bluuebunny/crossref_metadata_2025 huggingface dataset:
Comprehension of emotion in neurodegenerative disorders
Authors:   , Davis Kelly L. , Chute Douglas L.
Published: July 2021

Recent evidence indicates that the posterior corpus callosum is smaller in patients with Alzheimer's disease (AD). Conversely, it has been demonstrated that patients with frontal systems deficits also have degradation of the anterior corpus callosum. Although these investigations indicate possible morphological relationships between the corpus callosum and cortical structures in neurodegenerative disorders, the relationship between specific neuropsychological measure of cognitive functioning and morphological measurements of the corpus callosum have not been established. This investigation examined the relationship between degeneration of the corpus callosum using magnetic resonance imagine (MRI) and neuropsychological data in cognitively demented patients in an attempt to identify a neuropsychological index of cortical and cognitive integrity. It was hypothesized that mid-saggital area measurements of the posterior corpus callosum would be related to cognitive measures of memory and language. Similarly, it was predicted that measurements of the anterior corpus callosum would be related to assessments of executive function. Further, it was predicted that selective degradation of anterior and posterior callosal structures would discriminate between subcortical ischaemic vascular dementia (IVD) and AD, respectively. Participants included nine individuals diagnosed with AD and eight with IVD, who were comparable for age (AD-79.78 yrs., SD=4.02; IVD=76.75, SD=5.06), education, level of dementia, depression and handedness. Contrary to expectations, negative correlations were found between measures of working memory and anterior regions of the corpus callosum (r=-.72, p<.001). Also, positive correlations associated measures of long delay verbal declarative memory (r=.55, p<.05). Also contrary to expectations, posterior regions were negatively associated with clock drawing to command (r=-.62, p<.001), and positively correlated with measure of graphomotor perseverations (r=.51, p<.05). Area measurements of callosal regions did not discriminate between groups, however, the mean values for all regions suggested the corpora callosa of the AD group was larger than that of the ischaemic vascular cohort. In context of recent literature comparing various dementia groups to healthy referents, it appears that the morphology of the corpus callosum is a sensitive, yet not specific index of cortical integrity. The implications of these unanticipated results and suggestions for future investigation are discussed.
Combined use of multiple monoclonal antibodies targeting epidermal growth factor receptor for improved cancer therapeutics
Authors:   , Kamat Vishal Gopalkrishna , Papazoglou Elisabeth S.
Published: July 2021

Epidermal growth factor receptor (EGFR) overexpression and its deregulated signaling is one of the hallmarks of multiple neoplasms. Although the use of monoclonal antibodies (mAbs) binding to the ectodomain of EGFR has shown promising results in inhibiting tumor progression, clinical failures in the anticipated outcome resulted in exploring new modalities for improved treatment. During the initial phase of this thesis, we observed that combined use of two EGFR targeting mAbs - mAb425 (EMD55900) and C225 (Cetuximab/Erbitux), synergistically inhibited the growth and EGF dependent signaling of EGFR overexpressing breast cancer cells. This observation has led to an effort to identify the mechanisms that govern the synergistic behavior. Binding competition and mutagenesis studies showed that mAb425 and C225 had distinct binding epitopes. mAb425/C225 combination inhibited EGF binding more efficiently than individual mAbs. EGF disrupted mAb-EGFR complexes containing individual mAbs but not the complexes with mAb combination. Further flow cytometry and surface plasmon resonance analysis suggested that both the mAbs were able to recognize most of the conformational states of EGFR. Overall, these results indicate that simultaneous binding of two non-competing mAbs, mAb425 and C225 stabilizes the inactive form of the receptor which EGF cannot recognize; thus achieving efficient inhibition of EGF binding. We also observed that co-incubation with mAb425 and C225 resulted in enhanced EGFR downregulation, compared to individual mAbs. The use of Fab fragments showed no significant receptor internalization. Monovalent Fab fragments failed to inhibit cell growth and EGF dependent signal transduction, suggesting that EGFR crosslinking by bivalent IgG molecules is required for inhibition. Live cell confocal imaging showed that mAb combination significantly reduced receptor recycling. Collectively these results suggest that EGFR oligomerization by mAb425/C225 combination is vital for synergistic receptor downregulation. We believe that the mechanisms of synergy presented may be further extended to other mAb combinations. Such combinations could synergize by adopting the efficient ligand blocking, faster EGFR downregulation, or a combination of both these mechanisms. We hope that the information gained from these studies may be used as a model to guide researchers to engineer novel mAbs and accelerate their transition from bench to clinic.
Mechanisms of interaction of non-thermal plasma with living cells
Authors:   , Kalghatgi Sameer Ulhas , Friedman Gary G.
Published: July 2021

