Abstracts for 12th Annual Postdoc Research Exhibition

Abstracts for Postdocs Poster Session

First Session: #1 - #18; Second Session: #19 - #36
 

1. MULTIPLE MODES OF TRANSCRIPTIONAL REGULATION IN S. CEREVISIAE BY THE SAGA COMPLEX

Dr. Chitvan Mittal; BMB; Faculty PI: Dr. B. Franklin Pugh

Multi-subunit complexes offer several avenues to regulate transcription. Spt-Ada-Gcn5-Acetyltransferase (SAGA) complex in yeast is a 2 MDa complex that harbors functionally distinct modules. Each of these modules interacts with distinct machineries to regulate various aspects of transcription. SAGA is a stress responsive co-activator, which rapidly binds to chromatin to activate genes that alleviate the stress response. Another such complex, TFIID, works in a more housekeeping fashion. Together, TFIID and SAGA regulate a variety of aspects of transcription. The order of events and the mechanism by which these complexes regulate transcription, particularly on a genomic scale remains uncertain. To better define these events in a comprehensive manner, we utilized a combination of knockout and conditional depletion approaches to dissect the contribution of SAGA and TFIID components to PIC assembly and polymerase enrichment. Our high resolution ChIP-exo data reveals preferential binding of SAGA at the previously characterized SAGA-dominated genes, particularly upon heat shock, along with rapid dissociation from the ribosomal protein genes (RPGs). We find that SAGA makes a predominant contribution to PIC assembly at only a subset of genes, and cannot be fully compensated by TFIID. In contrast, there is a widespread dependence of PIC assembly on TFIID. This is consistent with early studies defining separate but overlapping roles of SAGA and TFIID. Overall, our results suggest that SAGA is a key player in maintaining transcriptionally active state of chromatin, and this is achieved in multiple ways. We discuss distinct modes of gene regulation by SAGA, both under rich growth and environmental stress conditions.

2. Personalized Blood Glucose Management in Intensive Care Units to Reduce Morbidity and Mortality

Dr. Rammah Abohtyra; BME and nerve scienceFaculty PI: Prof. Bruce Gluckman

There are approximately 4 million people in the US enter the Intensive Care Units (ICUs) per year, with an average rate of 500,000 deaths each year. Blood glucose management (with 80-110 mg/dl as target range) remains one of the most challenging aspects in the Intensive Care Unit (ICU), and associated with adverse outcomes including hypoglycemia (low blood sugar < 80 mg/dl) and hyperglycemia (high blood sugar > 110 mg/dl), independently associated with a greater risk of death. Indeed, recent evidence suggests maintain an adequate blood glucose level is difficult to safely and effectively achieve for all patients. However, personalizing blood glucose management (predict and control) for ICU patients is an essential element of maintaining an adequate blood glucose level to improve patient's outcomes and save patient's life. Our objective is to: understand the patient's glucose dynamics under certain circumstances, build a patient-specific model, and then develop a personalized control scheme to predict, correct, and control the blood glucose response of each patient. The ICU patient's blood glucose dynamics is described by a complex and non-linear model, whose dynamics is based on different fundamental mechanisms of metabolic systems. The underlying mechanism is built based on multi-compartment models with specific components (e.g., liver, blood plasma, pancreas, muscle/adipose tissues, brain, and sets of biochemical reactions) representing the relevant physiological behaviors. These models will be incorporated with data assimilation, a technique borrowed from physics and engineering, to generate real-time, personalized, adaptable glucose forecasts.We developed a novel approach to predict the blood glucose behavior of ICU patients. This approach is developed based on patient-specific characteristics, and the physiological components of the model. We test our approach across several blood glucose systems.

Theoretical results and simulations show that our approach can predict the dynamics of blood glucose of an individual ICU patient, and can potentially be used in a model-based control framework to design new therapeutic approaches for regulating the blood glucose level of the ICU patients.

3. Enzymatic Dissection of Maize Cell Wall Structure

     Qian Zhang; Department of biology; Faculty PI: Prof. Daniel Cosgrove

Primary cell walls of grasses differ from those of dicots in various ways: glucuronoarabinoxylans (GAXs) dominate the matrix and are crosslinked through ferulate side chains; pectins and xyloglucans are reduced in amount; and mixed linkage β-glucans are transiently present. To understand the nanoscale structure of grass cell walls, we are studying the outer epidermal wall of maize (Zea mays L.) coleoptiles. Our approach: digest the wall with specific treatments and analyze with carbohydrate binding module (CBM)-labeling, atomic force microscopy (AFM), and field emission scanning electron microscopy (FESEM). Our goal is to uncover the spatial locations and interactions between different polysaccharides and their roles in wall structure, mechanics and growth.

4. Integrated annotations and analyses of small RNA-producing loci from 48 diverse plant genomes

Dr. Alice Lunardon; Plant Biology; Faculty PI: Prof. Michael J Axtell    

Sequencing of plant endogenous small RNAs (sRNAs) has produced so far a very large amount of data. microRNA annotations derived from sRNA-seq experiments are stored in miRBase but we still lack a database for storing short interfering sRNA (siRNA) annotations, making it impossible to easily use the current published information as a resource for further studies. We created the first integrated database where a large dataset of sRNA-seq data from 48 model and crop species is analyzed consistently to produce comprehensive and comparable sets of annotations of sRNA loci. We used 1,333 sRNA-seq libraries and we annotated >2.7 million high-confidence sRNA loci: MIRNA and siRNA loci. Describing where siRNAs originate in the genome is fundamental to understand their functions. We observed that loci expressing predominantly 24 nucleotides (nt) siRNAs are the dominant type of locus in all flowering plants and are enriched upstream of protein-coding genes but are also found in large numbers inside genes in introns. Interestingly, genes targeted by 24nt siRNAs are enriched in cytochromes P450, disease resistance genes, xenobiotic transmembrane transporters and other genes involved in the response to environmental stresses. Loci expressing 21nt siRNAs are also quite common and are strongly enriched in the gene body regions, particularly in exons. Although rarer than in dicots, we described all the genes producing 21nt siRNAs in monocots, revealing conserved and species-specific cases. All annotations are freely available at plantsmallrnagenes.science.psu.edu, a web-server that we created for the scientific community to store, visualize and analyze sRNA data.

