Role of the ARF Tumor Suppressor in Osteoclasts

The ARF tumor suppressor is upregulated upon oncogenic stress. ARF can suppress cell proliferation in both p53-dependent and -independent mechanisms. We have focused on ARF\u27s ability to suppress protein synthesis in a p53-independent manner. Given that protein synthesis and the cell cycle are coordinately controlled, this arm of ARF tumor suppression also contributes to the restraint of cell proliferation. Our lab has recently shown that basal ARF suppresses protein synthesis in mitotic cells. The focus of my dissertation has been to determine whether basal ARF regulates cell growth in a post-mitotic setting. We used the osteoclast: OC) as a model for post-mitotic growth. We attempted to generate osteoclast-specific Arf loss using a Cre-expressing mouse, in which Cre is controlled by the Cathepsin K promoter: CtskCre/+). Surprisingly, we generated Arf -/- mice as demonstrated by genotyping, loss of ARF expression in the testis, and a phenotype comparable to traditional Arf -/- mice. Furthermore, both Cathepsin K and Cre are expressed in reproductive tissues, which results in Cre activity within gametes as confirmed by crossing CtskCre/+ mice with ROSA reporter mice. Finally, we found that Cathepsin K loss enhances serum estradiol levels. Together, this data suggests that Cathepsin K-driven Cre will not consistently result in OC-specific gene loss and may lead to misinterpretation of phenotypes generated to study the function of OC genes. In parallel, we have analyzed the role of ARF during osteoclastogenesis in vitro and found that Arf loss enhances osteoclastogenesis as demonstrated by OC number and size, protein markers of osteoclastogenesis, and increased bone resorption. Enhanced osteoclastogenesis upon Arf loss is independent of both proliferation and p53. Furthermore, we demonstrated enhanced protein synthesis and ribosome activity during osteoclastogenesis in Arf -/- cells. As an alternative approach to studying Arf loss in vivo, we generated radiation chimeras and challenged them with RANKL. We found that Arf loss results in elevated bone resorption due, at least in part, to increased osteoclastogenesis in vivo. This data collectively suggests that ARF regulates proliferation-independent cell growth, a function that is physiologically relevant both in vitro and in vivo

Spectral Sequences and Khovanov Homology

In this thesis, we will focus on two main topics; the common thread between both will be the existence of spectral sequences relating Khovanov homology to other knot invariants. Our first topic is an invariant MKh(L) for links in thickened disks with multiple punctures. This invariant is different from but inspired by both the Asaeda-Pryzytycki-Sikora (APS) homology and its specialization to links in the solid torus. Our theory will be constructed from a Z^n-filtration on the Khovanov complex, and as a result we will get various spectral sequences relating MKh(L) to Kh(L), AKh(L), and APS(L). Our second topic is the Dowlin spectral sequence, which has E_2-page isomorphic to the reduced Khovanov homology Kh(L), and which converges to the knot Floer homology HFK(L) on the E_infinity-page. While it was previously known that these two pages are link invariants, we prove that every page is an invariant by defining weak maps on the underlying filtered complex which correspond to Reidemeister moves. This result is based on joint work with Samuel Tripp

The Pairing Mechanism in HTSC investigated by Electronic Raman Scattering

By means of electronic Raman scattering we investigated the symmetry of the energy gap Delta(k), its temperature dependence and its variation with doping of well characterized Bi2Sr2CaCu2O8+delta single crystals. The oxygen content delta was varied between the under- and the overdoped regime by subsequently annealing the same single crystal in Ar and O2, respectively. The symmetry analysis of the polarized electronic Raman scattering is consistent with a d_x^2-y^2-wave symmetry of the energy gap in both regimes. The gap ratio 2Delta_max/k_BT_c and its temperature dependence changes with doping similar to predictions of theories based on paramagnon coupling.Comment: 3 pages, LaTeX, 2 ps figures available on request to [email protected]

Más allá del Concilio. El catolicismo holandés, un laboratorio de renovación eclesial (1960-1975)

Durante los años conciliares, la evolución de la sociedad holandesa hacia la izquierda está marcada por el desarrollo de una cultura joven y de flower power, pero también por las manifestaciones estudiantiles y por un endurecimiento de la acción sindical. Este cambio se traduce en la Iglesia católica en la aparición de comunidades de base y parroquias críticas. Los ejemplos analizados en el artículo, ponen de manifiesto sus preocupaciones: modernización de la liturgia pero también crítica de la sociedad y contestación del funcionamiento eclesial –particularmente el celibato eclesiástico y los obstáculos puesto a la intercomunión entre católicos y protestantes–. Ampliamente mediatizada, especialmente a través del grupo de sacerdotes contestatarios, la Septuaginta, la experiencia de izquierdas del catolicismo holandés tuvo un gran eco internacional alrededor de los años 60-70, antes de perder su base social y declinar rápidamente.Over the course of the conciliar years, progressive social movements arose in Dutch society. These were marked by the spread of youth culture and «flower power» as well as student demonstrations and the radicalization of trade unions. In the Catholic Church, this transformation was reflected in the emergence of grassroots communities and «critical parishes». Their main concerns were: the modernization of the liturgy, social critique and protest targeting the way the Church operated, particularly concerning ecclesiastical celibacy and the obstacles to intercommunion between Catholics and Protestants. Widely covered in the media, particularly thanks to the efforts of the Septuagint, a group of protesting priests, the experience of the Dutch Catholic left was closely observed abroad in the late 1960s and early 1970s. It subsequently lost its social basis and rapidly declined

Spectral GRID invariants and Lagrangian cobordisms

We prove that the filtered GRID invariants of Legendrian links in link Floer homology, and consequently their associated invariants in the spectral sequence, obstruct decomposable Lagrangian cobordisms in the symplectization of the standard contact structure on $\mathbb{R}^3$, strengthening a result by Baldwin, Lidman, and the fifth author.Comment: 24 pages, 11 figure

Da formação inicial ao desenvolvimento profissional docente: análises e reflexões sobre os processos formativos

Este artigo analisa os elementos constituintes da formação de professores e do desenvolvimento profissional docente. A reflexão parte da formação inicial e contínua e segue apresentando como o desenvolvimento profissional ocorre a partir desses processos formativos. Dessa forma, os objetivos deste estudo voltaram-se para distinguir os elementos constituintes da formação de professores em relação à formação inicial, à formação contínua e ao desenvolvimento profissional docente; identificar as necessidades específicas da formação inicial e do desenvolvimento profissional; assinalar as características essenciais de programas de desenvolvimento profissional eficazes. Os principais autores que sustentam as análises aqui propostas são Formosinho (2009), Marcelo (1999), Flores (2003), Day (2001) e Oliveira-Formosinho (2009). A pesquisa bibliográfica conduziu o desenvolvimento do estudo e a abordagem qualitativa possibilitou a análise do material coletado para analisar o objeto proposto. As análises indicam que a formação inicial é uma etapa que permite a constituição profissional do sujeito; a formação contínua é um processo permanente de estudo e entendimento da prática que possibilita compreender as diferentes situações que ocorrem em sala de aula; e o desenvolvimento profissional requer que a ação do professor ocorra para que a partir da experiência produza-se a análise e a reflexão advindos dessa prática possibilitando que o desempenho profissional docente se aprimore. Os resultados obtidos ampliaram a compreensão sobre a formação de professores, suas especificidades, os programas de desenvolvimento profissional docente e as possíveis dicotomias que incidem nesses programas