151 research outputs found

    Probing Physical Properties at the Nanoscale

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    Everyday devices ranging from computers and cell phones to the LEDs inside traffic lights exploit quantum mechanics and rely on precisely controlled structures and materials to function optimally. Indeed, the goal in device fabrication is to control the structure and composition of materials, often at the atomic scale, and thereby fine-tune their properties in the service of ever-more-sophisticated technology. Researchers have imaged the structures of materials at atomic scales for nearly half a century, often using electrons, x rays, or atoms on sharp tips (see the article by Tien Tsong in PHYSICS TODAY, March 2006, page 31). The ability to survey properties of the materials has proven more challenging. In recent years, however, advances in the development of scanning probe microscopy have allowed researchers not only to image a surface, but also to quantify its local characteristics— often with a resolution finer than 10 nm. We highlight several SPM techniques here, with an emphasis on those that address electronic and dielectric properties of materials and devices

    Relevance of proteins from CRISP family for fertility: studies on knockout animal models

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    Las proteínas CRISP1-4 (Cysteine-Rich Secretory Proteins) se expresan en el tracto reproductor masculino de mamíferos y participan en el proceso de fertilización. El objetivo general de esta Tesis Doctoral ha sido estudiar la relevancia de las mismas para la fertilidad. En primer lugar, sabiendo que la proteína espermática CRISP2 participa en el proceso de fusión de gametas, nos propusimos estudiar su relevancia para la fertilidad a través del empleo de animales knockout (KO). Si bien los machos KO resultaron fértiles, los mismos exhibían deficiencias en la fertilización in vivo. Asimismo, estudios de fertilización in vitro revelaron que los espermatozoides KO presentaban defectos en su capacidad para penetrar las envolturas del ovocito y fusionarse con el mismo. Consistentemente, estos espermatozoides mostraban menores niveles de hiperactividad así como un aumento exacerbado de los niveles de Ca2+ intracelular durante la capacitación. En conjunto, estos resultados apoyan la relevancia de CRISP2 no solo para la fertilización sino también para la fertilidad de un individuo. Por otro lado, teniendo en cuenta que se han encontrado menores niveles de CRISP2 en pacientes infértiles con problemas en la motilidad espermática, el segundo objetivo consistió en estudiar si dichos defectos en la motilidad están asociados a una desregulación del Ca2+. Apoyando los resultados correspondientes al primer objetivo, observamos una asociación negativa entre la expresión de CRISP2 y el aumento de Ca2+ intracelular que ocurre durante la capacitación, indicando que CRISP2 cumpliría un rol en la regulación de Ca2+ en el espermatozoide humano. Asimismo, observamos que la entrada de Ca2+ que ocurre a través de CatSper podía prevenirse inhibiendo la fosforilación de proteínas en tirosina que se observa durante la capacitación, sugiriendo que la modulación de esta vía podría utilizarse como estrategia terapéutica en espermatozoides con niveles alterados de Ca2+. Finalmente, teniendo en cuenta la alta similitud de secuencia y la redundancia funcional entre las proteínas CRISP, como tercer objetivo evaluamos el fenotipo reproductivo de animales deficientes en más de una proteína CRISP simultáneamente. Si bien la fertilidad de los animales doble KO para Crisp2 y Crisp4 fue normal, los ratones deficientes en tres o en las cuatro proteínas CRISP presentaron severos defectos de fertilidad asociados a fallas en la fertilización observadas tanto in vivo como in vitro, confirmando no solo la relevancia de estas proteínas para la fertilidad sino también la existencia de mecanismos de cooperación funcional entre miembros de la familia. En conjunto, estos estudios contribuirán a una mejor comprensión de los mecanismos involucrados en el proceso de fertilización contribuyendo al desarrollo de mejores métodos de diagnóstico y tratamiento de la infertilidad así como de regulación de la fertilidad.The Cysteine-Rich Secretory Proteins (CRISP1-4) are expressed in the mammalian male reproductive tract and participate in the fertilization process. The main aim of this Thesis has been to study the relevance of CRISP proteins for fertility. In first place, based on the proposed role of the sperm protein CRISP2 in gamete fusion in both rodents and humans, and the evidence in humans showing that aberrant expression of this protein is associated with male infertility, we evaluated the relevance of CRISP2 for fertility by studying the phenotype of Crisp2 knockout (KO) mice. Our results showed that while mutant males presented normal fertility, they exhibited clear defects in in vivo fertilization. In addition, in vitro fertilization studies revealed that CRISP2-deficient sperm exhibited deficiencies to penetrate the egg vestments and to fuse with the egg. Consistent with this, KO sperm showed lower levels of hyperactivation as well as an exacerbated increase in intracellular Ca2+ levels during capacitation. Together, these results support the relevance of CRISP2 for both fertilization and fertility. Secondly, considering that lower levels of CRISP2 were detected in infertile patients with sperm motility problems, the second objective of this work was to investigate if those motility defects could be associated with a dysregulation in intracellular Ca2+ levels. Supporting our previous results, we observed a negative correlation between the intracellular Ca2+ increase during capacitation and CRISP2 expression, suggesting that, as in rodents, CRISP2 plays a role in the regulation of Ca2+ in human sperm. Moreover, we observed that Ca2+ entry through CatSper could be prevented by inhibiting the proteins tyrosine phosphorylation that occurs during capacitation, suggesting that the modulation of this signaling cascade could be used as a therapeutic strategy in sperm with altered levels of Ca2+. Finally, taking into account the high sequence similarity and the functional redundancy between the CRISP proteins, we next evaluated the reproductive phenotype of mice lacking more than one CRISP protein simultaneously. Although the fertility of Crisp2 and Crisp4 double KO mice was normal, the animals lacking three or the four CRISP proteins exhibited severe defects in their fertility associated with deficiencies in in vivo and in vitro fertilization, confirming not only the relevance of these proteins for fertility but also the existence of a functional cooperation among CRISP family members. Altogether, we consider that these studies will contribute to a better understanding of the molecular mechanisms underlying the fertilization process, as well as to the development of new methods of diagnosis and treatment of infertility and fertility regulation.Fil: Brukman, Nicolás Gastón. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina

