Design of target systems for production of PET nuclides

Target designs are presented for production of 11C, 13N, 15O and 18F by proton and deuteron reactions. Seven targets of two basic configurations (gas and water) and their respective manifold and control systems are detailed with design specifications and operational characteristics for the production of 11C-CO2, 11C-HCN, 13N-NH+4, 15O-O2, 18F-F- and 18F-F2 precursors. Short irradiation times (5-20 min) and high current (30 [mu]A) are used to produce near theoretical quantities of labeled PET precursors.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/27972/1/0000403.pd

Autoradiographic study of the effects of pulsed electromagnetic fields on bone and cartilage growth in juvenile rats

Application of pulsed electromagnetic fields (PEMF) has been used in growth and repair of non-union bone fractures. The similarities between the fibrocartilage callus in non-union bone fractures and the secondary cartilage in the mandibular condyle, both histologically and functionally, lead naturally to study the effects of PEMFs on growth in the condyle. The purposes of this study were: (1) to describe the effects of PEMFs on the growth of the condyle using autoradiography, [3H]-proline and [3H]-thymidine, and (2) to differentiate between the effects of the magnetic and electrical components of the field. Male pre-adolescent Sprague-Dawley rats (28 days old) were divided into three experimental groups of five animals each: (1) PEMF-magnetic (M), (2) PEMF-electrical (E) and (3) control, and were examined at three different times--3, 7 and 14 days of exposure. Each animal was exposed to the field for 8 h per day. Histological coronal sections were processed for quantitative autoradiography to determine the mitotic activity of the condylar cartilage and the amount of bone deposition. The PEMF (magnetic or electrical) had statistically significant effects only on the thickness of the articular zone, with the thickness in the PEMF-M group being the most reduced. Length of treatment was associated with predictable significant changes in the thickness of the condylar cartilage zones and the amount of bone deposition. As the animals aged, less condylar growth was observed and generally the highest mean thicknesses were found in the 3- and 7-day groups; likewise as more bone was deposited, the 7-day measurements of proline-band thickness were significantly greater than the 3-day measurements. Thus, the PEMF-M had a negative effect on the chondrogenic layer of the articular zone, but no other chondrogenic or osteogenic effects were noted.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/31040/1/0000717.pd

ASME 88-1CE-6, presented at the Energy-Source Technology Conference and Exhibition

Fig. 5 Velocity versus anguiar dispiacement (V8 engine) attained from the inertia value using the least squares method is consistently smaller than the reference data, and eventually leads to larger velocity estimation error than the average method Some precautions are needed when applying the least squares method to compute the engine inertia value. For engines operating at high speeds, the velocity related term in Eq. (1) could be very large compared with the other terms. This could result in some confusing situations. For instance, engines might decelerate over some portion of the engine operation cycle while the net external torque accelerating the engine is positive; or engines might accelerate while the net external torque is negative. These operation situations might make negative engine inertia value estimations possible, which is not feasible. In other cases, engines might have very small accelerations or decelerations while net external torque is moderate to large. For these cases, the calculation might lead to very large engine inertia values, which is not feasible either. The cases mentioned above are most likely to occur when engines operate at high speeds. Those erroneous data corresponding the situations above must be Altered out before applying the least squares method to the engine inertia value computation. The criterion used in this study to decide whether data should be used to calculate the engine inertia values is to check the quotient of the net external torque divided by the engine acceleration. This quotient should not be too large or too small relative to the average engine inertia value. Those data whose quotient are significantly away from the average engine inertia value are likely to fall in the situations mentioned above, and those data should not be used in the engine inertia value computation. V Conclusions The engine inertia values calculated by the least squares method guarantees minimum acceleration and velocity estimation errors for engine operating at constant average velocities. As for monotonically accelerating and decelerating engines, simulations in the study show that the engine model with an inertia calculated by the least squares method leads to smaller estimation errors in acceleration but larger estimation errors in velocity than the constant inertia engine model with an average inertia. It is important that the user knows the type of engine, its range of operation, and the type of loading in order to calculate an optimal engine inertia for the control purpose. This study has provided guidance in understanding the effects of engine performance variables and in calculating an appropriate estimate for the engine inertia. Acknowledgment

Strategic foresight: towards enhancing leadership capabilities and business sustainability

СЕКЦИЯ 9. АКТУАЛЬНЫЕ ФИНАНСОВЫЕ И ЭКОНОМИЧЕСКИЕ АСПЕКТЫ РАЗВИТИЯ ОТРАСЛЕ

Direct simultaneous production of [15O]water and [13N]ammonia or [18F]fluoride ion by 26 MeV proton irradiation of a double chamber water target

