The hallmarks of cancer.

The human genome holds an extraordinary trove of information about human development, physiology, medicine and evolution. Here we report the results of an international collaboration to produce and make freely available a draft sequence of the human genome. We also present an initial analysis of the data, describing some of the insights that can be gleaned from the sequence.

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Initial sequencing and analysis of the human genome.

The emergence of order in natural systems is a constant source of inspiration for both physical and biological sciences. While the spatial order characterizing for example the crystals has been the basis of many advances in contemporary physics, most complex systems in nature do not offer such high degree of order. Many of these systems form complex networks whose nodes are the elements of the system and edges represent the interactions between them. 
Traditionally complex networks have been described by the random graph theory founded in 1959 by Paul Erdohs and Alfred Renyi. One of the defining features of random graphs is that they are statistically homogeneous, and their degree distribution (characterizing the spread in the number of edges starting from a node) is a Poisson distribution. In contrast, recent empirical studies, including the work of our group, indicate that the topology of real networks is much richer than that of random graphs. In particular, the degree distribution of real networks is a power-law, indicating a heterogeneous topology in which the majority of the nodes have a small degree, but there is a significant fraction of highly connected nodes that play an important role in the connectivity of the network. 
The scale-free topology of real networks has very important consequences on their functioning. For example, we have discovered that scale-free networks are extremely resilient to the random disruption of their nodes. On the other hand, the selective removal of the nodes with highest degree induces a rapid breakdown of the network to isolated subparts that cannot communicate with each other. 
The non-trivial scaling of the degree distribution of real networks is also an indication of their assembly and evolution. Indeed, our modeling studies have shown us that there are general principles governing the evolution of networks. Most networks start from a small seed and grow by the addition of new nodes which attach to the nodes already in the system. This process obeys preferential attachment: the new nodes are more likely to connect to nodes with already high degree. We have proposed a simple model based on these two principles wich was able to reproduce the power-law degree distribution of real networks. Perhaps even more importantly, this model paved the way to a new paradigm of network modeling, trying to capture the evolution of networks, not just their static topology.

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Statistical mechanics of complex networks

A genetic model for colorectal tumorigenesis

http://www.maths.qmul.ac.uk/%7Elatora/report_06.pdf

Complex networks: Structure and dynamics

The invention relates to inhibitory nucleotide signal sequences or “INS” sequences in the genomes of lentiviruses. In particular the invention relates to the AGG motif present in all viral genomes. The AGG motif may have an inhibitory effect on a virus, for example by reducing the levels of, or maintaining low steady-state levels of, viral RNAs in host cells, and inducing and/or maintaining in viral latency. In one aspect, the invention provides vaccines that contain, or are produced from, viral nucleic acids in which the AGG sequences have been mutated. In another aspect, the invention provides methods and compositions for affecting the function of the AGG motif, and methods for identifying other INS sequences in viral genomes.

Viral inhibitory nucleotide sequences and vaccines

Adenoviruses have been isolated from a number of different species including man (33 serotypes), monkeys, mice, dogs, cows, birds (Green, 1970), and frogs (Clark et al., 1973). The most extensively studied adenoviruses are those of human origin. In particular, we now know a great deal about the structure and replication of the DNA from human adenoviruses types 2 and 5. For this reason this review will be restricted to a discussion of these two viruses.

The Isolation and Characterization of DNA Binding Proteins Specific for Adenovirus Infected Cells

Verfahren zur Optimierung der Impfstoffproduktion

Polyoma and SV40 are small DNA tumor viruses whose well-defined properties have made them ideal subjects for intensive investigation over the last ten years (Black, 1968; Eckhart, 1968; Crawford, 1969; Green, 1970; Sambrook, 1972; Butel, Tevethia and Melnick, 1972). The DNA of these viruses has been extensively characterized by Vinograd and his collaborators (Vinograd and Lebowitz, 1966; Bauer and Vinograd, 1968; Radloff, Bauer and Vinograd, 1967) and by Crawford (Crawford and Black, 1964; Crawford, 1969). They have shown that the genome of SV40 is a single closed-circular molecule of double-stranded DNA containing about 12–15 negative superhelical turns and has a molecular weight of about 3 x 106 daltons. Over the last four years experiments from a number of laboratories working on the mechanism of SV40 DNA replication have yielded a clear outline of the events of viral DNA replication (for a recent review see Levine, 1973). These events may be conveniently divided into four stages: 1) initiation, 2) polynucleotide chain propagation, 3) segregation of the two newly-made daughter molecules, and 4) maturation of the progeny molecules.

Arnold J. Levine

Papers

Viral inhibitory nucleotide sequences and vaccines

The Isolation and Characterization of DNA Binding Proteins Specific for Adenovirus Infected Cells

Verfahren zur Optimierung der Impfstoffproduktion

An Analysis of the Structure of the Replicating Fork During Discontinuous Synthesis of SV40 DNA and the Detection of Gap Circle Intermediates

Methoden zur identifizierung von Angenzien, die das AGG-Motif binden