    Expanded tonality in three early piano works of Béla Bartók (1881-1945)

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    Bart6k's own expanded tonal ("supradiatonic") pronouncements reveal that his music, notwithstanding tonally camouflaging surface details, clearly had a tonal foundation which in many respects is a reaction to the emerging atonalism of Schonberg. Analysis of three piano works (1908 - 1916) reveal that Bart6k's tonal language embraced intuitively the expanded tonal idiom. The harmonic resources Bart6k employed to obscure tonicisation embrace double-degree constructions, quartal formations, chords of addition and omission and other irregular constructions. Diatonic tonal pillars are evident in pedal points, tonic triads and dominant to tonic root movement. Through an application of the Riemann function theory expanded by Hartmann's supposition of fully-chromaticised scales tonal syntax (especially secondphase Strauss cadences or closes) becomes apparent within an expanded tonal product. The analyses conclude that Bart6k's inimitable "sound-world" is a twentieth-century manifestation of traditional tonality's primary tenets.MusicologyM.Mus

    Reconfiguring the burnt scar: a landscape architectural response to the Knysna fires of June 2017

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    June 2017 will be remembered by South Africans for decades to come. A moment when Mother Nature showed her true power and the only options was to get out her path or watch in awe. Within 72hours 20 000 hectares of land and in excess of 800 homes were burnt in the Knysna region along the Garden Route. While fires are not uncommon in this area, this fire had all the conditions to make it 'The Perfect fire'. It was simply a matter of time for these conditions to align. This project begins with an understanding of conditions that caused the fire using the agent of time. Time, according to French philosopher, Henri Lefebvre, can be classified into three categories; Linear Time, Event Time and Cyclical Time. Through this process one is able to isolate the solvable from the unsolvable environmental conditions and thus an on going proposal for intervention can be proposed. The process of reconfiguring the burnt scar begins through the implementation of immediate solutions and long term planning. This project traverses a variety of scales due to the types of fuel load that contributed to the fire. The large areas of unmanaged fynbos, the pine plantations that border Knysna region and the havoc caused as it ripped through the urban settlements down to the domestic garden scale. At a regional scale the the reconfiguring of the burnt scar requires a management system that is responsible for immediate controlling of erosion post fire. As well as the monitoring and the implementation of controlled ecological burns of fynbos stands and the removal of alien invasive species. Furthermore, it is proposed that the reconfiguring of the burnt scar requires a restructuring of the commercial plantations and the establishment of critical fire breaks affecting the urban interface. The introduction of fire resistant non-native commercial trees mass scale present a landscape character and scenic value to the region that calls upon the ideals of the Picturesque. A significant contributing factor the fire was the fuel load within the suburban environment. This project proposes a vegetation palette that property owners could use in a variety of ways to form domestic scale fire break, that when in-conjunction with neighbours, a district break is established

    High-resolution characterization of defects in oxide thin films

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    Nanometer sized defects in thin HfOx films are detected by atomic force microscopy facilitated leakage current measurements. Differences in the electrical properties of individual defects were distinguished. The effects of two mechanisms that localize the tip-sample interaction and increase spatial resolution were calculated. The expected increase in tip-sample current due to stress induced phase transformations and band gap narrowing has been calculated, and a behavior diagram is presented that shows the pressure necessary to generate a detectable current increase as a function of tip radius

    Evolutionary analysis of genes coding for Cysteine-RIch Secretory Proteins (CRISPs) in mammals

