bluuebunny/crossref_metadata_2025 huggingface dataset:
Functional properties of patient-derived human immunodeficiency virus type 1 long terminal repeat and the transactivator protein Tat
Authors:   , Li Luna , Su Ying-Hsiu , Wigdahl Brian
Published: July 2024

The human immunodeficiency virus type 1 (HIV-1) long terminal repeat (LTR) regulates viral gene expression. The viral transactivator protein Tat plays a pivotal role in transcriptional activation via interaction with the transactivation response element (TAR) of viral RNA. Studies in the pre-HAART era demonstrated HIV-1-infected peripheral blood (PB)-derived LTR variants containing a C-to-T change at position 3 of C/EBP site I (3T), or at position 5 of Sp site Ill (5T) were preferentially encountered in late stage disease. The 3T and 5T configurations exhibited low binding affinity for their cognate transcription factors. Our recent studies conducted during the HAART era have identified a number of HIV-1-infected patients within the DREXELM ED HIV/AIDS Genetic Analysis Cohort harboring LTR variants containing 5T Sp III. Transient expression analyses demonstrated that most LTRs containing either the 5T or co-selected 3T/5T configurations exhibited basal, stimulated, and Tat-mediated transcription activities similar to LTRs carrying the conB sequence at these LTR binding sites in Jurkat T cells and monocytic U-937 cells. However, the patient 19 clone 18 5T-containing LTR could not be transactivated by either the laboratory strain IIIB Tat or by Tat derived from the patient 19. When nucleotide +32 (A) of the TAR element of the defective 19-18 LTR was changed to conB (G), Tat-mediated LTR transactivation was only partially restored. However, this could be further enhanced by changing the sequence of the three Sp binding sites to the conB sequence. Results also indicate that selective pressures are likely placed on the virus at least during discrete phases of HIV disease that result in a viral LTR-Tat structural complex that may be more optimized for more effective viral transcription, possibly in specific cellular phenotypes. Furthermore, results are reported that suggest the HIV-1 Tat exon II may contain molecular determinants that play an important role in LTR-directed Tat-mediated transactivation at low concentrations of transactivator protein. The results suggest that genetic variation in Tat exon II may have more impact on Tat-mediated transactivation at low Tat concentrations that may be present during activation from latency, as compared to productive replication in CD4+ T cells.
Lipoproteins and exchangeable apolipoproteins
Authors:   , Boyle Kathleen Erin , Lund-Katz Sissel
Published: July 2024

Although the importance of apolipoprotein transfer in lipoprotein remodeling was recognized, the mechanism of apolipoprotein transfer between lipoprotein species was not defined. The goal of this research was to define the mechanism of exchange or transfer of apolipoproteins between lipoprotein particles. The approach was to monitor the transfer of a single apolipoprotein from donor to acceptor lipoprotein particles. The following aims were addressed. Aim 1: To delineate the kinetics and mechanism of passive exchange/transfer of apoCIII molecules between human VLDL and HDL3. Aim 2: To determine the impact of apolipoprotein structure on the passive exchange/transfer of apolipoproteins between VLDL and HDL3. Aim 3: To delineate the kinetics and mechanism of passive exchange/transfer of apoC molecules between human LDL and HDL3. Kinetic studies confirmed an aqueous diffusion mechanism mediated the transfer of apoCIII molecules between VLDL and HDL3 particles. Apolipoprotein net charge, as conferred by terminal sialic acid residues, did not impact the transfer of apoCIII from donor VLDL to acceptor HDL3 particles. ApoE transfer also was suggested to proceed by an aqueous diffusion mechanism. Comparison of kinetic parameters generated with apoC and apoE suggested that apolipoprotein conformation played a role in the transfer of apolipoproteins. Kinetic studies also suggested that the highly curved surface and surface crowding on apoB-containing lipoprotein particles affected the ability of exchangeable apolipoprotein to equilibrate into and transfer from the particle.
First order statistics of speckle around a scatterer volume density edge and edge detection in ultrasound images
Authors:   , Li Yue , Shankar P Mohana , Newhouse Vernon Leopold
Published: July 2024

Ultrasonic imaging plays an important role in medical imaging. But the images exhibit a granular structure, commonly known as speckle. The speckle tends to mask the presence of low-contrast lesions and reduces the ability of a human observer to resolve fine details. Our interest in this research is to examine the problem of edge detection and come up with methods for improving the visualization of organ boundaries and tissue inhomogeneity edges. An edge in an image can be formed either by acoustic impedance change or by scatterer volume density change (or both). The echo produced from these two kinds of edges has different properties. In this work, it has been proved that the echo from a scatterer volume density edge is the Hilbert transform of the echo from a rough impedance boundary (except for a constant) under certain conditions. This result can be used for choosing the correct signal to transmit to optimize the performance of edge detectors and characterizing an edge. The signal to noise ratio of the echo produced by a scatterer volume density edge is also obtained. It is found that: (1) By transmitting a signal with high bandwidth ratio and low center frequency, one can obtain a higher signal to noise ratio. (2) For large area edges, the farther the transducer is from the edge, the larger is the signal to noise ratio. But for small area edges, the nearer the transducer is to the edge, the larger is the signal to noise ratio. These results enable us to maximize the signal to noise ratio by adjusting these parameters. (3) The signal to noise ratio is not only related to the ratio of scatterer volume densities at the edge, but also related to the absolute value of scatterer volume densities. Some of these results have been proved through simulation and experiment. Different edge detection methods have been used to detect simulated scatterer volume density edges to compare their performance. A so-called interlaced array method has been developed for speckle reduction in the images formed by synthetic aperture focussing technique, and experiments have been done to evaluate its performance.
A characterization of nanohole grating refractive index sensors for biosensing applications
Authors:   , Bellingham Alyssa , Fontecchio Adam
Published: July 2024

