Acid-base disturbances have serious clinical consequences and are particularly critical in patients whose cardiopulmonary function is compromised. Cellular transport of NH3 and NH4+ has important physiological significance in the regulation of acid-base balance. In the kidney, production and excretion of NH3/NH4+ is critical for net acid excretion. Recently, two non-erythroid glycoproteins (Rhbg and Rhcg) belonging to the Rh family were suggested to be involved in NH3/NH4+ transport. Thus far, the functional properties of these membrane proteins as transport mechanisms are not resolved. In this study, we expressed Rh proteins in Xenopus oocytes and demonstrated that they transport both NH4+ and NH3. As such, the Rh transporters are unique in being able to transport both the ionic and the neutral gaseous components of ammonia. Previous studies have shown that DIDS, a stilbene derivative known to inhibit anion exchangers, was shown to inhibit CO2 transport by AQP1. This led us to hypothesize that DIDS might also inhibit transport of other gases such as NH3 by Rh proteins. We therefore conducted the present study to test the effects of DIDS on NH4+ and NH3 transport by Rh glycoproteins. To do so we used ion-selective microelectrodes and two-electrode voltage clamp to measure changes in surface pH (pHs) and whole cell currents (I) induced by NH3/NH4+ and methyl ammonium (MA/MA+) with or without DIDS. All experiments were conducted in Xenopus oocytes expressing Rhbg. Rhbg was expressed by injecting the oocytes with cRNA of the cloned genes. Control oocytes were injected with H2O. Our results indicate that in oocytes expressing Rhbg, exposure to 5mM NH4Cl (NH3/NH4+) caused a decrease in surface pH (pHs) and an inward current. The decrease in pHs is caused by NH3 influx whereas the inward current is due to electrogenic NH4+ influx. In the presence of DIDS, exposure to 5mM NH4Cl caused a significantly smaller decrease in pHs and current. The %inhibition of pHs and ΔI were 33% and 49%, respectively (P<0.05). Similarly, exposing oocytes expressing Rhbg to 5mM MA/MA+ (a substitute to NH3/NH4+) caused a decrease in pHs and an inward current. In the presence of DIDS, the MA/MA+ induced changes in pHs and current were also inhibited (37% and 63%, respectively; P<0.05). DIDS had no effect on NH3/NH4+ transport in H2O-injected oocytes (not expressing Rhbg). In summary, our data support the following conclusions: 1) RhAG and Rhbg transport both the ionic NH4+ and the neutral NH3 species. 2) Transport of NH4+ is electrogenic. 3) RhAG and Rhbg expression both enhance MA transport, an electroneutral component. 4) Like Rhbg, RhAG also transports MA+, an electrogenic component. The charged MA+ seems to be a direct substrate for RhAG whose transport likely resembles that of NH4 +. 5) Rhcg is likely to be a predominantly NH3 transporter. 6) RhAG and Rhbg are unlikely to be NH4 +/H+ exchangers. Regarding the effect of DIDS, our data also indicate that 1) DIDS partially inhibits the transport of NH3 and MA by Rhbg without affecting endogenous NH3 and MA transport. 2) DIDS also inhibits the electrogenic transport of NH4 + and MA+ by Rhbg. 3) DIDS is the only inhibitor shown to block both gas (NH3) and ionic (NH4 +) transport by Rhbg. / acase@tulane.edu

