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  • About
  • The Global ETD Search service is a free service for researchers to find electronic theses and dissertations. This service is provided by the Networked Digital Library of Theses and Dissertations.
    Our metadata is collected from universities around the world. If you manage a university/consortium/country archive and want to be added, details can be found on the NDLTD website.
11

Έρευνα σχέσης τοπικότητας-ανταγωνιστικότητας cluster επιχειρήσεων Περιφέρειας Ηπείρου-Αργολίδας

Κυρίτσης, Τζέιμς Σαμουήλ 01 August 2014 (has links)
Η παρούσα μελέτη αφορά την διερεύνηση ενός cluster επιχειρήσεων μεταποίησης τροφίμων στην περιφέρεια της Ηπείρου και της Αργολίδας. Πρόθεση της, είναι να ερευνήσει τις αιτίες συγκέντρωσης των επιχειρήσεων αυτών στις περιοχές, τους λόγους για τους οποίους επιλέγουν οι παλαιότερες επιχειρήσεις να παραμείνουν στην ιστορική τους βάση και ωθούν νέες επιχειρήσεις να εγκατασταθούν στην περιοχή. Ερευνά τα ειδή των σχέσεων και τις συνεργασίες που αναπτύσσουν μεταξύ τους οι επιχειρήσεις, αν αναπτύσσουν, αλλά και τις σχέσεις τους με τους προμηθευτές και τους πελάτες τους. / The current study is about a cluster of food processing companies in Ipiros and Argolida Greece and the reasons why the choose the particular locations for their establishments.
12

Contribuicao ao estudo das consequencias quimicas da reacao (n, gamma) nos compostos n-benzoil n-fenil hidroxilaminato de cobre e n-benzoil N-(o) toluil hidroxilaminato de cobre

NAKANISHI, CASUE 09 October 2014 (has links)
Made available in DSpace on 2014-10-09T12:32:24Z (GMT). No. of bitstreams: 0 / Made available in DSpace on 2014-10-09T14:10:30Z (GMT). No. of bitstreams: 1 03135.pdf: 1843926 bytes, checksum: 6a5bb0439cd164e64d829b870c943fcd (MD5) / Tese(doutoramento) / IPEN/T / Instituto de Pesquisas Energeticas e Nucleares - IPEN/CNEN-SP
13

Contribuicao ao estudo das consequencias quimicas da reacao (n, gamma) nos compostos n-benzoil n-fenil hidroxilaminato de cobre e n-benzoil N-(o) toluil hidroxilaminato de cobre

NAKANISHI, CASUE 09 October 2014 (has links)
Made available in DSpace on 2014-10-09T12:32:24Z (GMT). No. of bitstreams: 0 / Made available in DSpace on 2014-10-09T14:10:30Z (GMT). No. of bitstreams: 1 03135.pdf: 1843926 bytes, checksum: 6a5bb0439cd164e64d829b870c943fcd (MD5) / Tese(doutoramento) / IPEN/T / Instituto de Pesquisas Energeticas e Nucleares - IPEN/CNEN-SP
14

A design of a microprogrammed instructional computer

Tarigan, Pernantin January 1985 (has links)
No description available.
15

Copper-64 radiopharmaceuticals for receptor-mediated tumor imaging and radiotherapy