5. Characterization of dairy and vegan proteins through ion protein interactions

Dr. Ehsan Mahdinia; Food Science; Faculty PI: Federico M. Harte

There is a growing demand these days for high protein drinks and shakes obtained from dairy or vegan protein isolates As the food industry seeks protein isolates for improved functionality, the thorough understanding of the physicochemical properties of such proteins becomes critical to enhance stability and the protein content of such super nutrient drinks Our results show that ionic environments using food certified salts help unlock the functionality of plant protein and dairy casein structures by understanding the physicochemical stimuli leading to protein dissociation, and determining the functionality of monomeric forms alone or in combination with polysaccharides and ion protein interactions

6. Plasticity and constraints on human stature: A 9,000 year perspective from ancient DNA and skeletal data

Dr. Stephanie Marciniak; Anthropology; Faculty PI: Dr. George H. Perry

The origin and spread of farming in Europe 9,000 years ago led to the emergence of complex urban societies, population increases, and exposure to new diseases. Fascinatingly, despite the positive impacts of agriculture, bioarchaeological analyses of human skeletal remains during this period suggest that early farmers may have experienced relatively poorer health than individuals practicing foraging subsistence strategies. Here, we combine: i) the analysis of DNA from 65 ancient European individuals to characterize the genetic contribution to phenotypic height for each, with ii) an estimate of their actual height based on the skeletal measurements. Genetic variation and environmental forces simultaneously impact the observed variation in human height. One of the most important factors impacting the growth trajectory includes perturbations due to nutritional deficiency or disease experienced in childhood, which can result in shorter than expected adult height, and also manifest skeletally on teeth and bones. Since modern genomic data have been used to identify millions of genetic variants affecting height, we compared the predicted (genetic) height contributions and observed (skeletal) height for each prehistoric individual alongside skeletal indicators of childhood stress before, during and after the agricultural transition. Our integrated approach highlights how gene-environment interactions impacted individual growth outcomes in prehistory.

7. Understanding failure of high-performance concrete with semantic deep-learning

Dr. Anna Madra; Civil and Environmental Engineering; Faculty PI: Dr. Michael Hillman

Predicting the failure of complex materials such as high-performance concrete is not an easy task. The damage mechanism strongly depends on the microstructure of the material, which is heterogeneous, and thus difficult to model numerically. On the other hand, the experimental study of damage geometry, e.g., retrieved from X-ray microtomographic scans, is also not trivial; damage geometry is compound and complex, defying simple methods of classification. To make damage characterization possible, we propose a two-step approach. Firstly, we divide damage geometry into primitives and their clusters. These are measured with geometric descriptors that have a clear physical interpretation. The geometric descriptors of primitives and clusters are then used to train a Convolutional Neural Network (CNN) to classify damage morphology. The descriptors with high coefficients in the CNN are then deemed as playing a crucial role in the damage mechanism, and thus can serve to validate numerical models, especially meshfree models of material fracture.

      8. Time-of-Flight Secondary Ion Mass Spectrometry (ToF-SIMS) : Biological Applications

Dr. Sebastiaan Van Nuffel; Materials Research Institute              

Time-of-Flight Secondary Ion Mass Spectrometry (ToF-SIMS) is a powerful imaging mass spectrometry technique that allows for three-dimensional chemical imaging by combining molecular ion imaging and depth profiling, which offers a novel, label-free way to investigate biological samples such as tissue sections and even single cells. A lateral resolution down to 200 nm can be achieved by using a bismuth liquid metal ion gun as an analysis beam and a depth resolution down to 10 nm can be achieved by using an argon gas cluster ion beam for sputtering. Its strength as an imaging technique is that it provides full molecular information, i.e. different mass fragments will be observed for different chemistries. ToF-SIMS can detect elements as well as inorganic and organic molecules with a mass smaller than 2000 Da. The types of biomolecules that can be observed are nucleobases, amino acids, sugars, metabolites and intact lipids. It is also possible to detect non-native compounds such as drugs and toxins. The ability of imaging mass spectrometry to investigate the localization of specific native and non-native compounds in single cells and tissue sections in a label-free manner creates exciting, new avenues for biological, medical and pharmaceutical research. There is a clear potential for this technique in various fields of research, in particular lipid metabolism and signaling.

9. Flow and Scour around Porous Hydraulic Structures

Dr. Hassan Ismail; Civil and Environmental Engineering; Faculty PI: Dr. Xiaofeng Liu

River restoration structures built from accumulations of wood alter flow conditions in rivers. As do their natural counterparts, engineered restoration structures provide a range of ecological services including providing fish habitat and promoting biological productivity as well physical services such as land-building, bank stabilization, and flood mitigation. In the design of these complex, porous structures, engineers predict scour-hole depths using equations developed for nonporous bridge piers. Through laboratory testing, it was found that those equations fail to match measured scour depths since they do not account for the altered flow conditions due to the structures’ porosity. From the measured turbulence intensities, velocities, and bed elevations, conceptual models were developed comparing flow and scour near porous versus nonporous structures, and a proposed equation was developed that accounts for the structure’s porosity.

10. Is special education service receipt a risk factor for socioemotional maladjustment in middle school?

Dr. Adrienne Woods; Education Policy Studies; Faculty PI: Dr. Paul L. Morgan

Although effects of varying program dosage and timing are commonly tested in social program evaluation, such estimates have been essentially absent from studies of how receipt of special education services is related to students’ social-emotional adjustment. We used nationally representative data (N = 5,865) to estimate predicted effects of K-8th grade special education dosage and timing on students’ self-reported social-emotional adjustment. Prior studies have typically compared students with disabilities (SWD) to students without disabilities. This has likely produced upwardly biased estimates of negative effects of special education on social-emotional adjustment. We found that comparing SWD to other SWD (n = 1,132) yielded smaller, largely null estimates of special education’s predicted effects on social-emotional adjustment. These findings suggest that special education services may not be as detrimental to social-emotional adjustment as previously suggested.

