Magnetic variation anomalies in northern England and southern Scotland

Single-station transfer functions linking the time variations of the vertical and horizontal components of the magnetic field at stations in northern England and southern Scotland have been compiled into a uniform data set. From hypothetical event analysis we show here that there are two distinct anomalies in the Borders region. One runs south-west to north-east, immediately to the south-east of the Southern Uplands Fault; the second follows the Northumberland Basin, and seems to exist because the conductive sedimentary rocks filling the basin create a link between the Irish and North Seas. If the Iapetus suture is marked by a conductivity anomaly, as has been suggested, these results place it beneath the Southern Uplands, unless it is masked by the surface conductor in the Northumberland Basin

Noise correlation in PET, CT, SPECT and PET/CT data evaluated using autocorrelation function: a phantom study on data, reconstructed using FBP and OSEM

BACKGROUND: Positron Emission Tomography (PET), Computed Tomography (CT), PET/CT and Single Photon Emission Tomography (SPECT) are non-invasive imaging tools used for creating two dimensional (2D) cross section images of three dimensional (3D) objects. PET and SPECT have the potential of providing functional or biochemical information by measuring distribution and kinetics of radiolabelled molecules, whereas CT visualizes X-ray density in tissues in the body. PET/CT provides fused images representing both functional and anatomical information with better precision in localization than PET alone. Images generated by these types of techniques are generally noisy, thereby impairing the imaging potential and affecting the precision in quantitative values derived from the images. It is crucial to explore and understand the properties of noise in these imaging techniques. Here we used autocorrelation function (ACF) specifically to describe noise correlation and its non-isotropic behaviour in experimentally generated images of PET, CT, PET/CT and SPECT. METHODS: Experiments were performed using phantoms with different shapes. In PET and PET/CT studies, data were acquired in 2D acquisition mode and reconstructed by both analytical filter back projection (FBP) and iterative, ordered subsets expectation maximisation (OSEM) methods. In the PET/CT studies, different magnitudes of X-ray dose in the transmission were employed by using different mA settings for the X-ray tube. In the CT studies, data were acquired using different slice thickness with and without applied dose reduction function and the images were reconstructed by FBP. SPECT studies were performed in 2D, reconstructed using FBP and OSEM, using post 3D filtering. ACF images were generated from the primary images, and profiles across the ACF images were used to describe the noise correlation in different directions. The variance of noise across the images was visualised as images and with profiles across these images. RESULTS: The most important finding was that the pattern of noise correlation is rotation symmetric or isotropic, independent of object shape in PET and PET/CT images reconstructed using the iterative method. This is, however, not the case in FBP images when the shape of phantom is not circular. Also CT images reconstructed using FBP show the same non-isotropic pattern independent of slice thickness and utilization of care dose function. SPECT images show an isotropic correlation of the noise independent of object shape or applied reconstruction algorithm. Noise in PET/CT images was identical independent of the applied X-ray dose in the transmission part (CT), indicating that the noise from transmission with the applied doses does not propagate into the PET images showing that the noise from the emission part is dominant. The results indicate that in human studies it is possible to utilize a low dose in transmission part while maintaining the noise behaviour and the quality of the images. CONCLUSION: The combined effect of noise correlation for asymmetric objects and a varying noise variance across the image field significantly complicates the interpretation of the images when statistical methods are used, such as with statistical estimates of precision in average values, use of statistical parametric mapping methods and principal component analysis. Hence it is recommended that iterative reconstruction methods are used for such applications. However, it is possible to calculate the noise analytically in images reconstructed by FBP, while it is not possible to do the same calculation in images reconstructed by iterative methods. Therefore for performing statistical methods of analysis which depend on knowing the noise, FBP would be preferred

L,L-Diaminopimelate Aminotransferase from Chlamydomonas reinhardtii: A Target for Algaecide Development

In some bacterial species and photosynthetic cohorts, including algae, the enzyme l,l-diaminopimelate aminotransferase (DapL) (E.C. 2.6.1.83) is involved in the anabolism of the essential amino acid L-lysine. DapL catalyzes the conversion of tetrahydrodipicolinate (THDPA) to l,l-diaminopimelate (l,l-DAP), in one step bypassing the DapD, DapC and DapE enzymatic reactions present in the acyl DAP pathways. Here we present an in vivo and in vitro characterization of the DapL ortholog from the alga Chlamydomonas reinhardtii (Cr-DapL). The in vivo analysis illustrated that the enzyme is able to functionally complement the E. coli dap auxotrophs and was essential for plant development in Arabidopsis. In vitro, the enzyme was able to inter-convert THDPA and l,l-DAP, showing strong substrate specificity. Cr-DapL was dimeric in both solution and when crystallized. The structure of Cr-DapL was solved in its apo form, showing an overall architecture of a α/β protein with each monomer in the dimer adopting a pyridoxal phosphate-dependent transferase-like fold in a V-shaped conformation. The active site comprises residues from both monomers in the dimer and shows some rearrangement when compared to the apo-DapL structure from Arabidopsis. Since animals do not possess the enzymatic machinery necessary for the de novo synthesis of the amino acid l-lysine, enzymes involved in this pathway are attractive targets for the development of antibiotics, herbicides and algaecides

Altered microRNA expression in frontotemporal lobar degeneration with TDP-43 pathology caused by progranulin mutations