Eiblmaier, Martin 18 April 2008 (has links) (PDF)
This study investigated several somatostatin analogues labeled with copper-64 for imaging and targeted therapy of SSTr positive cancer. Among three new cross-bridged bifunctional chelators coupled to Y3-TATE, 64Cu-CB-TE2A-Y3-TATE had the most favorable tumor targeting properties. The introduction of ionizable linker groups could not remedy the slow clearance from the kidney, and other modifications will be necessary to resolve this issue. The emerging idea of using the copper-64-labeled somatostatin antagonist 64Cu-CB-TE2A-sst2-ANT as a tumor targeting agent will require further experimentation. This radiopharmaceutical showed promising initial results in a biodistribution study in male Lewis rats, however, it should be compared to 111In-DOTA-sst2-ANT in the same model. Nuclear localization of copper-64 from two somatostatin analogues differing in their chelate stability strengthened the hypothesis of copper-64 dissociation from the bifunctional chelator prior to trafficking to the nucleus. However, the increased nuclear uptake of copper-64 from the less stable 64Cu-TETA-Y3-TATE did not result in a significant effect on cell killing of A427-7 cells. In experiments with [64Cu]copper acetate and the EGFR-antibody 64Cu-DOTA-cetuximab, the tumor suppressor protein p53 was identified as a mediator of the nuclear transport of copper. 64Cu-DOTA-cetuximab was also utilized in five cervical cancer cell lines with a wide range of EGFR expression. EGFR quantification by saturation receptor binding, and EGFR function as determined via internalization of 64Cu-DOTA-cetuximab closely followed the expression pattern of these cell lines found via EGFR mRNA profiling. This constitutes a first step in the evaluation of cetuximab for the treatment, and of 64Cu-DOTA-cetuximab for the imaging of advanced cervical cancer, as EGFR expression on the tumor cell surface clearly can be quantified and visualized with this experimental system. Copper-64 has been used in this study to probe the basic biochemical process of intracellular copper trafficking, and for the targeting of cell surface receptors via radiolabeled peptides and antibodies, providing an example of the powerful combination of radiopharmaceutical chemistry and cell biology.
16

Synthese und Charakterisierung Cyclam-basierter Multimere als Basis für Radiopharmaka

Röhrich, Anika 21 July 2009 (has links) (PDF)
Verbindungen mit einer Vielzahl von Oberflächeneinheiten (Multimere) sind im Hinblick auf eine nuklearmedizinische Anwendung von besonderem Interesse, da durch definierte Strukturmodifizierung das Bindungsverhalten an bestimmte Zielstrukturen, die Löslichkeit und damit die Bioverteilung und Pharmakokinetik beeinflusst werden können. Baut man eine Verbindung so auf, dass sich im Inneren ein metallbindendes Zentrum befindet, ergibt sich einerseits die Möglichkeit, das Radiometall chemisch stabil zu binden, andererseits durch genannte Oberflächenfunktionalisierung eine spezifische Bindung im Zielgewebe zu erreichen. Im Rahmen dieser Arbeit wurden neuartige mehrfunktionale Verbindungen mit einer Cyclam-Kerneinheit synthetisiert. Cyclam bildet mit Cu(II)-Ionen äußerst stabile Komplexe, was im Hinblick auf eine radiopharmazeutische Anwendung der Radiometallkomplexe von 64Cu oder 67Cu für diagnostische und therapeutische Zwecke äußerst interessant ist. Für eine symmetrische Mehrfachfunktionalisierung wurde auf ein Tetraamin mit Cyclamkern zurückgegriffen. Die Kupplung von vier Dansylchlorid-Einheiten war erfolgreich. Über geschützte Glucosyl-Isothiocyanate wurden Derivate mit vier Zuckereinheiten gewonnen. Nach der Entfernung der Schutzgruppen wurde die Bindung an das kohlenhydratbindende Lektin Concanavalin A mittels isothermer Kalorimetrie bestimmt. Es war ein deutlicher Anstieg der Stabilitätskonstante K im Vergleich zu den monomeren Zuckern zu beobachten. Die Kinetik der Cu(II)-Komplexierung wurde UV/Vis-spektroskopisch bestimmt. Wegen der langsamen Cu-Komplexierungskinetik der Thioharnstoff-verbrückten Glycodendrimere wurde der Schwerpunkt bei den nachfolgenden Untersuchungen zur Kupplung von Peptiden über Amidbindungen gelegt. Nach zahlreichen erfolglosen Kupplungsversuchen von Peptiden mit einer freien Aminogruppe an Cyclamtetrapropionsäure im organischen Medium wurden im wässrigen Milieu Cyclamderivate mit ein bis zu drei Peptideinheiten durch Peptidkupplung erzeugt. Die Synthese kupplungsfähiger Peptidisothiocyanate blieb erfolglos. Schließlich führte eine Michael-Addition von Acrylamid-Arg-Tyr-OH und Acrylamid-Neurotensin(8-13)-OH an Cyclam zu den gewünschten tetrameren Verbindungen. Das Neurotensintetramer mit vier zielsuchenden Einheiten wurde für weiterführende radiochemische und radiopharmakologische Untersuchungen eingesetzt. Es kann unter milden Bedingungen sehr effizient mit 64Cu radiomarkiert werden, wobei eine spezifische Aktivität von 12 GBq pro µmol und Markierungsausbeuten von durchschnittlich 95-98% erzielt werden können. Erwartungsgemäß werden die Neurotensineinheiten unter diesen Bedingungen abgebaut, wobei im Vergleich zu freiem H-Neurotensin(8-13)-OH, welches innerhalb von zwei Minuten abgebaut wird, die In-vivo-Halbwertszeit des Tetramers 34 Minuten beträgt. Es konnte keine Transmetallierung beziehungsweise Transchelatisierung beobachtet werden, was die Stabilität des Komplexes zeigt. PET-Untersuchungen nach Applikation des 64Cu-markierten Neurotensin-Tetramers wiesen eine erhöhte Anreicherung von radioaktiver Substanz in Tumoren von LoVo- und HT29-Mäusen nach. Um zu unsymmetrischen Cyclamderivaten mit dem Ziel der gleichzeitigen Einführung zielsuchender, löslichkeitsvermittelnder und fluoreszierender Einheiten zu gelangen, wurden unterschiedliche Schutzgruppen eingesetzt. Die Blockierung primärer Aminogruppen eines Cyclam-Derivates mit MMTr-, Boc- und Z-Schutzgruppen lieferte Produkte, die sauber isoliert, aber nicht selektiv entschützt werden konnten. Daher wurden die Aminstickstoffatome des Cyclams direkt geschützt. Ausgehend von Cyclam-Boc3 konnten über Kupplungsreaktionen Aminosäure- und Dipeptidmethylester als unsymmetrische Cyclamderivate gewonnen werden. Damit ist ein Syntheseweg entwickelt worden, der die Darstellung unsymmetrischer Cyclamderivate mit einer definierten Anzahl von gewünschten biologisch aktiven Molekülen beziehungsweise löslichkeitsvermittelnder oder fluoreszierender Einheiten gestattet.
17

