SERpredict: Detection of tissue- or tumor-specific isoforms generated through exonization of transposable elements

Background: Transposed elements (TEs) are known to affect transcriptomes, because either new exons are generated from intronic transposed elements (this is called exonization), or the element inserts into the exon, leading to a new transcript. Several examples in the literature show that isoforms generated by an exonization are specific to a certain tissue (for example the heart muscle) or inflict a disease. Thus, exonizations can have negative effects for the transcriptome of an organism. Results: As we aimed at detecting other tissue- or tumor-specific isoforms in human and mouse genomes which were generated through exonization of a transposed element, we designed the automated analysis pipeline SERpredict (SER = Specific Exonized Retroelement) making use of Bayesian Statistics. With this pipeline, we found several genes in which a transposed element formed a tissue- or tumor-specific isoform. Conclusion: Our results show that SERpredict produces relevant results, demonstrating the importance of transposed elements in shaping both the human and the mouse transcriptomes. The effect of transposed elements on the human transcriptome is several times higher than the effect on the mouse transcriptome, due to the contribution of the primate-specific Alu element

A study of the effect of forcing function characteristics on human operator dynamics in manual control

The effect of the spectrum of the forcing function on the human pilot dynamics in manual control was investigated. A simple compensatory tracking experiment was conducted, where the controlled element was of a second-order dynamics and the forcing function was a random noise having a dominant frequency. The dominant frequency and the power of the forcing function were two variable parameters during the experiment. The results show that the human pilot describing functions are dependent not only on the dynamics of the controlled element, but also on the characteristics of the forcing function. This suggests that the human pilot behavior should be expressed by the transfer function taking into consideration his ability to sense and predict the forcing function

Survivability: The Human Element

Modern warship design is facing a number of drivers in terms of design, procurement and operation and these have both direct and indirect impacts on issues such as survivability and the human element. Guidance has been developed regarding Human Factors Integration (HFI), but this has generally focussed on detail design and fatigue. The UK MOD HFI Initiative describes HFI with 7 more holistic domains which are seen to have wider ship design impacts. This paper considers three current drivers on warship design for their impacts on survivability in the context of the human element. There were seen to be some interactions between different aspects of modern warship design and operation that again require a more holistic assessment of HF issues. The paper concludes that, although a more holistic approach is required, the increasing computerisation of the preliminary ship design process should allow tools to be developed to support this

Human Apolipoprotein B Transgenic Mice Generated with 207- and 145-Kilobase Pair Bacterial Artificial Chromosomes. Evidence that a distant 5'-element confers appropriate transgene expression in the intestine

We reported previously that ~80-kilobase pair (kb) P1 bacteriophage clones spanning either the human or mouse apoB gene (clones p158 and p649, respectively) confer apoB expression in the liver of transgenic mice, but not in the intestine. We hypothesized that the absence of intestinal expression was due to the fact that these clones lacked a distant DNA element controlling intestinal expression. To test this possibility, transgenic mice were generated with 145- and 207-kb bacterial artificial chromosomes (BACs) that contained the human apoB gene and more extensive 5'- and 3'-flanking sequences. RNase protection, in situ hybridization, immunohistochemical, and genetic complementation studies revealed that the BAC transgenic mice manifested appropriate apoB gene expression in both the intestine and the liver, indicating that both BACs contained the distant intestinal element. To determine whether the regulatory element was located 5' or 3' to the apoB gene, transgenic mice were generated by co-microinjecting embryos with p158 and either the 5'- or 3'-sequences from the 145-kb BAC. Analysis of these mice indicated that the apoB gene's intestinal element is located 5' to the structural gene. Cumulatively, the transgenic mouse studies suggest that the intestinal element is located between -33 and -70 kb 5' to the apoB gene

iForgot: a model of forgetting in robotic memories

Much effort has focused in recent years on developing more life-like robots. In this paper we propose a model of memory for robots, based on human digital memories, though our model incorporates an element of forgetting to ensure that the robotic memory appears more human and therefore can address some of the challenges for human-robot interaction

The effect of boundary constraints on finite element modelling of the human pelvis

The use of finite element analysis (FEA) to investigate the biomechanics of anatomical systems critically relies on the specification of physiologically representative boundary conditions. The biomechanics of the pelvis has been the specific focus of a number of FEA studies previously, but it is also a key aspect in other investigations of, for example, the hip joint or new design of hip prostheses. In those studies, the pelvis has been modelled in a number of ways with a variety of boundary conditions, ranging from a model of the whole pelvic girdle including soft tissue attachments to a model of an isolated hemi-pelvis. The current study constructed a series of FEA models of the same human pelvis to investigate the sensitivity of the predicted stress distributions to the type of boundary conditions applied, in particular to represent the sacro-iliac joint and pubic symphysis. Varying the method of modelling the sacro-iliac joint did not produce significant variations in the stress distribution, however changes to the modelling of the pubic symphysis were observed to have a greater effect on the results. Over-constraint of the symphysis prevented the bending of the pelvis about the greater sciatic notch, and underestimated high stresses within the ilium. However, permitting medio-lateral translation to mimic widening of the pelvis addressed this problem. These findings underline the importance of applying the appropriate boundary conditions to FEA models, and provide guidance on suitable methods of constraining the pelvis when, for example, scan data has not captured the full pelvic girdle. The results also suggest a valid method for performing hemi-pelvic modelling of cadaveric or archaeological remains which are either damaged or incomplete

The strong enhancer element in the immediate early region of the human cytomegalovirus genome

The human cytomegalovirus (HCMV), a member of the herpesvirus group, was found to possess a strong transcription enhancer in the immediate early gene region. Co-transfection of enhancerless SV40 DNA with randomly fragmented HCMV DNA yielded two SV40-like recombinant viruses , each containing HCMV DNA fragments that were substituting for the missing SV40 enhancer. The two inserts , 341 and 262 bp in length , are overlapping segments of genuine viral DNA representing part of the 5'flanking region of the major immedistte early gene i n HCMV. Studies with deletion mutants showed that different nonoverlapping subsets of the HCMV enhancer region can substitute for the 72 bp repeats of SV40. Transient expression assays indicated that the HCMV enhancer is significantly stronger than the SV40 element, activating cis-linked heterologous promoters in a wide spectrum of cultured cells. It appears that the HCMV enhancer is positively regulated by viral immediate early genes

The human ankyrin 1 promoter insulator sustains gene expression in a β-globin lentiviral vector in hematopoietic stem cells.

Lentiviral vectors designed for the treatment of the hemoglobinopathies require the inclusion of regulatory and strong enhancer elements to achieve sufficient expression of the β-globin transgene. Despite the inclusion of these elements, the efficacy of these vectors may be limited by transgene silencing due to the genomic environment surrounding the integration site. Barrier insulators can be used to give more consistent expression and resist silencing even with lower vector copies. Here, the barrier activity of an insulator element from the human ankyrin-1 gene was analyzed in a lentiviral vector carrying an antisickling human β-globin gene. Inclusion of a single copy of the Ankyrin insulator did not affect viral titer, and improved the consistency of expression from the vector in murine erythroleukemia cells. The presence of the Ankyrin insulator element did not change transgene expression in human hematopoietic cells in short-term erythroid culture or in vivo in primary murine transplants. However, analysis in secondary recipients showed that the lentiviral vector with the Ankyrin element preserved transgene expression, whereas expression from the vector lacking the Ankyrin insulator decreased in secondary recipients. These studies demonstrate that the Ankyrin insulator may improve long-term β-globin expression in hematopoietic stem cells for gene therapy of hemoglobinopathies