Chest radiography doses with film screen : is further reduction possible?

Peer reviewedPublisher PD

Possible attenuation of the G2 DNA damage cell cycle checkpoint in HeLa cells by extremely low frequency (ELF) electromagnetic fields

BACKGROUND: The issue remains unresolved as to whether low frequency magnetic fields can affect cell behaviour, with the possibility that they may be in part responsible for the increased incidence of leukaemia in parts of the population exposed to them. METHODS: Combined treatment of HeLa cells with gamma-irradiation (1, 3 and 5 Grays) and extra low frequency magnetic fields of ~50 Hz was carried out under rigorously controlled conditions. RESULTS: Synchronised cells progressing from S-phase arrived at mitosis on average marginally ahead of irradiation controls not exposed to ELF. In no instance out of a total of twenty separate experiments did this "double-insult" further delay entry of cells into mitosis, as had been anticipated. CONCLUSION: This apparently "non-genotoxic" agent (ELF) appears to be capable of affecting cells that would normally arrest for longer in G2, suggesting a weakening of the stringency of the late cycle (G2) checkpoint

Qualifying Prosecutorial Immunity Through Brady Claims

This Article considers the soundness of the doctrine of absolute immunity as it relates to Brady violations. While absolute immunity serves to protect prosecutors from civil liability for good-faith efforts to act appropriately in their official capacity, current immunity doctrine also creates a potentially large class of injury victims—those who are subjected to wrongful imprisonment due to Brady violations—with no access to justice. Moreover, by removing prosecutors from the incentive-shaping forces of the tort system that are thought in other contexts to promote safety, absolute immunity doctrine may under-incentivize prosecutorial compliance with constitutional and statutory requirements and increase criminal justice system error. The Article seeks to identify ways to use the civil justice system to promote prosecutorial compliance with Brady, while recognizing the need to provide appropriate civil protections to enable prosecutors to fulfill their unique role within the criminal justice system. After developing a novel taxonomy of Brady cases, evaluating such cases against basic tort principles, and considering the prosecutorial community’s views regarding appropriate Brady remedies, it proposes a statutory modification of absolute immunity that might better regulate and incentivize prosecutor behavior, reduce wrongful convictions, and improve access to justice

A Shape Memory Polymer for Intracranial Aneurysms: An Investigation of Mechanical and Radiographic Properties of a Tantalum-Filled Shape Memory Polymer Composite

An intracranial aneurysm can be a serious, life-threatening condition which may go undetected until the aneurysm ruptures causing hemorrhaging within the brain. The typical treatment method for large aneurysms is by embolization using platinum coils. However, in about 15% of the cases treated by platinum coils, the aneurysm eventually re-opens. The solution to the problem of aneurysm recurrence may be to develop more bio-active materials, including certain polymers, to use as coil implants. In this research, a shape memory polymer (SMP) was investigated as a potential candidate for aneurysm coils. The benefit of a shape memory polymer is that a small diameter fiber can be fed through a micro-catheter and then change its shape into a three-dimensional configuration when heated to body temperature. The SMP was tested to determine its thermo-mechanical properties and the strength of the shape recovery force. In addition, composite specimens containing tantalum filler were produced and tested to determine the mechanical effect of adding this radio-opaque metal. Thermo-mechanical testing showed that the material exhibited a shape recovery force a few degrees above Tg. The effects of the metal filler were small and included depression of Tg and recovery force. SMP coils deployed inside a simulated aneurysm model demonstrated that typical hemodynamic forces would not hinder the shape recovery process. The x-ray absorption capability the tantalum-filled material was characterized using x-ray diffractometry and clinical fluoroscopy. Diffractometry revealed that x-ray absorption increased with tantalum concentration, however, not as the rule of mixtures would predict. Fluoroscopic imaging of the composite coils in a clinical setting verified the radio-opacity of the material.M.S.Committee Chair: Janet Hampikian; Committee Member: Brent Carter; Committee Member: Roger Narayan; Committee Member: Zhuqing Zhan

Structural variant-based pangenome construction has low sensitivity to variability of haplotype-resolved bovine assemblies