Obtenção de sitemas poliméricos microparticulados para o aumento da velocidade de dissolução do efavirenz na terapia anti-HIV

COSTA, Salvana Priscylla Manso 26 February 2016 (has links)
Submitted by Irene Nascimento (irene.kessia@ufpe.br) on 2016-08-11T19:25:05Z No. of bitstreams: 2 license_rdf: 1232 bytes, checksum: 66e71c371cc565284e70f40736c94386 (MD5) SALVANA PRISCYLLA MANSO COSTA_PPGIT_CCB_2016.pdf: 8213740 bytes, checksum: c0b4ea6211a86ddfa6dab45ce846ee02 (MD5) / Made available in DSpace on 2016-08-11T19:25:05Z (GMT). No. of bitstreams: 2 license_rdf: 1232 bytes, checksum: 66e71c371cc565284e70f40736c94386 (MD5) SALVANA PRISCYLLA MANSO COSTA_PPGIT_CCB_2016.pdf: 8213740 bytes, checksum: c0b4ea6211a86ddfa6dab45ce846ee02 (MD5) Previous issue date: 2016-02-26 / CAPES / efavirenz (EFZ) é considerado uma das drogas anti-HIV mais utilizadas, porém é classificado como fármaco de classe II (baixa solubilidade, alta permeabilidade), segundo o sistema de classificação biofarmacêutica, apresentando problemas de absorção no trato gastrointestinal e, consequentemente, biodisponibilidade inadequada para sua ação terapêutica. Assim, este trabalho objetivou desenvolver sistemas microparticulados com polímeros inovadores afim de contornar estes entraves através da técnica de dispersões sólidas (DS). Para o desenvolvimento de DS com o EFZ, realizaram-se, inicialmente, estudos teóricos e práticos que permitiram selecionar o PVP-K30, o PVPVA 64 SOLUPLUS e HPMCAS como carreadores da formulação. As DS com esses polímeros foram preparadas pelo método do solvente. A análise de Difração de raios-X (DRX) mostrou que os polímeros são capazes de manter o EFZ em sua forma amorfa até uma concentração de 80% fármaco. Através dos estudos de dissolução in vitro, verificou-se que o sistema DS PVPVA 64 – EFZ 10% seria o mais promissor, uma vez que o mesmo foi capaz de aumentar em até seis vezes a AUC quando comparado ao fármaco isolado, além de manter os níveis de supersaturação por um período de 120 minutos. Os sistemas DS PVP-K30 – EFZ 10% e DS HPMCAS – EFZ 10% obtiveram bons resultado no estudo de dissolução in vitro e, assim, também foram selecionados. O método para quantificação do EFZ otimizado foi co-validado de acordo com o preconizado pela RE nº 899/03 da ANVISA e pelo ICH e demonstrou-se: linear, preciso e exato para os parâmetros avaliados. A caracterização físico-química das DS com PVP K-30 e PVPVA 64 através de técnicas calorimétricas, microscópicas e espectrofotométricas evidenciou a conversão do EFZ para o seu estado amorfo e verificou que o PVPVA 64 interage de maneira mais efetiva quando comparado ao PVP-K30. No entanto com base nos resultados preliminares do estudo de estabilidade acelerada, pode-se observar que tanto o PVP K-30 quanto o PVPVA 64 foram capazes de inibir a cristalização do fármaco, ao final de três meses de estudo. O comportamento e a estabilidade térmica do EFZ e da DS PVPVA 64 – EFZ 10% foram investigados por TG, DSC, DSC fotovisual e pirolisador acoplado a CG/MS. Foram observadas diferenças entre as curvas TG do fármaco puro e aquela do produto farmacêutico, devido à presença do polímero. Bem como, pôde-se observar que a DS promoveu uma proteção térmica ao EFZ, mostrando uma boa qualidade da formulação. Para os parâmetros cinéticos obtidos nas condições não-isotérmica e isotérmica, os valores da Ea para a DS foi igual a 101 e 132 kJ/mol, respectivamente, enquanto que os valores de Ea para o EFZ, segundo a literatura, estão entre 88 – 93 kJ/mol. A ordem da cinética de degradação da DS foi de primeira ordem, diferentemente do EFZ puro, que é de ordem zero. Além