Destination Areas (DAs)

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Destination Areas provide faculty and students with new tools to identify and solve complex, 21st-century problems in which Virginia Tech already has significant strengths and can take a global leadership role. The initiative represents the next step in the evolution of the land-grant university to meet economic and societal needs of the world.

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Association of Blood Biomarkers With Acute Sport-Related Concussion in Collegiate Athletes: Findings From the NCAA and Department of Defense CARE Consortium
McCrea, Michael A.; Broglio, Steven P.; McAllister, Thomas W.; Gill, Jessica M.; Giza, Christopher C.; Huber, Daniel L.; Harezlak, Jaroslaw; Cameron, Kenneth L.; Houston, Megan N.; McGinty, Gerald T.; Jackson, Jonathan C.; Guskiewicz, Kevin M.; Mihalik, Jason P.; Brooks, M. Alison; Duma, Stefan M.; Rowson, Steven; Nelson, Lindsay D.; Pasquina, Paul; Meier, Timothy B.; Foroud, Tatiana; Katz, Barry P.; Saykin, Andrew J.; Campbell, Darren E.; Svoboda, Steven J.; Goldman, Joshua T.; DiFiori, John P. (2020-01-24)
Question Is sport-related concussion associated with levels of traumatic brain injury biomarkers in collegiate athletes? Findings In this case-control study of 504 collegiate athletes with concussion, contact sport control athletes, and non-contact sport athletes, the athletes with concussion had significant elevations in multiple traumatic brain injury biomarkers compared with preseason baseline and with 2 groups of control athletes without concussion during the acute postinjury period. Meaning These results suggest that blood biomarkers can be used as research tools to inform the underlying pathophysiological mechanism of concussion and provide additional support for future studies to optimize and validate biomarkers for potential clinical use in sport-related concussion. This case-control study examines the association between sport-related concussion and levels of traumatic brain injury biomarkers in collegiate athletes. Importance There is potential scientific and clinical value in validation of objective biomarkers for sport-related concussion (SRC). Objective To investigate the association of acute-phase blood biomarker levels with SRC in collegiate athletes. Design, Setting, and Participants This multicenter, prospective, case-control study was conducted by the National Collegiate Athletic Association (NCAA) and the US Department of Defense Concussion Assessment, Research, and Education (CARE) Consortium from February 20, 2015, to May 31, 2018, at 6 CARE Advanced Research Core sites. A total of 504 collegiate athletes with concussion, contact sport control athletes, and non-contact sport control athletes completed clinical testing and blood collection at preseason baseline, the acute postinjury period, 24 to 48 hours after injury, the point of reporting being asymptomatic, and 7 days after return to play. Data analysis was conducted from March 1 to November 30, 2019. Main Outcomes and Measures Glial fibrillary acidic protein (GFAP), ubiquitin C-terminal hydrolase-L1 (UCH-L1), neurofilament light chain, and tau were quantified using the Quanterix Simoa multiplex assay. Clinical outcome measures included the Sport Concussion Assessment Tool-Third Edition (SCAT-3) symptom evaluation, Standardized Assessment of Concussion, Balance Error Scoring System, and Brief Symptom Inventory 18. Results A total of 264 athletes with concussion (mean [SD] age, 19.08 [1.24] years; 211 [79.9%] male), 138 contact sport controls (mean [SD] age, 19.03 [1.27] years; 107 [77.5%] male), and 102 non-contact sport controls (mean [SD] age, 19.39 [1.25] years; 82 [80.4%] male) were included in the study. Athletes with concussion had significant elevation in GFAP (mean difference, 0.430 pg/mL; 95% CI, 0.339-0.521 pg/mL; P < .001), UCH-L1 (mean difference, 0.449 pg/mL; 95% CI, 0.167-0.732 pg/mL; P < .001), and tau levels (mean difference, 0.221 pg/mL; 95% CI, 0.046-0.396 pg/mL; P = .004) at the acute postinjury time point compared with preseason baseline. Longitudinally, a significant interaction (group x visit) was found for GFAP (F-7,F-1507.36 = 16.18, P < .001), UCH-L1 (F-7,F-1153.09 = 5.71, P < .001), and tau (F-7,F-1480.55 = 6.81, P < .001); the interaction for neurofilament light chain was not significant (F-7,F-1506.90 = 1.33, P = .23). The area under the curve for the combination of GFAP and UCH-L1 in differentiating athletes with concussion from contact sport controls at the acute postinjury period was 0.71 (95% CI, 0.64-0.78; P < .001); the acute postinjury area under the curve for all 4 biomarkers combined was 0.72 (95% CI, 0.65-0.79; P < .001). Beyond SCAT-3 symptom score, GFAP at the acute postinjury time point was associated with the classification of athletes with concussion from contact controls (beta = 12.298; 95% CI, 2.776-54.481; P = .001) and non-contact sport controls (beta = 5.438; 95% CI, 1.676-17.645; P = .005). Athletes with concussion with loss of consciousness or posttraumatic amnesia had significantly higher levels of GFAP than athletes with concussion with neither loss of consciousness nor posttraumatic amnesia at the acute postinjury time point (mean difference, 0.583 pg/mL; 95% CI, 0.369-0.797 pg/mL; P < .001). Conclusions and Relevance The results suggest that blood biomarkers can be used as research tools to inform the underlying pathophysiological mechanism of concussion and provide additional support for future studies to optimize and validate biomarkers for potential clinical use in SRC.
