A Novel Binding Protein for Fibroblast Growth Factors (FGF-BP2):Cloning, Expression Profile, Tumorigenic Activity and Regulation of Gene Expression by Fetal Bovine Serum and Retinoic Acid.

Angiogenesis is one of the essential alterations in cell physiology that dictate malignant growth and metastasis and has long been a major focus in molecular cancer research. More than a dozen distinct proteins are currently known to induce proliferation of endothelial cells in vitro and/or angiogenesis in vivo. Some of the most effective and best-studied angiogenic factors are fibroblast growth factors (FGFs) that are potent stimulators of new blood vessel formation during tumor growth. However, some FGFs (aFGF and bFGF) are upon secretion immobilized in the extracellular matrix (ECM) and unable to reach their high affinity receptors. There are several possible mechanisms by which bFGF can be released from its matrix storage site and thus activated. One established mechanism is the action of an FGF binding protein (FGF-BP1). FGF-BP1 activates bFGF and is thus able to stimulate tumor cell proliferation and angiogenesis. Recently a human cDNA clone containing an open reading frame for a protein, which shows amino acid sequence similarity of 21% and homology of 41 % to FGF-BP1 was discovered. This novel molecule was named FGF-BP2. In this study the FGF-BP2 expression profile under physiological conditions in normal human tissue and in the pathological setting of tumor cell lines was evaluated by Northern Blotting analysis. Following its in vitro gene regulation by various drugs and growth factors was studied. Finally the FGF-BP2 cDNA was cloned into an expression vector, the gene was overexpressed in the human adrenal carcinoma cell line SW-13 and then analyzed for its tumorigenic potential in soft agar growth assays. This study revealed a widespread FGF-BP2 mRNA expression in normal human tissue. Among 36 tumor cell lines tested though, FGF-BP2 mRNA expression was limited to all of the melanoma cell lines. Interestingly, no FGF-BP2 mRNA expression was detected in normal human neonatal melanocytes. Furthermore it was evaluated if some of the well defined mechanisms for gene regulation that are known for FGF-BP1 also exist for FGF-BP2 as tested in two melanoma cell lines. However, in contrast to what is known for FGF-BP1 it was neither possible to show a significant up-regulation of the FGF-BP2 mRNA expression by Fetal Bovine Serum, EGF and TPA, nor was any down-regulation inducible by all-trans retinoic acid. Finally it was shown that FGF-BP2 overexpression in the human adrenal carcinoma cell line SW-13 promotes a bFGF-dependent colony formation in vitro, indicating its tumorigenic potential. This study demonstrates that the novel FGF-binding protein has not only structural but also functional similarities to FGF-BP1. Its biological activity, together with other data that are not presented here suggest that FGF-BP2 is like FGF-BP1 a tumor promoting agent that may solubilize matrix bound bFGF. However, FGF-BP2 shows a different expression pattern from FGF-BP1 and does not seem to follow similar mechanisms of transcriptional or posttranscriptional gene regulation. Most interesting though seems to be the function that FGF-BP2 might have in melanoma progression since it is known that bFGF and its activated signal pathway play a crucial role in the development of melanoma

Program equivalence for a concurrent lambda calculus with futures

Reasoning about the correctness of program transformations requires a notion of program equivalence. We present an observational semantics for the concurrent lambda calculus with futures Lambda(fut), which formalizes the operational semantics of the programming language Alice ML. We show that natural program optimizations, as well as partial evaluation with respect to deterministic rules, are correct for Lambda(fut). This relies on a number of fundamental properties that we establish for our observational semantics

On proving the equivalence of concurrency primitives

Various concurrency primitives have been added to sequential programming languages, in order to turn them concurrent. Prominent examples are concurrent buffers for Haskell, channels in Concurrent ML, joins in JoCaml, and handled futures in Alice ML. Even though one might conjecture that all these primitives provide the same expressiveness, proving this equivalence is an open challenge in the area of program semantics. In this paper, we establish a first instance of this conjecture. We show that concurrent buffers can be encoded in the lambda calculus with futures underlying Alice ML. Our correctness proof results from a systematic method, based on observational semantics with respect to may and must convergence

Formation and accretion history of terrestrial planets from runaway growth through to late time: implications for orbital eccentricity

Remnant planetesimals might have played an important role in reducing the orbital eccentricities of the terrestrial planets after their formation via giant impacts. However, the population and the size distribution of remnant planetesimals during and after the giant impact stage are unknown, because simulations of planetary accretion in the runaway growth and giant impact stages have been conducted independently. Here we report results of direct N-body simulations of the formation of terrestrial planets beginning with a compact planetesimal disk. The initial planetesimal disk has a total mass and angular momentum as observed for the terrestrial planets, and we vary the width (0.3 and 0.5AU) and the number of planetesimals (1000-5000). This initial configuration generally gives rise to three final planets of similar size, and sometimes a fourth small planet forms near the location of Mars. Since a sufficient number of planetesimals remains, even after the giant impact phase, the final orbital eccentricities are as small as those of the Earth and Venus.Comment: 36 pages, 9 figures, 1 table, Accepted in Ap

Towards a Knowledge Graph based Speech Interface

Applications which use human speech as an input require a speech interface with high recognition accuracy. The words or phrases in the recognised text are annotated with a machine-understandable meaning and linked to knowledge graphs for further processing by the target application. These semantic annotations of recognised words can be represented as a subject-predicate-object triples which collectively form a graph often referred to as a knowledge graph. This type of knowledge representation facilitates to use speech interfaces with any spoken input application, since the information is represented in logical, semantic form, retrieving and storing can be followed using any web standard query languages. In this work, we develop a methodology for linking speech input to knowledge graphs and study the impact of recognition errors in the overall process. We show that for a corpus with lower WER, the annotation and linking of entities to the DBpedia knowledge graph is considerable. DBpedia Spotlight, a tool to interlink text documents with the linked open data is used to link the speech recognition output to the DBpedia knowledge graph. Such a knowledge-based speech recognition interface is useful for applications such as question answering or spoken dialog systems.Comment: Under Review in International Workshop on Grounding Language Understanding, Satellite of Interspeech 201

Adequacy of compositional translations for observational semantics

We investigate methods and tools for analysing translations between programming languages with respect to observational semantics. The behaviour of programs is observed in terms of may- and must-convergence in arbitrary contexts, and adequacy of translations, i.e., the reflection of program equivalence, is taken to be the fundamental correctness condition. For compositional translations we propose a notion of convergence equivalence as a means for proving adequacy. This technique avoids explicit reasoning about contexts, and is able to deal with the subtle role of typing in implementations of language extension

On correctness of buffer implementations in a concurrent lambda calculus with futures

Motivated by the question of correctness of a specific implementation of concurrent buffers in the lambda calculus with futures underlying Alice ML, we prove that concurrent buffers and handled futures can correctly encode each other. Correctness means that our encodings preserve and reflect the observations of may- and must-convergence. This also shows correctness wrt. program semantics, since the encodings are adequate translations wrt. contextual semantics. While these translations encode blocking into queuing and waiting, we also provide an adequate encoding of buffers in a calculus without handles, which is more low-level and uses busy-waiting instead of blocking. Furthermore we demonstrate that our correctness concept applies to the whole compilation process from high-level to low-level concurrent languages, by translating the calculus with buffers, handled futures and data constructors into a small core language without those constructs