Obras espirituales del venerable Padre, maestro Fr. Luis de Granada del Orden de Santo Domingo : repartidas en tres tomos ... /

Mode of access: Internet.

Elógio de la réina católica Doña Isabel, al que siguen várias ilustraciones sobre su reinado,

"Apéndice do documentos ineditos": p. 577-611.

History of the reign of Ferdinand and Isabella the Catholic /

Includes bibliographical references and index.

Spray dried combinations of lactoferrin with antibiotics appear superior to monotherapy for reducing biofilm formation by pseudomonas aeruginosa

SD Apo Lactoferrin-Tobramycin/Gentamicin Combinations are superior to monotherapy in the eradication of Pseudomonas aeruginosa Biofilm in the lungs Wilson Oguejiofor1, Lindsay J. Marshall1, Andrew J. Ingham1, Robert Price2, Jag. Shur2 1School of Life and Health Sciences, Aston University, Birmingham, UK. 2School of Pharmacy and Pharmacology, University of Bath, Bath, UK. KEYWORDS: lactoferrin, apo lactoferrin, spray drying, biofilm, cystic fibrosis Introduction Chronic lung infections from the opportunistic pathogeen Pseudomonas aeruginosa has been recognised as a major contributor to the incidences of high morbidity and mortality amongst cystic fibrosis (CF) patients (1,2). Currently, strategies for managing lung infections in CF patients involves the aggressive use of aerosolised antibiotics (3), however, increasing evidence suggests that the biofilm component of P. aeruginosa in the lower airway remains unperturbed and is associated with the development of antibiotic resistance. If this is so then, there is an urgent need to suitably adjust the current treatment strategy so that it includes compounds that prevent biofilm formation or disrupt established biofilms. It is well understood that biofilm formation is strongly dependent on iron (Fe3+) availability (4), therefore aerosolised anti-infective formulations which has the ability to chelate iron may essentially be a well suited therapy for eliminating P. aeruginosa biofilms on CF airway epithelial cells (5). In this study, we report the use of combination therapy; an aminoglycosides (tobramycin and gentamicin) and an antimicrobial peptide (lactoferrin) to significantly deplete P. aeruginosa biofilms. We demonstrate that lactoferrin-tobramycin and lactoferrin-gentamicin combinations are superior to the single antibiotic regime currently being employed to combat P. aeruginosa biofilms. MATERIALS AND METHOD Antibiotics: The antibiotics used in this study included gentamicin and tobramycin supplied by Fagron, UK. Bacterial strain and growth conditions: Pseudomonas aeruginosa strain PAO1 was provided by Prof. Peter Lambert of Aston University, Birmingham UK. The Strains were routinely grown from storage in a medium supplemented with magnesium chloride, glucose and casamino acids. Dialysis of lactoferrin: Apo lactoferrin was prepared by dialyzing a suspension of lactoferrin for 24 hrs at 4 °C against 20 mmol/L sodium dihydrogen phosphate, 20 mmol/L sodium acetate and 40 mmol/L EDTA (pH 3.5). Ferric ion (Fe3+) removal was verified by atomic absorption spectroscopy measurements. Spray drying of combinations of lactoferrin and apo lactoferrin with the different aminoglycosides: Combinations of tobramycin and gentamicin with the different preparations of lactoferrin were spray dried (SD) as a 2% (w/v) aqueous suspension. The spray drying parameters utilized for the production of suitable micron-sized particles includes: Inlet temperature, 180°C, spray flow rate, 606 L/hr; pump setting, 10%; aspirator setting, 85% (34m3/hr) to produce various outlet temperatures ranging from 99 - 106°C. Viability assay: To test the bactericidal activity of the various combinations, a viability assay was performed as previously described by Xu, Xiong et al. (6) with some modifications. Briefly, 10µL of ~ c. 6.6 x 107 CFU mL-1 P. aeruginosa strain PAO1 suspension were incubated (37°C, 60 mins) with 90 µL of a 2 µg/mL concentration of the various combinations and sampled every 10 mins. After incubation, the cells were diluted in deionised water and plated in Mueller hinton agar plates. Following 24 h incubation of the plates at 37°C, the percentage of viable cells was determined relative to incubation without added antibiotics. Biofilm assay: To test the susceptibility of the P. aeruginosa strain to various antibiotics in the biofilms mode of growth, overnight cultures of P. aeruginosa were diluted 1:100 into fresh medium supplemented with magnesium chloride, glucose and casamino acids. Aliquots of the dilution were dispensed into a 96 well dish and incubated (37°C, 24 h). Excess broth was removed and the number of colony forming units per milliliter (CFU/mL) of