Thermal plasmas and lasers have been widely used in medicine to cut, ablate and cauterize tissues through heating; in contrast, non-thermal plasma produces various highly active molecules and atoms without heat. As a result, its effects on living cells and tissues could be selective and tunable. This makes non-thermal plasma very attractive for medical applications. However, despite several interesting demonstrations of non-thermal plasma in blood coagulation and tissue sterilization, the biological and physical mechanisms of its interaction with living cells are still poorly understood impeding further development of non-thermal plasma as a clinical tool. Although several possible mechanisms of interaction have been suggested, no systematic experimental work has been performed to verify these hypotheses. Using cells in culture, it is shown in this work that non-thermal plasma created by dielectric barrier discharge (DBD) has dose-dependent effects ranging from increasing cell proliferation to inducing apoptosis which are consistent with the effects of oxidative stress. DNA damage is chosen as a marker to assess the effects of oxidative stress in a quantitative manner. It is demonstrated here that plasma induced DNA damage as well as other effects ranging from cell proliferation to apoptosis are indeed due to production of intracellular reactive oxygen species (ROS). We found that DNA damage is initiated primarily by plasma generated active neutral species which cannot be attributed to ozone alone. Moreover, it is found that extracellular media and its components play a critical role in the transfer of the non-thermal plasma initiated oxidative stress into cells. Specifically, it is found that the peroxidation efficiency of amino acids is the sole predictor of the ability of the medium to transfer the oxidative stress induced by non-thermal plasma. Phosphorylation of H2AX, a DNA damage marker, following plasma treatment is found to be ATR dependent and ATM independent, suggesting that non-thermal plasma may induce formation of bulky lesions unlike ionizing radiation (IR) or H₂O₂ which primarily produce DNA double strand breaks. Moreover, it is found that the pathway by which plasma generated oxidative stress is transferred across cellular membranes does not involve lipid peroxidation by-products, although lipid peroxidation does occur.
Characterization of environmentally-friendly alkali activated slag cements and ancient building materials
Authors:   , Sakulich Aaron Richard , Barsoum Michel W.
Published: July 2021

Alternative cement technologies are an area of increasing interest due to growing environmental concerns and the relatively large carbon footprint of the cement industry. Many new cements have been developed, but one of the most promising is that made from granulated, ground blast furnace slag activated by a high-pH solution. Another is related to the discovery that some of the pyramid limestone blocks may have been cast using a combination of diatomaceous earth activated by lime which provides the high pH needed to dissolve the diatomaceous earth and bind the limestone aggregate together. The emphasis of this thesis is not on the latter - which was explored elsewhere - but on the results supplying further evidence that some of the pyramid blocks were indeed reconstituted limestone. The goal of this work is to chemically and mechanically characterize both alkali-activated slag cements as well as a number of historic materials, which may be ancient analogues to cement. Alkali activated slag cements were produced with a number of additives; concretes were made with the addition of a fine limestone aggregate. These materials were characterized mechanically and by XRD, FTIR, SEM, and TGA. Samples from several Egyptian pyramids, an 'ancient floor' in Colorado, and the 'Bosnian Pyramids' were investigated. In the cements, it has been unequivocally shown that C-S-H, the same binding phase that is produced in ordinary portland cement, has been produced, as well as a variety of mineral side products. Significant recarbonation occurs during the first 20 months, but only for the Na2CO3-activated formulae. Radiocarbon dating proves that the 'Bosnian Pyramids' and 'ancient floors' are not made from any type of recarbonated lime; however, Egyptian pyramid limestones were finite, thus suggesting that they are of a synthetic nature. XRD and FTIR results were inconclusive, while TGA results indicate the limestones are identical to naturally occurring limestones, and SEM/EDS analysis shows the presence of a Si-rich species.
Mobility management architecture and modeling for label switched networks (mobility label based network)
Authors:   , Berzin Oleg , Daryoush Afshin S.
Published: July 2021

With the proliferation of IP based mobile applications network layer mobility management is expected to play an increasingly significant role in the architectures of the mobile networks. The mobile network evolution offers higher data rates and lower latencies that target mobile-to-mobile traffic patterns and applications that are all based on IP. However, the underlying network layer mobility management schemes employed in the 3G and 4G architectures are not optimized for mobile-to-mobile traffic patterns and result in the user- as well as the network-facing performance penalties that may be considered as inhibiting factors in the network evolution. We present a Mobility Label Based Network (MLBN) - a new approach to the network layer mobility management that relies on Multi-Protocol Label Switching (MPLS) and provides native integration between the MPLS-aware control and the MPLS-based forwarding planes. MLBN is a scalable, survivable hierarchical mobility management system capable of providing macro- and micro-mobility for IPv4 or IPv6 mobile hosts or routers without the use of Mobile IP while guaranteeing optimal traffic routing between the communicating mobile devices. MLBN uses MPLS to decouple the IP address assigned to a mobile node or a prefix served by a mobile router from the logical topology of the IP network thus resolving a topological conflict associated with the move of a mobile node from a home to a foreign IP network. When a user connects to the MLBN the mobile device is associated with a Mobility Label while maintaining the original IP address. The Mobility Label is then bound to the device's IP address at the edge of the MLBN and this binding is advertised using the MPLS-aware control plane protocol into the label switched network. We show that it is possible to effectively update the network following the mobile node movements and perform optimal packet routing based on the modifiable sequence of the Label Switched Paths.
Ultrasound sensitive polymeric drug carriers for treatment of solid tumors
Authors:   , Eisenbrey John , Wheatley Margaret A.
Published: July 2021