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    Cysteine-RIch Secretory Proteins (CRISP) are expressed in the reproductive tract of mammalian males and are involved in fertilization and related processes. Due to their important role in sperm performance and sperm-egg interaction, these genes are likely to be exposed to strong selective pressures, including postcopulatory sexual selection and/or male-female coevolution. We here perform a comparative evolutionary analysis of Crisp genes in mammals. Currently, the nomenclature of CRISP genes is confusing, as a consequence of discrepancies between assignments of orthologs, particularly due to numbering of CRISP genes. This may generate problems when performing comparative evolutionary analyses of mammalian clades and species. To avoid such problems, we first carried out a study of possible orthologous relationships and putative origins of the known CRISP gene sequences. Furthermore, and with the aim to facilitate analyses, we here propose a different nomenclature for CRISP genes (EVAC1-4, "EVolutionarily-analyzed CRISP") to be used in an evolutionary context.Fil: Arévalo, Lena. Consejo Superior de Investigaciones Científicas. Museo Nacional de Ciencias Naturales; España. Universitat Bonn; AlemaniaFil: Brukman, Nicolás Gastón. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Cuasnicu, Patricia Sara. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Roldan, Eduardo R. S.. Consejo Superior de Investigaciones Científicas. Museo Nacional de Ciencias Naturales; Españ

    CRISP (Cysteine Rich Secretory Proteins) as novel regulators of epididymal epithelium differentiation

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    Epididymal CRISP1 and CRISP4 associate with the sperm surface during maturation and are key mediators of fertilization. Whereas single knockout (KO) males for these molecules showed in vitro sperm fertilizing defects but normal fertility, all double KO (DKO) animals for these proteins exhibited impaired in vivo fertilization and fertility. In addition, one third of DKO showed bigger testes and epididymides not observed in single KO. Based on this, in the present work we investigated the mechanisms underlining this DKO phenotype. Histological studies of DKO testes and epididymides showed that whereas mice with normal tissues (Group 1) were not different from controls, those with bigger organs (Group 2) had clear histological defects as well as an abnormal presence of immune cells in the interstitium and lumen. RT-qPCR for different immunomodulator molecules revealed higher levels of Il-6 and Il-10 and a downregulation of Tgf-β in DKO from Group 2 not observed in Group 1. Interestingly, immunofluorescence experimentsusing specific markers for each of the different epididymal epithelial cells revealed fewer and shorter basal cell projections in the initial segment known as axiopodia, defects in principal cells and clear cells with an immature phenotype in both groups. Accompanying these epithelial changes, males from both groups also exhibited an increase in intraluminal pH. Altogether, these observations support the relevance of CRISP proteins for male fertility through their involvement in epididymal epithelium differentiation and luminal acidification which are critical for sperm maturation and storage.Fil: Carvajal, Guillermo. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Brukman, Nicolás Gastón. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Weigel Muñoz, Mariana. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Battistone, Maria Agustina. Harvard Medical School; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Guazzone, Vanesa Anabella. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas; ArgentinaFil: Lustig, Livia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas; ArgentinaFil: Breton, Sylvie. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas; Argentina. Harvard Medical School; Estados UnidosFil: Cuasnicú, Patricia S.. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina7th International Conference on the EpididymisMontrealCanadáEpididymis 7 Committe

    Prospectus, January 10, 1969

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    VOTE VOTE VOTE!; Spring Concert in March; Tuition Up; 3 New Clubs on Campus; PP Presents First Dynamic Duo; Ask Charlie Brown; Danville Dumps PC, 91-67; IM to Begin Soon; Palma Hits 21 in Loss; Springfield Next Foe; Parkland Falls 89-82https://spark.parkland.edu/prospectus_1969/1014/thumbnail.jp

    Functional redundancy and compensation: deletion of multiple murine Crisp genes reveals their essential role for male fertility

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    Mammalian Cysteine-RIch Secretory Protein (CRISP) family includes four members present in sperm and reported to regulate Ca2+ channels and fertilization. Based on our previous observations using single knockouts models and suggesting the existence of functional compensation among CRISP proteins, we investigated their relevance for male fertility by generating multiple Crisp gene mutants by CRISPR/Cas9 technology. Whereas targeting of Crisp1 and Crisp3 yielded subfertile males with early embryo developmental defects, the same deletion in zygotes from fertile Crisp2−/−.Crisp4−/− mice led to the generation of both triple and quadruple knockout mice exhibiting a complete or severe disruption of male fertility due to a combination of sperm transport, fertilization, and embryo developmental defects linked to intracellular Ca2+ dysregulation. These observations reveal that CRISP proteins are essential for male fertility and organize in functional modules that contribute distinctly to fertility success, bringing insights into the mechanisms underlying functionalredundancy/compensation in protein families and emphasizing the importance of generating multiple and not just single knockout which might be masking the true functional relevance of family genes.Fil: Curci, Ludmila. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Brukman, Nicolás Gastón. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Weigel Muñoz, Mariana. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Rojo, Daniela. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; ArgentinaFil: Carvajal, Guillermo. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Sulzyk, Valeria. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Gonzalez, Soledad Natalia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Rubinstein, Marcelo. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; ArgentinaFil: Da Ros, Vanina Gabriela. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Cuasnicu, Patricia Sara. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentin
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