the planktonic bacteria was quantified. The biofilms were then washed and stained with 0.1% (w/v) crystal violet for 15 mins at room temperature. Following vigorous washing with water, the stained biofilms were solubilized in 30% acetic acid and the absorbance at 550nm of a 125 µL aliquot was determined in a microplate reader (Multiskan spectrum, Thermo Scientific) using 30% acetic acid in water as the blank. Aliquots of the broth prior to staining were used as an indicator of the level of planktonic growth. RESULTS AND DISCUSSION Following spray drying, the mean yield, volume weighted mean diameter and moisture content of lactoferrin powder were measured and were as follows (Table 1 and table 2); Table 1: Spray drying parameters FormulationInlet temp (°C)Outlet temp (°C)Airflow rate (L/hr)Mean yield (%)Moisture content (%) SD Lactoferrin18099 - 10060645.2 ±2.75.9 ±0.4 SD Apo Lactoferrin180100 - 10260657.8 ±1.85.7 ±0.2 Tobramycin180102 - 10460682.1 ±2.23.2 ±0.4 Lactoferrin + Tobramycin180104 - 10660687.5 ±1.43.7 ±0.2 Apo Lactoferrin + Tobramycin180103 - 10460676.3 ±2.43.3 ±0.5 Gentamicin18099 - 10260685.4 ±1.34.0 ±0.2 Lactoferrin + Gentamicin180102 - 10460687.3 ±2.13.9 ±0.3 Apo Lactoferrin + Gentamicin18099 -10360680.1±1.93.4 ±0.4 Table 2: Particle size distribution d10 d50d90 SD Lactoferrin1.384.9111.08 SD Apo Lactoferrin1.284.7911.04 SD Tobramycin1.254.9011.29 SD Lactoferrin + Tobramycin1.175.2715.23 SD Apo Lactoferrin + Tobramycin1.115.0614.31 SD Gentamicin1.406.0614.38 SD Lactoferrin + Gentamicin1.476.2314.41 SD Apo Lactoferrin + Gentamicin1.465.1511.53 The bactericidal activity of the various combinations were tested against P. aeruginosa PAO1 following a 60 minute incubation period (Figure 1 and Figure 2). While 2 µg/mL of a 1:1 combination of spray dried apo lactoferrin and Gentamicin was able to completely kill all bacterial cells within 40 mins, the same concentration was not as effective for the other antibiotic combinations. However, there was an overall reduction of bacterial cells by over 3 log units by the other combinations within 60 mins. Figure 1: Logarithmic plot of bacterial cell viability of various combinations of tobramycin and lactoferrin preparations at 2µg/mL (n = 3). Figure 2: Logarithmic plot of bacterial cell viability of various combinations of gentamicin and lactoferrin preparations at 2µg/mL (n = 3). Crystal violet staining showed that biofilm formation by P. aeruginosa PAO1 was significantly (ANOVA, p < 0.05) inhibited in the presence of the different lactoferrin preparations. Interestingly, apo lactoferrin and spray dried lactoferrin exhibited greater inhibition of both biofilm formation and biofilm persistence (Figure 2). Figure 2: Crystal violet staining of residual biofilms of P. aeruginosa following a 24hr incubation with the various combinations of antibiotics and an exposure to 48 hr formed biofilms. CONCLUSION In conclusion, combination therapy comprising of an antimicrobial peptide (lactoferrin) and an aminoglycosides (tobramycin or gentamicin) provides a feasible and alternative approach to monotherapy since the various combinations are more efficient than the respective monotherapy in the eradication of both planktonic and biofilms of P. aeruginosa. ACKNOWLEDGEMENT The authors would like to thank Mr. John Swarbrick and Friesland Campina for their generous donation of the Lactoferrin. REFERENCES 1.Hassett, D.J., Sutton, M.D., Schurr, M.J., Herr, A.B., Caldwell, C.C. and Matu, J.O. (2009), "Pseudomonas aeruginosa hypoxic or anaerobic biofilm infections within cystic fibrosis airways". Trends in Microbiology, 17, 130-138. 2.Trust, C.F. (2009), "Antibiotic treatment for cystic fibrosis". Report of the UK Cystic Fibrosis Trust Antibiotic Working Group. Consensus document. London: Cystic Fibrosis Trust. 3.Garcia-Contreras, L. and Hickey, A.J. (2002), "Pharmaceutical and biotechnological aerosols for cystic fibrosis therapy". Advanced Drug Delivery Reviews, 54, 1491-1504. 4.O'May, C.Y., Sanderson, K., Roddam, L.F., Kirov, S.M. and Reid, D.W. (2009), "Iron-binding compounds impair Pseudomonas aeruginosa biofilm formation, especially under anaerobic conditions". J Med Microbiol, 58, 765-773. 5.Reid, D.W., Carroll, V., O'May, C., Champion, A. and Kirov, S.M. (2007), "Increased airway iron as a potential factor in the persistence of Pseudomonas aeruginosa infection in cystic fibrosis". European Respiratory Journal, 30, 286-292. 6.Xu, G., Xiong, W., Hu, Q., Zuo, P., Shao, B., Lan, F., Lu, X., Xu, Y. and Xiong, S. (2010), "Lactoferrin-derived peptides and Lactoferricin chimera inhibit virulence factor production and biofilm formation in Pseudomonas aeruginosa". J Appl Microbiol, 109, 1311-1318.