Astrocyte Mechano-Activation by High-Rate Overpressure Involves Alterations in Structural and Junctional Proteins
Hlavac, Nora; VandeVord, Pamela J. (Frontiers, 2019-02-22)
Primary blast neurotrauma represents a unique injury paradigm characterized by high-rate overpressure effects on brain tissue. One major hallmark of blast neurotrauma is glial reactivity, notably prolonged astrocyte activation. This cellular response has been mainly defined in primary blast neurotrauma by increased intermediate filament expression. Because the intermediate filament networks physically interface with transmembrane proteins for junctional support, it was hypothesized that cell junction regulation is altered in the reactive phenotype as well. This would have implications for downstream transcriptional regulation via signal transduction pathways like nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB). Therefore, a custom high-rate overpressure simulator was built for in vitro testing using mechanical conditions based on intracranial pressure measurements in a rat model of blast neurotrauma. Primary rat astrocytes were exposed to isolated high-ratemechanical stimulation to study cell junction dynamics in relation to their mechano-activation. First, a time course for “classical” features of reactivity was devised by evaluation of glial fibrillary acidic protein (GFAP) and proliferating cell nuclear antigen (PCNA) expression. This was followed by gene and protein expression for both gap junction (connexins) and anchoring junction proteins (integrins and cadherins). Signal transduction analysis was carried out by nuclear localization of two molecules, NF-kB p65 and mitogen-activated protein kinase (MAPK) p38. Results indicated significant increases in connexin-43 expression and PCNA first at 24 h post-overpressure (p < 0.05), followed by structural reactivity (via increased GFAP, p < 0.05) corresponding to increased anchoring junction dynamics at 48 h post-overpressure (p < 0.05). Moreover, increased phosphorylation of focal adhesion kinase (FAK) was observed in addition to increased nuclear localization of both p65 and p38 (p < 0.05) during the period of structural reactivity. To evaluate the transcriptional activity of p65 in the nucleus, electrophoretic mobility shift assay was conducted for a binding site on the promoter region for intracellular adhesion molecule-1 (ICAM-1), an antagonist of tight junctions. A significant increase in the interaction of nuclear proteins with the NF-kB site on the ICAM-1 corresponded to increased gene and protein expression of ICAM-1 (p < 0.05).
Augmentation of brain tumor interstitial flow via focused ultrasound promotes brain-penetrating nanoparticle dispersion and transfection
Curley, Colleen T.; Mead, Brian P.; Negron, Karina; Kim, Namho; Garrison, William J.; Miller, G. Wilson; Kingsmore, Kathryn M.; Thim, E. Andrew; Song, Ji; Munson, Jennifer M.; Klibanov, Alexander L.; Suk, Jung Soo; Hanes, Justin; Price, Richard J. (2020-04)
The delivery of systemically administered gene therapies to brain tumors is exceptionally difficult because of the blood-brain barrier (BBB) and blood-tumor barrier (BTB). In addition, the adhesive and nanoporous tumor extra-cellular matrix hinders therapeutic dispersion. We first developed the use of magnetic resonance image (MRI)-guided focused ultrasound (FUS) and microbubbles as a platform approach for transfecting brain tumors by targeting the delivery of systemically administered "brain-penetrating" nanoparticle (BPN) gene vectors across the BTB/BBB. Next, using an MRI-based transport analysis, we determined that after FUS-mediated BTB/BBB opening, mean interstitial flow velocity magnitude doubled, with "per voxel" flow directions changing by an average of similar to 70 degrees to 80 degrees. Last, we observed that FUS-mediated BTB/BBB opening increased the dispersion of directly injected BPNs through tumor tissue by >100%. We conclude that FUS-mediated BTB/BBB opening yields markedly augmented interstitial tumor flow that, in turn, plays a critical role in enhancing BPN transport through tumor tissue.