11. Superresolution Second Harmonic Generation Microcsopy

Dr. Bin Dong; Department of Chemical Engineering; Faculty PI: Dr. Seong H Kim

Second harmonic generation (SHG) microscopy as one of the typical nonlinear optical microscope, was well known as it's advantages in detecting non-labeled systems, such as twon dimensional materials, quantum dots and highly organized tissues like collagen and cornea. However, the resolution of nonlinear microscopies are mostly above the optical diffraction limit (200nm), here, we modified the source of the light, used an axicon to modulate the Gaussian beam in to the Bessel beam, and successfully improve the resolution of SHG up to about 80 nm on the sample of G shape gold pattern.

     12. The moderating role of socioeconomic status on relations between level of responsibility and cortical thinning during adolescence

Dr. Giorgia Picci; Human Development and Family Studies; Faculty PI: Dr. Emma Rose                

The development of autonomy and goal-directed behaviors are key milestones of adolescence. Expectations from parents to engage in responsible behaviors(e.g., household chores, outside work) may support this emergent process by recruiting brain regions that subserve executive functions (EFs) which, when in deficit, underlie a range of poor outcomes. Adolescent responsibility, however, may exert either beneficial or detrimental effects, depending upon the context; e.g., parental pressure to be responsible may induce stress. Outcomes related to responsibility may be moderated by family resources (SES), indicative of whether parental demands for responsibility are due either to need or personal choice. The relationship between level of responsibility and neurocognitive development has yet to be examined. Further, such a study requires delineation of contexts likely to play a role in helpful vs. harmful effects of responsibility. We explored relationships between responsibility, SES (low vs. high), and brain structure in drug-naïve adolescents (N=108;11-14 years; 57 females). Contrary to expectation, in low SES (and not high SES), higher levels of responsibility corresponded with cortical thinning in regions implicated in EF (i.e. left precuneus and right middle frontal) (d=.8), which may indicate that higher levels of responsibility in stressful environments are related to accelerated cortical thinning. In high SES, responsibility positively correlated with performance in a problem-solving task (Stockings of Cambridge)(d=.7). These results suggest a moderating role of SES in the positive vs. negative effects of responsibility on adolescent neurobiology and behavior, with greater responsibility predicting potentially impaired development of regions subserving EF in low SES and improved EF behavior for those in higher SES.

13. Reversal of a treatment-resistant, depression-related brain state with the Kv7 channel opener retigabine

Dr. Mengyang Feng; Biology; Faculty PI: Dr. Bernhard Luscher

Neuroinflammation is associated with increased vulnerability to diverse psychiatric conditions, including treatment-resistant major depressive disorder (MDD). Here we assessed whether high fat diet (HFD) induced neuroinflammation may be suitable to model a treatment-resistant depressive-like brain state in mice. Male and female mice were fed a HFD for 18 weeks, followed by quantitation of glucose tolerance, inflammatory markers of brain tissue (TNFα, IL-6, IL-1β, Iba-1), neural excitability in the prelimbic cortex (PLC), as well as assessment of emotional reactivity and hedonic behavior in a battery of behavioral tests. In addition, we assessed the behavioral responsiveness of mice to fluoxetine, desipramine, ketamine, and the Kv7/KCNQ channel opener and anticonvulsant retigabine. HFD exposure lead to glucose intolerance and neuroinflammation in male mice, with similar but non-significant trends in females. Neuroinflammation of males was associated with anxious-depressive-like behavior and defects in working memory, along with neural hyperexcitability and increased Ih currents of pyramidal cells in the PLC. The behavioral changes were largely resistant to chronic treatment with fluoxetine and desipramine, as well as ketamine. By contrast, retigabine normalized neural excitability and Ih currents recorded from slices of HFD-treated animals and substantially normalized most of the behavioral deficits, without effects in control diet exposed animals. Thus, treatment resistant depressive-like brain states that are associated with chronic neuroinflammation may involve hyperexcitability of pyramidal neurons and can be effectively ameliorated by agents that reduce intrinsic neural excitability.

14. Perturbed whole-body vitamin A kinetics induced by iron deficiency is corrected by dietary iron repletion in rats

Dr.Yaqi Li; Nutritional Sciences; Faculty PI: Dr. A. Catharine Ross        

Iron deficiency is known to interrupt vitamin A (VA) metabolism, but the ability of iron repletion to restore VA metabolism in iron-deficient rats is not well understood. Here, we investigated the effects of dietary iron repletion on VA status in rats with pre-existing iron deficiency. Weanling Sprague-Dawley rats were fed a VA-marginal diet containing either a normal level of iron (control group, CN) or reduced iron (iron-deficient group, ID-); after 5 weeks, four rats/group were euthanized for baseline measurements. Then a 3H-labeled retinol emulsion was administered to the rats (n=6 CN, n=10 ID-) as tracer to initiate the kinetic study. On d 21 after dosing, n=5 ID- rats were switched to the CN diet, generating an iron repletion group (ID+). Blood samples were collected at 34 time points up to 92 days after dosing, when all rats were euthanized for endpoint measurements. At baseline, ID- rats developed iron deficiency, with reduced plasma VA (0.67 vs. 1.20 µmol/L) and higher liver VA storage (265 vs. 187 nmol). On d 92, iron deficiency persisted in ID- rats, accompanied by 2-times higher liver VA (456 nmol vs.190 nmol in ID- and CN rats) but lower plasma VA (0.64 vs. 0.94 µmol/L). ID+ rats not only recovered from iron deficiency, but also exhibited less liver VA sequestration (276 nmol) and normal plasma VA (0.91 µmol/L). Our results suggest that iron repletion can remove the inhibitory effect of iron deficiency on hepatic mobilization of VA and restore plasma retinol concentrations in iron-deficient rats.

15. Impact of Biofuel Blends on Black Carbon Emissions from a Gas Turbine Engine      

      Dr. Raju Kumal; EMS Energy Institute; Faculty PI: Dr. Randy Vander Wall

Fuel composition specifications have traditionally been assigned tight given the multiple physical and combustion constraints imposed by engine class and use. A prime example is Jet A produced for commercial aviation consumption by jet aircraft. With a view towards renewable feedstock while decreasing the CO2 footprint associated with jet travel, biofuels are receiving increasing interest. Presently, biofuels are being tested as blends with conventional Jet A fuel, given present design reliance upon a minimal aromatic content. Biofuels, even blended, offer additional benefits such as reduced black carbon emission. Presently there is little data on the reduction or operative mechanisms, given the limited accessibility for full-scale jet engine testing coupled with comprehensive emissions characterization. Presented here is an overview of black carbon emissions as gauged by varied TEM analyses for a J-85 turbojet fueled with Jet A as well as with blends of Jet A using Camelina biofuel. These tests were conducted by the U.S. Environmental Protection Agency, in cooperation with Arnold Engineering and Development Complex (AEDC, U.S. Air Force), as part of a series of studies entitled VAriable Response In Aircraft nvPM Testing (VARIAnT) field campaigns.

