Delivery of antisense oligodeoxyribonucleotides against the human epidermal growth factor receptor into cultured KB cells with liposomes conjugated to folate via polyethylene glycol.

Antisense oligodeoxyribonucleotides targeted to the epidermal growth factor (EGF) receptor were encapsulated into liposomes linked to folate via a polyethylene glycol spacer (folate-PEG-liposomes) and efficiently delivered into cultured KB cells via folate receptor-mediated endocytosis. The oligonucleotides were a phosphodiester 15-mer antisense to the EGF receptor (EGFR) gene stop codon (AEGFR2), the same sequence with three phosphorothioate linkages at each terminus (AEGFR2S), a randomized 15-mer control of similar base composition to AEGFR2 (RC15), a 14-mer control derived from a symmetrized Escherichia coli lac operator (LACM), and the 5'-fluorescein-labeled homologs of several of the above. Cellular uptake of AEGFR2 encapsulated in folate-PEG-liposomes was nine times higher than AEGFR2 encapsulated in nontargeted liposomes and 16 times higher than unencapsulated AEGFR2. Treatment of KB cells with AEGFR2 in folate-PEG-liposomes resulted in growth inhibition and significant morphological changes. Curiously, AEGFR2 and AEGFR2S encapsulated in folate-PEG-liposomes exhibited virtually identical growth inhibitory effects, reducing KB cell proliferation by > 90% 48 hr after the cells were treated for 4 hr with 3 microM oligonucleotide. Free AEGFR2 caused almost no growth inhibition, whereas free AEGFR2S was only one-fifth as potent as the folate-PEG-liposome-encapsulated oligonucleotide. Growth inhibition of the oligonucleotide-treated cells was probably due to reduced EGFR expression because indirect immunofluorescence staining of the cells with a monoclonal antibody against the EGFR showed an almost quantitative reduction of the EGFR in cells treated with folate-PEG-liposome-entrapped AEGFR2. These results suggest that antisense oligonucleotide encapsulation in folate-PEG-liposomes promise efficient and tumor-specific delivery and that phosphorothioate oligonucleotides appear to offer no major advantage over native phosphodiester DNA when delivered by this route.

Efectos del cambio climático y usos del suelo sobre los recursos hídricos de la cuenca del río Tordera (Barcelona, España)

Se presentan los efectos del cambio global en la cuenca del río Tordera (España) para el periodo 2000-2050, escenarios climáticos A2 (medio-alto) definidos por el Panel Intergubernamental del Cambio Climático (IPCC, 200) y escenarios socioeconómicos (cambios previstos en la cuenca) denominados estable y tendencial. Los efectos sobre los recursos hídricos se han analizado de forma conjunta superficial-subterránea mediante una metodológica de tipo acoplado. Para establecer los impactos futuros sobre los recursos hídricos se ha seleccionado el Modelo de Circulación Global ECHAM5 (Max Planck Institute). Los resultados obtenidos indican una disminución de la precipitación del 11.3% y un aumento de la temperatura de 1ºC, respecto a los valores históricos de la zona. De acuerdo a la proyección futura (2050) sobre cambios en los recursos hídricos, la escorrentía superficial obtenida mediante simulación con el código HEC-HMS 3.4 experimenta una reducción del 31.8% respecto al valor histórico y la recarga natural, estimada mediante VISUAL-Balan, se reduce en un 11.7%. El balance en el acuífero deltaico simulado mediante MODFLOW 2009.1 Pro muestra igualmente una disminución de los parámetros del balance. Los cambios del uso del suelo previstos de acuerdo a la legislación vigente (escenarios socioeconómicos) no conducen a la generación de un impacto apreciable en los recursos hídricos; según los escenarios definidos la variación de precipitación y temperatura son los parámetros fundamentales del cambio previsto.

Calcareous nannofossil abundance and datums of ODP Leg 189 sites

Quaternary sediments were recovered at all five sites drilled during Ocean Drilling Program (ODP) Leg 189 in the Tasmanian Gateway. Two of these sites lie north of the present-day Subtropical Front (STF), and three sites lie south of the STF. Quaternary sediments recovered at Sites 1168, 1170, 1171, and 1172 were studied in detail to determine the calcareous nannofossil biostratigraphy and construct an age model for these sediments. The Pliocene/Pleistocene boundary was identified by the last occurrence (LO) of Discoaster brouweri at Site 1172 and approximated by the LO of Calcidiscus macintyrei at the other sites because of a lack of discoasterids. A hiatus encompassing the entire Helicosphaera sellii Zone was tentatively identified at Sites 1168 and 1172 by the coincident LOs of C. macintyrei and H. sellii. Similar hiatuses have been noted at ODP Site 1127 on the Great Australian Bight, Deep Sea Drilling Project Site 282 off the Tasman subcontinent, and ODP Site 1165 in Prydz Bay, Antarctica.

Tratados de paz, amistad, comercio y extradición y convención consular, entre las repúblicas de Guatemala, Costa-Rica, Honduras, Nicaragua y El Salvador /

Mode of access: Internet.

El hule; su historia, naturaleza, cultivo quimica y tecnica,

Mode of access: Internet.

Coleção das leis.

The laws of each year are published in 2 parts, entitle "Atos do poder legislativo" and "Atos do poder exectutivo" respectively.

Neues Kochbuch für die deutsch-amerikanische Küche : zuverlässige und geprüfte Rezepte zur Bereitung der verschiedenen Speisen und Getränke von Backwerk, Eingemachtem u.s.w. : nach den besten dutschen und amerikanischen Koch Büchern bearbeitet, hauptsächlich nach den ausgezeichnete Kochbuch /

Recipes taken from several cookbooks, including books by Henriette Davidis and Henriette Löffler.

Church and state in Massachusetts, 1691-1740 /

Microfiche originally published in the series: Library of American civilization ; LAC 11732.

Finches;

Mode of access: Internet.

Wild pigeons and doves.

Mode of access: Internet.

Budgerigar guide; detailed breeding methods.

Mode of access: Internet.

The talking budgie (Australian shell parrakeet)

Mode of access: Internet.

Journal d'un voyage fait par ordre du roi dans l'Amérique Septentrionale : adressé à Madame la Duchesse de Lesdiguières /

"Avec Approbation et Privilège du Roy."