Utility of telomerase-pot1 fusion protein in vascular tissue engineering.

While advances in regenerative medicine and vascular tissue engineering have been substantial in recent years, important stumbling blocks remain. In particular, the limited life span of differentiated cells that are harvested from elderly human donors is an important limitation in many areas of regenerative medicine. Recently, a mutant of the human telomerase reverse transcriptase enzyme (TERT) was described, which is highly processive and elongates telomeres more rapidly than conventional telomerase. This mutant, called pot1-TERT, is a chimeric fusion between the DNA binding protein pot1 and TERT. Because pot1-TERT is highly processive, it is possible that transient delivery of this transgene to cells that are utilized in regenerative medicine applications may elongate telomeres and extend cellular life span while avoiding risks that are associated with retroviral or lentiviral vectors. In the present study, adenoviral delivery of pot1-TERT resulted in transient reconstitution of telomerase activity in human smooth muscle cells, as demonstrated by telomeric repeat amplification protocol (TRAP). In addition, human engineered vessels that were cultured using pot1-TERT-expressing cells had greater collagen content and somewhat better performance in vivo than control grafts. Hence, transient delivery of pot1-TERT to elderly human cells may be useful for increasing cellular life span and improving the functional characteristics of resultant tissue-engineered constructs.

An immunoglobulin C kappa-reactive single chain antibody fusion protein induces tolerance through receptor editing in a normal polyclonal immune system.

Understanding immune tolerance mechanisms is a major goal of immunology research, but mechanistic studies have generally required the use of mouse models carrying untargeted or targeted antigen receptor transgenes, which distort lymphocyte development and therefore preclude analysis of a truly normal immune system. Here we demonstrate an advance in in vivo analysis of immune tolerance that overcomes these shortcomings. We show that custom superantigens generated by single chain antibody technology permit the study of tolerance in a normal, polyclonal immune system. In the present study we generated a membrane-tethered anti-Igkappa-reactive single chain antibody chimeric gene and expressed it as a transgene in mice. B cell tolerance was directly characterized in the transgenic mice and in radiation bone marrow chimeras in which ligand-bearing mice served as recipients of nontransgenic cells. We find that the ubiquitously expressed, Igkappa-reactive ligand induces efficient B cell tolerance primarily or exclusively by receptor editing. We also demonstrate the unique advantages of our model in the genetic and cellular analysis of immune tolerance.

Mitochondrial fusion is regulated by Reaper to modulate Drosophila programmed cell death.

In most multicellular organisms, the decision to undergo programmed cell death in response to cellular damage or developmental cues is typically transmitted through mitochondria. It has been suggested that an exception is the apoptotic pathway of Drosophila melanogaster, in which the role of mitochondria remains unclear. Although IAP antagonists in Drosophila such as Reaper, Hid and Grim may induce cell death without mitochondrial membrane permeabilization, it is surprising that all three localize to mitochondria. Moreover, induction of Reaper and Hid appears to result in mitochondrial fragmentation during Drosophila cell death. Most importantly, disruption of mitochondrial fission can inhibit Reaper and Hid-induced cell death, suggesting that alterations in mitochondrial dynamics can modulate cell death in fly cells. We report here that Drosophila Reaper can induce mitochondrial fragmentation by binding to and inhibiting the pro-fusion protein MFN2 and its Drosophila counterpart dMFN/Marf. Our in vitro and in vivo analyses reveal that dMFN overexpression can inhibit cell death induced by Reaper or γ-irradiation. In addition, knockdown of dMFN causes a striking loss of adult wing tissue and significant apoptosis in the developing wing discs. Our findings are consistent with a growing body of work describing a role for mitochondrial fission and fusion machinery in the decision of cells to die.

