The Neurofibromatosis 2 tumor suppressor merlin in cytoskeleton organization and cell cycle regulation

Neurofibromatosis 2 (NF2) is a dominantly inherited disorder, which predisposes to multiple tumours of the nervous system, typically schwannomas and meningiomas. Biallelic inactivation of the NF2 gene occurs both in sporadic and NF2-related schwannomas and in most meningiomas. The NF2 gene product merlin (or schwannomin) is structurally related to the ERM proteins, ezrin, radixin and moesin, which act as molecular linkers between the actin cytoskeleton and the plasma membrane. Merlin is a tumor suppressor that participates in cell cycle regulation. Merlin s phosphorylation status appears to be associated with its tumour suppressor activity, i.e. non-phosphorylated merlin functions as a tumour suppressor, whereas protein phosphorylation results in loss of functional activity. This thesis study was initiated to investigate merlin s role as a tumor suppressor and growth inhibitor. These studies show, that like many other tumor suppressors, also merlin is targeted to the nucleus at some stages of the cell cycle. Merlin s nuclear localization is regulated by cell cycle phase, contact inhibition and adhesion. In addition, a potential nuclear binding partner for merlin was identified, Human Enhancer of Invasion 10 (HEI10), a cyclin B interacting protein. Many tumor suppressors interact with microtubules and this thesis work shows that also merlin colocalizes with microtubules in mitotic structures. Merlin binds microtubules directly, and increases their polymerization in vitro and in vivo. In addition, primary mouse Schwann cells lacking merlin displays disturbed microtubule cytoskeleton. Fourth part of this thesis work began from the notion that PKA phosphorylates an unidentified site from the merlin N-terminus. Our studies show that serine 10 is a target for PKA and modulation of this residue regulates cytoskeletal organization, lamellipodia formation and cell migration. In summary, this thesis work shows that merlin s role is much more versatile than previously thought. It has a yet unidentified role in the nucleus and it participates in the regulation of both microtubules and the actin cytoskeleton. These studies have led to a better understanding of this enigmatic tumor suppressor, which eventually will aid in the design of specific drugs for the NF2 disease.

Isaak Schoeneberg, founder of the Veteran's organization in Salzkoffen, Westfalen, on the organization's 60th anniversary.

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The story of my family : The German-Jewish family of Hermann Nelki /

History of the Nelki and Russo families in Berlin; concentrates mainly on first half of the 20th century; most members of the family were physicians; persecution in Nazi period; emigration to England; attached is the story of Eva Edith Ehrlich who survived the war years in Berlin in hiding.

The File Marked "Rita". Selections from the Letters of Herbert Mueller and Rita Klein (1939-1945) 1939-1946

Exchange of letters between Herbert Mueller and Rita Klein after Mueller's emigration to England in 1939; Rita Klein's attempt to obtain divorce; suicide attempt by her husband Leo Klein; correspondence through intermediaries after outbreak of World War II; notice of Rita Klein's deportation to Auschwitz; (translation from original German)

Memoirs : Heida Hermanns Holde /

The author's mother Alice Goldschmidt was a gifted piano player, who studied with Carl Maria Breithaupt and became his most talented student. Childhood recollections. Early musical awakening. Outbreak of World War One. Recollections of air raids and scarceness of food. Inflation and political instability in post-war Germany. Piano lessons by her mother from an early age. Heida made her debut at age fourteen with the Wiesbaden Symphony under the conductor Carl Schuricht, who became a close mentor and friend. Close relationship to her mother, who had a great influence on her professional career. Heida had a number of outstanding teachers, among them Artur Schnabel, Karl Leimer and Egon Petri. Heida was accepted as a student of Petri at the "Hochschule fuer Musik" in Berlin, where she studied between 1922-1925. Salon at her aunt's house with guests such as the playwright Georg Kaiser and Siegfried Wagner. Her sister Elsie received her Ph.D. in economics and moved to Berlin as well. Heida graduated from the "Hochschule" in 1925. Soon after she won an international piano competition in Berlin. Engagements with various conductors such as Max Fiedler and Otto Klemperer. Private lessons with Arthur Schnabel and Carl Friedberg, the co-founder of Juilliard. Due to occasional experiences of antisemitism during her music career Heida decided to change her name from Goldschmidt to Hermanns. Position at the "Hoch Conservatory" in Frankfurt. Encounter with the music critic Artur Holde, Heida's future-husband. Engagement and wedding in 1932. Move to Berlin.