<p>Detta examensarbete utfördes under våren 2009 och avhandlar bestämning av fixpunkter i ett höjdnät med hjälp av statiska Global Navigation Satellite System (GNSS) mätningar. Ämnet är högaktuellt med tanke på att många kommuner står inför en övergång till Rikets Höjdsystem 2000 (RH 2000). Det kan vara ett problem vid en sådan övergång om det finns isolerade delar av det lokala höjdnätet som inte är anslutet till huvudnätet. Tidigare har den enda lösningen på ett sådant problem varit att genomföra ett höjdavvägningståg, ett både kostsamt och tidskrävande företag. Syftet med denna studie är att ge svar på hur noggrant det går att göra en höjdbestämning av fixpunkter med statisk GNSS-mätning.</p><p> Fältarbetet har utförts i Sandvikens kommun där ett antal höjdfixpunkter i RH 2000 nätet använts som referens vid GNSS-mätningar. Ett nät bestående av sju mätpunker etablerades i anslutning till RH 2000 höjdfixar. Fem av dessa användes sedan som passpunkter för att höjdbestämma två centralt belägna mätpunkter i nätet. För kontroll av mätningarna användes den kända avvägda höjden på de sökta punkterna. Mätningarna utfördes med fyra stycken Leica GX1230+ GNSS-mottagare som etablerades på punkterna i tre fyratimmarssessioner. Mätningarna utfördes i två kampanjer med tre veckors mellanrum.</p><p>Efterberäkning av GNSS- mätdata gjordes med Leica Geo Office 7 (LGO 7) och Surfer 8. Kontroll av resultaten gjordes genom matrisberäkningar i Microsoft Excel. Resultaten baseras på en sammanslagning av de båda mätkampanjerna. Avvikelserna visade sig ligga i ett spann på ca 3–5 mm ± punktmedelfelet (<strong>σ</strong>_H)lägre än de precisionsavvägda RH 2000 höjderna. Det faktum att samtliga GNSS-mätta höjder ligger 3–5 mm lägre än officiella RH 2000-höjder tyder på att ett systematiskt fel upptäckts. Slutligen, visar detta arbete att genom att kombinera frekvenser kan medelfelet bli så bra som 3 mm vid höjdbestämning med hjälp av statisk GNSS-mätning.</p>

Biotinylated and non-biotinylated copolymers of ethylene oxide (EO) and 2-(diethylamino)ethyl methacrylate (DEAEMA) were synthesized by the atom transfer radical polymerization technique (ATRP). The chemical compositions of the copolymers as determined by NMR are represented by PEO₁₁₃PDEAEMA₇₀ and biotin-PEO₁₀₄PDEAEMA₉₃ respectively. The aggregation behavior of these polymers in aqueous solutions at different pHs and ionic strengths was studied using a combination of potentiometric titration, dynamic light scattering (DLS), static light scattering (SLS), and transmission electron microscopy (TEM). Both PEO-b-PDEAEMA and biotin-PEO-b-PDEAEMA diblock copolymers form micelles at high pH with hydrodynamic radii (Rh) of about 19 and 23 nm, respectively. At low pH, the copolymers are dispersed as unimers in solution with Rh of about 6-7 nm. However, at a physiological salt concentration (cs) of about 0.16M NaCl and a pH of 7-8, the copolymers form large loosely packed Guassian chains, which were not present at the low cs of 0.001M NaCl. The critical micelle concentrations (CMC) and the cytotoxicity of the copolymers were investigated to determine a suitable polymer concentration range for future biological applications. Both PEO-b-PDEAEMA and biotin-PEO-b-PDEAEMA diblock copolymers possess identical CMC values of about 0.0023 mg/g, while the cytotoxicity test indicated that the copolymers are not toxic up to 0.05mg/g (> 83% cell survival at this concentration). / Singapore-MIT Alliance (SMA)

Detta examensarbete utfördes under våren 2009 och avhandlar bestämning av fixpunkter i ett höjdnät med hjälp av statiska Global Navigation Satellite System (GNSS) mätningar. Ämnet är högaktuellt med tanke på att många kommuner står inför en övergång till Rikets Höjdsystem 2000 (RH 2000). Det kan vara ett problem vid en sådan övergång om det finns isolerade delar av det lokala höjdnätet som inte är anslutet till huvudnätet. Tidigare har den enda lösningen på ett sådant problem varit att genomföra ett höjdavvägningståg, ett både kostsamt och tidskrävande företag. Syftet med denna studie är att ge svar på hur noggrant det går att göra en höjdbestämning av fixpunkter med statisk GNSS-mätning.  Fältarbetet har utförts i Sandvikens kommun där ett antal höjdfixpunkter i RH 2000 nätet använts som referens vid GNSS-mätningar. Ett nät bestående av sju mätpunker etablerades i anslutning till RH 2000 höjdfixar. Fem av dessa användes sedan som passpunkter för att höjdbestämma två centralt belägna mätpunkter i nätet. För kontroll av mätningarna användes den kända avvägda höjden på de sökta punkterna. Mätningarna utfördes med fyra stycken Leica GX1230+ GNSS-mottagare som etablerades på punkterna i tre fyratimmarssessioner. Mätningarna utfördes i två kampanjer med tre veckors mellanrum. Efterberäkning av GNSS- mätdata gjordes med Leica Geo Office 7 (LGO 7) och Surfer 8. Kontroll av resultaten gjordes genom matrisberäkningar i Microsoft Excel. Resultaten baseras på en sammanslagning av de båda mätkampanjerna. Avvikelserna visade sig ligga i ett spann på ca 3–5 mm ± punktmedelfelet (σH) lägre än de precisionsavvägda RH 2000 höjderna. Det faktum att samtliga GNSS-mätta höjder ligger 3–5 mm lägre än officiella RH 2000-höjder tyder på att ett systematiskt fel upptäckts. Slutligen, visar detta arbete att genom att kombinera frekvenser kan medelfelet bli så bra som 3 mm vid höjdbestämning med hjälp av statisk GNSS-mätning.