disso, através da equação de Arrhenius, pôde-se sugerir uma estabilidade de sete meses para a formulação. Os valores dos parâmetros cinéticos determinados pelos métodos isoconvencionais obtiveram valores de Ea na faixa de 88 – 95 kJ.mol-1, isto indica uma boa correlação entre os métodos aplicados. Uma vez que os valores de Ea variaram de acordo com o grau de conversão (a), pode-se verificar que o processo de degradação do EFZ se faz por mecanismos do tipo contração geométrica e nucleação. Dessa forma, a partir do estudo, obteve-se DS estáveis e adequadas para superar as limitações de solubilidade do efavirenz. / Efavirenz (EFV) is considered one of the most widely used anti-HIV drugs, but the drug is classified as class II (low solubility, high permeability) according to the biopharmaceutical classification system, having problems with absorption in the gastrointestinal tract and thereby inadequate bioavailability for its therapeutic action. Thus, this study aimed to overcome these barriers through the technique of solid dispersions (SD). For the development of SD with EFZ theoretical and practical studies were initially held which allowed the selection of PVP-K30, PVPVA 64, SOLUPLUS and HPMCAS as carriers of the formulation. The SD systems with these polymers were prepared by the solvent method. The analysis of X-ray diffraction (XRD) showed that the polymers are able to maintain EFZ in its amorphous form up to a concentration of 80% of drug. Through the in vitro dissolution studies, it was found that the SD system PVPVA 64 - EFV 10% would be the most promising since it was able to increase up to six times the AUC when compared to the drug alone, and to maintain the levels of supersaturation for a period of 120 minutes. The SD systems PVP- K30 - EFZ 10% and HPMCAS – EFZ 10% achieved good result during the in vitro dissolution study and, thus, it was also selected. The method for quantification of co-optimized EFZ was validated according to the criteria of the RE nº 899/03 of ANVISA and the ICH and demonstrated: linear, precise and accurate for all parameters evaluated.The physico-chemical characterization of the SD systems with PVP K-30 and PVPVA 64 through calorimetric, microscopic and spectroscopic techniques revealed the conversion of EFZ to its amorphous state and found that the PVPVA 64 interacts more effectively when compared to PVP- K30. However, based on preliminary results of the accelerated stability study, it can be seen that the PVP K-30 polymer was the most inhibitory effect crystallization of the drug after six months of study. The behavior and thermal stability of EFZ and SD PVPVA 64 - EFV 10% were investigated by TG, DSC, DSC photovisual and pyrolyzer coupled with GC/MS. Differences between the TG curves of the pure drug and the pharmaceutical product were observed due to the presence of the polymer. Also, it was observed that the SD promoted a thermal protection of EFZ, showing the good quality of the formulation. Regarding the kinetic parameters obtained for the non-isothermal and isothermal conditions, the activation energy (Ae) values of the SD were equal to 101 and 132 kJ/mol, respectively, while the Ae values for the EFV, according to literature, are between 88 - 93 kJ/mol. Besides that, a first-reaction order was found for the SD, unlike the one for the pure EFZ, which was a zero-reaction order. Furthermore, by the Arrhenius equation, it could be suggested that the formulation would remain stable for seven months. In conclusion, in this study, we obtained stable and adequate SD systems to overcome the solubility limitations of efavirenz.
18