Huffman Binary Coding of WLN Symbols for File-Compression

Construction of Huffman binary codes for WLN symbols is described for the compression of a WLN file. Here, a parenthesized representation of the tree structure is used for computer encoding.

1-D hydrogen-bonded organization of hexanuclear {3d-4f-5d} complexes: evidence for slow relaxation of the magnetization for [{LMe2Ni(H2O)Ln(H2O)4.5}2{W(CN)8}2] with Ln = Tb and Dy

Heterometallic {3d-4f-5d} aggregates with formula [{LMe2Ni(H2O)Ln(H2O)4.5}2{W(CN)8}2]·15H2O, (LMe2 stands for N,N-2,2-dimethylpropylenedi(3-methoxysalicylideneiminato) Schiff-base ligand) with Ln = Gd, Tb, Dy, have been obtained by reacting bimetallic [LMe2Ni(H2O)2Ln(NO3)3] and Cs3{W(CN)8} in H2O. The hexanuclear complexes are organized in 1-D arrays by means of hydrogen bonds established between the solvent molecules coordinated to Ln and the CN ligands of an octacyanometallate moiety. The X-ray structure was solved for the Tb derivative. Magnetic behavior indicates ferromagnetic {W–Ni} and {Ni–Ln} interactions (JNiW = 18.5 cm-1, JNiGd = 1.85 cm-1) as well as ferromagnetic intermolecular interactions mediated by the H-bonds. Dynamic magnetic susceptibility studies reveal slow magnetic relaxation processes for the Tb and Dy derivatives, suggesting SMM type behavior for these compounds.

Photocopies of previous file of orders of service

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Organization of the Board of Trustees

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Dessy : desktop search and synchronization

Current smartphones have a storage capacity of several gigabytes. More and more information is stored on mobile devices. To meet the challenge of information organization, we turn to desktop search. Users often possess multiple devices, and synchronize (subsets of) information between them. This makes file synchronization more important. This thesis presents Dessy, a desktop search and synchronization framework for mobile devices. Dessy uses desktop search techniques, such as indexing, query and index term stemming, and search relevance ranking. Dessy finds files by their content, metadata, and context information. For example, PDF files may be found by their author, subject, title, or text. EXIF data of JPEG files may be used in finding them. User–defined tags can be added to files to organize and retrieve them later. Retrieved files are ranked according to their relevance to the search query. The Dessy prototype uses the BM25 ranking function, used widely in information retrieval. Dessy provides an interface for locating files for both users and applications. Dessy is closely integrated with the Syxaw file synchronizer, which provides efficient file and metadata synchronization, optimizing network usage. Dessy supports synchronization of search results, individual files, and directory trees. It allows finding and synchronizing files that reside on remote computers, or the Internet. Dessy is designed to solve the problem of efficient mobile desktop search and synchronization, also supporting remote and Internet search. Remote searches may be carried out offline using a downloaded index, or while connected to the remote machine on a weak network. To secure user data, transmissions between the Dessy client and server are encrypted using symmetric encryption. Symmetric encryption keys are exchanged with RSA key exchange. Dessy emphasizes extensibility. Also the cryptography can be extended. Users may tag their files with context tags and control custom file metadata. Adding new indexed file types, metadata fields, ranking methods, and index types is easy. Finding files is done with virtual directories, which are views into the user’s files, browseable by regular file managers. On mobile devices, the Dessy GUI provides easy access to the search and synchronization system. This thesis includes results of Dessy synchronization and search experiments, including power usage measurements. Finally, Dessy has been designed with mobility and device constraints in mind. It requires only MIDP 2.0 Mobile Java with FileConnection support, and Java 1.5 on desktop machines.