Combustion reactions and turbulence induced mixing in a jet engine are highly convolved. Fuel composition, in particular component classes, manifest different reactions and associated kinetics under these conditions. NvPM aggregate morphology, primary particle size and their internal nanostructure are reflective of these differences. Mapping these physical measures against fuel composition and across engine powers provides insights into the combustion dynamics within the combustor section of the engine.

It was found that aggregate size depends less upon power with decreasing fuel aromatic levels. It is hypothesized that fuel carried aromatics lead to high power sensitivity for aggregate size because of turbulent fuel-air mixing (or relative lack thereof). With decreasing fuel aromatic levels, aromatics required for particle nucleation (and as species contributing to particle growth) can only form via pyrolysis reactions, which are dependent both on temperature and local alkane fuel/oxygen concentrations (equivalence ratio, ). Higher powers increase temperature but also increase turbulence which in turn decreases the average  of fuel-rich regions while shortening their lifetime. This balance of competing effects is manifested by lowered dependence of aggregate size upon power level, as quantified by the statistical correlations. Given the higher H/C ratio for biofuel blends compared to Jet-A, nanostructure increases with blend level for the power level measured. These findings highlight important considerations of using biofuel over the conventional fuel in aircraft to minimize the emission of hazardous particulate matter to protect human health and environment.

Aggregate size appears to depend less upon power with decreasing fuel aromatic levels. Why? Fuel carried aromatics lead to high power sensitivity for aggregate size because of turbulence fuel-air mixing (or relative lack thereof). With decreasing fuel aromatic levels, aromatics required for particle nucleation (and as species contributing to particle growth) can only form via pyrolysis reactions, which are dependent both on temperature and local fuel/oxygen concentrations (equivalence ratio, ϕ). Higher powers increase temperature but also increases turbulence which in turn decreases the average ϕ of fuel-rich regions while shortening their lifetime. This balance of competing effects is manifested by lowered dependence of aggregate size upon power level as quantified by the statistical correlations. Given the higher H/C ratio for biofuel blends compared to Jet-A, nanostructure curvature increases with blend level for the power level measured. These findings highlight important considerations of using biofuel over the conventional fuel in aircraft to minimize the emission of hazardous particulate matter to protect human health and environment.

16. Expanding the Soil and Water Assessment Tool for modeling the transport of contaminants of emerging concern in agricultural watersheds.

Dr. Lidiia Iavorivska; Agricultural and Biological Engineering; Faculty PI: Dr. Heather Gall        

Contaminants of emerging concern (CECs), including hormones and pharmaceuticals, have been detected in water bodies worldwide and can affect aquatic organisms and human health. CECs are introduced into the environment from wastewater discharges and from agricultural sources when animal and human residuals (manure and biosolids) are applied to fields as fertilizers, that later are washed off by precipitation to streams and lakes. To help with making long‐term land management decisions that consider the fate and transport of pollutants, hydrologic computer models, such as Soil and Water Assessment Tool (SWAT), are often used. SWAT model has been widely applied for evaluating hydrologic transport of nutrients, sediment, and pesticides at scales ranging from individual fields to watersheds, however the transport of CECs is not currently represented in SWAT. We are developing a new module to expand SWAT capabilities in simulating the fate and transport of hormones in agricultural landscapes. The module will be based on the Hormone Export and Recovery Dynamics (HERD) model (Gall et al., 2016) that will be adapted and incorporated into SWAT source code. The SWAT-HERD simulation results can be used to understand how land management decisions across different seasons influence risks to ecosystems downstream. The model can serve as a decision‐support tool to make recommendations that balance crop fertilizer needs with the potential for release of CECs from the fields through runoff and leaching. The new module will be tested and validated using data collected at intensely monitored agricultural research plots in Central Pennsylvania.

17. Structure and function of an unusual flavodoxin from the domain Archaea

Dr. Divya Prakash; Biochemistry and Molecular Biology; Faculty PI: Prof. James G Ferry

Numerous flavodoxins (Flds) from phylogenetically and metabolically diverse species in the domain Bacteria have been structurally and biochemically characterized, and their electron transport roles in various metabolisms documented. Remarkably, although the genomes of species in the domain Archaea are replete with annotations for

Flds, none have been investigated. Here we describe the structural, biochemical and physiological characterization of an unusual Fld (FldA) from Methanosarcina acetivorans that is up regulated when grown with acetate versus methanol suggesting an electron transport role in the pathway of acetoclastic methanogenesis. In contrast to all generic Flds, FldA is less acidic and stabilizes an anionic semiquinone with a notably low negative midpoint potential for the semiquinone/hydroquinone couple (Esq/hq = −464 + 2.61 mV). FldA mediates transfer of low potential electrons from the CO dehydrogenase/acetyl-CoA decarbonylase to the membrane-bound electron transport chain that generates a sodium gradient driving ATP synthesis. The results indicate that FldA affords an energy-conserving advantage over ferredoxin during acetotrophic growth that is at the thermodynamic limit. Replacing ferredoxin also conserves iron for essential metalloenzymes giving cells an additional advantage in the iron-limiting marine environment from which M. acetivorans was isolated.

18. Association between soil and root microbiomes and within-farm-spatial-variation of soybean yields: The bacterial perspective.