Voyager-Neptune Telemetry: The DSN 70 Meter Antenna Upgrade

Hall, Justin R., McClure, Donald H. 10 1900 (has links)
International Telemetering Conference Proceedings / October 26-29, 1987 / Town and Country Hotel, San Diego, California / The Deep Space Network is responsible for the acquisition of in-situ science and engineering measurements and navigation data from spacecraft whose missions are to explore the Solar System. It must respond to new opportunities in the mission set supported so as to maintain or enhance mission science value. The large capital investment in such a Network mandates an evolutionary design approach wherein upgrades can be effected at low cost, and if appropriate, on existing capability. The 64-Meter antenna design, completed in 1963, is an example of this approach, in that it has permitted a relatively low-cost upgrade which increases performance significantly. The technology assessment was completed in 1975, and the option was exercised in 1986, when needed. Several key characteristics of the DSN design approach, the costs to upgrade performance over the past several decades, and some fundamental constraints on performance are discussed. Finally, the specific 70-Meter upgrade task and resulting overall benefits to Voyager-Neptune and the mission set are summarized.
19

The greening of Colorado: effective community planning strategies around the legalization of recreational marijuana

Victory, Colin January 1900 (has links)
Master of Regional and Community Planning / Department of Landscape Architecture/Regional and Community Planning / Katherine Nesse / In November of 2012, the state of Colorado officially ended an 80 year national prohibition of recreational marijuana by voting to pass Amendment 64. This shift in state policy generated a multitude of economic opportunities for jurisdictions throughout the state. However, the location and volume of production and sale that is authorized is ultimately determined at the city and county level. Localities in Colorado are charged with regulating the new industry in the same manner as they do other locally unwanted land uses (LULUs) such as sex-oriented businesses, halfway houses and liquor stores. This paper examines community planning approaches involving the legalization of recreational marijuana in rural Colorado. The goal of this report is to serve as a document that can be used by jurisdictions that are poised to legalize in the future, as a reference when examining best practice for the regulation of a new recreational marijuana industry. I collected data through one-on-one interviews with city and county planners throughout Colorado. The focus of the research is two-fold: to determine what approach the planning staff took towards managing recreational marijuana in their jurisdiction and to determine why the planning staff chose the approach that they did. Through the course of this research, I have found that conservative communities are treating recreational marijuana shops as nuisance or vice businesses and are using there zoning and regulatory powers to push the shops outside of city limits. Progressive communities have taken a more inclusive approach and in return are profiting from the new market. The struggle between state law and local public perception in these jurisdictions may be the major reason why some communities are not benefiting from the public revenue being generated by Amendment 64.
20

Estudio de la inactivación por ultra alta presión de homogeneización de microorganismos en alimentos líquidos. Valoración de los procesos de limpieza y desinfección del equipo

