblasts (dFBs) are an essential component of skin; they not only produce and organize the extracellular matrix of the dermis, but also are essential for wound healing, hair growth, fibrosis and defense against infection. Fibroblast heterogeneity has long been recognized in mouse and human skin, but the cellular hierarchy and mechanisms governing fibroblast heterogeneity are incompletely understood. Here, we used single-cell RNAsequencing to study how cellular heterogeneity of murine skin is turned at the transcriptional level during post-natal periods using single cells isolated from the skin of new born (P1), young (3 weeks) and adult (2 month) mice. Unbiased clustering of >10,000 single-cell transcriptomes revealed 29 distinct population of the skin. Within these clusters, Pdgfra clearly marked 13 dFB clusters, which were then re-clustered into 23 dFB clusters. Pseudotime analyses of these dFB clusters identified a Pdgfra + CD24 hi Thy1 lo Sca1 lo progenitor population that was highly abundant in neonatal skin early in life but declined in adulthood. Pseudotime analyses revealed that this progenitor population gave rise to several FB subtypes, including dermal papillary FBs, reticular FBs that produce high levels of type1 collagen, adipocytes that produce antimicrobial peptide Camp as well as the interstitial reticular FB that are enriched with inflammatory gene signature during post-natal development. The ability of this progenitor population to commit to collagen 1 producing reticular dFB and to differentiate into adipocytes was confirmed by primary dFB culture in vitro. Together, our study allows the reconstruction of gene expression programs during fibroblast development and provides insights into how fibroblasts develop heterogeneity from progenitors during adulthood.
10.11 Relations Between Inflammation and Reward-Seeking Behaviors in Youth with Depression and Obesity
Journal of the American Academy of Child & Adolescent Psychiatry, 2020

Biological Psychiatry, 2020
Results: Extraversion scores were used to predict changes in SUI scores, after controlling for ca... more Results: Extraversion scores were used to predict changes in SUI scores, after controlling for caffeine group and changes in PAI Depression. Although all SUI scores remained within normal limits, Extraversion was significantly associated with increased suicidal ideation following TSD, b¼.463, partial r ¼.512, p¼.013. The association was only present for those receiving placebo (r¼.602, p¼.03), but not caffeine. Conclusions: Higher trait Extraversion was associated with reduced resilience to suicidal ideation during TSD, particularly among those who did not receive repeated doses of caffeine each night. Although scores were within normal limits, findings point to a potential trait-like vulnerability factor for negative or catastrophic thinking that may further our understanding of the phenomenology of suicide. Caffeine may be protective against these effects.

Biophysical Journal, 2020
pre-diabetic cardiomyopathy (pre-DC). Cytosolic Ca measurements were performed in ventricular myo... more pre-diabetic cardiomyopathy (pre-DC). Cytosolic Ca measurements were performed in ventricular myocytes derived from mice affected by CPVT (CASQ2 Knockout or Cnull) or pre-DC (chronic fructose diet, FDT). The effects of pharmacological modulators of mitochondrial Ca (mCa) on arrhythmogenic Ca waves were examined. Kaempferol, an activator of the mitochondrial Ca uniporter (MCU) complex, abolished Ca waves in Cnull cells but exacerbated Ca waves in FDT cells. Moreover, the MCU inhibitor Ru360 increased Ca wave frequency in Cnull cells but inhibited Ca waves in FDT cells. Cyclosporine A (CsA), an inhibitor of mitochondrial permeability transition pore, increased Ca wave frequency in Cnull cells but failed to do so in FDT cells. CGP37157, a mitochondrial Na-Ca exchanger inhibitor, increased Ca wave frequency in both Cnull and FDT cells. MCa content was increased in Cnull vs WT cells, as measured by examining the FCCP induced increase in diastolic Ca after blocking SR Ca uptake and sarcolemmal Ca fluxes. Additionally, increased mitochondrial ROS generation was detected in Cnull cells treated with CsA or CGP37157. Moreover, CaMKII inhibition by KN93 reversed the exacerbation of Ca waves by kaempferol or CsA in FDT or Cnull cells, respectively. Collectively, our results suggest that mitochondria differentially influence myocyte Ca handling, acting either as a source of ROS or a Ca buffer, in different cardiac disease settings.
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Papers by Nicholas Rodriguez