Ultrasound contrast agents (UCA) are comprised of microbubbles stabilized by a shell. The benefits of ultrasound (US) to parenteral drug delivery are well documented. In conjunction with US-induced cavitation of co-administered UCA they include an increase in drug efficacy due to increases in both vascular gap junctions and cellular membrane permeabilities. We have developed a drug-loaded UCA which upon reaching the desired site (generally a solid tumor) ruptures under the influence of the focused US. UCA cavitation, combined with acoustic radiation forces, and the enhanced permeation and retention effect (EPR) are expected to increase tumor uptake of the produced fragments, providing a sustained, intratumoralrelease of any associated drug. In this thesis, poly (lactic acid) (PLA) UCA have been developed for drug delivery utilizing doxorubicin (Dox). These agents provide 15-20 dB of US contrast enhancement both in vitro and in vivo. The agents have been optimized to encapsulate Dox while maintaining a high sensitivity to US. Prior to sonication these agents have a mean diameter of 1.4-1.8 [mu]m, restricting them to the vasculature until rupture. In vitro data indicate particles reach sizes of 200-400 nm after sonication. Electron microscopy of ruptured particles depicts both fragmentation and shriveling of shells, resulting in sub-micron, drug loaded particles. In vitro these agents become significantly more potent to the human breast cancer cell line MDA-MB-231 after sonication, nearly doubling the degree of cell death compared to non-insonated controls (p=0.0272). Microscopy shows that Dox from the fragments is transported to the cell nucleus once within the cell. Additionally, during US triggered generation, Dox eluting species can be forced through a 0.4 [mu]m membrane. These data demonstrate potential for a PLA-Dox UCA platform to deliver Dox eluting nanoparticles to the tumor interstitium. Elution profiles have been measured, indicating that 76% of drug payload is released over a 24 day period. Studies using VX2 tumors in rabbits show the activated platform is detectable within tumor vasculature and results in substantial increases in intratumoral drug levels with greater than a 100% increase in delivery efficiency compared to the noninsonated platform (p=0.004)
Comparison of acceptance-based and standard cognitive-based coping strategies for craving sweets in overweight and obese women
Authors:   , Hoffman Kimberly Lynn , Herbert James D. , Forman Evan M.
Published: July 2021

Though obesity is reaching epidemic proportions, behavioral weight management programs have proven to be only moderately effective in the short-term, and minimally effective in the long-term. The limited success of behavioral interventions for weight loss is likely due to the difficulty that participants experience in trying to adhere to the behavioral regimen necessary for weight loss. Most importantly, weight loss and maintenance require strict adherence to a low-calorie diet, which requires the ability to resist food cravings. The present study utilized an analogue paradigm to investigate the effectiveness of coping strategies for sweet cravings. The primary objective of this study was to determine what type of coping strategy would be most effective at helping overweight and obese women manage sweet cravings and whether the effectiveness varied as a function of susceptibility to the presence of food and tendency to engage in emotional eating. Seventy-three overweight and obese women were recruited from the community and were randomized to one of three groups: a standard cognitive-based coping strategy group, an acceptance-based coping strategy group, or a no intervention group for managing cravings for sweets. Because converging evidence suggested that the no intervention group was non-compliant with study requirements, comparisons between the two active intervention groups were emphasized. The overall pattern suggested that acceptance-based coping strategies may offer an advantage in helping overweight and obese women manage and resist acting on sweet cravings. In particular, this study suggests that acceptance-based strategies may be especially beneficial for those who demonstrate the highest levels of susceptibility to the presence of food and tendency to engage in emotional eating. While the findings must be considered cautiously given several limitations of the study design (e.g., problems with the no intervention group and small sample size), the results raise the possibility that acceptance-based approaches may have an important place in obesity management programs.
Posttraumatic stress in adolescents with HIV and its relationship with treatment adherence
Authors:   , Weinberger Beverley Slome , Kloss Jacqueline D.
Published: July 2021