Briñez Zambrano, Wilfido José 10 March 2006 (has links)
El objetivo principal de esta Tesis Doctoral fue evaluar la inactivación bacteriana usando Ultra Alta Presión de Homogeneización (UHPH) a 300 + 30 MPa de las cepas Listeria innocua ATCC 33090, Escherichia coli ATCC 10536, Escherichia coli O157:H7 CCUG 44857, Staphylococcus aureus ATCC 13565 y Staphylococcus carnosus CECT 4491 inoculadas en leche entera, leche desnatada y zumo de naranja. También, intentamos estudiar el efecto de la temperatura de entrada de la leche y del zumo en la máquina de alta presión sobre la letalidad y producción de daños subletales en estos microorganismos, así como la habilidad de estos para sobrevivir, recuperarse y crecer en condiciones de refrigeración después del tratamiento de UHPH. Dado que no existían protocolos previos de limpieza y desinfección de la máquina de UHPH que garantizara la correcta desinfección entre un ensayo y otro, el experimento 1 tuvo como objetivo evaluar la eficacia bactericida como reducción decimal (DR) de una mezcla de ácido peracético y peróxido de hidrógeno (PAHP) contra cepas de Staphylococcus, Listeria y Escherichia coli en presencia de diferentes tipos de materia orgánica, tiempos de exposición y concentración de desinfectante. También se desarrollo de un procedimiento de limpieza y desinfección eficiente adaptado a la máquina de UHPH. Una vez ajustado y evaluado, el proceso de desinfección, el experimento 2 tuvo como finalidad evaluar la eficacia bactericida de los tratamientos de UHPH contra Listeria innocua ATCC 33090 inoculada en leche entera UHT y zumo de naranja UHT, así como estudiar el efecto de la temperatura de entrada en la máquina sobre la letalidad y la producción de daños subletales en este microorganismo. Así mismo se estudió su habilidad de sobrevivir, repararse y crecer almacenado en refrigeración después del tratamiento de UHPH. Los experimentos 3 y 4 tuvieron como objetivo evaluar la inactivación por UHPH de Escherichia coli ATCC 10536 y Escherichia coli O157:H7 CCUG 44857 inoculadas en leche entera UHT, leche desnatada UHT y zumo de naranja UHT, considerando el efecto de la temperatura de entrada de la leche y el zumo, en los valores de letalidad y la capacidad del tratamiento de producir daños subletales en estas cepas. También estudiamos la habilidad de estos microorganismos de sobrevivir, repararse y crecer durante su conservación a 4,0 ºC tras el tratamiento de UHPH. El experimento 5 tuvo como propósito evaluar la inactivación inducida por UHPH en Staphylococcus aureus ATCC 13565 y Staphylococcus carnosus CECT 4491 inoculados en leche entera UHT y zumo de naranja UHT, considerando el efecto de la temperatura de entrada de la muestra en los valores de letalidad, así como la producción de daños subletales en estas cepas, y su capacidad de sobrevivir, repararse y crecer almacenados a bajas temperaturas tras el tratamiento de UHPH. Con respecto a la evaluación del desinfectante, Staphylococcus spp. mostró mayor resistencia a bajas concentraciones de desinfectante que las cepas de Escherichia coli y Listeria spp. El huevo fue la materia orgánica con mayor capacidad interferente mientras que el zumo de naranja presentó la menor capacidad interferente. Sin embargo, el PAHP fue efectivo (reducciones > 5 log UFC/mL) a concentraciones superiores a 0,1 % y 10 minutos de exposición, en todos los casos. No fueron encontradas diferencias estadísticas entre cepas patógenas y no patógenas del mismo grupo. En cuanto a los tratamientos de inactivación por UHPH, en Listeria innocua ATCC 33090, tanto la temperatura de entrada como el tipo de matriz influenciaron significativamente (P &#8804; 0,05) su inactivación, que fue mayor a una temperatura de entrada de 20 ºC. Los tratamientos por UHPH no causaron daños subletales en Listeria innocua. Durante el almacenamiento a 4 ºC después de los tratamientos, los recuentos de Listeria innocua en leche aumentaron alrededor de 2 unidades logarítmicas entre los días 0 y 9, mientras que en zumo de naranja disminuyeron 2,5 unidades logarítmicas entre los días 0 y 18. El nivel de inactivación fue similar para ambas cepas de Escherichia coli en leche y no fueron detectados daños subletales después de los tratamientos tanto en leche como en zumo de