Polymer Interactions with Nucleic Acids Under Various Physiological Conditions

The goal of this project is to improve our understanding of nucleic acid interactions with cationic polymers with the theory that the polymers could protect the nucleic acids from degradation caused by biological enzymes. We seek to understand what the limitations of the cationic polymers are which, in this case, is mainly polymer-DNA compatibility. This experiment utilized peptide-dextran hybrid polymers with differing functionalizations to condense anionic nucleic acids into nanometer-sized polyplexes. Techniques of dynamic light scattering and zeta-potential were utilized to determine the particle sizes and surface charges of polyplexes. In this experiment, dextran with a molecular weight of 20 kDa was used. The dextran was then functionalized in four combinations: R3H3C or R5H5C conjugations each with and without CB-functionality. Additionally, N/P ratios of 0, 1, 5, 10, 20, and 30 were tested for each combination. The results, quantified in Tables 1 to 4, and summarized in Figure 10 and Figure 11 near the end of this document, indicate dextran polymer compatibility with DNA improves with the addition of CB-functionality, using the larger R5H5C peptide over R3H3C, and increasing N/P ratios

Carbon nanotube-rich domain effects on bulk electrical properties of nanocomposites

Carbon nanotube (CNT)/epoxy composites are intriguing materials that enable materials scientists and engineers to tailor structural and electrical properties for applications in the automotive and aerospace industries. Recent insights into CNT-rich domain formation and its influence on electrical properties raise questions about which processing variables can be used to tune the overall electrical conductivity. Here, we investigate how mass fraction and curing temperature influence these electrical properties. CNT nanocomposites were fabricated varying the mass fraction of CNT and the epoxy curing temperature. First, scanning lithium ion microscopy coupled with transmission electron microscopy were employed to investigate the morphology of CNT-rich domains that formed more readily at elevated curing temperatures than during room temperature curing. Then, oscillatory shear rheology measurements of the unfilled curing epoxy informed a simple kinetic argument to explain the CNT-rich domain formation. Finally, the electrical conductivity (both alternating and direct current) was characterized with a novel microwave cavity perturbation spectroscopy technique (alternating current conductivity) and a standard four-point probe station (direct current conductivity). The overarching conclusion of the work was that the CNT-rich domains formed a secondary percolated network surrounded by an almost completely unfilled epoxy matrix that allowed for higher conductivities at lower loadings. This work demonstrates that perfect dispersion of the nanoparticulate is, at least in this instance, not necessarily the preferred morphology

Three-Dimensional Radiofrequency Tissue Tightening: A Proposed Mechanism and Applications for Body Contouring

The use of radiofrequency energy to produce collagen matrix contraction is presented. Controlling the depth of energy delivery, the power applied, the target skin temperature, and the duration of application of energy at various soft tissue levels produces soft tissue contraction, which is measurable. This technology allows precise soft tissue modeling at multiple levels to enhance the result achieved over traditional suction-assisted lipectomy as well as other forms of energy such as ultrasonic and laser-generated lipolysis

The effects of thermal capsulorrhaphy of medial parapatellar capsule on patellar lateral displacement

<p>Abstract</p> <p>Background</p> <p>The effectiveness of thermal shrinkage on the medial parapatellar capsule for treating recurrent patellar dislocation is controversial. One of reasons why it is still controversial is that the effectiveness is still qualitatively measured. The purpose of this study was to quantitatively determine the immediate effectiveness of the medial parapatellar capsule shrinkage as in clinical setting.</p> <p>Methods</p> <p>Nine cadaveric knees were used to collect lateral displacement data before and after medial shrinkage or open surgery. The force and displacement were recorded while a physician pressed the patella from the medial side to mimic the physical exam used in clinic. Ten healthy subjects were used to test the feasibility of the technique on patients and establish normal range of lateral displacement of the patella under a medial force. The force applied, the resulting displacement and the ratio of force over displacement were compared among four data groups (normal knees, cadaveric knees before medial shrinkage, after shrinkage and after open surgery).</p> <p>Results</p> <p>Displacements of the cadaveric knees both before and after thermal modification were similar to normal subjects, and the applied forces were significantly higher. No significant differences were found between before and after thermal modification groups. After open surgery, displacements were reduced significantly while applied forces were significantly higher.</p> <p>Conclusion</p> <p>No immediate difference was found after thermal shrinkage of the medial parapatellar capsule. Open surgery immediately improved of the lateral stiffness of the knee capsule.</p