Evaluation de DI-fusion: Le dépôt officiel de l'ULB

info:eu-repo/semantics/published

Policy-centric integration and dynamic composition of autonomic computing techniques

This paper presents innovative work in the development of policy-based autonomic computing. The core of the work is a powerful and flexible policy-expression language AGILE, which facilitates run-time adaptable policy configuration of autonomic systems. AGILE also serves as an integrating platform for other self-management technologies including signal processing, automated trend analysis and utility functions. Each of these technologies has specific advantages and applicability to different types of dynamic adaptation. The AGILE platform enables seamless interoperability of the different technologies to each perform various aspects of self-management within a single application. The various technologies are implemented as object components. Self-management behaviour is specified using the policy language semantics to bind the various components together as required. Since the policy semantics support run-time re-configuration, the self-management architecture is dynamically composable. Additional benefits include the standardisation of the application programmer interface, terminology and semantics, and only a single point of embedding is required.

Rapid Implementation and Optimisation of DSP Systems on FPGA-Centric Hetrogeneous Platforms

This paper, chosen as a best paper from the 2005 SAMOS Workshop on Computer Systems: describes the for the first time the major Abhainn project for automated system level design of embedded signal processing systems. In particular, this describes four key novelties: novel algorithm modelling techniques for DSP systems, automated implementation realisation, algorithm transformation for system optimisation and automated inter-processor communication. This is applied to two complex systems: a radar and sonar system. In both cases technology which allows non-experts to automatically create low-overhead, high performance embedded signal processing systems is exhibited.

Fusion rules for merging uncertain information

In previous papers, we have presented a logic-based framework based on fusion rules for merging structured news reports. Structured news reports are XML documents, where the textentries are restricted to individual words or simple phrases, such as names and domain-specific terminology, and numbers and units. We assume structured news reports do not require natural language processing. Fusion rules are a form of scripting language that define how structured news reports should be merged. The antecedent of a fusion rule is a call to investigate the information in the structured news reports and the background knowledge, and the consequent of a fusion rule is a formula specifying an action to be undertaken to form a merged report. It is expected that a set of fusion rules is defined for any given application. In this paper we extend the approach to handling probability values, degrees of beliefs, or necessity measures associated with textentries in the news reports. We present the formal definition for each of these types of uncertainty and explain how they can be handled using fusion rules. We also discuss the methods of detecting inconsistencies among sources.

Fast heating of ultrahigh-density plasma as a step towards laser fusion ignition

ate studies(2) and fusion energy research(3,4). Laser-driven implosions of spherical polymer shells have, for example, achieved an increase in density of 1,000 times relative to the solid state(5). These densities are large enough to enable controlled fusion, but to achieve energy gain a small volume of compressed fuel (known as the 'spark') must be heated to temperatures of about 10(8) K (corresponding to thermal energies in excess of 10 keV). In the conventional approach to controlled fusion, the spark is both produced and heated by accurately timed shock waves(4), but this process requires both precise implosion symmetry and a very large drive energy. In principle, these requirements can be significantly relaxed by performing the compression and fast heating separately(6-10); however, this 'fast ignitor' approach(7) also suffers drawbacks, such as propagation losses and deflection of the ultra-intense laser pulse by the plasma surrounding the compressed fuel. Here we employ a new compression geometry that eliminates these problems; we combine production of compressed matter in a laser-driven implosion with picosecond-fast heating by a laser pulse timed to coincide with the peak compression. Our approach therefore permits efficient compression and heating to be carried out simultaneously, providing a route to efficient fusion energy production.

Fast Heating scalable to laser fusion ignition

Rapid heating of a compressed fusion fuel by a short-duration laser pulse is a promising route to generating energy by nuclear fusion1, and has been demonstrated on an experimental scale using a novel fast-ignitor geometry2. Here we describe a refinement of this system in which a much more powerful, pulsed petawatt (1015 watts) laser creates a fastheated core plasma that is scalable to fullscale ignition, significantly increasing the number of fusion events while still maintaining high heating efficiency at these substantially higher laser energies. Our findings bring us a step closer to realizing the production of relatively inexpensive, full-scale fast-ignition laser facilities.