Sub-wavelength periodic structures imprinted in metallic films give rise to enhanced transmission features which are sensitive to changes in refractive index at the surface. Variations in the transmission spectral output can be quantified to detect the concentration of analyte in a solution and the surface of the film can be readily modified with a variety of synthetic recognition elements, biomolecules, and well-established silane chemistry to allow for molecule recognition at the surface of the grating. These nanohole gratings can also be used to couple light into planar optical waveguides, which make ideal signal transducers because of their sturdiness, easy patterning of reagents, and easy incorporation of polymer materials. This thesis seeks to characterize nanohole structures imprinted on aluminum thin films as refractive index sensors that can be incorporated as transduction elements into biosensing technologies as well as to provide a path to optimization of an integrated biosensing device. Aluminum, a previously unexamined material for these nanohole array imprinted devices, was used as the metallic thin film in this thesis. The material demonstrated similar enhanced transmission effects to well known plasmonic materials like silver and gold, which cost significantly more than aluminum. The aluminum film was imprinted with a periodic nanoscale array of holes using an etching procedure, and then evaluated as a refractive index sensor. The bulk sensitivity of the nanohole array samples was determined through solvent characterization as well as exposure to varying thicknesses of a deposited layer of polymer. The ability of the potential transduction element to detect affinity reactions occurring at the surface was evaluated using well known biomolecular recognition experiments as well as synthetic recognition experiments using molecularly imprinted polymer films (MIPs). MIPs are biomimetic recognition elements that can be created for a variety of molecular structures, enable large-scale chip fabrication, are reusable, and offer superior stability when exposed to solvents and temperature extremes. The potential to combine the nanohole array transducer element with this synthetic recognition element is examined in this thesis. A theoretical optimization of the grating pitch for optimal detection capability was performed and the future path of optimizing an integrated biosensing device is discussed.
Functional consequences of developmental changes in the actomyosin and microtubule cytoskeleton in axonal morphogenesis
Authors:   , Jones Steven L. , Gallo Gianluca
Published: July 2024

Formation of the nervous system requires the establishment of functional connections between individual neurons and specific target tissue. During early embryonic development neurons extend axons from their cell bodies that are directed to their targets by a specialized structure at the tip of the axon termed the growth cone. The growth cone is highly dynamic and directs axon extension by responding to guidance cues in the extracellular environment of the developing embryo. The growth cone is dependent on the dynamics and organization of the actin filament (F-actin) and microtubule (MT) cytoskeleton. In the older postnatal or adult nervous system, the ability of axons to undergo directed axon extension is required for the re-establishment of functional connectivity after injury. Failure of axons to regenerate is due in part to an inhibitory extracellular environment. However, mounting evidence suggests that the diminished capacity to regenerate is also partly due to changes that occur within neurons during development. In this thesis I show that both the F-actin and MT cytoskeleton undergo developmental changes in the organization and levels of cytoskeletal proteins between embryonic day (E) 7 and E14 in chick dorsal root ganglion (DRG) neurons and that these changes have functional consequences on the mechanism of axon extension. Although both F-actin and MTs contribute to axon extension at both E7 and E14, the mechanism of axon extension changes from a mechanism strictly dependent on F-actin and partly dependent on MTs at E7 to one more dependent on MT dynamics and less on F-actin by E14. Furthermore, the levels of the F-actin motor protein myosin II undergo a developmental down-regulation between E7 and E14. The down-regulation of myosin II levels is accompanied by a decrease in the requirement for myosin II in axon extension, and contributes to a transition from an extension mode of axon development to an arborization/branching mode. Collectively, these observations demonstrate that developmental changes in the neuronal cytoskeleton have consequences on the mechanisms of axon extension.
The role of protein phosphatase 2A during meiosis I in Saccharomyces cerevisiae
Authors:   , Nolt Jocelyn Kibbe , Nickels Joseph T
Published: July 2024

