Targeted delivery of DNA encoding cytotoxic proteins through high-affinity fibroblast growth factor receptors

Nonviral DNA delivery strategies for gene therapy have generally been limited by a lack of specificity and efficacy. However, ligand-mediated endocytosis can specifically deliver DNA in vitro to cells bearing the appropriate cognate receptors. Similarly, in order to circumvent problems related to efficacy, DNA must encode proteins with high intrinsic activities. We show here that the ligand basic fibroblast growth factor (FGF2) can target FGF receptor-bearing cells with DNA encoding therapeutic proteins. Delivery of genes encoding saporin, a highly potent ribosomal inactivating protein, or the conditionally cytotoxic herpes simplex virus thymidine kinase, a protein that can kill cells by activating the prodrug ganciclovir, is demonstrated. The saporin gene was codon optimized for mammalian expression and demonstrated to express functional protein in a cell-free assay. FGF2-mediated delivery of saporin DNA or thymidine kinase DNA followed by ganciclovir treatment resulted in a 60 and 75% decrease in cell number, respectively. Specificity of gene delivery was demonstrated in competition assays with free FGF2 or with recombinant soluble FGF receptor. Alternatively, when histone H1, a ligand that binds to cell surface heparan sulfate proteoglycans ("low-affinity" FGF receptors), was used to deliver DNA encoding thymidine kinase, no ganciclovir sensitivity was observed. These findings establish the feasibility of using ligands such as FGF2 to specifically deliver genes encoding molecular chemotherapeutic agents to cells.     

Sensor location optimization for fault diagnosis with a comparison to linear programming approaches

The critical importance of sustaining fault diagnosis, as a major system tool, is unquestionable if the high performance and reliability of increasingly complex engineering systems is to be sustained over time and across a wide operating range. However, it is quite difficult to retain the joint ability of fault detection and isolation as it requires a strong system architecture. That is why, before designing an industrial supervision system, the determination of a system’s monitoring ability based on technical specifications is important as finding the source of the failure is not trivial in systems with a large number of components and complex component relationships. This paper presents an efficient and cost-effective fault detection and isolation (FDI) scheme that evolved from an earlier work [1]. FDI specifications are translated into constraints of the optimization problem considering that the whole set of analytical redundancy relations has been generated, under the assumption that all candidate sensors are installed and later on tested by an optimization algorithm using binary and relaxed versions of linear and nonlinear programming. By doing so, critical information about the presence or absence of a fault is gained in the shortest possible time, with not only confirmation of the findings but also an accurate unfolding in time of the finer details of the fault, thus completing the overall diagnostic picture of the system under test. The proposed scheme is evaluated extensively on a two-tank process used in industry, exemplified by a benchmarked laboratory-scale coupled-tank system.     

Investigation on Structural,Morphological, Optical and Ammonia Sensing Properties Indium Doped Nano Crystalline ZnO Thin Films Synthesized by Spray Pyrolysis Technique

In the present work, nanostructured In doped ZnO thin films were synthesized using spray pyrolysis technique with different molarity concentrations (0.001–0.004). X-ray diffraction patterns confirms the polycrystalline nature of the films with hexagonal structure. The crystallite size is going to be increases with increase in dopant concentration. The field-emission scanning electron micrograph of undoped ZnO exhibits spherical shaped particles with intergrain pores and the intergrain pores decreases with increases in indium concentration. The transmittance and band gap is going to be decreases with increase in indium concentration. The ammonia (NH₃) sensing properties of the undoped ZnO and In doped ZnO thin films were carried out at room temperature and the sensing responses of the samples towards NH₃ concentrations were reported.     

Exploring differential trends in severe and fatal child pedestrian injury in New South Wales, Australia (1997–2006)

The study explores trends in severe and fatal child pedestrian injuries in New South Wales (NSW), over the 10-year period 1997–2006, in comparison to adults and for various subgroups. Data on pedestrian injury (reported as fatalities or hospitalisations) were obtained from the Traffic Accident Database System (TADS; Roads and Traffic Authority of New South Wales) which captures road traffic events reported to police, and from the NSW Admitted Patients Data Collection (APDC) which captures all hospital inpatient separations. Annual percentage changes in injury counts and rates were compared using Poisson regression. A substantial drop in the pedestrian injury rate was observed; however, the rate of decline was steeper for children (aged less than 15 years) than for adults. The drop in child pedestrian injury was manifest in both the police report data and the hospital admission data. The annual percentage decrease was significantly greater for boys than for girls, and the three major urban centres compared with elsewhere in the state. No differences were detected in the annual rate decrease between school days and non-school days (a proxy for safe school zones), or between different road types (a proxy for restricted speed limits). Past research suggests that injury rate reductions are not solely due to decreased exposure. There remains, however, limited data on the extent of pedestrian mobility. Differences in relative reduction in pedestrian injury rates suggest a differential benefit arising from road safety initiatives.     

Design and Experimental Evaluation of a Database-Assisted V2V Communications System Over TV White Space

In the past years, many works have demonstrated the applicability of Coarse-Grained Reconfigurable Array (CGRA) accelerators to optimize loops by using software pipelining approaches. They are proven to be effective in reducing the total execution time of multimedia and signal processing applications. However, the run-time reconfigurability of CGRAs is hampered overheads introduced by the needed translation and mapping steps. In this work, we present a novel run-time translation technique for the modulo scheduling approach that can convert binary code on-the-fly to run on a CGRA. We propose a greedy approach, since the modulo scheduling for CGRA is an NP-complete problem. In addition to read-after-write dependencies, the dynamic modulo scheduling faces new challenges, such as register insertion to solve recurrence dependences and to balance the pipelining paths. Our results demonstrate that the greedy run-time algorithm can reach a near-optimal ILP rate, better than an off-line compiler approach for a 16-issue VLIW processor. The proposed mechanism ensures software compatibility as it supports different source ISAs. As proof of concept of scaling, a change in the memory bandwidth has been evaluated. In this analysis it is demonstrated that when changing from one memory access per cycle to two memory accesses per cycle, the modulo scheduling algorithm is able to exploit this increase in memory bandwidth and enhance performance accordingly. Additionally, to measure area and performance, the proposed CGRA was prototyped on an FPGA. The area comparisons show that a crossbar CGRA (with 16 processing elements and including an 4-issue VLIW host processor) is only 1.11 × bigger than a standalone 8-issue VLIW softcore processor.     

Minimum thickness of elliptical masonry arches

In this paper, we compute the minimum thickness and the location of the imminent intrados hinge of symmetric elliptical masonry arches when subjected to their weight. While this problem (Couplet’s problem) was solved rigorously for semicircular arches more than a century ago, no results have been available for elliptical arches. Motivated from the recent growing interest in identifying the limit equilibrium states of historic structures, this paper first computes two neighboring physically admissible thrust-lines which can just be located in elliptical arches by adopting either a polar or a cartesian coordinate system. These two distinguishable, physically admissible thrust-lines are neighboring thrust-lines to Hooke’s catenary which is not a physically admissible thrust-line as has been shown recently. Accordingly, the paper shows that the answer for the minimum thickness of symmetric elliptical masonry arches is not unique and that it depends on the coordinate system adopted and the associated stereotomy exercised. This result is confirmed by developing a variational formulation after selecting the appropriate directions of the rupture that initiates at the intrados hinge. The paper concludes that Hooke’s limiting catenary, although not a physically admissible thrust-line, offers a conservative value for the minimum thickness in most practical configurations.