Compressive Mechanical Properties of Porcine Brain: Experimentation and Modeling of the Tissue Hydration Effects
Prabhu, Raj K.; Begonia, Mark T.; Whittington, Wilburn R.; Murphy, Michael A.; Mao, Yuxiong; Liao, Jun; Williams, Lakiesha N.; Horstemeyer, Mark F.; Sheng, Jianping (MDPI, 2019-05-07)
Designing protective systems for the human head—and, hence, the brain—requires understanding the brain’s microstructural response to mechanical insults. We present the behavior of wet and dry porcine brain undergoing quasi-static and high strain rate mechanical deformations to unravel the effect of hydration on the brain’s biomechanics. Here, native ‘wet’ brain samples contained ~80% (mass/mass) water content and ‘dry’ brain samples contained ~0% (mass/mass) water content. First, the wet brain incurred a large initial peak stress that was not exhibited by the dry brain. Second, stress levels for the dry brain were greater than the wet brain. Third, the dry brain stress–strain behavior was characteristic of ductile materials with a yield point and work hardening; however, the wet brain showed a typical concave inflection that is often manifested by polymers. Finally, finite element analysis (FEA) of the brain’s high strain rate response for samples with various proportions of water and dry brain showed that water played a major role in the initial hardening trend. Therefore, hydration level plays a key role in brain tissue micromechanics, and the incorporation of this hydration effect on the brain’s mechanical response in simulated injury scenarios or virtual human-centric protective headgear design is essential.
Convection-Enhanced Delivery: Connection to and Impact of Interstitial Fluid Flow
Stine, Caleb A.; Munson, Jennifer M. (Frontiers, 2019-10-02)
Convection-enhanced delivery (CED) is a method used to increase transport of therapeutics in and around brain tumors. CED works through locally applying a pressure differential to drive fluid flow throughout the tumor, such that convective forces dominate over diffusive transport. This allows therapies to bypass the blood brain barrier that would otherwise be too large or solely rely on passive diffusion. However, this also drives fluid flow out through the tumor bulk into surrounding brain parenchyma, which results in increased interstitial fluid (IF) flow, or fluid flow within extracellular spaces in the tissue. IF flow has been associated with altered transport of molecules, extracellular matrix rearrangement, and triggering of cellularmotility through a number ofmechanisms. Thus, the results of a simple method to increase drug delivery may have unintended consequences on tissue morphology. Clinically, prediction of dispersal of agents via CED is important to catheter design, placement, and implementation to optimize contact of tumor cells with therapeutic agent. Prediction software can aid in this problem, yet we wonder if there is a better way to predict therapeutic distribution based simply on IF flow pathways as determined from pre-intervention imaging. Overall, CED based therapy has seen limited success and we posit that integration and appreciation of altered IF flow may enhance outcomes. Thus, in this manuscript we both review the current state of the art in CED and IF flow mechanistic understanding and relate these two elements to each other in a clinical context.