Evaluation of the measurement of refractive error by the PowerRefractor:a remote, continuous and binocular measurement system of oculomotor function

Background/aim: The technique of photoretinoscopy is unique in being able to measure the dynamics of the oculomotor system (ocular accommodation, vergence, and pupil size) remotely (working distance typically 1 metre) and objectively in both eyes simultaneously. The aim af this study was to evaluate clinically the measurement of refractive error by a recent commercial photoretinoscopic device, the PowerRefractor (PlusOptiX, Germany). Method: The validity and repeatability of the PowerRefractor was compared to: subjective (non-cycloplegic) refraction on 100 adult subjects (mean age 23.8 (SD 5.7) years) and objective autarefractian (Shin-Nippon SRW-5000, Japan) on 150 subjects (20.1 (4.2) years). Repeatability was assessed by examining the differences between autorefractor readings taken from each eye and by re-measuring the objective prescription of 100 eyes at a subsequent session. Results: On average the PowerRefractor prescription was not significantly different from the subjective refraction, although quite variable (difference -0.05 (0.63) D, p = 0.41) and more negative than the SRW-5000 prescription (by -0.20 (0.72) D, p<0.001). There was no significant bias in the accuracy of the instrument with regard to the type or magnitude of refractive error. The PowerRefractor was found to be repeatable over the prescription range of -8.75D to +4.00D (mean spherical equivalent) examined. Conclusion: The PowerRefractor is a useful objective screening instrument and because of its remote and rapid measurement of both eyes simultaneously is able to assess the oculomotor response in a variety of unrestricted viewing conditions and patient types.

Задачи за програмиране на итеративни процеси

Доклад, поместен в сборника на Националната конференция "Образованието в информационното общество", Пловдив, октомври, 2006 г.

Állami támogatások és gazdasági teljesítmény. Támogatás-túladagolás a magyar gazdaságfejlesztésben? (An overdose of state aid in the Hungarian economy)

Magyarországon az elmúlt évtizedben a vállalatoknak nyújtott állami támogatás GDP-arányosan számolva az európai uniós átlag 2,7-szerese volt. A cikk megvizsgálja, hogy a támogatások hatása megjelenik-e a magyar gazdaság beruházási, foglalkoztatási, jövedelemtermelési teljesítményében és versenyképességében. Arra a következtetésre jut, hogy egyik területen sem jobb a helyzet, mint azokban az országokban, amelyekben lényegesen alacsonyabb a támogatási arány. A mikroszintű elemzések, értékelések sem támasztják alá azt a vélekedést, hogy az állami támogatások érzékelhetően javítják a gazdasági teljesítményt. A források bősége önmagában is okoz hatékonysági problémákat, mert sok program és szervezet versenyez egymással. A rossz (gyengébb hatékonysági követelményeket támasztó) programok kiszorítják a jó programokat. Ha a versenyképességet érdemben befolyásoló tényezők, például a kedvező jogi szabályozási környezet és az üzleti szolgáltatások jól működő piacai nem adottak, akkor ezek hiányát nem ellensúlyozza a támogatások magas szintje. Magyarország az idén indult hétéves programozási időszakban tovább kívánja növelni a vállalatoknak nyújtott állami támogatások mértékét, miközben nincs egyértelmű válasz arra a kérdésre, hogy milyen módon növelhető a támogatási rendszer jelenleg alacsony hatékonysága. _____ State aid given to enterprises as a proportion of Hungary�s GDP has been 2.7 times the EU average over the past decade. The article examines whether any impact of this high level of state aid can be discerned in investment, employment, income- generation performance, or competitiveness of the Hungarian economy. It seems that in none of these areas is the situation better than in countries that have a markedly lower rate of state aid. Micro-level analyses and evaluations do not support the belief that state aid appreciably improves economic performance. A wealth of resources on its own can cause problems with efficiency, as many programs and organizations compete with each other. Bad (less demanding) programs nudge out the good ones. If the factors significantly determining competitiveness, including a favourable legal and regulatory environment and well-functioning markets of business services, are not in place, a high level of state aid cannot be a proxy for them. In the seven-year programming period beginning this year, Hungary plans to further increase the amount of state aid to enterprises, while there is no clear answer as to how to improve the currently poor efficiency of the state aid system.