A Systems Biology Approach to Drug Targets in Pseudomonas aeruginosa Biofilm

Antibiotic resistance is an increasing problem in the health care system and we are in a constant race with evolving bacteria. Biofilm-associated growth is thought to play a key role in bacterial adaptability and antibiotic resistance. We employed a systems biology approach to identify candidate drug targets for biofilm-associated bacteria by imitating specific microenvironments found in microbial communities associated with biofilm formation. A previously reconstructed metabolic model of Pseudomonas aeruginosa (PA) was used to study the effect of gene deletion on bacterial growth in planktonic and biofilm-like environmental conditions. A set of 26 genes essential in both conditions was identified. Moreover, these genes have no homology with any human gene. While none of these genes were essential in only one of the conditions, we found condition-dependent genes, which could be used to slow growth specifically in biofilm-associated PA. Furthermore, we performed a double gene deletion study and obtained 17 combinations consisting of 21 different genes, which were conditionally essential. While most of the difference in double essential gene sets could be explained by different medium composition found in biofilm-like and planktonic conditions, we observed a clear effect of changes in oxygen availability on the growth performance. Eight gene pairs were found to be synthetic lethal in oxygen-limited conditions. These gene sets may serve as novel metabolic drug targets to combat particularly biofilm-associated PA. Taken together, this study demonstrates that metabolic modeling of human pathogens can be used to identify oxygen-sensitive drug targets and thus, that this systems biology approach represents a powerful tool to identify novel candidate antibiotic targets

Assessment of Metabolic Phenotypes in Patients with Non-ischemic Dilated Cardiomyopathy Undergoing Cardiac Resynchronization Therapy

Studies of myocardial metabolism have reported that contractile performance at a given myocardial oxygen consumption (MVO2) can be lower when the heart is oxidizing fatty acids rather than glucose or lactate. The objective of this study is to assess the prognostic value of myocardial metabolic phenotypes in identifying non-responders among non-ischemic dilated cardiomyopathy (NIDCM) patients undergoing cardiac resynchronization therapy (CRT). Arterial and coronary sinus plasma concentrations of oxygen, glucose, lactate, pyruvate, free fatty acids (FFA), and 22 amino acids were obtained from 19 male and 2 female patients (mean age 56 ± 16) with NIDCM undergoing CRT. Metabolite fluxes/MVO2 and extraction fractions were calculated. Flux balance analysis (FBA) was performed with MetaFluxNet 1.8 on a metabolic network of the cardiac mitochondria (189 reactions, 230 metabolites) reconstructed from mitochondrial proteomic data (615 proteins) from human heart tissue. Non-responders based on left ventricular ejection fraction (LVEF) demonstrated a greater mean FFA extraction fraction (35% ± 17%) than responders [18 ± 10%, p = 0.0098, area under the estimated ROC curve (AUC) was 0.8238, S.E. 0.1115]. Calculated adenosine triphosphate (ATP)/MVO2 using FBA correlated with change in New York Heart Association (NYHA) class (rho = 0.63, p = 0.0298; AUC = 0.8381, S.E. 0.1316). Non-responders based on both LVEF and NYHA demonstrated a greater mean FFA uptake/MVO2 (0.115 ± 0.112) than responders (0.034 ± 0.030, p = 0.0171; AUC = 0.8593, S.E. 0.0965). Myocardial FFA flux and calculated maximal ATP synthesis flux using FBA may be helpful as biomarkers in identifying non-responders among NIDCM patients undergoing CRT

Epidemiology and Treatment Guidelines of Negative Symptoms in Schizo-phrenia in Central and Eastern Europe: A Literature Review

AIM: To gather and review data describing the epidemiology of schizophrenia and clinical guidelines for schizophrenia therapy in seven Central and Eastern European countries, with a focus on negative symptoms. Methods : A literature search was conducted which included publications from 1995 to 2012 that were indexed in key databases. Results : Reports of mean annual incidence of schizophrenia varied greatly, from 0.04 to 0.58 per 1,000 population. Lifetime prevalence varied from 0.4% to 1.4%. One study reported that at least one negative symptom was present in 57.6% of patients with schizophrenia and in 50-90% of individuals experiencing their first episode of schizophrenia. Primary negative symptoms were observed in 10-30% of patients. Mortality in patients with schizophrenia was greater than in the general population, with a standardized mortality ratio of 2.58-4.30. Reasons for higher risk of mortality in the schizophrenia population included increased suicide risk, effect of schizophrenia on lifestyle and environment, and presence of comorbidities. Clinical guidelines overall supported the use of second-generation antipsychotics in managing negative symptoms of schizophrenia, although improved therapeutic approaches are needed. Conclusion : Schizophrenia is one of the most common mental illnesses and poses a considerable burden on patients and healthcare resources alike. Negative symptoms are present in many patients and there is an unmet need to improve treatment offerings for negative symptoms beyond the use of second-generation antipsychotics and overall patient outcomes