Dr. Ananda Bandara; Plant Pathology & Environmental Microbiology; Faculty PI: Dr. Paul Esker

The occurrence of high and low yielding sites within a farm has been a common yield limiting issue in soybean growing states. The causes behind such yield variations are currently unknown. We hypothesize that the potential differences of soil/root associated bacterial communities contribute to within-farm-spatial-variation of soybean yields (WFSVSY). Therefore, the objective of this study was to explore the bacterial communities of samples collected from high and low yielding sites at V1 and R8 soybean growth stages (SGS). Bulk soil (BS), rhizosphere soil (RS), and soybean root (R) samples were collected from eight farms in Pennsylvania (five high and low sites per farm). DNA extracted from samples were subjected to PCR targeting bacterial 16S rRNA genes (515F/806R primers) and amplicons were sequenced using MiSeq platform. The β-diversity analysis did not distinctly cluster data points based on yield (high/low), farm, or SGS for BS and RS samples. For R samples, a clear clustering was observed based on SGS. In BS, α-diversity was similar among high and low yield sites, however higher α-diversity was observed in high yield sites for both RS and R. While RS showed higher α-diversity at V1 compared to R8, the opposite was observed for R. There were no noticeable differences in relative abundances at the phyla level across high and low sites at V1 and R8. In-depth analysis will be performed to see whether specific bacterial taxa drive WFSVSY in Pennsylvania.

19. Accessibility of the front face of PCNA regulates human TLS pathway choice

Dr. Mingjie Li; Chemistry; Faculty PI: Dr. Mark Hedglin

Translesion DNA synthesis (TLS) bypasses DNA lesions encountered during S-phase and is critical for cell survival after exposure to DNA-damaging agents. In humans, Rad6/Rad18 selectively attaches single ubiquitin moieties (i.e. monoubiquitination) to proliferating cell nuclear antigen (PCNA) sliding clamps encircling primer/template (P/T) junctions that are stalled at DNA lesions. TLS occurs via PCNA monoubiquitination-independent and -dependent pathways and both contribute to cell survival. The interaction of Rad6/Rad18 with PCNA is paramount to PCNA monoubiquitination and remains poorly defined.  Many PCNA-binding proteins, particularly DNA polymerases (pols), converge on PCNA encircling stalled P/T junctions and all interact in a similar manner with the universal binding sites on PCNA. We reasoned that if Rad6/Rad18 utilizes the universal binding sites (or overlapping sites) then PCNA monoubiquitination may be suppressed by pols involved in TLS. On the other hand, if Rad18 utilizes a unique, non-overlapping site on PCNA then monoubiquitination may be independent of these factors.  Results from extensive studies reveal that; 1) a Y-family (pol η) and a B-family (pol δ) pol critical to TLS both inhibit monoubiquitination of PCNA by Rad6/Rad18 and; 2) the observed inhibition is dependent on the interaction of these pols with PCNA encircling DNA. These studies suggest that Rad6/Rad18 utilizes the universal PCNA-binding sites or overlapping sites and, hence is inhibited by PCNA-binding proteins that restrict access of Rad6/Rad18 to these sites. These findings provide valuable insight into the nature of the interaction between Rad6/Rad18 and PCNA and have important implications for the division of human TLS pathways. 

20. Economic Nano-additive to Improve Cement Sealing Capability

Dr. Maryam Tabatabaei; Energy and Mineral Engineering; Faculty PI: Dr. Arash Dahi Taleghani              

The primary objective of this study is introducing low-cost graphite nanoplatelets (GNPs) for oil well cementing that improves long-term wellbore isolation and the durability of the hydrated cement.  To seek this goal, we first propose methodologies to modify the surface properties of the nano-additives to disperse them in the cement paste.  We expect to improve the cement integrity by controlling the micro-cracks initiation and their propagation.  Then, experiments are conducted to assess enhanced mechanical behavior of the prepared cement nanocomposite.

21. Comparing approaches for capturing bacterial assemblages associated with symptomatic (bacterial blotch) and asymptomatic mushroom (Agaricus bisporus) caps

Dr. Samuel Martins; PPEM; Faculty PI: Dr. Carolee Bull

Bacterial blotch is a complex of diseases, caused by Pseudomonas tolaassi and other Pseudomonas spp., whose growth and survival may be influenced by other microorganisms associated with mushroom caps. The objectives of this work were to compare methods for extracting DNA from mushroom caps to assess bacterial composition and describe and quantify the composition of bacteria in and on symptomatic and asymptomatic mushroom caps. Mushrooms with blotch symptoms (n=50) and asymptomatic mushrooms (n=50) were collected at an organic farm in Pennsylvania and processed. Bacteria were removed from mushrooms by sonication to target surface-associated bacteria (washate), from whole mushrooms post-sonication to target bacteria within or tightly adhering to the mushrooms (post-washate), or from whole macerated mushrooms to target all mushroom-associated bacteria in one sample (whole). Bacterial composition was determined through sequencing of amplified fragments of the V4 hypervariable region of the 16S rRNA gene on an Illumina MiSeq. Bacterial composition differed significantly based on mushroom health status and community removal method. Regardless of sampling approach, Proteobacteria and Bacteroidetes appeared as the most dominant phyla. We found that Pseudomonas spp. were overrepresented on mushroom surfaces (washate method), regardless of mushroom health status. This research made strides in describing the mushroom cap microbiome and established sampling methods that will allow researchers to target studies and isolation of specific bacterial taxa.

22. Infant growth measurements across care settings: Implications from the WEE Baby Care study

Dr. Holly Harris; Center for Childhood Obesity Research; Faculty PI. Dr. Jennifer Savage Williams          

Community and clinical health services available to low-income families provide a sustainable, community-wide systems approach to preventing rapid infant weight gain, a predictor of future obesity. Success in such interventions requires the accurate and ongoing evaluation of infant growth. Discrepancies between care providers’ assessment of infant growth presents challenges in delivering effective, multidisciplinary obesity prevention education to parents through conflicting messaging. WEE Baby Care is a pragmatic randomized clinical trial using electronic health records to coordinate personalized care between pediatric primary care providers and the Women, Infant and Children community nutritionists. Mothers (N=289) and their full-term newborns were randomized to a ‘responsive parenting’ intervention with coordinated care between settings or the ‘standard control’ group. We examine a subset of the WEE Baby Care infants to describe the consistency in anthropometric measurements and weight classification between community and clinical care settings. At 6-months old (average), almost half of participants had plausible anthropometric assessments at both a pediatric well child and community nutrition visit (n=134 infants). Documented infant weight-for-age (WFA) assessments between clinical and community settings were strongly associated (b=0.96, p<.0001). Nevertheless, 6% of infants were misclassified as overweight or obese (WFA≥ 85th percentile) based on discrepancies between child weight records. Precision of infant length-for-age measurements varied between care providers (b=0.73, p<.0001). Despite agreement in infant weight measures across care settings, indicators that factor in length may lead to errant interpretations of body composition. Owing to variations in length between care settings, some low-income parents may receive conflicting messages regarding infant growth.

