Vale of York 3-D borehole interpretation and cross-sections study

The Vale of York between Doncaster and Scunthorpe in the south and York and Bugthorpe in the north is largely underlain by bedrock of the Sherwood Sandstone Group – one of the regions principal aquifers. Significant superficial deposits of Quaternary age overlie the Sherwood Sandstone. This study aims to investigate the nature of these superficial deposits with respect to their relationship with the underlying aquifer. The Vale of York project area represents a varied glaciated terrain, consisting of pro-glacial finegrained sediments, coarser glaciofluvilal sediments and extensive glacial tills. These diverse superficial units vary in thickness throughout the project area. The hydrogeological nature of the natural superficial sequence is consequently highly variable. Units may be considered as aquitards, while others may act as aquifers, providing a potential pathway to the underlying sandstone. The classification of lithologies as aquifer or aquitard is described in detail in this report. To investigate the hydrogeological nature of the superficial sequence, six east-west and three north-south lithostratigraphical cross-sections were constructed. A range of geoscientific information was considered, including existing geological mapping and over 3000 fully attributed and coded boreholes. The cross-sections show a subdivision of the superficial sequence into lithostratigraphical units. Each unit is described in detail in this report. In addition, a series of thematic maps were generated from the lithological component of the digital borehole data. Total superficial aquifer and superficial aquitard maps show how the lithological nature of the superficial sequence varies across the area. Rockhead elevation and superficial thickness maps indicate where the sandstone aquifer outcrops at the ground surface. In summary, four main lithostratigraphical units overlie the Sherwood Sandstone Group aquifer in the project area: a basal sequence of glaciofluvial sand and gravel (interpreted as a superficial aquifer), glaciolacustrine laminated silt & clay (aquitard), glacial till comprising sandy gravelly clay (aquitard), and a cover sequence of fluvial and aeolian sand, clay and peat (aquifer / aquitard). The correlations illustrate that in certain areas, superficial deposits are thin or absent and that in these areas the Sherwood Sandstone aquifer comes directly to ground surface

Improved SOT (Hinode mission) high resolution solar imaging observations

We consider the best today available observations of the Sun free of turbulent Earth atmospheric effects, taken with the Solar Optical Telescope (SOT) onboard the Hinode spacecraft. Both the instrumental smearing and the observed stray light are analyzed in order to improve the resolution. The Point Spread Function (PSF) corresponding to the blue continuum Broadband Filter Imager (BFI) near 450 nm is deduced by analyzing i/ the limb of the Sun and ii/ images taken during the transit of the planet Venus in 2012. A combination of Gaussian and Lorentzian functions is selected to construct a PSF in order to remove both smearing due to the instrumental diffraction effects (PSF core) and the large-angle stray light due to the spiders and central obscuration (wings of the PSF) that are responsible for the parasitic stray light. A Max-likelihood deconvolution procedure based on an optimum number of iterations is discussed. It is applied to several solar field images, including the granulation near the limb. The normal non-magnetic granulation is compared to the abnormal granulation which we call magnetic. A new feature appearing for the first time at the extreme- limb of the disk (the last 100 km) is discussed in the context of the definition of the solar edge and of the solar diameter. A single sunspot is considered in order to illustrate how effectively the restoration works on the sunspot core. A set of 125 consecutive deconvolved images is assembled in a 45 min long movie illustrating the complexity of the dynamical behavior inside and around the sunspot.Comment: 15 pages, 22 figures, 1 movi

Reconstructing the 3-D Trajectories of CMEs in the Inner Heliosphere

A method for the full three-dimensional (3-D) reconstruction of the trajectories of coronal mass ejections (CMEs) using Solar TErrestrial RElations Observatory (STEREO) data is presented. Four CMEs that were simultaneously observed by the inner and outer coronagraphs (COR1 and 2) of the Ahead and Behind STEREO satellites were analysed. These observations were used to derive CME trajectories in 3-D out to ~15Rsun. The reconstructions using COR1/2 data support a radial propagation model. Assuming pseudo-radial propagation at large distances from the Sun (15-240Rsun), the CME positions were extrapolated into the Heliospheric Imager (HI) field-of-view. We estimated the CME velocities in the different fields-of-view. It was found that CMEs slower than the solar wind were accelerated, while CMEs faster than the solar wind were decelerated, with both tending to the solar wind velocity.Comment: 17 pages, 10 figures, 1 appendi