Convective forces increase CXCR4-dependent glioblastoma cell invasion in GL261 murine model
Cornelison, R. Chase; Brennan, Caroline E.; Kingsmore, Kathryn M.; Munson, Jennifer M. (Nature Publishing Group, 2019-11-18)
Glioblastoma is the most common and malignant form of brain cancer. Its invasive nature limits treatment efficacy and promotes inevitable recurrence. Previous in vitro studies showed that interstitial fluid flow, a factor characteristically increased in cancer, increases glioma cell invasion through CXCR4- CXCL12 signaling. It is currently unknown if these effects translate in vivo. We used the therapeutic technique of convection enhanced delivery (CED) to test if convective flow alters glioma invasion in a syngeneic GL261 mouse model of glioblastoma. The GL261 cell line was flow responsive in vitro, dependent upon CXCR4 and CXCL12. Additionally, transplanting GL261 intracranially increased the populations of CXCR4+ and double positive cells versus 3D culture. We showed that inducing convective flow within implanted tumors indeed increased invasion over untreated controls, and administering the CXCR4 antagonist AMD3100 (5 mg/kg) effectively eliminated this response. These data confirm that glioma invasion is stimulated by convective flow in vivo and depends on CXCR4 signaling. We also showed that expression of CXCR4 and CXCL12 is increased in patients having received standard therapy, when CED might be elected. Hence, targeting flow-stimulated invasion may prove beneficial as a second line of therapy, particularly in patients chosen to receive treatment by convection enhanced delivery.
Cultivating Emerging & Black Swan Technologies
Mahajan, Roop L. (2012-09-15)
Decision-adjusted driver risk predictive models using kinematics information
Mao, Huiying; Guo, Feng; Deng, Xinwei; Doerzaph, Zachary R. (Elsevier, 2021-06)
Accurate prediction of driving risk is challenging due to the rarity of crashes and individual driver heterogeneity. One promising direction of tackling this challenge is to take advantage of telematics data, increasingly available from connected vehicle technology, to obtain dense risk predictors. In this work, we propose a decision-adjusted framework to develop optimal driver risk prediction models using telematics-based driving behavior information. We apply the proposed framework to identify the optimal threshold values for elevated longitudinal acceleration (ACC), deceleration (DEC), lateral acceleration (LAT), and other model parameters for predicting driver risk. The Second Strategic Highway Research Program (SHRP 2) naturalistic driving data were used with the decision rule of identifying the top 1% to 20% of the riskiest drivers. The results show that the decision-adjusted model improves prediction precision by 6.3% to 26.1% compared to a baseline model using non-telematics predictors. The proposed model is superior to models based on a receiver operating characteristic curve criterion, with 5.3% and 31.8% improvement in prediction precision. The results confirm that the optimal thresholds for ACC, DEC and LAT are sensitive to the decision rules, especially when predicting a small percentage of high-risk drivers. This study demonstrates the value of kinematic driving behavior in crash risk prediction and the necessity for a systematic approach for extracting prediction features. The proposed method can benefit broad applications, including fleet safety management, use-based insurance, driver behavior intervention, as well as connected-vehicle safety technology development.
Dielectrophoretic differentiation of mouse ovarian surface epithelial cells, macrophages, and fibroblasts using contactless dielectrophoresis
Salmanzadeh, Alireza; Kittur, Harsha; Sano, Michael B.; Roberts, Paul C.; Schmelz, Eva M.; Davalos, Rafael V. (American Institute of Physics, 2012-06-01)
Ovarian cancer is the leading cause of death from gynecological malignancies in women. The primary challenge is the detection of the cancer at an early stage, since this drastically increases the survival rate. In this study we investigated the dielectrophoretic responses of progressive stages of mouse ovarian surface epithelial (MOSE) cells, as well as mouse fibroblast and macrophage cell lines, utilizing contactless dielectrophoresis (cDEP). cDEP is a relatively new cell manipulation technique that has addressed some of the challenges of conventional dielectrophoretic methods. To evaluate our microfluidic device performance, we computationally studied the effects of altering various geometrical parameters, such as the size and arrangement of insulating structures, on dielectrophoretic and drag forces. We found that the trapping voltage of MOSE cells increases as the cells progress from a non-tumorigenic, benign cell to a tumorigenic, malignant phenotype. Additionally, all MOSE cells display unique behavior compared to fibroblasts and macrophages, representing normal and inflammatory cells found in the peritoneal fluid. Based on these findings, we predict that cDEP can be utilized for isolation of ovarian cancer cells from peritoneal fluid as an early cancer detection tool. (C) 2012 American Institute of Physics. [http://dx.doi.org/10.1063/1.3699973] Actual pdf downloaded from NCBI.