23. Emergent viruses and their interactions in Aedes aegypti: Mayaro and Zika virus coinfected mosquitoes can successfully transmit both pathogens.

       Dr. Marco Brustolin; Entomology; Faculty PI: Prof. Jason L. Rasgon

The emergence of arboviral outbreaks represents one of the most challenging issues for human and animal health and can be complicated by the simultaneous circulation of multiple arbovirus in affected regions. However, little is known about the vector-pathogen interactions during a co-circulation scenario. In this study we explored the effect of simultaneous intake of Mayaro virus (Togaviridae) and Zika virus (Flaviviridae) on Ae. aegypti vector competence. After exposing Ae. aegypti mosquitoes to an infectious blood meal containing either one or both pathogens, we analyzed viral titers in body, legs and saliva using a focus forming assay at day 7 and 14 post feeding. Results demonstrate that Ae. aegypti can support both viruses concurrently and that coinfected mosquitoes can efficiently transmit both viruses at the same time. The data also suggest that these pathogens can interact in complex ways during the co-infection process.

24. Nonlinear Shear Rheology of iPPs melts

Dr. Daniele Parisi; Materials Science and Engineering; Faculty PI: Dr. Ralph Colby

Strong flow fields are inevitable components of polymer processing. When semicrystalline polymers are involved, such conditions might induce conformational changes and ordering. This phenomenon is known as Flow Induced Crystallization (FIC). These flow-induced modifications in the polymer crystallinity and crystalline morphology strongly affect the mechanical properties of the final product, attracting the interest of both industrial and academic researchers.1–4 In this experimental work we investigate the nonlinear rheological response under shear flow of a set of isotactic polypropylene (iPP) melts with different molecular characteristics (polydispersity and molar mass distribution). The results obtained in this work can certainly contribute to open new routes for a better understanding on such a complex phenomenon of Flow Induced Crystallization.

25. RootRobot: A Field-based Platform for Maize Root System Architecture Phenotyping

Dr. Xiaomeng Shi; Agricultural and Biological Engineering; Faculty PI. Dr. Paul Heinemann

Field-based phenotyping technologies using automation and image processing can increase the efficiency of quantifying architectures of plant roots. In order to achieve accurate phenotyping results, the first step is to prepare root samples appropriately before imaging and analysis. For maize root architecture phenotyping, the preprocessing steps include excavating maize roots from the soil and removing dirt from the excavated roots. Currently, these operations are conducted manually, resulting in low-throughput with slow processing time. To automate the pre-processing steps and obtain a massive number of images in the field to be used for reconstructing high-resolution 3D phenotyping data, we developed a highly automated field-based platform, the RootRobot. The RootRobot consists of two field units: (1) Mobile Unit, and (2) Imaging Unit. The Mobile Unit collects root samples from a field and preprocesses samples for imaging with an automatic pipeline of excavating, cutting, and cleaning at a target speed of 6 seconds per root. Lab and field experiments were conducted to test the performance of each automated preprocessing step. The Imaging Unit was developed to be a separate field station to automatically acquire and store images from each root sample. The imaging procedure was designed to obtain, store, and transfer 3600 high-resolution images for each root sample in minutes. With greater speed and precision, the RootRobot will accelerate the research on phenotyping the underlying root architecture.

26. Motility of Enzyme-Powered Vesicles

Dr. Subhadip Ghosh; Chemistry; Faculty PI: Dr. Ayusman Sen                

Autonomous nanovehicles powered by energy derived from chemical catalysis have potential applications as active delivery agents. For in vivo applications, it is necessary that the engine and its fuel, as well as the chassis itself, be biocompatible. Enzyme molecules have been shown to display enhanced motility through substrate turnover and are attractive candidates as engines; phospholipid vesicles are biocompatible and can serve as cargo containers. Herein, we describe the autonomous movement of vesicles with membrane-bound enzymes in the presence of the substrate. We find that the motility of the vesicles increases with increasing enzymatic turnover rate. The enhanced diffusion of these enzyme-powered systems was further substantiated in real time by tracking the motion of the vesicles using optical microscopy. The membrane-bound protocells that move by transducing chemical energy into mechanical motion serve as models for motile living cells and are key to the elucidation of the fundamental mechanisms governing active membrane dynamics and cellular movement.

27. Searching for Dark Matter with the LZ Experiment

Dr. David Woodward; Physics; Faculty PI: Dr. Carmen Carmona

Dark matter appears to make up more than 80% of the mass of the universe. It controls how galaxies rotate, bends light from distant stars and is essential to explain the structure of our universe. Yet it has never been directly observed, and because it does not emit or absorb light of any wavelength, it is very difficult to see in a particle detector.

LUX-ZEPLIN (LZ) is a dark matter direct-detection experiment, with a team of 250 scientists and engineers from around the world. It will use a state-of-the-art low-background detector, which is currently being deployed a mile underground at the Sanford Underground Research Facility (SURF) in South Dakota. LZ will start operations next year, and is projected to be the most sensitive instrument ever built in the hunt for dark matter.

The Penn State group has been heavily involved in prototyping and testing the cryogenic and circulation systems for the experiment, as well as simulation and analysis work in preparation for the first science data. I will give an overview of the project and describe some of the key activities Penn State has been involved in as part of this international collaboration.