Objective: The introduction of HAART has led to increased life expectancy among youth with HIV, however, it poses challenges including complex drug regimens that require strict adherence by patients. Treatment adherence by youth with HIV is generally considered suboptimal, although adherence reports vary by the method of assessment used. Given the prevailing problem of treatment adherence in this population, research has focused on identifying factors contributing to nonadherence. Research on adults with HIV and children with other chronic illnesses suggests that posttraumatic stress disorder (PTSD), posttraumatic stress symptoms (PTSS), and health beliefs may be important factors relating to nonadherence. This study investigated the prevalence of PTSS in a sample of adolescents and young adults perinatally and behaviorally-infected with HIV. The relationship of PTSS with treatment adherence and the role of internal health locus of control (IHLC) were explored. Methods: Twenty-eight participants (M age = 17.14, SD = 3.05; range = 12-22) recruited from a pediatric immunology clinic completed measures of life events, posttraumatic stress symptoms, and health locus of control. Measures of treatment adherence used included: viral load count, CD4 count, and provider ratings of adherence. Results: Findings revealed relatively good adherence levels and low disease severity among the sample. Eighty-two percent of participantsreported experiencing a least one HIV-related traumatic event and 75% of participants reported experiencing at least one non-HIV related traumatic event. Posttraumatic stress symptom severity scores fell in the moderate range of severity for both HIV-related and general traumas. No differences were found in trauma scores based on mode of transmission or developmental level (adolescents vs. young adults). Provider ratings of adherence and viral load were correlated with PTSS. IHLC did not demonstrate a significant indirect effect on the relationship between treatment adherence and PTSS. Discussion: Difficulties in recruitment for this study point to the many stressors facing youth with HIV and the barriers to successful recruitment of ethnic minority participants in research. Findings highlight the need to address psychosocial problems among youth with HIV, in particular posttraumatic stress, in order to improve treatment adherence and health outcomes. Further research is needed to clarify the role of health beliefs as they relate to health-promoting behaviors in this population. Additionally, future research is needed to establish standardized, valid, reliable, and cost-effective measures of adherence. Barriers to recruitment and retention of ethnic minority participants must also be addressed. Findings are limited by small sample size, low power, and restriction of range in data.
Semi-degradable, multi-functional hydrogels for the repair of articular cartilage defects
Authors:   , Spiller Kara Lorraine , Lowman Anthony M.
Published: July 2021

Cartilage cannot undergo spontaneous repair because of a lack of access to the blood supply, so cartilage defects progressively deteriorate into osteoarthritis. The typical approach for tissue engineering is the cultivation of cells on degradable scaffolds such as poly(glycolic acid) (PGA). The cartilage tissue that results from this method integrates well with surrounding tissue when implanted into cartilage defects. However, the mechanical and biochemical properties are inferior to healthy cartilage, and the tissue eventually degrades. Poly(vinyl alcohol) (PVA) hydrogels, on the other hand, have long been studied for cartilage replacement because of their similar mechanical and material properties, but their complete lack of integration with surrounding cartilage as implants has impeded their utility. The combination of the integrative properties of PGA scaffolds with the mechanical properties of PVA hydrogels may allow their use as implants. PVA hydrogels were made porous through a novel technique of microparticle incorporation. Average pore sizes ranged from 60 to 300[mu]m. Cartilage cells could be seeded throughout the porous network and induced to develop healthy cartilage tissue. Since PVA hydrogels are nondegradable, the result was a hybrid hydrogel-cartilage construct that may integrate well with surrounding tissue. Moreover, the nondegradable nature of the PVA hydrogel would prevent the mechanical properties from diminishing over time, as is the case with degradable scaffolds. These superporous, semi-degradable hydrogels were evaluated as cartilage replacement materials in terms of their dynamic structure, mechanical properties, and swelling properties, over the course of swelling in model osmotically conditioned systems. The hydrogels were then characterized for their ability to support cartilage formation by encapsulated cells and the effects of controlled release of growth factors to enhance cartilage formation and integration between the hydrogels and the surrounding tissue. The results demonstrate that these PVA-based hydrogels have the potential to effectively replace damaged cartilage, because they have similar mechanical and swelling properties that are stable over the long-term, and support cartilage formation and integration with surrounding tissue. A novel technique is also described for evaluating the swelling properties of biomaterials in a model system that can be applied to many other types of biomaterials and tissues.
Ion transport in polymer/ionic liquid films
Authors:   , Gwee Liang , Elabd Yossef A.
Published: July 2021

Solid state-polymer electrolytes with high ionic conductivities are the subject of extensive research for a wide variety of electrochemical applications that include batteries, fuel cells, solar cells, super capacitors and actuators. However, the use of traditional polymer electrolytes is limited due to their reliance on volatile solvents for ion dissociation. The use of non-volatile organic solvents known as ionic liquids (ILs) in polymer electrolytes has recently been explored to overcome this limitation, but fundamental insights regarding the factors that affect ion conductivity in polymer/IL systems are missing. Ionic liquids are intriguing solvents due to their negligible vapor pressures, high ionic conductivities, wide electrochemical windows, and excellent chemical stability. In this work, we focus on the solid-state properties of polymer/IL mixtures and their potential impact to solid-state energy devices. Neutral homopolymer/IL mixtures and charged homopolymer (imidazolium-based polymerized IL)/ionic liquid mixtures were prepared to study the effect of compatibility and glass transition temperature on ion transport. Also, neutral diblock copolymer/ionic liquid mixtures were used to study the effect of IL content on nanoscale morphology and its subsequent impact on ion transport. In addition, the transport and mechanical properties of an actuator were investigated using a new experimental technique that was developed specifically for this purpose. The experiment uses time-resolved FTIR-ATR spectroscopy to study ion diffusion on a molecular level in a polymer/IL actuator when it was subject to an external electric field, while simultaneously measuring polymer strain using a real-time imaging.
Neural plasticity following anterior temporal lobectomy
Authors:   , Mechanic-Hamilton Dawn J. , Williams J. Michael
Published: July 2021