A simple double liquid chamber target was developed to provide the option for simultaneous production of [15O]H2O and either 13N or 18F using a single proton beam. Irradiation of natural water in a thin aluminium front chamber produced [15O]H2O by the 16O(p, pn)15O reaction directly. Large (0.5-1.0 Ci) doses of sterile [15O]H2O (> 99.95% radionuclide purity) were routinely prepared in 1 min from end of 20 [mu]A bombardments using this target and an in-line mixed bed ion exchange column purification. Water in the thin front chamber degraded proton energies on exit to 20-18 MeV. The rear silver liquid chamber was threefold thick to 17 MeV protons in water and it efficiently produced either 13N by the 16O(p, [alpha])13N reaction or [18F]fluoride ion by the 18O(p, n)18F reaction. Both target chambers were overpressurized with at least 6 atm of gas to minimize boiling/cavitation of water at high beam currents. Using hydrogen as the overpressure gas on the back chamber and an in-line anion exchange column radionuclidic cleanup process, high yields of sterile, aqueous [13N]NH3 (40-200 mCi; 20 [mu]A) were produced directly from the back chamber at the same time that [15O]H2O was being produced from the front chamber. The combination of this target system with a cyclotron capable of generating 26-30 MeV protons provides great flexibility and simplicity for rapid, high volume production of the three best validated and most widely used radiopharmaceuticals at the present time in clinical positron emission tomography: [15O]H2O, [13N]NH3 and [18F]FDG.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/28943/1/0000780.pd

Prevalence of antibodies against Neospora caninum in dogs from urban areas in Central Poland

Neospora caninum is a protozoan parasite which causes abortion in cattle as well as reproduction problems and neurological disorders in dogs. To assess the prevalence of the parasite in urban dogs in the Mazovian Voivodeship, Central Poland, serum samples from 257 dogs were analyzed for the presence of specific IgG antibodies. The examined dogs visited three private veterinary clinics located in Warsaw due to control tests, vaccinations, or other reasons not directly connected with neosporosis. Using ELISA and Western blot, antibodies against the parasite were detected in 56 out of 257 dogs, giving a prevalence of 21.7%. A greater prevalence was observed in female dogs than in males, 28% and 17.3%, respectively, and the differences were statistically significant (p < 0.05). There were no significant differences in seroprevalence of Neospora infection within the age groups (p > 0.05). This study indicates the presence of N. caninum in the Mazovian Voivodeship, in dogs which live in urban areas and exposure of these dogs to the parasite. The fact that seropositive dogs had no contact with cattle confirms the important role of dogs in the parasite’s epidemiology

Innate Immune Response to Viral Infections in Primary Bronchial Epithelial Cells is Modified by the Atopic Status of Asthmatic Patients

Purpose In order to gain an insight into determinants of reported variability in immune responses to respiratory viruses in human bronchial epithelial cells (HBECs) from asthmatics, the responses of HBEC to viral infections were evaluated in HBECs from phenotypically heterogeneous groups of asthmatics and in healthy controls. Methods HBECs were obtained during bronchoscopy from 10 patients with asthma (6 atopic and 4 non-atopic) and from healthy controls (n=9) and grown as undifferentiated cultures. HBECs were infected with parainfluenza virus (PIV)-3 (MOI 0.1) and rhinovirus (RV)-1B (MOI 0.1), or treated with medium alone. The cell supernatants were harvested at 8, 24, and 48 hours. IFN-α, CXCL10 (IP-10), and RANTES (CCL5) were analyzed by using Cytometric Bead Array (CBA), and interferon (IFN)-β and IFN-λ1 by ELISA. Gene expression of IFNs, chemokines, and IFN-regulatory factors (IRF-3 and IRF-7) was determined by using quantitative PCR. Results PIV3 and RV1B infections increased IFN-λ1 mRNA expression in HBECs from asthmatics and healthy controls to a similar extent, and virus-induced IFN-λ1 expression correlated positively with IRF-7 expression. Following PIV3 infection, IP-10 protein release and mRNA expression were significantly higher in asthmatics compared to healthy controls (median 36.03-fold). No differences in the release or expression of RANTES, IFN-λ1 protein and mRNA, or IFN-α and IFN-β mRNA between asthmatics and healthy controls were observed. However, when asthmatics were divided according to their atopic status, HBECs from atopic asthmatics (n=6) generated significantly more IFN-λ1 protein and demonstrated higher IFN-α, IFN-β, and IRF-7 mRNA expressions in response to PIV3 compared to non-atopic asthmatics (n=4) and healthy controls (n=9). In response to RV1B infection, IFN-β mRNA expression was lower (12.39-fold at 24 hours and 19.37-fold at 48 hours) in non-atopic asthmatics compared to atopic asthmatics. Conclusions The immune response of HBECs to virus infections may not be deficient in asthmatics, but seems to be modified by atopic status