Analytical methods used clinically in Sweden for detection and quantification of fetal hemoglobin (HbF) in maternal blood are either the microscopic method Kleinhauer Betkes test (KBT) or high performance liquid chromatography. A more modern alternative to detect and quantify HbF+ erythrocytes is flow cytometry. The aim of this project was therefore to evaluate the commercial kit "Fetal Cell Count kit" using flow cytometry. The kit used two antibodies; one directed against the specific γ-chain of HbF protein and the other directed against the intracellular enzyme carbanhydrase (CA), which is found in all erythrocytes in adults. The resulting data showed good precision, sensitivity and linearity. A reference interval based on male blood donors was determined to &lt;0.1 % HbF+ erythrocytes and &lt;1.3 %F-cells. The kit is well suited to detect and quantify F-cells. It could be used as a important tool to follow-up patients withβ-thalassemia and sickle cell anemia. However the kit was not as useful for detection and quantification of HbF+ erytrocytes in fetomaternal hemorrhage induced by Rhimmunization.

OBJETIVO: Identificar las principales complicaciones fetales y del recién nacido así como los factores de riesgo de la Isoinmunización Rh. DISEÑO: Estudio Descriptivo Analítico Retrospectivo. LUGAR: Instituto Especializado Materno Perinatal, MINSA. MATERIAL Y MÉTODO: 116 gestantes Rh negativo que se atendieron el 0000maternas y neonatales para determinar las diferencias entre los casos de grupo control se utilizaron las pruebas de significación estadísticas Chi2 y prueba t de Studen. RESULTADOS: De 54,418 partos atendidos en la institución durante este período, se obtuvieron 116 (0,21%) madres Rh negativo que cumplieron con los criterios de inclusión, de las cuales el 12,1%(14) presentaron isoinmunización Rh. La edad promedio de las madres sensibilizadas fue de 30 años, se observo una mayor incidencia en multíparas (50%) y un menor número de control pre natal (1-3) en comparación de las madres sensibilizadas (>4). El 50% de las madres sensibilizadas presentaron antecedentes de aborto, 14,3% antecedentes de óbito y de transfusión y el 21,4% antecedente de hidrops y kernicterus; Siendo estas variables factores de riesgo de presentar isoinmunización. La tasa de cesárea fue de 78,6%, se encontró mayor porcentaje de partos prematuros en la madres sensibilizadas. El Apgar promedio en los recién nacidos fue de 6 al minuto y 8 a los 5minutos. Las complicaciones fetales más frecuentes fueron: ictericia anemia e hidrops y la mortalidad fetal fue de 7,1%(1). CONCLUSIONES: Es necesario evaluar la prevención mediante los estudios de los factores de riesgo teniendo en consideración que los niños que presentaron isoinmunización Rh se encontraron en el grupo en el cual la madre no recibió gammaglobulina anti-D profiláctica y que por lo tanto no tuvieron un adecuado control prenatal en anteriores embarazos ya sea por el factor económico, por el factor ignorancia o por la poca cobertura de éste. Por ello es necesario establecer políticas dirigidas a la promoción y prevención. Palabras claves: isoinmunización Rh, factores de riesgo, complicación fetal y neonatal.

The complex molecule of the title compound, [Rh2{N(C6H5)COCH3}4(C8H7N)2], exhibits inversion symmetry. The four acetamidate ligands bridging the dirhodium core are arranged in a 2,2-trans manner with two N atoms and two O atoms coordinating to each RhIIatom trans to one another. The Neq - Rh - Rh - Oeq torsion angles on the acetamidate bridge vary between -4.07 (5) and -6.78 (7)°. The axial nitrile ligands complete the distorted octahedral coordination sphere of each RhIIatom and show a nonlinear coordination with Rh - N - C bond angles of 151.6 (3) and 152.5 (3)°. The bond lengths of the two nitrile triple bonds are 1.133 (5) and 1.137 (5) Å.