The Beacon, February 2, 2011

Vol. 22, Issue 9, 8 pages

Theorizing suburban public space in Kendall

The purpose of this study was to determine whether public space in the suburbs has the same settings as that of a central city or if it has its own characteristics. In order to approach this problem the area of Kendall was thoroughly studied by examining aerial maps, historic images and writings of local historians such as Donna Knowles Born. Heavy emphasis was placed on the transformation of the original one-mile grid characteristic of the city of Miami. As the area of Kendall was being developed, the grid was transformed into an irregular and organic method of laying out a street system that directly affected pedestrian life. It became evident, therefore, that Kendall is primarily geared toward automobile movement, thus affecting the setting of public space. This also restricted social events forcing them to concentrate in specific places like the malls. These findings demonstrated that malls are centers of social interaction concentrating many social activities in one place. In other words, a mall serves as a common meeting place in the otherwise vast spread of the suburbs. This thesis also explains how public spaces in a suburban context can affect the community by working as filtering agents between the immediate context of a particular site and the overall city. The project, a "Wellness Center and Park" for the Kendall area, was an exploration of these filtering agents and the transitions they engendered. The research upon which this project was based recognized the important role of the site's history as well as extrapolating as to its future potential.

DISCURSO DA MARCA: uma abordagem da semiose comunicacional da marca

A tese aborda a constituição do significado da marca sob a perspectiva de seu discurso na sociedade de consumo. Por meio dos objetivos propostos, (a) a descrição do processo comunicacional da marca como um discurso social; (b) a demonstração da constituição do significado da marca pela circulação de efeitos de sentido; e (c) a articulação da teoria social que fundamenta o processo, intenta-se explorá-la como possibilidade teórica explicativa por meio do discursivo na semiose social. A tese justifica-se pelo desenvolvimento de uma abordagem comunicacional para a constituição do significado da marca (relevância teoria) e pela possibilidade de interferência na realidade social a partir do conhecimento de como a marca institui-se como um discurso social (relevância social). Trata-se de um trabalho teórico, de natureza qualitativa, a partir de uma pesquisa exploratória, com vistas a propor a construção de uma semiose da marca. Concluiu-se que é teoricamente pertinente a constituição do significado da marca contemporânea fundamentalmente por um processo de produção de sentido social na sociedade de consumo.

Transcriptomic Analysis of the Host Response and Innate Resilience to Enterotoxigenic Escherichia coli Infection in Humans.

BACKGROUND: Enterotoxigenic Escherichia coli (ETEC) is a globally prevalent cause of diarrhea. Though usually self-limited, it can be severe and debilitating. Little is known about the host transcriptional response to infection. We report the first gene expression analysis of the human host response to experimental challenge with ETEC. METHODS: We challenged 30 healthy adults with an unattenuated ETEC strain, and collected serial blood samples shortly after inoculation and daily for 8 days. We performed gene expression analysis on whole peripheral blood RNA samples from subjects in whom severe symptoms developed (n = 6) and a subset of those who remained asymptomatic (n = 6) despite shedding. RESULTS: Compared with baseline, symptomatic subjects demonstrated significantly different expression of 406 genes highlighting increased immune response and decreased protein synthesis. Compared with asymptomatic subjects, symptomatic subjects differentially expressed 254 genes primarily associated with immune response. This comparison also revealed 29 genes differentially expressed between groups at baseline, suggesting innate resilience to infection. Drug repositioning analysis identified several drug classes with potential utility in augmenting immune response or mitigating symptoms. CONCLUSIONS: There are statistically significant and biologically plausible differences in host gene expression induced by ETEC infection. Differential baseline expression of some genes may indicate resilience to infection.