Profiling cytotoxic microRNAs in pediatric and adult glioblastoma cells by high-content screening, identification, and validation of miR-1300

MicroRNAs play an important role in the regulation of mRNA translation and have therapeutic potential in cancer and other diseases. To profile the landscape of microRNAs with significant cytotoxicity in the context of glioblastoma (GBM), we performed a high-throughput screen in adult and pediatric GBM cells using a synthetic oligonucleotide library representing all known human microRNAs. Bioinformatics analysis was used to refine this list and the top seven microRNAs were validated in a larger panel of GBM cells using state-of-the-art in vitro assays. The cytotoxic effect of our most relevant candidate was assessed in a preclinical model. Our screen identified ~100 significantly cytotoxic microRNAs with 70% concordance between cell lines. MicroRNA-1300 (miR-1300) was the most potent and robust candidate. We observed a striking binucleated phenotype in miR-1300 transfected cells due to cytokinesis failure followed by apoptosis. This was also observed in two stem-like patient-derived cultures. We identified the physiological role of miR-1300 as a regulator of endomitosis in megakaryocyte differentiation where blockade of cytokinesis is an essential step. In GBM cells, where miR-1300 is normally not expressed, the oncogene Epithelial Cell Transforming 2 (ECT2) was validated as a direct key target. ECT2 siRNA phenocopied the effects of miR-1300, and ECT2 overexpression led to rescue of miR-1300 induced binucleation. We showed that ectopic expression of miR-1300 led to decreased tumor growth in an orthotopic GBM model. Our screen provides a resource for the neuro-oncology community and identified miR-1300 as a novel regulator of endomitosis with translatable potential for therapeutic application

Macrorheology of cystic fibrosis, chronic obstructive pulmonary disease & normal sputum

<p>Abstract</p> <p>Background</p> <p>Prior microrheologic assessments of selected, microlitre plugs of cystic fibrosis (CF) sputum suggest no intrinsic rheologic abnormality. However, such analyses may not be representative of CF sputum as a whole. We therefore reassessed this question using whole sputum macrorheology. Additionally, we wished to further explore the relationships between sputum rheology, inflammation and infection.</p> <p>Methods</p> <p>Dynamic oscillatory macrorheometry was performed on whole expectorated sputum from stable adults with CF (n = 18) and COPD (n = 12) and induced sputum from normal controls (n = 7). Concomitant sputum inflammatory mediator levels were measured in CF and COPD samples. Sputum collected from CF subjects (n = 6) at commencement and completion of intravenous antibiotic therapy for an infective exacerbation was also assessed.</p> <p>Results</p> <p>CF sputum neutrophil elastase activity (NE) was significantly related to degree of sputum purulence (p = 0.049) and correlated significantly with measures of sputum viscoelasticity (r = 0.696, p = 0.008 for storage modulus G' at 9 Hz). There were significant differences in viscoelasticity between subject groups when samples were compared irrespective of appearance/degree of sputum purulence. However, the macrorheology of mucoid CF sputum did not differ from normal sputum (eg median (range) G' at 9 Hz 2.25 (0.79, 3.26) vs 2.04 (1.4,4.6) Pa, p = 1). In contrast, mucoid COPD samples demonstrated significantly greater viscoelasticity (G' at 9 Hz 4.5 (2.4, 23) Pa) than sputum from both CF (p = 0.048) & normal subjects (p = 0.009). Antibiotic therapy during exacerbations was associated with significant reductions in CF sputum viscoelasticity, with mean (SD) G' at 9 Hz decreasing from 28.5 (11.5) Pa at commencement to 6.4 (4.6) Pa on day 7 (p = 0.01).</p> <p>Conclusion</p> <p>The macrorheologic properties of whole, mucoid CF sputum are not different from normal, confirming the results of prior microrheologic studies. Instead, CF sputum viscoelasticity is related to secondary infection, decreases with intravenous antibiotic therapy and correlates with inflammation. In contrast, COPD sputum demonstrates inherently greater viscoelasticity, providing a novel target for potential therapeutic interventions.</p