This study followed patients with temporal lobe epilepsy from pre to post-surgical status in order to investigate neuroplasticity and recovery of memory function. Functional changes were characterized using BOLD fMRI acquisition during a scene memory encoding task. Neuropsychological testing provided a means of investigating memory function over time. Twenty patients, who were included in a prior investigation, were entered into this study before surgery, those who completed surgery (N=14) and were eligible were studied at one time-point after surgery and a cohort of those patients (N=11) were studied at an additional time-point after surgery. Fifteen controls were studied, with ten controls returning for a second scanning session. Patterns of functional activation were examined over time throughout the whole brain, as an asymmetry score between the posterior temporal lobe on the ipsilesional and contralesional side, and within the hippocampus and parahippocampus on the contralesional side. Age of onset, side of seizure and neuropsychological outcome were examined as factors contributing to neural plasticity. Subjects with a late age of onset showed declines on more neuropsychological measures than those with an early age of onset. Control HPF asymmetries remained relatively stable across time, while the subjects with TLE showed increases in asymmetry post-surgically. Whole brain activation pattern changes were evident in the posterior temporal lobes in both right and left-side seizure groups from the pre to first post-surgical scan. The right-side seizure group showed a reversal of change in activation at the second post-surgical time-point, as well as an effect of age of onset which included medial frontal activation for the early onset group. The right-side seizure subjects consistently showed more contralateral (left-side) activation, compared to subject with left-side seizure. The HPF asymmetries became larger after surgery for both groups combined. Right and left-side seizure groups showed negative correlations between change in visual memory and post-surgical contralateral activation and positive correlations between change in verbal memory measures and post-surgical contralateral activation. Overall, subjects with TLE showed both functional and dysfunctional changes in activation from the pre to post-surgical time-points.
Immune-nanotoxicity of zinc oxide nanoparticles
Authors:   , McHugh Michael D. , Papazoglou Elisabeth S.
Published: July 2021

The prospect of nanotechnology is exciting not only for its promise to miniaturize complex devices, but perhaps even more so because of the unconventional characteristics exhibited by many nano-sized materials. Zinc oxide (ZnO) nanoparticles are being explored for applications ranging from sunscreens, to advanced textiles, to self-charging electronic devices. As their industrial production accelerates, attention must be given to their potential to interact with organisms and ecosystems in unexpected ways. The goal of this work was to assess the interaction of ZnO nanoparticles with immune cell cultures consisting of various cell types to identify the mechanisms underlying ZnO nanotoxicity. Using immunofluorescent staining and flow cytometry, the effect of ZnO nanoparticles on various murine immune cell types was studied. After preliminary viability testing using AnnexinV and Live/Dead staining, ZnO were shown to be significantly more toxic than titanium dioxide nanoparticles and gold nanoparticles, and they began inducing apoptosis within eight hours in culture at 50 [mu]g/ml. To evaluate the role of particle uptake into cells and explore surface modification techniques applicable to ZnO nanoparticles, a coating of polyethylene glycol (PEG) was conjugated to the nanoparticle surface through hydrogen-bonding, but it did not attenuate nanotoxicity. Upon further characterization, the PEGylated ZnO surface was found to have adsorbed serum proteins, possibly due to the non-uniform molecular architecture of PEG. Protein adsorption may have therefore been responsible for permitting nanoparticle internalization. As an alternative, ZnO nanoparticle-treated cells were treated with extracellular inhibitors of suspected ROS and cation mechanisms, and the antioxidant enzyme catalase was found to significantly reduce ZnO nanotoxicity, implicating a role of extracellular H₂O₂. Using an intracellular reactive oxygen detection dye, 2',7'-di-chlorofluorescein diacetate, ZnOnanoparticles were shown to induce an "oxidative burst" within the cell, which was not reduced by catalase. Taken together, catalase inhibition studies reveal that ZnO nanotoxicity within splenocyte cultures may act largely through apoptotic signaling between cell types. Future strategies to engineer safe nano ZnO may therefore include catalase-mimicking components, such as nano platinum.
Reconstruction of cluster masses using particle based lensing
Authors:   , Deb Sanghamitra , Goldberg David M.
Published: July 2021