naranja. La temperatura de entrada así como el tipo de matriz influenciaron (P &#8804; 0,05) el grado de inactivación en las cepas de Escherichia coli, alcanzando su máximo nivel a una temperatura de entrada de 20 ºC. La evolución de los recuentos viables durante el almacenamiento a 4,0 ºC de muestras presurizadas fue similar en leche entera y desnatada, aunque la cepa E. coli ATCC 10536 no mostró diferencias significativas entre los días 0 y 9 de almacenamiento, mientras que la cepa E. coli CCUG 44857 mostró una tendencia decreciente de aproximadamente 0,3 unidades logarítmicas. En zumo de naranja, las cepas de Escherichia coli mostraron una mayor tendencia decreciente y la cepa CCUG 44857 fue más resistente al bajo pH, manteniendo recuentos altos para el día 27. En cepas de Staphylococcus, la temperatura de entrada, la matriz y la cepa influenciaron significativamente (P &#8804; 0,05) el nivel de inactivación, alcanzando sus mayores niveles a 20 ºC. No se observaron daños subletales tras los tratamientos en ninguno de los casos. La evolución de los recuentos viables de ambas cepas mostró una fuerte tendencia decreciente después del día 3 de almacenamiento a 4,0 ºC en zumo de naranja, mientras que la cepa Staphylococcus carnosus CECT 4491 mostró una baja tendencia y una gran resistencia cuando fue inoculada en leche y presurizada a bajas temperaturas. El PAPH fue efectivo contra todas las cepas probadas a concentraciones por encima de 0,1 % y tiempos de exposición superiores a 10 minutos para todos los tipos de materias orgánicas estudiadas. Los tratamientos de UHPH de leche entera, desnatada y zumo de naranja a 300 + 30 MPa y una temperatura de entrada de 6 y 20 ºC fueron eficientes para reducir los recuentos viables de Listeria innocua ATCC 33090, Escherichia coli ATCC 10536, Escherichia coli O157:H7 CCUG 44857, Staphylococcus aureus ATCC 13565 y Staphylococcus carnosus CECT 4491. La letalidad incrementó con la temperatura de entrada, sugiriendo un claro efecto de la temperatura en los valores de letalidad. El tipo de matriz influenció significativamente tanto la eficacia de los tratamientos de UHPH como la capacidad de crecimiento durante el subsiguiente periodo de almacenamiento a bajas temperaturas. Los tratamientos de UHPH no causaron daños subletales aparentes en ninguno de los casos. La tecnología de las UHPH puede ofrecer una prominente alternativa para la pasteurización de la leche, zumos y otros alimentos líquidos combinado con la posibilidad de incrementar la temperatura de entrada de las muestras antes del proceso. / The main objective of this Doctoral Thesis was to evaluate the bacterial inactivation using Ultrahigh-pressure Homogenisation (UHPH) to 300 + 30 MPa of Listeria innocua ATCC 33090, Escherichia coli ATCC 10536, Escherichia coli O157:H7 CCUG 44857, Staphylococcus aureus ATCC 13565 and Staphylococcus carnosus CECT 4491 inoculated into whole milk, skim milk and into orange juice. Also, we intended to study the effect of inlet temperature of the milk and orange juice in the machine on the lethality and production of sublethal injuries in these microorganisms and its ability for survival, repair and growth in refrigerated storage after UHPH treatment. The objective of experiment 1 was to evaluate the bactericidal efficacy as decimal reduction (DR) of a mixture of peracetic acid and hydrogen peroxide (PAHP) against strains of Staphylococcus, Listeria and Escherichia coli in presence of different organic matter types, exposure times and disinfectant concentrations. Also, we develop an efficient procedure of cleaning and disinfection adapted to the UHPH machine. Experiment 2 had the purpose of evaluating the bactericidal efficacy of UHPH treatments against Listeria innocua ATCC 33090 inoculated into UHT milk and UHT orange juice. We also studied the effect of inlet temperature on the degree of inactivation of this microorganism and the capacity of this UHPH treatment to cause sublethal injuries when inoculated into whole milk and orange juice. We also determined its ability for survival, repair and growth under refrigeration after the UHPH treatment. The experiments 3 and 4 had as objective to evaluate the inactivation by UHPH of Escherichia coli ATCC 10536 and Escherichia coli O157:H7 CCUG 44857 