Distinguishing the Unique Neuropathological Profile of Blast Polytrauma
Hubbard, W. Brad; Greenberg, Shaylen; Norris, Carly; Eck, Joseph; Lavik, Erin; VandeVord, Pamela J. (Hindawi, 2017-03-23)
Traumatic brain injury sustained after blast exposure (blast-induced TBI) has recently been documented as a growing issue for military personnel. Incidence of injury to organs such as the lungs has decreased, though current epidemiology still causes a great public health burden. In addition, unprotected civilians sustain primary blast lung injury (PBLI) at alarming rates. Often, mild-to-moderate cases of PBLI are survivable with medical intervention, which creates a growing population of survivors of blast-induced polytrauma (BPT) with symptoms from blast-induced mild TBI (mTBI). Currently, there is a lack of preclinical models simulating BPT, which is crucial to identifying unique injury mechanisms of BPT and its management. To meet this need, our group characterized a rodent model of BPT and compared results to a blast-induced mTBI model. Open field (OF) performance trials were performed on rodents at 7 days after injury. Immunohistochemistry was performed to evaluate cellular outcome at day seven following BPT. Levels of reactive astrocytes (GFAP), apoptosis (cleaved caspase-3 expression), and vascular damage (SMI-71) were significantly elevated in BPT compared to blast-induced mTBI. Downstream markers of hypoxia (HIF-1α and VEGF) were higher only after BPT. This study highlights the need for unique therapeutics and prehospital management when handling BPT.
Dynamic Analysis and Design Optimization of a Drag-Based Vibratory Swimmer
Tahmasian, Sevak; Jafaryzad, Arsam; Bulzoni, Nicolas L.; Staples, Anne E. (MDPI, 2020-03-22)
Many organisms achieve locomotion via reciprocal motions. This paper presents the dynamic analysis and design optimization of a vibratory swimmer with asymmetric drag forces and fluid added mass. The swimmer consists of a floating body with an oscillatory mass inside. One-dimensional oscillations of the mass cause the body to oscillate with the same frequency as the mass. An asymmetric rigid fin attached to the bottom of the body generates asymmetric hydrodynamic forces, which drive the swimmer either backward or forward on average, depending on the orientation of the fin. The equation of motion of the system is a time-periodic, piecewise-smooth differential equation. We use simulations to determine the hydrodynamic forces acting on the fin and averaging techniques to determine the dynamic response of the swimmer. The analytical results are found to be in good agreement with vibratory swimmer prototype experiments. We found that the average unidirectional speed of the swimmer is optimized if the ratio of the forward and backward drag coefficients is minimized. The analysis presented here can aid in the design and optimization of bio-inspired and biomimetic robotic swimmers. A magnetically controlled microscale vibratory swimmer like the one described here could have applications in targeted drug delivery.
Focused ultrasound actuation of shape memory polymers; acoustic-thermoelastic modeling and testing
Bhargava, Aarushi; Peng, Kaiyuan; Stieg, Jerry; Mirzaeifar, Reza; Shahab, Shima (The Royal Society of Chemistry, 2017-09-18)
Controlled drug delivery (CDD) technologies have received extensive attention recently. Despite recent efforts, drug releasing systems still face major challenges in practice, including low efficiency in releasing the pharmaceutical compounds at the targeted location with a controlled time rate. We present an experimentally-validated acoustic-thermoelastic mathematical framework for modeling the focused ultrasound (FU)-induced thermal actuation of shape memory polymers (SMPs). This paper also investigates the feasibility of using SMPs stimulated by FU for designing CDD systems. SMPs represent a new class of materials that have gained increased attention for designing biocompatible devices. These polymers have the ability of storing a temporary shape and returning to their permanent or original shape when subjected to external stimuli such as heat. In this work, FU is used as a trigger for noninvasively stimulating SMP-based systems. FU has a superior capability to localize the heating effect, thus initiating the shape recovery process only in selected parts of the polymer. The multiphysics model optimizes the design of a SMP-based CDD system through analysis of a filament as a constituting basestructure and quantifies its activation under FU. Experimental validations are performed using a SMP filament submerged in water coupled with the acoustic waves generated by a FU transducer. The modeling results are used to examine and optimize parameters such as medium properties, input power and frequency, location, geometry and chemical composition of the SMP to achieve favorable shape recovery of a potential drug delivery system.