Clusters of galaxies are among the richest astrophysical data systems, but to truly understand these systems, we need a detailed study of the relationship between observables and the underlying cluster dark matter distribution. Gravitational lensing is the most direct probe of dark matter, but many mass reconstruction techniques assume that cluster light traces mass, or combine different lensing signals in an ad hoc way. In this talk, we will describe "Particle Based Lensing" (PBL), a new method for cluster mass reconstruction, that avoids many of the pitfalls of previous techniques. PBL optimally combines lensing information of varying signal-to-noise, and makes no assumptions about the relationship between mass and light.we will describe mass reconstructions in three very different, but very illuminating cluster systems: the "Bullet Cluster"(1E 0657-56), A901/902 and A1689. The "Bullet Cluster" is a system of merging clusters made famous by the first unambiguous lensing detection of dark matter. A901/902 is a multi-cluster system with four peaks, and provides an ideal laboratory for studying cluster interaction. we am particularly interested In measuring and correlating the dark matter clump ellipticities. A1689 is one of the richest clusters known, and has significant substructure at the core. It is also my first exercise in optimally combining weak and strong gravitational lensing in a cluster reconstruction. we find that the dark matter distribution is significantly clumpier than indicated by X-ray maps of the gas.we conclude by discussing various potential applications of PBL to existing and future data.
Microencapsulation for therapeutic applications
Authors:   , Dhoot Nikhil , Wheatley Margaret A.
Published: July 2021

Microencapsulation has proved to be a powerful technique in the field of drug delivery. A great deal of research is directed towards studying the use of various microencapsulation systems for that purpose. This study investigates the use of microencapsulation in alginate for protein delivery and delivery of gene therapy products for the treatment of spinal cord injury. Liposomes were encapsulated in alginate to form a drug delivery system which allows for multiple control points for drug release. We found that the crosslinking ion has a marked effect on the release profile. PC/Chol and PC/PG/Chol liposomes encapsulated in Ca²⁺ crosslinked alginate released protein rapidly in the form of a burst which was eliminated by crosslinking the alginate with Ba2+. Liposome composition also plays an important role in the release from microencapsulated liposomes. DOPC and DOPC/Chol liposomes showed a delayed pulse of protein release which could be useful for vaccine delivery. Unextruded REV's demonstrated the capability of obtaining protein release in a pulsatile manner after encapsulation in alginate. Our studies also showed that encapsulation in alginate made the liposomes leakier and this was the result of a co-operative effect of alginate and the crosslinking ions. Fibroblasts that were genetically engineered to produce BDNF were encapsulated in alginate. In vitro studies showed that the encapsulated cells continue to grow, express the transgene and BDNF is released from the microcapsules in an active form. These encapsulated cells were transplanted into the injured spinal cord of rats that were not immune suppressed. We found that the encapsulated cells survived in vivo and continued to express the transgene. This showed that encapsulation protected the cells from the host immune system. The transplanted capsules evoked a non-specific immune response and also resulted in sprouting of axons in the transplant area. The axonal growth observed increased with time. Behavioral studies showed a recovery of function in the injured forelimb of the rats almost up to baseline levels over 5 weeks. Finally, we studied a peptide-alginate conjugate as a permissive surface for growth of neurons such that it could be applied in combination with the encapsulated cells.
Distribution and abundance of non-native red-eared slider turtles (Trachemys scripta elegans) and native red-bellied turtles (Pseudemys rubriventris)
Authors:   , Stone Julia Elizabeth , Avery Harold W. , Spotila James Robert
Published: July 2021

Habitat destruction and introduction of non-native species are among the greatest threats to the Earth's biodiversity. The threatened red-bellied turtle, Pseudemys rubriventris, historically prevalent throughout the Mid-Atlantic region, is now restricted to a few fragmented wetlands. In addition to destruction of wetland habitat, introduction of the nonnative red-eared slider turtle, Trachemys scripta, may play an important role in the decline of red-bellied turtle populations. Because the niches occupied by these two turtle species overlap, the invasion of red-eared slider turtles represent a threat to the red-bellied turtle as a competitor for limited wetland resources. In 2005 and 2006 we assessed 52 wetlands throughout Southeastern Pennsylvania for the occurrence of red-eared slider turtles in historic red-bellied turtle habitat. Trachemys scripta occurred at 25 of the 52 wetlands. Thus, T. scripta are pervasive within the geographic range of P. rubriventris in Southeastern Pennsylvania. From 2007 to 2009 I used mark-recapture to determine relative abundances of the two species in different wetlands. GIS-based landscape data was used to determine relationships between habitat degradation and relative abundances of both turtle species. I found a negative relationship between our human impact rank and the relative abundance of P. rubriventris. I found a lower relative abundance of red-bellied turtles in wetlands in public parks. There was no significant difference in relative abundance between the two methods, trapping and observation of basking turtles. Four observation visits were sufficient to detect turtles. The data provide wildlife and habitat management agencies important information on the relationship between invasive T. scripta, the state threatened P. rubriventris and wetland characteristics.
Life stress, social problem solving and asthma
Authors:   , McCormick Sean P. , Nezu Christine M.
Published: July 2021