inoculated into UHT whole milk, UHT skim milk and UHT orange juice considering the effect of inlet temperature on the lethality values and the production of sublethal injuries in these strains. We also studied the ability of the microorganisms to repair and growth during storage at 4.0 ºC after treatment. The experiment 5 had as purpose to evaluate the inactivation induced by UHPH of Staphylococcus aureus ATCC 13565 and Staphylococcus carnosus CECT 4491 inoculate into UHT whole milk and UHT orange juice considering the effect of inlet temperature of sample on the lethality values reached and the production of sublethal injuries in these strains, as well as their ability to survive, repair and growth when stored at low temperatures after UHPH treatments. In the evaluation of the disinfectant, Staphylococcus spp. showed more resistance at low concentrations of disinfectant than strains of E. coli and Listeria spp. Egg was the organic matter with the greatest interfering capacity and orange juice was the one with least interfering capacity. However PAHP was effective (reductions > 5 log CFU/mL) in all cases from 0.1 % PAHP and 10 min of exposure. No statistical differences were found between pathogenic and non pathogenic strains in the same group. Concerning the effect of UHPH treatment, in Listeria innocua ATCC 33090 both the inlet temperature and the food matrix influenced significantly (P < 0.05) the level of inactivation reached, which was higher in whole milk with inlet at 20 ºC. The UHPH treatment caused few or no sublethal injuries in L. innocua. During storage at 4.0 ºC after treatments, counts increased by approximately two logarithmic units from days 0 to 9 in whole milk, while in orange juice counts diminished by approximately 2.5 logarithmic units from days 0 to 18. The level of inactivation was similar for both strains of E. coli and no sublethal injuries were detected after treatments in milk as in juice of orange. Both the inlet temperature and the type of milk influenced significantly (P < 0.05) the degree of inactivation reached in both strains of E. coli, being higher at 20 ºC. The evolution of viable counts during storage at 4.0 ºC was similar in whole and skim milk but although ATCC 10536 strain counts did not show significant differences between the days 0 and 9 of storage, the strain CCUG 44857 showed a decreasing tendency of approximately 0.3 logarithmic units. In orange juice the strains of Escherichia coli showed a greater decreasing tendency and the strain CCUG 44857 was more resistant at low pH, maintaining high viable counts until 27th of storage. In Staphylococcus strains the inlet temperature, food matrix and the strain influenced significantly (P < 0.05) the lethality level, which was higher with 20 ºC of inlet temperature. We not observed sublethal injuries after treatments in any case. The evolution of viable counts showed for both strains a very strong decreasing tendency after 3 days of storage at 4 ºC for orange juice, although S. carnosus CECT 4491 showed a low decreasing tendency and great resistance when was inoculated in milk and pressurized at low temperatures. The PAHP was effective against all strains tested at concentrations above 0.1 % and exposure times over 10 minutes for all the organic matters studied. The UHPH treatments of whole milk, skim milk and orange juice at 300 + 30 MPa at inlet temperatures of 6 and 20 ºC were efficient to reduce the viable counts of Listeria innocua ATCC 33090, Escherichia coli ATCC 10536, Escherichia coli O157:H7 CCUG 44857, Staphylococcus aureus ATCC 13565 and Staphylococcus carnosus CECT 4491. The lethality increased with the inlet temperature, suggesting a clear effect of the temperature on the lethality values. The kind of matrix significantly influenced both the efficacy of the treatment and the growing capability during the subsequent storage period at low temperatures. Apparently UHPH treatment (300 + 30 MPa) did not cause significant sublethal injuries in any of the cases. UHPH technology may offer a promising alternative to the pasteurization of milk, juices and others liquid foods in combination with an increase of the inlet temperature of the sample before the process.

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