This work is concentrated on the thermodynamic and kinetic aspects of water, alcohols, alkyl halides, ethers, and lactones bound and activated by the electrophilic [Cp'Ru(N0)] +2 and [Cp’Ru (NO)(CH3)] + centers (Cp' = cyclopentadienyl group). Counterions in these systems include OSO2CF3- (OTf-) and [(3, 5-(CF3)2C6H3)4B]- ([BAr4']-). The displacement of OTf- in Cp'Ru(N0) (0Tf)2 by H20 in dichloromethane is exothermic but entropically unfavorable due to the required reorganization of the solvent cage around released triflate ions. Thermodynamic parameters are also determined for OTf displacement by chloride and tetrahydrofuran (THF) using the 19F nuclear magnetic resonance (NMR) spectroscopy. The conversion of the [Cp’Ru (NO)(OH2)2] +2 to [Cp’Ru (NO)(μ-OH)} 2 +2 in aqueous solutions is characterized thermodynamically and kinetically by potentiometric and NMR methods. The results of the study of rhodium triflato complex trans- [Rh (CO)(PPh3)2(OTf)] show that OTf coordinates to the metal center in wet dichloromethane solutions, but the compound crystallizes as a water-coordinated triflate salt trans- [Rh (CO)(PPh3)2(OH2)] [OTf]. Thermodynamic parameters for alcohol (methanol, ethanol, isopropanol) binding to the Cp*Ru(N0) (0Tf)2 are determined from the 19F NMR spectroscopic data. The kinetics of the oxidation of alcohols to aldehydes or ketones via Ru (II) >>> Ru (0) redox process is studied by NMR methods. The results of the study support {3-hydrogen elimination mechanism, comprising one of the very few mechanistic investigations on reactions of this kind. Alkyl iodides are found to bind to the [Cp*Ru (NO)(CH3)] + fragment via displacement of a THF ligand in the presence of a BAr4 •-counterion, forming alkyl halide complexes that convert to [Cp’Ru (NO)(μ-I)]2+2. The mixed ruthenium-chromium complex [CpCr (NO)2(μ-I) (Ru (Cp’) (NOW is characterized as primarily a [Ru-I >> Cr] system as opposed to a [Ru << I-Cr] model. The complex [Cp*Ru (NO)(CH3) (THF)] is found to catalyze aerobic oxidation of THF to -y-butyrolactone. The new -y-butyrolactone ruthenium complex is isolated and characterized by X-ray methods in the solid state. The mechanism of catalytic oxidation is studied by 18O-labeled infrared spectroscopic methods. Radical decomposition of the intermediate hydroperoxy-tetrahydrofuran gives 1, 6-diol-diformate [CH(O)-(CH2)6-CH(O)]. The radical mechanism for the catalytic oxidation of THF is proposed.

No description available.