28. Simulations of influence of marine atmospheric boundary layer (MABL) on downhill storm

Dr. Fan Wu; EMS; Faculty PI: Dr. Kelly Lombardo    

The influence of stable marine atmospheric boundary layer (MABL) on downhill storm is investigated using 2D ideal numerical simulations. A storm is designed to be initiated on the plateau and then move down to the bottom of MABL with different depths and temperatures. The results show that the downhill storm interacts with the MABL by the collision of cold pool outflow and the upslope sea breeze. The post-collision updraft is mainly determined by the characteristics of MABL, that is, the forced updraft’s speed and depth increase with the deeper and colder MABL, which could trigger new convections on the slope. The differences of the post-collision vertical motion depend on the buoyancy and depth of cold pool outflow relative to the upslope see breeze. When the outflow is less buoyant and deeper, the updraft in front of the cold pool edge tend to be tilted behind and drawn in the internal gravity wave which is not efficient at lifting air into the storm. When the buoyancy and depth of upslope wind are close to those of the outflow, the updraft is more vertical that could uplift more air into the storm. The force of the post-collision updraft is dominated by the inertial vertical acceleration which is related to the convergence of the two flows. Precipitation enhancement on the slope is also more significant in the simulation with deeper and colder MABL and more sensitive to MABL’s depth. These simulations maybe helpful to reveal the mechanism of coastal storm initiation and heavy rainfall.

29. Networked Cooperative Control of Multiagent Systems

Dr. Ahmet Taha; Aerospace Engineering; Faculty PI: Dr. Eric Johnson 

This poster considers the stability and stabilization of linear heterogeneous multiagent systems including unknown leader dynamics and sampled-data information to avoid continuous communication. Sample-and-hold nature of the communications are modeled as time-delays which are sawtooth functions. We derived the linear matrix inequalities (LMI) conditions for L2-gain and decay rate estimation considering the cases the sampling instants of each agent are either time synchronous or not. Then, the controllers are synthesized to maximize decay rate using structured Lyapunov - Krasovskii functionals and a non-linear optimization method, specifically, cone complementarity algorithm. A numerical example is presented to demonstrate the efficiency of the results.

30. Scaffold-free Bioprinting of Zonally-stratified Human Articular Cartilage

Dr. Yang Wu; Engineering Science and Mechanics; Faculty PI: Dr. Ibrahim Ozbolat

Advances in bioprinting facilitates the assembly of cells and biomaterials spatially to replicate complex heterogeneity of native tissues, such as cartilage. The heterogeneous and anisotropic articular cartilage is generally studied as a layered structure of ‘zones’ with unique composition and architecture. However, such zonal stratification is difficult to recapitulate using current approaches, which can be attributed to the lack of proper spatial control on cell orientation and matrix deposition. In this study, we present a novel hybrid bioprinting strategy to generate a zonally-stratified cartilage. Scaffold-free tissue strands (TSs) were made of human adipose-derived stem cells (ADSCs) and chondrocytes differentiated from ADSCs through culturing cells within tubular alginate capsules. Chondrocyte TSs with pre-differentiated ADSCs exhibited up-regulated expression of cartilage-specific markers in immunohistochemistry straining and quantitative measurement at both transcription and protein levels as compared to TSs with ADSCs being differentiated in the form of strands and TSs of ADSCs. In addition, TSs with pre-differentiated chondrocytes showed superior mechanical strength than the other two groups. Particularly, this study has been the first time to bioprint a zonally-stratified construct with vertically aligned TSs as a bottom zone and horizontally-aligned TSs as a superficial zone, in which the collagen fibers were highly aligned with designated orientation in each zone imitating the anatomical regions and matrix orientation of native cartilage tissue. The prominent findings highlighted the potential of this novel scaffold-free biofabrication approach for building biologically- and histologically-relevant cartilage.

31. Walking towards rapid phenotyping: A semi-automated workflow for the multimodal quantification, visualization, and statistical comparison of osteological variation using high resolution-CT data of the human calcaneus

Dr. Nicholas Stephens; Anthropology; Faculty PI: Dr. Tim Ryan

The skeleton tends to be the only record of an animal’s life following death and extended burial. For this reason, physical anthropologists and paleontologists alike focus on acquiring as much comparative skeletal data as possible, which has only increased with computational and methodological advances (e.g. medical/micro-CT). While these advances have allowed for more granular studies on bone shape and structure, there are few methods that compare multiple levels of variation on complete skeletal elements. Here we combine multiple software suites to sime-automatically quantify calcaneal shape variation, cortical thickness, and trabecular bone volume fraction (BV/TV) from micro-CT scans (~35-50 µm) of human calcanei from two North American archaeological populations (Norris Farm, n = 17 and Black Earth, n = 14). Primary shape differences (PC1-3 53%) were found for calcaneus in the talar articular angle, calcaneal length and width, as well as for the shape of the tuber (heel). An average shaped mesh and point cloud were  generated from the shape analysis, and then registered to the individual calcaneal meshes/points clouds. After averaging across corresponding vertices and points, we found that regions with higher Ct.Th values overlapped with those of high BV/TV. In comparing the populations, Black Earth had significantly higher Ct.Th, with significantly higher BV/TV, which extended farther into the central portions of the calcaneus. While preliminary, our results demonstrate the feasibility in creating a semiautomated workflow for multimodal comparisons of single skeletal elements, which is an important step towards developing rapid phenotyping for larger datasets containing multiple skeletal elements.

      32. BooleaBayes: Data-driven modeling predicts master transcriptional regulators of a drug-resistant subtype in small-cell lung cancer

Dr. David Wooten; Physics; Faculty PI: Dr. Réka Albert

Small-cell lung cancer (SCLC) is an aggressive disease, initially responsive to standard treatments, but that relapses rapidly, recalcitrant to further therapy. Recent work suggests that SCLC, previously viewed as a monolithic disease, may comprise multiple subtypes. Here, we hypothesized that different SCLC subtypes may be differentially sensitive to targeted treatments, and sought to identify new interventions that may abrogate the emergence of resistance.

Using RNAseq expression on 50 SCLC cell lines we identified distinct SCLC subtypes and gene co-expression programs. From a drug screen of more than 500 therapeutic agents, we found one subtype, named NEv2, to be broadly more resistant than the others, including to standard of care.

To understand the mechanistic basis of SCLC differentiation into NEv2, we assembled a regulatory network of transcription factors (TFs) differentially expressed across subtypes. A novel data-driven probabilistic Boolean modeling algorithm, named BooleaBayes, was able to explain the stability of distinct SCLC subtypes. In silico perturbations ranked TFs that may be knocked out (master regulators) or activated (master destabilizers) to destabilize each subtype. Specific to the NEv2 subtype, we predict ELF3 and NR0B1 are master regulators, and TCF3 is a master destabilizer.