Protein phosphatase 2A (PP2A) is a heterotrimeric serine/threonine phosphatase consisting of A and B regulatory subunits and a C catalytic subunit. PP2A regulates cellular events that include the cell cycle, nutrient sensing, p53 stability and various mitogenic signals. Our studies explored a less understood role of PP2A, meiosis, exploiting the yeast Saccharomyces cerevisiae as a model system. We demonstrate that PP2ACdc55 containing the human B/55 family B subunit ortholog, Cdc55, is required for progression through meiosis I. cdc55 null cells arrest prior to spore formation, yet enter the meiotic program as indicated by expression of early meiotic genes. Cells lacking Cdc55 remain mononucleated, express early and middle meiotic genes prematurely, and harbor defects in intergenic recombination, and premeiotic DNA replication. The meiosis I defect of cdc55 cells can not be suppressed by bypassing recombination, eliminating pachytene checkpoint function, or removal of inhibitory cyclin-dependent kinase phosphorylation. Elimination of the Rad9-dependent DNA damage checkpoint partially suppresses the meiosis I defect of cdc55 cells. We conclude PP2ACdc55 is required for the proper temporal coupling of multiple meiotic events and/or monitors these events to ensure their fidelity.
Suicide in schizophrenia
Authors:   , Barnett Belinda Elizabeth , Herbert James D
Published: July 2024

Suicide is the leading cause of premature death among individuals with schizophrenia. The identification of individuals who are at increased risk for suicide has proven extremely difficult. Using the Interview for Suicide in Schizophrenia, 3rd Revision (ISIS-3), this study assesses how risk for suicide in schizophrenia is understood by raters, and to identify and define subgroups of "at risk" patients based on the twenty subscales of the ISIS-3. Two hundred fifty-eight inpatients of a state hospital with a diagnosis of schizophrenia or schizoaffective disorder were interviewed using the ISIS-3. Cluster analytic techniques were performed using the subscales of the ISIS-3 as clustering variables, and four clusters with distinctly different profiles were identified. These profiles included a cluster defined primarily by "traditional" suicide risk factors such as high levels of depression, anxiety, hopelessness, suicidal ideation, and fewer reasons for living, a cluster defined by high levels of hostility and impulsivity, a cluster characterized by relatively lower levels of psychopathology and increased insight, and a cluster defined by a high incidence of command hallucinations and self-harm. These clusters were further characterized by differences in gender and diagnosis. Finally, the technique of stepwise logistic regression demonstrated that individuals judged to be at risk for suicide could be distinguished from those judged to be not at risk with a high degree of accuracy; correct classification was obtained for 85.2% of the subjects. These results show that for a chronically-ill, inpatient population, different subgroups of individuals at risk for suicide appear to exist, and can be differentiated from those judged to be "not at risk." Further investigation of these subgroup in a broader sample is warranted.
Quantitative evaluation of computational optical sectioning in fluorescence microscopy
Authors:   , Wang Yongping , Zietz Stanley , Zuckerman Ralph
Published: July 2024

Computational optical sectioning can reveal the three-dimensional microstructure of biomedical specimens without damaging the object. Conventional microscope images contain information at the focal plane, obscured by out-of-focus information from adjacent planes. Several computational optical sectioning methods have been developed to remove out-of-focus information, and have been applied in a number of published biomedical studies. However, because these mathematical models only approximate the imaging system, computational methods must have inherent limitations. As a consequence, such methods might provide false information about the object. Such limitations have long been ignored or underestimated. In order to understand better the limitations of computational methods, and to avoid misinterpreting their results, a quantitative evaluation of the strengths and weaknesses of such methods must be obtained. The present thesis is the first evaluation of computational methods which employs reliable physical models. An agar-yeast model of one-dimensional diffusion was employed to provide a predictable intensity gradient which was used to evaluate the restoration ability of computational sectioning methods in the low frequency range. For high frequency signals, fluorescent beads were used as the test objects to evaluate the faithfulness of the sectioning results. A specially designed orthogonal illumination system allowed the bead optical section to be directly observed using the same optical imaging system employed in testing the computational sectioning methods. Therefore, any discrepancies between the orthogonal plane image and the results of computational methods could be attributed solely to deficiencies in the computational methods. The experimental results demonstrate that none of the tested computational methods is capable of restoring low frequency 3-D information. Therefore, when computational methods are used to perform quantitative measurement of low frequency signals caution should be employed in interpreting the sectioning results. For high frequency signals, it was found that the computational sectioning results were statistically acceptable with regard to absolute object size; however, the artifacts and noise in such images were exaggerated by all tested methods. Moreover, the resultant images exhibited shape distortion. The effects of imperfections in the experimental point spread function on the resultant image were also evaluated.
Real-time transmission transfer capability assessment in a deregulated bulk power market
Authors:   , Yan Herbert Hung-Kwong , Fischl Robert
Published: July 2024