Correspondence with Mr. Joseph regarding organization of board

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Spatiotemporal Organization of AT- and GC-rich DNA and Their Association With Transition Proteins TP1 and TP2 in Rat Condensing Spermatids

Transition protein 1 (TP1) and TP2 replace histones during midspermiogenesis (stages 12-15) and are finally replaced by protamines. TPs play a predominant role in DNA condensation and chromatin remodeling during mammalian spermiogenesis. TP2 is a zinc metalloprotein with two novel zinc finger modules that condenses DNA in vitro in a GC-preference manner. TP2 also localizes to the nucleolus in transfected HeLa and Cos-7 cells, suggesting a GC-rich preference, even in vivo. We have now studied the localization pattern of TP2 in the rat spermatid nucleus. Colocalization studies using GC-selective DNA-binding dyes chromomycin A3 and 7-amino actinomycin D and an AT-selective dye, 4',6-diamidino-2-phenylindole, indicate that TP2 is preferentially localized to GC-rich sequences. Interestingly, as spermatids mature, TP2 and GC-rich DNA moves toward the nuclear periphery, and in the late stages of spermatid maturation, TP2 is predominantly localized at the nuclear periphery. Another interesting observation is the mutually exclusive localization of GC- and AT-rich DNA in the elongating and elongated spermatids. A combined immunofluorescence experiment with anti-TP2 and anti-TP1 antibodies revealed several foci of overlapping localization, indicating that TP1 and TP2 may have concerted functional roles during chromatin remodeling in mammalian spermiogenesis.

Social organization of household finance: Understanding artful financial systems in the home

In this paper we discuss results of a field study focused on understanding the ways money and financial issues are handled within family settings. Families develop ‘systems’ or methods through which they coordinate and manage their everyday financial activities. Through an analysis of our fieldwork data collected from fifteen families, we provide several examples of such systems, highlighting their qualities and illustrating how such systems come to support the handling of financial activities in the home. Our results show that these systems are developed with a careful consideration of familial values, relationships and routines; and incorporate the use of physical and digital tools. Consequently, we suggest that design should consider the use and non-use of technology when supporting household financial management, taking into account the richness of families’ existing organically formed practices surrounding financial systems. Finally, our findings point to the fact that financial management in the domestic setting is socially organized and is closely connected to supporting everyday household activities.

Three-dimensional organization of fenestrae labyrinths in liver sinusoidal endothelial cells

- Background/Aims Liver sinusoidal endothelial cell (LSEC) fenestrae are membrane-bound pores that are grouped in sieve plates and act as a bidirectional guardian in regulating transendothelial liver transport. The high permeability of the endothelial lining is explained by the presence of fenestrae and by various membrane-bound transport vesicles. The question as to whether fenestrae relate to other transport compartments remains unclear and has been debated since their discovery almost 40 years ago. - Methods In this study, novel insights concerning the three-dimensional (3D) organization of the fenestrated cytoplasm were built on transmission electron tomographical observations on isolated and cultured whole-mount LSECs. Classical transmission electron microscopy and atomic force microscopy imaging was performed to accumulate cross-correlative structural evidence. - Results and Conclusions The data presented here indicate that different arrangements of fenestrae have to be considered: i.e. open fenestrae that lack any structural obstruction mainly located in the thin peripheral cytoplasm and complexes of multifolded fenestrae organized as labyrinth-like structures that are found in the proximity of the perinuclear area. Fenestrae in labyrinths constitute about one-third of the total LSEC porosity. The 3D reconstructions also revealed that coated pits and small membrane-bound vesicles are exclusively interspersed in the non-fenestrated cytoplasmic arms.