Folic Acid-Conjugated Cellulose Nanocrystals Show High Folate-Receptor Binding Affinity and Uptake by KB and Breast Cancer Cells
Bittleman, Katelyn Rose; Dong, Shuping; Roman, Maren; Lee, Yong Woo (American Chemical Society, 2018-10-24)
The study evaluates cellulose nanocrystals (CNCs) as nanocarriers for targeted, intracellular delivery of molecular agents. CNCs were labeled with fluorescein-5′-isothiocyanate as an imaging agent and conjugated to folic acid (FA) as a targeting ligand. The CNC conjugates were characterized by UV–vis spectroscopy, ζ-potential analysis, dynamic light scattering, and atomic force microscopy. Cellular binding/uptake of the FA-conjugated CNCs by KB and MDA-MB-468 cells was quantified with cellular uptake assays. Internalization of the particles was confirmed by confocal microscopy. Uptake mechanisms were determined by inhibition studies with chlorpromazine and genistein. Binding affinity was qualitatively assessed with a free folate inhibition assay. Both KB and MDA-MB-468 cells exhibited significant and folate-receptor specific binding/uptake of FA-conjugated CNCs. Clathrin-mediated endocytosis was a significant uptake mechanism in both cell types, whereas caveolae-mediated endocytosis only played a significant role in MDA-MB-468 cells. Uptake inhibition of FA-conjugated CNCs by KB cells required high concentrations (>1 mM) of free FA. The observed FR-specific internalization of FA-conjugated CNCs by FR-positive cancer cells and tumors and their remarkable high affinity for the FR demonstrate the great potential of CNCs as novel nanocarriers for imaging agents and chemotherapeutics in the early detection and treatment of cancer.
Glial Activation in the Thalamus Contributes to Vestibulomotor Deficits Following Blast-Induced Neurotrauma
Dickerson, Michelle R.; Bailey, Zachary S.; Murphy, Susan F.; Urban, Michael J.; VandeVord, Pamela J. (2020-07-15)
Vestibular impairment has become a frequent consequence following blast-related traumatic brain injury (bTBI) in military personnel and Veterans. Behavioral outcomes such as depression, fear and anxiety are also common comorbidities of bTBI. To accelerate pre-clinical research and therapy developments, there is a need to study the link between behavioral patterns and neuropathology. The transmission of neurosensory information often involves a pathway from the cerebral cortex to the thalamus, and the thalamus serves crucial integrative functions within vestibular processing. Pathways from the thalamus also connect with the amygdala, suggesting thalamic and amygdalar contributions to anxiolytic behavior. Here we used behavioral assays and immunohistochemistry to determine the sub-acute and early chronic effects of repeated blast exposure on the thalamic and amygdala nuclei. Behavioral results indicated vestibulomotor deficits at 1 and 3 weeks following repeated blast events. Anxiety-like behavior assessments depicted trending increases in the blast group. Astrogliosis and microglia activation were observed upon post-mortem pathological examination in the thalamic region, along with a limited glia response in the amygdala at 4 weeks. These findings are consistent with a diffuse glia response associated with bTBI and support the premise that dysfunction within the thalamic nuclei following repeated blast exposures contribute to vestibulomotor impairment.
Hemostatic nanoparticles increase survival, mitigate neuropathology and alleviate anxiety in a rodent blast trauma model
Hubbard, W. Brad; Lashof-Sullivan, Margaret; Greenberg, Shaylen; Norris, Carly; Eck, Joseph; Lavik, Erin; VandeVord, Pamela J. (Springer Nature, 2018-07-13)
Explosions account for 79% of combat related injuries and often lead to polytrauma, a majority of which include blast-induced traumatic brain injuries (bTBI). These injuries lead to internal bleeding in multiple organs and, in the case of bTBI, long term neurological deficits. Currently, there are no treatments for internal bleeding beyond fluid resuscitation and surgery. There is also a dearth of treatments for TBI. We have developed a novel approach using hemostatic nanoparticles that encapsulate an anti-inflammatory, dexamethasone, to stop the bleeding and reduce inflammation after injury. We hypothesize that this will improve not only survival but long term functional outcomes after blast polytrauma. Poly(lactic-co-glycolic acid) hemostatic nanoparticles encapsulating dexamethasone (hDNPs) were fabricated and tested following injury along with appropriate controls. Rats were exposed to a single blast wave using an Advanced Blast Simulator, inducing primary blast lung and bTBI. Survival was elevated in the hDNPs group compared to controls. Elevated anxiety parameters were found in the controls, compared to hDNPs. Histological analysis indicated that apoptosis and blood-brain barrier disruption in the amygdala were significantly increased in the controls compared to the hDNPs and sham groups. Immediate intervention is crucial to mitigate injury mechanisms that contribute to emotional deficits.
