Vorsichtsmaßregeln für Käufer, Verkäufer, Pachter und Verpachter von Gütern

Aus eignen und andern Erfahrungen gesammelt von Johann Philipp Christian Muntz, Großherzogl. Sachsen-Weimar-Eisenach. Oekonomie-Rath etc. etc.

Dr. L. Rabenhorst's Kryptogamen-Flora von Deutschland, Oesterreich und der Schweiz

1,pt.6

Cosmos : a sketch of a physical description of the universe / By Alexander von Humboldt ; Translated from the German by E.C. Otté.

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Cosmos : a sketch of a physical description of the universe / By Alexander von Humboldt ; Translated from the German by E.C. Otté.

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Cosmos : a sketch of a physical description of the universe / By Alexander von Humboldt ; Translated from the German by E.C. Otté.

2

Cosmos : a sketch of a physical description of the universe / By Alexander von Humboldt ; Translated from the German by E.C. Otté.

1

Cosmos : a sketch of a physical description of the universe / By Alexander von Humboldt ; Translated from the German by E.C. Otté.

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Identification of the von Hippel–Lindau tumor-suppressor protein as part of an active E3 ubiquitin ligase complex

Mutations of von Hippel–Lindau disease (VHL) tumor-suppressor gene product (pVHL) are found in patients with dominant inherited VHL syndrome and in the vast majority of sporadic clear cell renal carcinomas. The function of the pVHL protein has not been clarified. pVHL has been shown to form a complex with elongin B and elongin C (VBC) and with cullin (CUL)-2. In light of the structural analogy of VBC-CUL-2 to SKP1-CUL-1-F-box ubiquitin ligases, the ubiquitin ligase activity of VBC-CUL-2 was examined in this study. We show that VBC-CUL-2 exhibits ubiquitin ligase activity, and we identified UbcH5a, b, and c, but not CDC34, as the ubiquitin-conjugating enzymes of the VBC-CUL-2 ubiquitin ligase. The protein Rbx1/ROC1 enhances ligase activity of VBC-CUL-2 as it does in the SKP1-CUL-1-F-box protein ligase complex. We also found that pVHL associates with two proteins, p100 and p220, which migrate at a similar molecular weight as two major bands in the ubiquitination assay. Furthermore, naturally occurring pVHL missense mutations, including mutants capable of forming a complex with elongin B–elongin C-CUL-2, fail to associate with p100 and p220 and cannot exhibit the E3 ligase activity. These results suggest that pVHL might be the substrate recognition subunit of the VBC-CUL-2 E3 ligase. This is also, to our knowledge, the first example of a human tumor-suppressor protein being directly involved in the ubiquitin conjugation system which leads to the targeted degradation of substrate proteins.

Role of transforming growth factor-α in von Hippel– Lindau (VHL)−/− clear cell renal carcinoma cell proliferation: A possible mechanism coupling VHL tumor suppressor inactivation and tumorigenesis

Mutations of the VHL tumor suppressor gene occur in patients with VHL disease and in the majority of sporadic clear cell renal carcinomas (VHL−/− RCC). Loss of VHL protein function is associated with constitutive expression of mRNAs encoding hypoxia-inducible proteins, such as vascular endothelial growth factor. Overproduction of angiogenic factors might explain why VHL−/− RCC tumors are so highly vascularized, but whether this overproduction is sufficient for oncogenesis still remains unknown. In this report, we examined the activity of transforming growth factor-α (TGF-α), another VHL-regulated growth factor. We show that TGF-α mRNA and protein are hypoxia-inducible in VHL−/− RCC cells expressing reintroduced VHL. In addition to its overexpression by VHL−/− RCC cells, TGF-α can also act as a specific growth-stimulatory factor for VHL−/− RCC cells expressing reintroduced wild-type VHL, as well as primary renal proximal tubule epithelial cells, the likely site of origin of RCC. This role is in contrast to those of other growth factors overexpressed by VHL−/− RCC cells, such as vascular endothelial growth factor and TGF-β1, which do not stimulate RCC cell proliferation. A TGF-α-specific antisense oligodeoxynucleotide blocked TGF-α production in VHL−/− RCC cells, which led to the dependence of those cells on exogenous growth factors to sustain growth in culture. Growth of VHL−/− RCC cells was also significantly reduced by a drug that specifically inhibits the epidermal growth factor receptor, the receptor through which TGF-α stimulates proliferation. These results suggest that the generation of a TGF-α autocrine loop as a consequence of VHL inactivation in renal proximal tubule epithelial cells may provide the uncontrolled growth stimulus necessary for the initiation of tumorigenesis.

Mind majick : a study of the paintings by Harry Smith

Harry Smith was an American artist who worked primarily in the 1940s through the 1980s. Although largely an obscure figure in American culture, Smith is most commonly recognized for his achievements in anthropology and ethnology, experimental cinema, and musicology. This master’s research paper is the first in-depth scholarly study of Harry Smiths’ achievements as a painter. Only a few of Smith’s paintings exist today, which explains why they have received so little attention. However, there is enough work and information available to weave together a chronological study of Smith’s occupation as a painter. In this paper, one will see how Smith’s work and interests in various fields of study influenced his painterly aesthetic, and how he was able to tie together all of his disparate diversions into cohesive and unified visions upon a twodimensional surface.