The transmission systems in the U.S. are interconnected. The enactment of the U.S. Energy Policy Act of 1992 established a new "open access" environment that has spurred bulk power marketing activities among electric utilities in the interconnected network. In bulk power marketing, a common practice is to assume that the power deliveries will flow through predetermined paths, although the actual amount and direction of transfers are controlled by the law of physics. This practice has created extraneous power flows, known as "parallel flows," on transmission systems. Depending on system conditions, these "parallel flows" can cause or aggravate transmission constraints in systems external to the transacting systems. With the proliferation of regional power transfers, it is obvious that one needs to obtain additional operating data, such as bus voltages and active power flows (megawatts), in the external systems in order to assess adequately the transmission transfer capability. This thesis presents the theory and algorithms of a method for estimating bus voltages and active power flows using available operating data in a control center. The theory states that the summation of voltage phase angle differences, taken in the same direction in a loop, is zero. The main contribution of this thesis is that it gives a new approach in estimating the operating state of a power system, thereby providing additional operating data which are otherwise not available in a control center. This method can therefore be used to estimate operating states in areas of the external systems that are electrically close to the internal system modeled in the control center. An illustration is provided using a 17-bus system. As this method can be easily implemented in the online computer system, the method is applicable in the real-time environment. This thesis also presents an approach using, in addition to the above method, artificial neural networks for real-time security assessment. The artificial neural networks are used as a security/insecurity predictor and as an estimator of post-contingency line flows and voltages. The overall approach for real-time transmission transfer capability assessment is presented as an enhancement to a typical Energy Management System to overcome some of the deficiencies in the current techniques.
Mechanistic investigation of the cationization process of matrix-assisted laser desorption/ionization time-of-flight mass spectrometry
Authors:   , Xiong Henry Y.
Published: July 2024

Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOFMS) is a powerful tool to characterize synthetic polymers. The goal of this study is to investigate the cationization process, one of the four parts, sample preparation, desorption, ionization and detection, occurring during MALDI-TOFMS analysis of synthetic polymer samples. The investigation of the cationization process, by analyzing small ethylene glycol oligomers by observing the effect of their end groups and their MALDI behavior (e.g. affinity order to the alkali metals) using a 23 factorial experiment design model, leads to conclude that the MALDI cationization process is not an equilibrium process in the gas phase. Ideally, under normal MALDI conditions, there might be no mass discrimination in terms of cationization affinity (bonding strength) between different size oligomers in the polymer distribution of polyethylene glycol (PEG). If the mass discrimination does occur, it might result from the difference of reaction rate for different oligomers. Further study indicates that the methyl end-group increases the affinity of alkali metal cations to the small oligomers. The alkali metal cation affinities, although they have limited effect on the molecular weight distribution for the three polymers (blends which have low Mn) tested in our experiments, will have a significant impact on the analysis of polymer blends of higher molecular weight distribution when the detection signal is more important to be used for the calculation of molecular weight. It is observed that the addition of NH4DHB to the sample or the use of electrospray to dry the sample increases the resolution of the mass spectrum. The sample preparation method using IAA with silver acetylacetonate (AgAcAc) added as the ionization reagent permits the MALDI/TOFMS analysis of hydrocarbon polymers, such as polystyrene and polybutadiene, up to 125,000 amu with consistent agreement of molecular weight and polydispersity determined by conventional methods. Copper is found to be an efficient cationization reagent for low molecular weight polystyrene. Laser desorption (LD) TOFMS is developed as a simple and accurate method to characterize the molecular weight of perfluorinated polyethers (PFPEs) up to 7,000 amu. Comparison of the results of MALDI and LD for PPG and LD for PFPE demonstrates experimentally the separation function of matrix materials for the first time.
Depressive symptoms and problem solving as predictors of adherence to the cardiac medical regimen
Authors:   , Deaner Stephanie Lynn , Nezu Arthur M.
Published: July 2024

Adherence to the cardiac medical regimen involves diet, smoking reduction, exercise, taking medications, stress modification, and appointment keeping. Prior investigations, which focused on appointment keeping at Phase 11 programs, found that 50% of patients have poor adherence (Clark, 1997; Comoss, 1988; Farmer & Gotto, 1992; Oldridge, 1988). These studies have advanced the understanding of medical and demographic factors related to adherence but have largely ignored psychological variables. The present study addresses this gap in the literature by hypothesizing that depressive symptoms, problem-solving, and their interaction will predict adherence to the six components of the cardiac medical regimen above and beyond demographic (i.e., age, gender, smoking status, occupation, and knowledge) and medical (i.e., diagnosis and disease severity) variables. Participants completed the self-report questionnaires Profile of Mood States (McNair, Lorr, & Droppleman, 1992), Social Problem-Solving Inventory - Revised Short Form (D'Zurilla, Nezu, Nezu, & Maydeu-Olivares, in press), and Health Behavior Scale (Miller, Johnson, Garrett, Wikoff, & McMahon, 1982). Multiple regression analyses were conducted on 57 cardiac rehabilitation participants (56% men; mean age 62, SD = 10 years; 60% Caucasian, 35% African-American, 3% Hispanic, and 2% Asian) enrolled in a Phase II program. Participants were diagnosed with either myocardial infarction (n = 15) or angina (n = 11) and/or had coronary artery bypass grafting (n = 25), percutaneous transluminal coronary angioplasty (n = 19), or stents (n = 14). It was found that 41% of the variability in smoking reduction adherence can be accounted for by depressive symptoms and the demographic and medical variables, F(9, 47) = 3.69, p = .001. About 47% of the variability in smoking reduction adherence can be attributed to problem solving, depressive symptoms, and the demographic and medical variables, F(10, 46) = 4.08, p < .001. About 77% of the variability in smoking reduction adherence can be accounted for by problem solving, depressive symptoms, their interaction, and the demographic and medical variables, F(11, 45) = 13.52, p < .001. Results suggest that tailored behavioral medicine treatment may be needed to increase adherence to the smoking reduction regimen for cardiac patients with more depressive symptoms and fewer problem-solving abilities.
Behavior of pultruded glass fiber reinforced plastic I-beams under monotonic and cyclic patch loads
Authors:   , Khalaf Mohamed Abdelmoaty , Elgaaly Mohamed
Published: July 2024