Asthma is an immuno-inflammatory condition of the respiratory system. Clinical wisdom and previous scientific research suggest that life stress negatively impacts asthma. However, the nature of the stress-asthma relationship remains largely unclear. One hypothesis is that stress plays a multifaceted role, affecting asthma through the nervous and immune systems, and through behavioral pathways, such as disease selfmanagement. Social problem-solving ability has been shown to play an important role in mediating the connections between stress and other chronic diseases, such as heart disease, diabetes and cancer. The coping abilities of individuals with asthma may also play a role as mediators of the stress-asthma relationship. The presented research is the first to examine the life stress and social problem-solving abilities of asthma patients in relation to their asthma control and asthma-related quality of life. The hypothesis that negative stressful life events would be associated with poor asthma control and asthmarelated quality of life was not supported. Likewise, tests of the hypothesis that social problem-solving would mediate the stress-asthma relationship could not be conducted due to lack of statistical power. However, a statistically significant correlation was found between social problem-solving and asthma control and asthma-related quality of life. Problem-solving styles and asthma-related quality of life exhibited the strongest correlation. These results suggest that the social problem-solving framework is a potentially important factor in asthma morbidity and may be potentially fruitful avenues for improving patient's capacity for successful asthma self-management.
Singular value decomposition based pipeline architecture for MIMO communication systems
Authors:   , Wang Yue , Nagvajara Prawat , Johnson Jeremy Russell
Published: July 2021

This thesis presents a design, implementation and performance benchmark of custom hardware for computing Singular Value Decomposition (SVD) of the radio communication channel characteristic matrix. Software Defined Radio (SDR) is a concept in which the radio transceiver is implemented by software programs running on a processor. SVD of the channel characteristic matrix is used in pre-coding, equalization and beamforming for Multiple Input Multiple Output (MIMO) and Orthogonal Frequency Division Modulation (OFDM) communication systems (e.g., IEEE 802.11n). Since SVD is computationally intensive, it may require custom hardware to reduce the computing time. The pipeline processor developed in this thesis is suitable for computing the SVD of a sequence of 2 x 2 matrices. A stream of 2x2 matrices is sent to the custom hardware, which returns the corresponding streams of singular values and unitary matrices. The architecture is based on the two sided Jacobi method utilizing Coordinate Rotation Digital Computer (CORDIC) algorithms. A 2x2 SVD prototype was implemented on Field-Programmable Gate Array (FPGA) for SDR applications. The 2x2 SVD prototype design can output the singular values and the corresponding unitary matrices in pipeline while operating at a data rate of 324 MHz on a Virtex 6 (xc6vlx240t-lff1156) FPGA. The prototype design consists of fifty-five CORDIC cores which takes 32 percent of available logic on the FPGA. It achieves the optimal pipeline rate equaled to the maximum hardware clock rate. The depth of the pipeline (latency) is 173 clock-cycles for 16-bit data hardware. The proposed architecture provides performance gains over standard software libraries, such as the ZGESVD function of Linear Algebra PACKage (LAPACK) library, which is based on Golub-Kahan-Reinsch SVD algorithm, when running on standard processors. The ZGESVD function of LAPACK implemented in Intel's Math Kernel Library (MKL) will achieve a projected data rate of 40 MHz on a 2.50 GHz Intel Quad (Q9300) CPU. The pipeline SVD hardware ban width equals the clock frequency and the data rate can reach 324 MHz on the ML605 board (Virtex 6 xc6vlx240t). The proposed architecture also has the potential to be easily extended to solve 4x4 SVD problems used in pre-coding and equalization schemes. The proposed algorithm and design have better performance for small matrices, even though the general timing complexity is n2 when compared to nlog(n) complexity of Brent-Luk-Van Loan (BLV) systolic array using non-pipeline 2x2 processors. The performance gain of the proposed design is at the cost of increased circuit area.
Population genetics and conservation of the American crocodile on the Pacific coast of Costa Rica
Authors:   , Cotroneo Laurie Anne , Spotila James Robert
Published: July 2021

Crocodylus acutus ranges widely in the American neo-tropics. It is listed as vulnerable by the International Union for the Conservation of Natural Fauna and Flora (IUCN) and on Appendix I of the Convention for the International Trade in Endangered Species of Wild Flora and Fauna (CITES). Despite this listing, C. acutus remains poorly studied throughout much of its range. The objective of this study was to characterize the population genetic structure of C. acutus, on the Pacific coast of Costa Rica. Population assessments were conducted in four areas, Las Baulas, Santa Rosa and Palo Verde National Parks and the Osa Conservation Area to determine encounter rates, size class distributions and distributions within the areas. Non-hatchling crocodiles were encountered at rates ranging from 1.2 to 4.3 crocodile km-1. These encounter rates were comparable to or higher than other crocodilian studies. I collected 183 samples and genotyped them at nine microsatellite loci to describe the genetic diversity, gene flow, population subdivision and landscape genetics of C. acutus on the Pacific coast of Costa Rica. Crocodile populations on the Pacific coast were moderately genetically diverse with an average heterozygosity of 0.57. No population was in Hardy-Weinberg Equilibrium at all nine microsatellite loci. This suggested that genetic change was occurring. This change was probably caused by migration into and out of areas along the Pacific coast. There were 2.4 effective migrants per generation along the entire coast. The isolation by distance model was not supported over a straight-line, coastline or a cost distance analysis. Crocodiles were hypothesized to use a combination of streams and rivers, oceanic and overland routes for dispersal. Two model-based clustering analyses indicated that crocodiles were segregated into three populations along the coast. Las Baulas National Park formed an isolated cluster with both methods. This level of population subdivision supported the presence of metapopulations along the Pacific coast of Costa Rica and not one panmictic population. The results of this study show that crocodile populations in Costa Rica should not be managed as separate entities. Instead, they should be managed as interacting units of one large population.
Development of computational fluid dynamics based multiple linear and neural network metamodels for bioaerosol fate and transport in indoor environments
Authors:   , Hoque Shamia , Haas Charles N. , Farouk Bakhtier
Published: July 2021