Immersion Bioprinting of Tumor Organoids in Multi-Well Plates for Increasing Chemotherapy Screening Throughput
Maloney, Erin; Clark, Casey; Sivakumar, Hemamylammal; Yoo, KyungMin; Aleman, Julio; Rajan, Shiny A. P.; Forsythe, Steven; Mazzocchi, Andrea R.; Laxton, Adrian W.; Tatter, Stephen B.; Strowd, Roy E.; Votanopoulos, Konstantinos I.; Skardal, Aleksander (MDPI, 2020-02-18)
The current drug development pipeline takes approximately fifteen years and $2.6 billion to get a new drug to market. Typically, drugs are tested on two-dimensional (2D) cell cultures and animal models to estimate their efficacy before reaching human trials. However, these models are often not representative of the human body. The 2D culture changes the morphology and physiology of cells, and animal models often have a vastly different anatomy and physiology than humans. The use of bioengineered human cell-based organoids may increase the probability of success during human trials by providing human-specific preclinical data. They could also be deployed for personalized medicine diagnostics to optimize therapies in diseases such as cancer. However, one limitation in employing organoids in drug screening has been the difficulty in creating large numbers of homogeneous organoids in form factors compatible with high-throughput screening (e.g., 96- and 384-well plates). Bioprinting can be used to scale up deposition of such organoids and tissue constructs. Unfortunately, it has been challenging to 3D print hydrogel bioinks into small-sized wells due to well–bioink interactions that can result in bioinks spreading out and wetting the well surface instead of maintaining a spherical form. Here, we demonstrate an immersion printing technique to bioprint tissue organoids in 96-well plates to increase the throughput of 3D drug screening. A hydrogel bioink comprised of hyaluronic acid and collagen is bioprinted into a viscous gelatin bath, which blocks the bioink from interacting with the well walls and provides support to maintain a spherical form. This method was validated using several cancerous cell lines, and then applied to patient-derived glioblastoma (GBM) and sarcoma biospecimens for drug screening.
Interactional dynamics of same-sex marriage legislation in the United States
Roy, Subhradeep; Abaid, Nicole (The Royal Society, 2017)
Understanding how people form opinions and make decisions is a complex phenomenon that depends on both personal practices and interactions. Recent availability of real-world data has enabled quantitative analysis of opinion formation, which illuminates phenomena that impact physical and social sciences. Public policies exemplify complex opinion formation spanning individual and population scales, and a timely example is the legalization of same-sex marriage in the United States. Here, we seek to understand how this issue captures the relationship between state-laws and Senate representatives subject to geographical and ideological factors. Using distancebased correlations, we study how physical proximity and stategovernment ideology may be used to extract patterns in statelaw adoption and senatorial support of same-sex marriage. Results demonstrate that proximal states have similar opinion dynamics in both state-laws and senators’ opinions, and states with similar state-government ideology have analogous senators’ opinions. Moreover, senators’ opinions drive statelaws with a time lag. Thus, change in opinion not only results from negotiations among individuals, but also reflects inherent spatial and political similarities and temporal delays. We build a social impact model of state-law adoption in light of these results, which predicts the evolution of state-laws legalizing same-sex marriage over the last three decades.