Advantages of pangenomes over linear reference assemblies for genome research have recently been established. However, potential effects of sequence platform and assembly approach, or of combining assemblies created by different approaches, on pangenome construction have not been investigated. Here we generate haplotype-resolved assemblies from the offspring of three bovine trios representing increasing levels of heterozygosity that each demonstrate a substantial improvement in contiguity, completeness, and accuracy over the current Bos taurus reference genome. Diploid coverage as low as 20x for HiFi or 60x for ONT is sufficient to produce two haplotype-resolved assemblies meeting standards set by the Vertebrate Genomes Project. Structural variant-based pangenomes created from the haplotype-resolved assemblies demonstrate significant consensus regardless of sequence platform, assembler algorithm, or coverage. Inspecting pangenome topologies identifies 90 thousand structural variants including 931 overlapping with coding sequences; this approach reveals variants affecting QRICH2, PRDM9, HSPA1A, TAS2R46, and GC that have potential to affect phenotype

Structural variant-based pangenome construction has low sensitivity to variability of haplotype-resolved bovine assemblies

Advantages of pangenomes over linear reference assemblies for genome research have recently been established. However, potential effects of sequence platform and assembly approach, or of combining assemblies created by different approaches, on pangenome construction have not been investigated. Here we generate haplotype-resolved assemblies from the offspring of three bovine trios representing increasing levels of heterozygosity that each demonstrate a substantial improvement in contiguity, completeness, and accuracy over the current Bos taurus reference genome. Diploid coverage as low as 20x for HiFi or 60x for ONT is sufficient to produce two haplotype-resolved assemblies meeting standards set by the Vertebrate Genomes Project. Structural variant-based pangenomes created from the haplotype-resolved assemblies demonstrate significant consensus regardless of sequence platform, assembler algorithm, or coverage. Inspecting pangenome topologies identifies 90 thousand structural variants including 931 overlapping with coding sequences; this approach reveals variants affecting QRICH2, PRDM9, HSPA1A, TAS2R46, and GC that have potential to affect phenotype

First gene-edited calf with reduced susceptibility to a major viral pathogen

Bovine viral diarrhea virus (BVDV) is one of the most important viruses affecting the health and well-being of bovine species throughout the world. Here, we used CRISPR-mediated homology-directed repair and somatic cell nuclear transfer to produce a live calf with a six amino acid substitution in the BVDV binding domain of bovine CD46. The result was a gene-edited calf with dramatically reduced susceptibility to infection as measured by reduced clinical signs and the lack of viral infection in white blood cells. The edited calf has no off-target edits and appears normal and healthy at 20 months of age without obvious adverse effects from the on-target edit. This precision bred, proof-of-concept animal provides the first evidence that intentional genome alterations in the CD46 gene may reduce the burden of BVDV-associated diseases in cattle and is consistent with our stepwise, in vitro and ex vivo experiments with cell lines and matched fetal clones

A Genome Wide Survey of SNP Variation Reveals the Genetic Structure of Sheep Breeds

The genetic structure of sheep reflects their domestication and subsequent formation into discrete breeds. Understanding genetic structure is essential for achieving genetic improvement through genome-wide association studies, genomic selection and the dissection of quantitative traits. After identifying the first genome-wide set of SNP for sheep, we report on levels of genetic variability both within and between a diverse sample of ovine populations. Then, using cluster analysis and the partitioning of genetic variation, we demonstrate sheep are characterised by weak phylogeographic structure, overlapping genetic similarity and generally low differentiation which is consistent with their short evolutionary history. The degree of population substructure was, however, sufficient to cluster individuals based on geographic origin and known breed history. Specifically, African and Asian populations clustered separately from breeds of European origin sampled from Australia, New Zealand, Europe and North America. Furthermore, we demonstrate the presence of stratification within some, but not all, ovine breeds. The results emphasize that careful documentation of genetic structure will be an essential prerequisite when mapping the genetic basis of complex traits. Furthermore, the identification of a subset of SNP able to assign individuals into broad groupings demonstrates even a small panel of markers may be suitable for applications such as traceability