Linear, quadratic, and artificial neural network (ANN) based metamodels were developed to predict bioaerosol fate and transport in indoor environments using computational fluid dynamic (CFD) simulations. The objective of the metamodels is to provide quick and relatively accurate information during emergencies. The response to the 2001 anthrax-release events indicate that decontamination of indoor spaces following the release of biological agents is challenging. The ability to efficiently and rapidly decontaminate rooms/buildings is limited by the lack of quantitative understanding of the behavior of bioaerosols and decontaminants in relation to building geometry, airflow pattern and surface properties. The work here addresses this challenge. The variables characterizing the system were identified and dimensionless groups were developed. Design of experiments was used to explore the design space and determine the multiple scenarios. The results derived from the CFD simulations of these scenarios were used to develop the metamodels. The CFD model comprised of multiple sub-models. Large eddy simulation (LES) with the Smagorinsky sub-grid scale model was applied to compute the airflow. Bioaerosols were modeled as a dispersed solid phase using the Lagrangian treatment. For inactivation studies disinfectant mass fraction was calculated by solving a mass transport equation. Kinetic decay constants were included for spontaneous decay of the disinfectant and for the reaction of the disinfectant with surfaces. An inactivation rate equation accounted for the reaction between the spores and the disinfectant. For the study of electrostatic forces the Poisson equation was solved to determine the electric field. The ANN based metamodels were most successful in predicting the number of viable bioaerosols remaining in an arbitrary enclosed space and their spatial heterogeneity. Sensitivity analysis showed that the ratio of the particle tracking time to residence time and the location of input and output with relation to the height of the room had the most impact. Mass fraction of the disinfectant, inactivation rate constant and contact time had the most influence on the inactivation of the spores. Screen voltage was the most significant variable influencing the dispersion of charged bioaerosols. To the best of the author's knowledge this is the first attempt of developing userfriendly models or metamodels for fate and transport of bioaerosols from CFD simulations. The metamodels besides being useful during emergencies also gives the opportunity to better understand the system and therefore provide information for designing more secure and safer indoor environments.
Optimization of wideband fiber optic hydrophone probe for ultrasound sensing applications
Authors:   , Minasamudram Rupa Gopinath , Daryoush Afshin S.
Published: July 2021

Acoustic characterization of medical ultrasound devices is needed for optimization of image quality in diagnostic applications and to ensure their safety and effectiveness in therapeutic applications. New generation of acoustic transducers operating at fundamental frequency 15 MHz are being developed and FDA requires that as many as 8 harmonics are considered for real-time pressuretime waveform measurements in dispersive nonlinear medium. Therefore, hydrophone probes are required to perform characterization of the acoustic output of these devices at least up to 100 MHz in terms of frequency response. The primary goal of this thesis is to develop a Fiber Optic Hydrophone Probe (FOHP) for spatial averaging free characterization of ultrasound field till 100 MHz. Spatial averaging free design of the sensor is based on optimization of fiber geometry to achieve an active fiber dimension of the order of 7 [mu]m to be comparable with half of the acoustic wavelength at 100 MHz. An innovative aspect of this work includes the development of a semi-empirical model for extraction of complex refractive index at optical wavelengths of 980 nm, 1480 nm and 1550 nm and stress-strain relationship of thin film gold for thickness ranging from 2nm-35nm. These are indispensable in modeling and optimization of 100 MHz FOHP in calculation of optimized pressure to voltage responsivity. For responsivity optimization, a novel multi-physics numerical model based on the Finite Element Method (FEM) was employed to solve electromagnetic, mechanics, and acoustics performance of the FOHP. The model and the selection of its input parameters, including coupled acousto-optic interaction of thin film gold, are based on published physical parameters and accurate extraction of various fiber parameters. Optimization results indicate that cylindrically etched FOHP with 6 [mu]m tip diameter and 5 nm gold coating provides the highest responsivity performance of - 234 dB re 1V/ [mu]Pa. The experimental verification of the thin film coated FOHP using 1 MPa pressure amplitude, produced unprecedented voltage responsivity between -234 and -254 dB re 1V/[mu]Pa or 2V/MPa and 200 mV/MPa, respectively. The optimum detection sensitivity of around 0.3 kPa is achieved by Relative Intensity Noise cancellation of 10 dB using balanced optical photo-detector.