Overall, BooleaBayes is a highly flexible, data-driven approach to identify mechanisms underlying the stability of transcriptionally regulated subtypes. In the case of cancer, we expect cells may be reprogrammed away from drug resistant subtypes, possibly toward drug sensitive subtypes. We thus anticipate BooleaBayes will be a powerful tool for identifying synergistic co-targets for treatments, blocking the emergence of resistance.

33. Wearable photoacoustic sensors aided by deep learning for real-time health care

Dr. Ajay Dangi; Biomedical Engineering; Faculty PI: Dr. Sri-Rajasekhar Kothapalli        

The presented research focuses on developing wearable and portable devices for photoacoustic imaging (PAI) and leveraging deep learning algorithms to obtain superior image characteristics. PAI uses a principle similar to that of thunder wherein pulsed optical illumination on absorbing tissue generates ultrasound signals; this enables non-invasive imaging similar to ultrasound imaging but with optical absorption-based contrast, thus allowing molecular and functional imaging of tissue. PAI systems, if realized in small form factors, can lead to portable and wearable devices ideally suited for point-of-care applications. Three different configurations of wearable and portable photoacoustic imaging devices that have been conceptualized and developed as part of this work are presented. Applicability of deep learning algorithms is explored to improve the image reconstruction process from the raw sensor data with reduced artifacts. Novel algorithms are also developed for spectral unmixing of the images to identify optical absorbers of interest.

34. Fetal adipose accumulation rate at 26-30 weeks gestation is associated with postnatal weight and adiposity

Dr. Emily Hohman; Center for Childhood Obesity Research; Faculty PI: Dr. Jennifer Savage Williams

Ultrasound estimates of fetal adiposity predict neonatal weight and adiposity. However, few studies have evaluated how rate of fetal adipose accumulation relates to postnatal outcomes. We followed fetal growth via monthly ultrasounds in pregnant women in an ancillary study of the Healthy Mom Zone gestational weight management intervention. Fetal adiposity was assessed via ultrasound at 26, 30, and 34 weeks gestation by measuring thickness of the abdominal subcutaneous adipose tissue (n=30) and the cross-sectional area of adipose tissue at the mid-femur (n=20). Rate of adipose accumulation was calculated as the difference between scans divided by number of days between scans. Birthweight was abstracted from medical records. Weight and body composition via air displacement plethysmography were measured at age 6 weeks in a subset of newborns (n=16). Rate of abdominal adipose accumulation did not differ between 26-30 weeks and 30-34 weeks (0.01±0.03 vs. 0.02±0.02 cm/week), but rate of mid-femur adipose accumulation increased from 26-30 to 30-34 weeks. (0.5±0.4 vs. 1.0±0.6 cm2/week, p=0.01). Gain in adiposity from 26-30 weeks at both the abdomen (r=0.51, p=0.004) and mid-femur (r=0.66, p=0.001) was associated with birthweight z-score; however, gain in adiposity from 30-34 weeks was not correlated with birthweight. Similar associations were seen for postnatal weight z-score. Percent body fat was correlated with abdominal adiposity accumulation from 26-30 weeks only (r=0.60, p=0.01). These preliminary data suggest that early gains in adiposity during gestation may be a determinant of postnatal adiposity. Additional research is needed to identify determinants of early fetal adipose accumulation for intervention development.

35. Speed regulation greatly decreases fall risk of a treadmill walking model

Dr. Navendu Patil; Kinesiology; Faculty PI: Prof. Jonathan B. Dingwell

Much of human walking appears stereotypical and is usually taken for granted, especially by healthy adults. However, to avoid falling and enhance stability, humans need to actively control their balance while walking. Indeed, the majority of falls in older people occur while walking, and frequently result in hip fractures and other serious injuries. Moreover, to achieve task goals, such as maintaining a desired walking speed or direction, humans need to regulate stepping movements to cope with physiological noise and external disturbances. How the active neuromuscular control and task-level regulation strategies employed by humans affect the dynamic stability of walking is of central importance to characterizing fall risk. Experiments have shown that humans walking on a treadmill strongly prioritize speed regulation from one stride to the next, not just on average. Why humans adopt speed regulation while treadmill walking over the equally rational strategy of maintaining absolute position, and what implications, if any, this has for fall risk, remains unresolved. Here, we use simulations to study a model system's ability to reject large disturbances when employing different task-level regulation strategies. To this end, we study the walking models’ global stability, a system characteristic believed to be intimately related with fall risk. Specifically, for a powered compass walker on a treadmill, we impose additional speed and position regulators. While both provide viable regulation strategies for treadmill walking, we find that speed regulation enlarges and regularizes the walker's stability region much more than position regulation. Our results thus suggest a functional connection between task-level motor regulation and global stability.

36. Gravitational Waves: Testing waveforms with full general relativity

Dr. Tommaso De Lorenzo; Physics; Faculty PI: Dr. Abhay Ashtekar       

The most common (and loud) sources of Gravitational Waves (GWs) for interferometers are binary systems composed by black holes and/or neutron stars. To extract the signal from the detectors’ noise, one needs accurate models—the waveform templates—showing how the signal we expect from General Relativity (GR) looks like. Unfortunately, the two-body problem in GR is impossible to solve analytically, and only relying on Numerical Relativity (NR) simulations is computationally too expensive. Therefore, approximate analytical methods, such as the Effective One Body (EOB) and Phenom schemes, that interpolate between the available NR simulations have been developed. Many choices are involved in the construction of such templates, resulting in systematic errors that can affect the quality of, for instance, parameter estimations of—or tests of GR with—detected sources. Nonetheless, these methods have played an invaluable role for the detections by the LIGO-Virgo collaboration.  So far, indeed, statistical errors are less than the systematic ones. The situation will change with third generation array of detectors and LISA, forcing the development of more accurate templates. This in turn requires new reliable procedures to evaluate accuracy, particularly in regions of parameter space where NR simulations are sparse. In this work we show how exact non-linear GR imposes an infinite number of sharp constraints on waveforms. This can provide what we need. In particular, we can for the first time compare the waveform against exact GR, instead of using NR simulations (with intrinsic errors) as substitute to the exact waveform.