<p>Abstract</p> <p>Background</p> <p>Frontotemporal lobar degeneration (FTLD) is a progressive neurodegenerative disorder that can be triggered through genetic or sporadic mechanisms. MicroRNAs (miRNAs) have become a major therapeutic focus as their pervasive expression and powerful regulatory roles in disease pathogenesis become increasingly apparent. Here we examine the role of miRNAs in FTLD patients with TAR DNA-binding protein 43 pathology (FTLD-TDP) caused by genetic mutations in the progranulin (<it>PGRN</it>) gene.</p> <p>Results</p> <p>Using miRNA array profiling, we identified the 20 miRNAs that showed greatest evidence (unadjusted P < 0.05) of dysregulation in frontal cortex of eight FTLD-TDP patients carrying <it>PGRN </it>mutations when compared to 32 FTLD-TDP patients with no apparent genetic abnormalities. Quantitative real-time PCR (qRT-PCR) analyses provided technical validation of the differential expression for 9 of the 20 miRNAs in frontal cortex. Additional qRT-PCR analyses showed that 5 out of 9 miRNAs (miR-922, miR-516a-3p, miR-571, miR-548b-5p, and miR-548c-5p) were also significantly dysregulated (unadjusted P < 0.05) in cerebellar tissue samples of <it>PGRN </it>mutation carriers, consistent with a systemic reduction in PGRN levels. We developed a list of gene targets for the 5 candidate miRNAs and found 18 genes dysregulated in a reported FTLD mRNA study to exhibit anti-correlated miRNA-mRNA patterns in affected cortex and cerebellar tissue. Among the targets is brain-specific angiogenesis inhibitor 3, which was recently identified as an important player in synapse biology.</p> <p>Conclusions</p> <p>Our study suggests that miRNAs may contribute to the pathogenesis of FTLD-TDP caused by <it>PGRN </it>mutations and provides new insight into potential future therapeutic options.</p

Inactivation of the dnaK gene in Clostridium difficile 630 Δerm yields a temperature-sensitive phenotype and increases biofilm-forming ability

Abstract Clostridium difficile infection is a growing problem in healthcare settings worldwide and results in a considerable socioeconomic impact. New hypervirulent strains and acquisition of antibiotic resistance exacerbates pathogenesis; however, the survival strategy of C. difficile in the challenging gut environment still remains incompletely understood. We previously reported that clinically relevant heat-stress (37–41 °C) resulted in a classical heat-stress response with up-regulation of cellular chaperones. We used ClosTron to construct an insertional mutation in the dnaK gene of C. difficile 630 Δerm. The dnaK mutant exhibited temperature sensitivity, grew more slowly than C. difficile 630 Δerm and was less thermotolerant. Furthermore, the mutant was non-motile, had 4-fold lower expression of the fliC gene and lacked flagella on the cell surface. Mutant cells were some 50% longer than parental strain cells, and at optimal growth temperatures, they exhibited a 4-fold increase in the expression of class I chaperone genes including GroEL and GroES. Increased chaperone expression, in addition to the non-flagellated phenotype of the mutant, may account for the increased biofilm formation observed. Overall, the phenotype resulting from dnaK disruption is more akin to that observed in Escherichia coli dnaK mutants, rather than those in the Gram-positive model organism Bacillus subtilis

The UK Biobank imaging enhancement of 100,000 participants: rationale, data collection, management and future directions

UK Biobank is a population-based cohort of half a million participants aged 40–69 years recruited between 2006 and 2010. In 2014, UK Biobank started the world’s largest multi-modal imaging study, with the aim of re-inviting 100,000 participants to undergo brain, cardiac and abdominal magnetic resonance imaging, dual-energy X-ray absorptiometry and carotid ultrasound. The combination of large-scale multi-modal imaging with extensive phenotypic and genetic data offers an unprecedented resource for scientists to conduct health-related research. This article provides an in-depth overview of the imaging enhancement, including the data collected, how it is managed and processed, and future direction

Imaging biomarker roadmap for cancer studies.

Imaging biomarkers (IBs) are integral to the routine management of patients with cancer. IBs used daily in oncology include clinical TNM stage, objective response and left ventricular ejection fraction. Other CT, MRI, PET and ultrasonography biomarkers are used extensively in cancer research and drug development. New IBs need to be established either as useful tools for testing research hypotheses in clinical trials and research studies, or as clinical decision-making tools for use in healthcare, by crossing 'translational gaps' through validation and qualification. Important differences exist between IBs and biospecimen-derived biomarkers and, therefore, the development of IBs requires a tailored 'roadmap'. Recognizing this need, Cancer Research UK (CRUK) and the European Organisation for Research and Treatment of Cancer (EORTC) assembled experts to review, debate and summarize the challenges of IB validation and qualification. This consensus group has produced 14 key recommendations for accelerating the clinical translation of IBs, which highlight the role of parallel (rather than sequential) tracks of technical (assay) validation, biological/clinical validation and assessment of cost-effectiveness; the need for IB standardization and accreditation systems; the need to continually revisit IB precision; an alternative framework for biological/clinical validation of IBs; and the essential requirements for multicentre studies to qualify IBs for clinical use.Development of this roadmap received support from Cancer Research UK and the Engineering and Physical Sciences Research Council (grant references A/15267, A/16463, A/16464, A/16465, A/16466 and A/18097), the EORTC Cancer Research Fund, and the Innovative Medicines Initiative Joint Undertaking (grant agreement number 115151), resources of which are composed of financial contribution from the European Union's Seventh Framework Programme (FP7/2007-2013) and European Federation of Pharmaceutical Industries and Associations (EFPIA) companies' in kind contribution