Imaging and Modeling of Myocardial Metabolism

Current imaging methods have focused on evaluation of myocardial anatomy and function. However, since myocardial metabolism and function are interrelated, metabolic myocardial imaging techniques, such as positron emission tomography, single photon emission tomography, and magnetic resonance spectroscopy present novel opportunities for probing myocardial pathology and developing new therapeutic approaches. Potential clinical applications of metabolic imaging include hypertensive and ischemic heart disease, heart failure, cardiac transplantation, as well as cardiomyopathies. Furthermore, response to therapeutic intervention can be monitored using metabolic imaging. Analysis of metabolic data in the past has been limited, focusing primarily on isolated metabolites. Models of myocardial metabolism, however, such as the oxygen transport and cellular energetics model and constraint-based metabolic network modeling, offer opportunities for evaluation interactions between greater numbers of metabolites in the heart. In this review, the roles of metabolic myocardial imaging and analysis of metabolic data using modeling methods for expanding our understanding of cardiac pathology are discussed

Generalization of auditory sensory and cognitive learning in typically developing children

Despite the well-established involvement of both sensory (“bottom-up”) and cognitive (“top-down”) processes in literacy, the extent to which auditory or cognitive (memory or attention) learning transfers to phonological and reading skills remains unclear. Most research has demonstrated learning of the trained task or even learning transfer to a closely related task. However, few studies have reported “far-transfer” to a different domain, such as the improvement of phonological and reading skills following auditory or cognitive training. This study assessed the effectiveness of auditory, memory or attention training on far-transfer measures involving phonological and reading skills in typically developing children. Mid-transfer was also assessed through untrained auditory, attention and memory tasks. Sixty 5- to 8-year-old children with normal hearing were quasi-randomly assigned to one of five training groups: attention group (AG), memory group (MG), auditory sensory group (SG), placebo group (PG; drawing, painting), and a control, untrained group (CG). Compliance, mid-transfer and far-transfer measures were evaluated before and after training. All trained groups received 12 x 45-min training sessions over 12 weeks. The CG did not receive any intervention. All trained groups, especially older children, exhibited significant learning of the trained task. On pre- to post-training measures (test-retest), most groups exhibited improvements on most tasks. There was significant mid-transfer for a visual digit span task, with highest span in the MG, relative to other groups. These results show that both sensory and cognitive (memory or attention) training can lead to learning in the trained task and to mid-transfer learning on a task (visual digit span) within the same domain as the trained tasks. However, learning did not transfer to measures of language (reading and phonological awareness), as the PG and CG improved as much as the other trained groups. Further research is required to investigate the effects of various stimuli and lengths of training on the generalization of sensory and cognitive learning to literacy skills

Structural Stability of Transparent Conducting Films Assembled from Length Purified Single-Wall Carbon Nanotubes

Single-wall carbon nanotube (SWCNT) films show significant promise for transparent electronics applications that demand mechanical flexibility, but durability remains an outstanding issue. In this work, thin membranes of length purified single-wall carbon nanotubes (SWCNTs) are uniaxially and isotropically compressed by depositing them on prestrained polymer substrates. Upon release of the strain, the topography, microstructure, and conductivity of the films are characterized using a combination of optical/fluorescence microscopy, light scattering, force microscopy, electron microscopy, and impedance spectroscopy. Above a critical surface mass density, films assembled from nanotubes of well-defined length exhibit a strongly nonlinear mechanical response. The measured strain dependence reveals a dramatic softening that occurs through an alignment of the SWCNTs normal to the direction of prestrain, which at small strains is also apparent as an anisotropic increase in sheet resistance along the same direction. At higher strains, the membrane conductivities increase due to a compression-induced restoration of conductive pathways. Our measurements reveal the fundamental mode of elasto-plastic deformation in these films and suggest how it might be suppressed