La presente Tesis Doctoral se encuentra dividida en dos Capítulos. En el Capítulo 1 se presentan los estudios realizados sobre la síntesis de ésteres insaturados derivados de BINOL, TADDOL y TTFOL y su aplicación en reacciones de hidroestannación radicalaria. El empleo de TFAA/H3PO4 no sólo provocó la apertura del diacetónido sino que además se observó una reorganización estructural selectiva, con retención de la configuración. Los nuevos diésteres obtenidos con simetría C2 lograron sintetizarse bajo condiciones suaves de reacción, con excelentes rendimientos y tiempos cortos. Asimismo, teniendo en cuenta antecedentes previos junto con un estudio por RMN dinámica, se realizó un estudio del mecanismo involucrado. La ruta sintética desarrollada resulta atractiva para la generación de derivados del tetrahidrofuran-3,4-diol, importantes en síntesis estereoselectiva. También, dada la importancia de los diésteres de BINOL en diversos campos, se buscó una ruta sintética adecuada para la generación de los mismos. Se estableció nuevamente que el uso de TFAA/H3PO4 dio los mejores resultados en lo que respecta a tiempos y rendimientos de reacción. Este mismo método se utilizó para la síntesis de ésteres del ácido cafeico, los cuales son de interés por su actividad biológica. En relación a los estudios de hidroestannación sobre diésteres insaturados derivados de TADDOL, se desarrollaron dos nuevos métodos que permitieron la síntesis estereoselectiva de macrolidos con variaciones en las condiciones de reacción respecto al método de referencia. Se observó que, según el diéster y el hidruro utilizado, se produjeron cambios sustanciales en la diasteroselectividad, los tiempos de reacción y los rendimientos obtenidos. La misma reacción fue estudiada para los nuevos diésteres insaturados de BINOL. En este caso, la hidroestannación radicalaria no tuvo lugar con ciclación intramolecular sino que se observó la existencia de aductos de mono y diadición. Asimismo, debido a la actividad catalítica que presentan ciertos haluros de trialquilestaño o dialquilestaño, se generaron los derivados bisiododifenilestannilados y bisclorodialquilestannilados, ambos con excelentes rendimientos y moderada diastereoselectividad. Finalmente, dada la importancia biológica de los -amino derivados, se estudió la generación de los mismos por reacción de Aza-Michael sobre los diésteres enantioméricamente puros derivados de TADDOL, BINOL y TTFOL. En el Capítulo 2, los estudios que se presentan se desarrollaron bajo el marco de una Beca para Jóvenes Docentes de la UNS en el Instituto de Investigaciones Biomédicas (IRB, Barcelona, España). Se realizaron reacciones de hidrogenación y Pauson-Khand asimétricas catalizadas por el complejo Rh-MaxPHOS. Se hicieron medidas cinéticas de la 2 velocidad de hidrogenación sobre los sustratos MAA y Z-MAC las cuales dieron resultados comparables a los obtenidos con el catalizador de referencia. Además, se logró disminuir la carga de catalizador para MAA. Así, la hidrogenación asimétrica de una serie de N-acil enamidas ocurrió con excelente grado de conversión y enantioselectividad. Posteriormente, se estudió el catalizador frente a reacciones de Pauson-Khand intramoleculares, siendo eficaz para la ciclización de varios 1,6-eninos con excesos enantioméricos de buenos a muy buenos. En ambos casos los productos generados son de potencial importancia biológica. / The present Doctoral Thesis is divided in two chapters. In Chapter 1, the studies about the synthesis of unsaturated esters derived from BINOL, TADDOL and TTFOL and their application in radical hydrostannation reactions is presented. The use of TFAA/H3PO4 caused not only the opening of the diacetonide but a selective structural reorganization with retention of the configuration too. The new diesters with C2 symmetry were synthesized under mild reaction conditions, excellent yields and in short time. The involved mechanism is proposed taking into account previous results together with a dynamic NMR study. The synthetic developed route is attractive for the generation of derivatives of tetrahydrofuran-3,4-diol, important in stereoselective synthesis. Also, and given the increasing interest in BINOL diesters in many fields, the search of new synthetic routes was studied. It was stablished that, again, the system TFAA/H3PO4 gave the best results in relation to yields and reaction time. Following with the esterification procedures, the excellent results obtained with the employment of this system, for the synthesis of caffeic acid esters due to the wide scope of biological applications. In the research about hydrostannation reactions of unsaturated esters of TADDOL, two new methods were developed that allowed the stereoselective synthesis of macrolides with variations on the reaction conditions in comparison with the reference method. It was observed that, according with the diester and the hydride used, substantial changes occurred related with diastereoselectivity. The same procedure was used for the new BINOL unsaturated diesters. In this case, the radical hydrostannation did not take place with intramolecular cyclization but the existence of mono- and diaddition products was determined. Also, and due to the catalytic activity that some trialkyl- and dialkyltin halides present, the corresponding bis-iododiphenylstannyl and bis-chlorodialkylstannyl derivatives were obtained, with both excellent yields and moderate diastereoselectivity. Finally, and 3 because of the potential biological applications of the -amino derivatives, the synthesis of this type of compounds by means of the Aza-Michael reaction was accomplished. In Chapter 2 are presented the studies made in the Biomedical Research Institute, (IRB, Barcelona, Spain) under a Young Researchers Fellowship (UNS). The asymmetric hydrogenation and Pauson-Khand reactions catalyzed by Rh-MaxPHOS complex were achieved. Kinetic measures on the rate of the hydrogenation reaction over MAA and Z-MAC substrates were done. The results observed here were comparative to those obtained with the reference catalyst. Besides, it was possible to reduce the catalyst charge for MAA. Thus, the asymmetric hydrogenation of a variety of N-acyl enamides happened with excellent conversion and enantioselectivity. Afterwards, the catalyst was studied in the intramolecular Pauson-Khand reactions and probed to be very efficient for the cyclization of some 1,6- enynes with good to very good enantiomeric excess.