Intercomparison of Small Unmanned Aircraft System (sUAS) Measurements for Atmospheric Science during the LAPSE-RATE Campaign
Barbieri, Lindsay; Kral, Stephan T.; Bailey, Sean C. C.; Frazier, Amy E.; Jacob, Jamey D.; Reuder, Joachim; Brus, David; Chilson, Phillip B.; Crick, Christopher; Detweiler, Carrick; Doddi, Abhiram; Elston, Jack; Foroutan, Hosein; González-Rocha, Javier; Greene, Brian R.; Guzman, Marcelo I.; Houston, Adam L.; Islam, Ashraful; Kemppinen, Osku; Lawrence, Dale; Pillar-Little, Elizabeth A.; Ross, Shane D.; Sama, Michael P.; Schmale, David G. III; Schuyler, Travis J.; Shankar, Ajay; Smith, Suzanne W.; Waugh, Sean; Dixon, Cory; Borenstein, Steve; de Boer, Gijs (MDPI, 2019-05-10)
Small unmanned aircraft systems (sUAS) are rapidly transforming atmospheric research. With the advancement of the development and application of these systems, improving knowledge of best practices for accurate measurement is critical for achieving scientific goals. We present results from an intercomparison of atmospheric measurement data from the Lower Atmospheric Process Studies at Elevation—a Remotely piloted Aircraft Team Experiment (LAPSE-RATE) field campaign. We evaluate a total of 38 individual sUAS with 23 unique sensor and platform configurations using a meteorological tower for reference measurements. We assess precision, bias, and time response of sUAS measurements of temperature, humidity, pressure, wind speed, and wind direction. Most sUAS measurements show broad agreement with the reference, particularly temperature and wind speed, with mean value differences of 1.6 ± 2.6 ∘ C and 0.22 ± 0.59 m/s for all sUAS, respectively. sUAS platform and sensor configurations were found to contribute significantly to measurement accuracy. Sensor configurations, which included proper aspiration and radiation shielding of sensors, were found to provide the most accurate thermodynamic measurements (temperature and relative humidity), whereas sonic anemometers on multirotor platforms provided the most accurate wind measurements (horizontal speed and direction). We contribute both a characterization and assessment of sUAS for measuring atmospheric parameters, and identify important challenges and opportunities for improving scientific measurements with sUAS.
Investigating dielectric properties of different stages of syngeneic murine ovarian cancer cells
Salmanzadeh, Alireza; Sano, Michael B.; Gallo-Villanueva, R. C.; Roberts, Paul C.; Schmelz, Eva M.; Davalos, Rafael V. (American Institute of Physics, 2013-01-01)
In this study, the electrical properties of four different stages of mouse ovarian surface epithelial (MOSE) cells were investigated using contactless dielectrophoresis (cDEP). This study expands the work from our previous report describing for the first time the crossover frequency and cell specific membrane capacitance of different stages of cancer cells that are derived from the same cell line. The specific membrane capacitance increased as the stage of malignancy advanced from 15.39 +/- 1.54 mF m(-2) for a non-malignant benign stage to 26.42 +/- 1.22 mF m(-2) for the most aggressive stage. These differences could be the result of morphological variations due to changes in the cytoskeleton structure, specifically the decrease of the level of actin filaments in the cytoskeleton structure of the transformed MOSE cells. Studying the electrical properties of MOSE cells provides important information as a first step to develop cancer-treatment techniques which could partially reverse the cytoskeleton disorganization of malignant cells to a morphology more similar to that of benign cells. (C) 2013 American Institute of Physics. [http://dx.doi.org/10.1063/1.4788921] Actual pdf downloaded from NCBI.
Lagrangian coherent structures are associated with fluctuations in airborne microbial populations
Tallapragada, Phanindra; Ross, Shane D.; Schmale, David G. III (American Institute of Physics, 2011-09-01)
Many microorganisms are advected in the lower atmosphere from one habitat to another with scales of motion being hundreds to thousands of kilometers. The concentration of these microbes in the lower atmosphere at a single geographic location can show rapid temporal changes. We used autonomous unmanned aerial vehicles equipped with microbe-sampling devices to collect fungi in the genus Fusarium 100 m above ground level at a single sampling location in Blacksburg, Virginia, USA. Some Fusarium species are important plant and animal pathogens, others saprophytes, and still others are producers of dangerous toxins. We correlated punctuated changes in the concentration of Fusarium to the movement of atmospheric transport barriers identified as finite-time Lyapunov exponent-based Lagrangian coherent structures (LCSs). An analysis of the finite-time Lyapunov exponent field for periods surrounding 73 individual flight collections of Fusarium showed a relationship between punctuated changes in concentrations of Fusarium and the passage times of LCSs, particularly repelling LCSs. This work has implications for understanding the atmospheric transport of invasive microbial species into previously unexposed regions and may contribute to information systems for pest management and disease control in the future.

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