The introduction of mass-produced glass fiber reinforced plastic (GFRP) structural shapes in bridges and other construction dictates the need to understand the fatigue behavior of these shapes. This study describes the fatigue performance of GFRP pultruded I-beams; an experimental study was conducted on both polyester and vinyl ester I-beams, under cyclic patch loads to monitor the fatigue performance, failure pattern, and stiffness degradation that could happen during the course of fatigue loading. The stress-range versus number of cycles, S-N curves, were produced for both polyester and vinyl ester beams considering the obtained mode of failure which was due to local crushing of the web matrix in the transverse direction under the applied patch load. An experimental study and finite element analysis were carried out to investigate the strength of these beams under the monotonically applied patch load because the obtained failure mode was the same like that under the cyclic load. Some equations were proposed to calculate the strength of pultruded beams under patch load and the minimum width of patch load required to avoid this local mode of failure.
A Comparison of worry in the psychiatric and community elderly
Authors:   , Tobey Beth K. , Herbert James D
Published: July 2024

There is a paucity of anxiety research that systematically focuses on geriatric populations. In particular, the manifestations of worry in the elderly have been given minimal attention. This study compared two groups of participants aged 60 and over in terms of self-reported worry: 41 participants living in the community versus 40 participants hospitalized for psychiatric disorders. All participants completed measures of worry (both the Penn State Worry Questionnaire and the Worry Scale), depression, social support, physical health and mobility, life satisfaction, and time perspective in order to determine which variables were most relevant to worry in the two groups. Results indicated a relationship between worry and all of the above variables, with the exception of past time perspective. In comparison to the community group, the psychiatric group endorsed higher levels of worry on the Penn State Worry Questionnaire and more negative views of the present and the future (based on results from the Time Perspective Scale); in addition, life satisfaction emerged as the best predictor of worry in this group. Differences in worry between the two groups are discussed, and implications for treatment are explored. In particular, these findings suggest greater efficacy in treatments for worry may be achieved by focusing on the present or the future rather than in the past.
Dimensional modeling
Authors:   , Jones Mary Elizabeth , Song Il-Yeol
Published: July 2024

Software design is a complex activity. A successful designer requires knowledge and training in specific design techniques combined with practical experience. Designing a dimensional model for a data warehouse embodies this challenge. This research presents Dimensional Design Patterns (DDPs) and their application to the design of dimensional models. We describe a metamodel of the DDPs and show their integration into Kimball's dimensional modeling design process so they can be applied to design problems using a known practice. By providing a metamodel and a method for DDP use, we combine theory and a practical design technique with the goal of increasing the efficiency and effectiveness of the software designer. The experimental results regarding the classroom use of DDPs revealed an increase in the correctness by 25% and the efficiency by 9% of students when designing a dimensional model. The DDPs are an effective method for the teaching and designing of a dimensional model. The next phase of research will apply the DDPs to dimensional models in an industry setting.
Development of ductile hybrid fiber reinforced polymer (D-H-FRP) reinforcement for concrete structures
Authors:   , Somboonsong Win , Harris Harry George , Ko Frank K
Published: July 2024

The corrosion of steel rebars has been the major cause of the reinforced concrete deterioration in transportation structures and port facilities. Currently, the Federal Highway Administration (FHWA) spends annually $31 billion for maintaining and repairing highways and highway bridges. The study reported herein represents the work done in developing a new type of reinforcement called Ductile Hybrid Fiber Reinforced Polymer or D-H-FRP using non-corrosive fiber materials. Unlike the previous FRP reinforcements that fail in a brittle manner, the D-H-FRP bars exhibit the stress-strain curves that are suitable for concrete reinforcement. The D-H-FRP stress-strain curves are linearly elastic with a definite yield point followed by plastic deformation and strain hardening resembling that of mild steel. In addition, the D-H-FRP reinforcement has integrated ribs required for concrete bond. The desirable mechanical properties of D-H-FRP reinforcement are obtained from the integrated design based on the material hybrid and geometric hybrid concepts. Using these concepts, the properties can be tailored to meet the specific design requirements. An analytical model was developed to predict the D-H-FRP stress-strain curves with different combination of fiber materials and geometric configuration. This model was used to optimize the design of D-H-FRP bars. An in-line braiding-pultrusion manufacturing process was developed at Drexel University to produce high quality D-H-FRP reinforcement in diameters that can be used in concrete structures. A series of experiments were carried out to test D-H-FRP reinforcement as well as their individual components in monotonic and cyclic tensile tests. Using the results from the tensile tests and fracture analysis, the stress-strain behavior of the D-H-FRP reinforcement was fully characterized and explained. Two series of concrete beams reinforced with D-H-FRP bars were studied. The D-H-FRP beam test results were then compared with companion steel reinforced concrete beams having the same ultimate strength. All D-H-FRP reinforced concrete beams show consistent performance with ultimate strengths and ductility similar to the steel reinforced control specimens and to theoretical predictions.
A characterization of merozoite surface protein-1 subunit antigen acquisition by dendritic cells and the immunogenicity of dendritic cell vaccination in a murine model of lethal malarial infection
Authors:   , Leiderman Yannek Isaac , Long Carole A.
Published: July 2024

Vaccination with the C-terminal portion of the major merozoite surface protein, MSP-1, is capable of protecting mice from challenge infection with an otherwise lethal murine malarial parasite when administered in Freund's adjuvant. Our laboratory has demonstrated that vaccination with the protective fragment in less potent adjuvants fails to confer protection from challenge infection with the lethal parasite Plasmodium yoelii 17XL. The inability to achieve clinical efficacy with selected MSP-1 vaccine candidates in an adjuvant suitable for use in humans is the chief impediment to translating these promising findings in a rodent malarial model to a human vaccine trial. Adjuvant-mediated recruitment of antigen-presenting cells (APCs) and the subsequent acquisition of immunogen at the site of inoculation are the seminal events in the initiation of vaccine-mediated immunity. In the experimental series described herein, we have characterized the acquisition of MSP-1 subunit antigens by murine dendritic cells (DCs) in vitro, and subsequently investigated the immunogenicity of malarial vaccine-candidate-loaded DCs in vivo. DCs exhibit differential uptake of the 42 kDa MSP-1 C-terminal fragment (MSP1-42), and a 19 kDa progeny polypeptide (MSP1-19) arising through proteolysis of MSP1-42. Internalization of MSP1-42 proceeds at a markedly greater rate compared with that of MSP1-19, and the kinetics of acquisition implicate a receptor-mediated mechanism in the acquisition of MSP1-42 by DCs in vitro. We have shown that DC-mediated uptake of MSP-1 subunit antigens may be enhanced through post-translational modification of antigen, or via the linkage of polypeptide epitopes that likely bind DC surface-expressed antigen receptors. DCs incubated with MSP1-42 in vitro elicited robust antigen-specific cellular and humoral responses subsequent to DC-based immunization of naive recipients. Indeed, DCs loaded with P. yoelii MSP1-42 derived from recombinant bacteria conferred protection from challenge infection with an otherwise lethal murine parasite that was comparable to protection conferred by antigen-in-FA. Practical methods of targeting antigen to DCs in situ are presently under development. We have provided proof-of-principle that targeting the 42 kDa fragment of MSP-1 to DCs establishes protective immunity from an otherwise lethal malarial challenge infection, and that mature, antigen-loaded DCs confer protection that is comparable to immunization with the gold-standard antigen-in-adjuvant formulation.
Examination of a model of Systemic Sclerosis, the Tight Skin 2 mouse
Authors:   , Long Kristen Brooke , Blankenhorn Elizabeth P
Published: July 2024

Objective. The Tight Skin (Tsk) 2 mouse model of Systemic Sclerosis (SSc) has many features of human disease including tight skin, an altered extracellular matrix (ECM), and antinuclear antibodies (ANAs). The mutation that causes SSc-like disease in Tsk2/+ mice is unknown. Tsk2/+ mice were bred to identify the gene, investigate the role of ANAs and toll-like receptor 7 (TLR7) signaling in disease development and progression, and evaluate fibrotic ECM changes that are difficult to study in patients with SSc. Approach. Tsk2/+ mice were bred to a B6.chr 1-A/J background to fine-map Tsk2. Tsk2/+ mice were also bred to mice with an extra copy of Tlr7 (Yaa), or to mice deficient in Tlr7 (TLR7KO) to investigate the role of TLR7 in disease. Skin was examined for fibrosis and blood samples were examined for ANA production. Skin samples from B6. Tsk2/+ and WT mice at various ages were examined for ECM alterations, cellular infiltrates and fibrotic gene expression levels. Results. Genotyping narrowed the Tsk2 interval to less than 3 megabases, containing seven known genes: Gulp1, Col3a1, Col5a2, Wdr75, Slc40a1, Dnahc7b and Slc30a10. Skin fibrosis in Tsk2/+ mice occurred 8 weeks after the development of the 'tight skin' phenotype. Dermal collagen accumulation was significantly increased in Tsk2/+ mice only after 10 weeks of age, and at 17 weeks of age B6. Yaa. Tsk2/+ male mice had significantly more fibrosis compared to B6. Tsk2/+ and TLR7KO. Tsk2/+ male mice. ANA production was not observed until at least 14 weeks of age, and was not different between Tsk2/+ and WT littermates. In pre-fibrotic skin of Tsk2/+ mice, there was increased expression of genes associated with fibrosis, and a significant increase in elastic fibers. This abnormal elastic fiber phenotype was also observed in diseased tissue from two patients with SSc. Conclusions. The new Tsk2 interval includes two strong candidate genes, Col3a1 and Col5a2. TLR7 signaling and ANA production are important contributors to disease severity, but are not necessary for disease initiation. The disease state in the Tsk2/+ mouse is progressive, and therefore this model is valuable for the examination of early, pre-fibrotic pathology that is otherwise challenging to examine in SSc.
The effect of parent education on the motor performance of premature infants and parent caregiving abilities
Authors:   , Unanue Rachel Anne , Westcott Sarah L
Published: July 2024

Physical therapists are active members of the medical team in the Neonatal Intensive Care Unit (NICU) and the Special Care Nursery (SCN) performing examination and interventions. This research project consists of two studies each examining the components of physical therapy. Physical therapists need to provide appropriate interventions to parents and their infants in the NICU and must use appropriate measurement tools during examination. The first study presented a model of family-centered care in the NICU to examine the effects of an individualized family-centered parent education program compared to providing parents general information on infant development. Parent caregiving abilities and preterm infant motor and postural control were examined. Twenty-five infant-parent dyads participated in this study. Results revealed parents in both groups increased their confidence levels in caregiving and parents in the family-centered group slightly improved their caregiving abilities compared to parents in the general information group although this was not significant. Infants whose parents received family-centered parent education showed fewer improvements in motor and postural control compared to infants whose parents received general information. Regardless of group, parents were satisfied with the parent education they received. The second study examined the responsiveness of the Test of Infant Motor Performance (TIMP) to changes in preterm infants and identified variables predictive of changes in TIMP scores. Twenty-five preterm infants in the NICU and SCN participated in this study. Results indicated that the TIMP is sensitive to changes in preterm infants, however, the TIMP does not discriminate infants based on a medical risk classification score. Infant variables associated with their effect on development did not predict changes in TIMP scores. Overall, parents were satisfied with the parent education they received. Both programs appear to have important information to provide to parents. Specific activities related to motor and postural control should also be added to parent education programs. The TIMP is sensitive to changes preterm infants make; however, the TIMP is not responsive to changes in preterm infants due to the lack of discrimination between risk groups.
Risk factors for marital discord among interfaith and interracial couples
Authors:   , Kohn Carolynn S. , Nezu Christine M. , Sayers Steven L.
Published: July 2024

The purpose of this investigation was twofold. The first objective was to examine clinical and theoretical explanations for intermarried couples' greater risk of divorce compared to homogeneous couples. It was hypothesized that compared to homogeneous couples, intermarried couples would report less family support, more severe problems with religion and family, more discrepant marital role beliefs, and greater discrepancies in acculturation. It was further hypothesized that intermarried couples' greater discrepancies in marital role beliefs would be associated with greater discrepancies in acculturation. The second objective was to examine for theoretical and clinical assumptions that intermarried couples with greater differences between the partners (i.e., interfaith/interracial couples) experience more distress and difficulties compared to intermarried couples with fewer differences between the partners (i.e., interfaith-only or interracial-only couples). Finally, exploratory analyses examined whether group status (intermarried versus homogeneous) would moderate the association between family support or communication/problem-solving skills and relationship satisfaction. Participants were 150 heterosexual couples (75 intermarried and 75 homogeneous couples), engaged or married less than 18 months, who completed a set of self-report measures. Results indicated that intermarried couples reported less family support, more severe problems with religion, and greater discrepancies in acculturation levels. Contrary to the hypothesis, no association was found between intermarried couples' acculturation and marital role belief discrepancies. In partial support of the hypothesis, results indicated that among intermarried couples, interfaith-only couples reported less distress and difficulties compared to interfaith/interracial couples. Contrary to the hypothesis, interfaith-only couples also reported less difficulties compared to interracial-only couples. Moreover, no differences were found between interracial-only and interfaith/interracial couples. Exploratory analyses revealed that group status moderated the association between communication/problem-solving skills and relationship satisfaction, such that communication/problem-solving skills were highly associated with relationship satisfaction among homogeneous couples only, and not among intermarried couples. These findings suggest that differences between couples at higher-risk versus lower risk for divorce, as well as the differential impact of culture and ethnicity on relationships, may have important implications for models of marital functioning and divorce prevention programs. Implications and limitations of these findings were discussed and recommendations for future research were made.
Chiral kinetic resolution of sulfoxides and selenoxides/carbanion hydroxylation using 2-sulfonyloxaziridines
Authors:   , Billmers Joanne Marie
Published: July 2024

2-Benzenesulfonyl-3-aryloxaziridines provide a novel class of aprotic oxidizing reagent useful for the conversion of sulfoxides to sulfones, selenides to selenoxides and carbanions to alcohols. The mechanism of oxaziridine oxygen transfer was investigated and involves nucleophilic attack on the electron deficient oxaziridine oxygen atom and subsequent oxygen transfer. The oxidative kinetic resolution of sulfoxides (R-S(O)-R') using chiral 2-sulfonyloxaziridines was found to produce optically active sulfoxides in 0.2-27% enantiomeric excess (e.e.). The configuration of the oxaziridine three-membered ring determines the configuration of sulfoxide obtained and the structure of the oxaziridine substituents affects the extent of asymmetric induction. An investigation of selenoxide (R-Se(O)-R') configurational lability was undertaken and resulted in the firs example of a simple optically active selenoxide, 2,4,6 triisopropylphenyl methyl selenoxide. This was prepared via a kinetic resolution process employing d-and 1-10 camphorsulfonamide. The racemization of optically active selenoxides through achiral hydrate formation resulting from addition of water across the Se-O bond has been proven to occur in simple chiral selenoxides and was found to be acid catalyzed. The carbanion hydroxylation properties of 2-benzenesulfonyl-3-aryloxaziridines were also investigated, producing alcohols and phenols from both aliphatic and aromatic Grignard and lithium reagents in good yield. The sulfonimine by-product of oxidation reacts competitively with nucleophiles to form carbon-substituted benzenesulfonamides. Resonance-stabilized enolate carbanions were also oxidized, producing (alpha)-hydroxylated carbonyl compounds. Esters and ketones were hydroxylated in good yield by treatment with potassium tert-butoxide in ether or THF and addition of the oxaziridine in hexamethyl phosphoramide (HMPA). 2-Benzenesulfonyl-3-aryloxaziridines have also successfully hydroxylated ketosteroids and silylenol ethers in good yield.
Influence of process parameters on microstructure and mechanical properties of lost foam aluminum castings
Authors:   , Wang Libo
Published: July 2024

A fundamental analysis was conducted to evaluate the metallurgical quality of aluminum castings produced by the lost foam process. Test castings were produced for a variety of processing conditions and analyzed to determine the microstructural parameters and mechanical properties. Various defects have been identified and characterized. The effects of grain refinement and modification on microstructure and mechanical properties have also been evaluated. It has been shown that the thermal gradients established during the filling of the mold have a significant effect on the solidification behavior. Both dendrite arm spacing (DAS) and grain size vary inversely with the distance from the ingate. The morphology and distribution of interdendritic phases varies along the length of flow. A segregated region containing a high concentration of alloying elements may be observed near the metal front. Bulk porosity levels in the casting are comparable to the values measured in green sand castings. Lost foam castings may contain large amounts of surface porosity and porosity near the metal front. Excessive glue at joints seems to contribute to the evolution of porosity in the casting. Other defects such as folds, laps and black inclusions may also be present in the casting. It has been shown that liquid degradation products have a critical role in determining casting quality. A pouring temperature of the order of 730 to 750[degrees]C and terminal flow velocity of 9 to 14 cm/s may be necessary to minimize defect formation. A minimum of 0.15% Ti is necessary to achieve substantial grain refinement. Optimum concentration of Sr for obtaining a fine and fibrous eutectic Si structure in the casting are between 0.01 to 0.015%. Mechanical properties of lost foam castings are better than or equal to the values measured in green sand castings, but are inferior to the properties in permanent mold castings.
Serotonin is an autocrine-paracrine survival factor for human acute T leukemic cells
Authors:   , Yin Jun , Jameson Bradford Aldrich
Published: July 2024

Serotonin (5-HT) is a critical multi-faceted bioamine that is generally synthesized in serotoninergic neurons of the central nervous system and in enterochromaffin cells in the gastrointestinal tract. It functions as a neurotransmitter, a vasoactive factor, an immune modulator and a growth/survival factor in the human body. This thesis provides evidence that serotonin and its receptors are present and functional in T leukemic cells. We have identified the presence of tryptophan hydroxylase (TPH1) (the rate-limiting enzyme involved in the metabolic conversion of tryptophan to serotonin) in CEM and Jurkat cells by RT-PCR and immunofluorescence methods. We have also evaluated its enzymatic activity by quantification of secreted 5-HT in the culture supernatants by HPLC-EC. Moreover, multiple 5-HT receptor subtypes have been detected on CEM and Jurkat cells by RT-PCR and Southern blot, including the 5-HT1A & 1B and three 5-HT2 receptor subtypes. Finally, published reports have shown that 5-HT regulates human PBMCs proliferation and cytokine secretion. Based on these observations, we propose that 5-HT may act as an autocrine-paracrine growth/survival factor for T leukemic cells. We have successfully identified the 5-HT1B receptor, from the fourteen pharmacologically distinct 5-HT receptor subtypes, as the key receptor regulating T cell growth and preventing T cell apoptosis through activating the P13K/Akt signaling pathway. We have also shown that the highly selective classical 5-HT1A antagonist Pindobind-5-HT1A, but not WAY-100635 and p-MPPF, can inhibit T leukemic cell proliferation and induce apoptosis through a non-classical 5-HT1A receptor coupled signaling pathway, which indicates that Pindobind-5-HT1A may interact with a novel "5-HT-related" receptor to execute its inhibitory effect on T leukemic cells. Future studies will focus on identification of this novel "5-HT-related" receptor and clarification of its molecular functional mechanism. Taken together, our data demonstrate that 5-HT is an autocrine-paracrine survival factor for human T leukemic cells. Antagonism of 5-HT1B receptor may provide a new clinical strategy to treat T cell leukemias and other immune disorders.