The PHENIX Experiment at RHIC

The physics emphases of the PHENIX collaboration and the design and current status of the PHENIX detector are discussed. The plan of the collaboration for making the most effective use of the available luminosity in the first years of RHIC operation is also presented.Comment: 5 pages, 1 figure. Further details of the PHENIX physics program available at http://www.rhic.bnl.gov/phenix

The 22-Year Hale Cycle in cosmic ray flux: evidence for direct heliospheric modulation

The ability to predict times of greater galactic cosmic ray (GCR) fluxes is important for reducing the hazards caused by these particles to satellite communications, aviation, or astronauts. The 11-year solar-cycle variation in cosmic rays is highly correlated with the strength of the heliospheric magnetic field. Differences in GCR flux during alternate solar cycles yield a 22-year cycle, known as the Hale Cycle, which is thought to be due to different particle drift patterns when the northern solar pole has predominantly positive (denoted as qA>0 cycle) or negative (qA0 cycles than for qA0 and more sharply peaked for qA0 solar cycles, when the difference in GCR flux is most apparent. This suggests that particle drifts may not be the sole mechanism responsible for the Hale Cycle in GCR flux at Earth. However, we also demonstrate that these polarity-dependent heliospheric differences are evident during the space-age but are much less clear in earlier data: using geomagnetic reconstructions, we show that for the period of 1905 - 1965, alternate polarities do not give as significant a difference during the declining phase of the solar cycle. Thus we suggest that the 22-year cycle in cosmic-ray flux is at least partly the result of direct modulation by the heliospheric magnetic field and that this effect may be primarily limited to the grand solar maximum of the space-age

Discovery and characterization of a specific inhibitor of serine-threonine kinase cyclin-dependent kinase-like 5 (CDKL5) demonstrates role in hippocampal CA1 physiology

Pathological loss-of-function mutations in cyclin-dependent kinase-like 5 (CDKL5) cause CDKL5 deficiency disorder (CDD), a rare and severe neurodevelopmental disorder associated with severe and medically refractory early-life epilepsy, motor, cognitive, visual, and autonomic disturbances in the absence of any structural brain pathology. Analysis of genetic variants in CDD has indicated that CDKL5 kinase function is central to disease pathology. CDKL5 encodes a serine-threonine kinase with significant homology to GSK3β, which has also been linked to synaptic function. Further, Cdkl5 knock-out rodents have increased GSK3β activity and often increased long-term potentiation (LTP). Thus, development of a specific CDKL5 inhibitor must be careful to exclude cross-talk with GSK3β activity. We synthesized and characterized specific, high-affinity inhibitors of CDKL5 that do not have detectable activity for GSK3β. These compounds are very soluble in water but blood-brain barrier penetration is low. In rat hippocampal brain slices, acute inhibition of CDKL5 selectively reduces postsynaptic function of AMPA-type glutamate receptors in a dose-dependent manner. Acute inhibition of CDKL5 reduces hippocampal LTP. These studies provide new tools and insights into the role of CDKL5 as a newly appreciated key kinase necessary for synaptic plasticity. Comparisons to rodent knock-out studies suggest that compensatory changes have limited the understanding of the roles of CDKL5 in synaptic physiology, plasticity, and human neuropathology

The delivery of personalised, precision medicines via synthetic proteins

Introduction: The design of advanced drug delivery systems based on synthetic and su-pramolecular chemistry has been very successful. Liposomal doxorubicin (Caelyx®), and liposomal daunorubicin (DaunoXome®), estradiol topical emulsion (EstrasorbTM) as well as soluble or erodible polymer systems such as pegaspargase (Oncaspar®) or goserelin acetate (Zoladex®) represent considerable achievements. The Problem: As deliverables have evolved from low molecular weight drugs to biologics (currently representing approximately 30% of the market), so too have the demands made of advanced drug delivery technology. In parallel, the field of membrane trafficking (and endocytosis) has also matured. The trafficking of specific receptors i.e. material to be recycled or destroyed, as well as the trafficking of protein toxins has been well characterized. This, in conjunction with an ability to engineer synthetic, recombinant proteins provides several possibilities. The Solution: The first is using recombinant proteins as drugs i.e. denileukin diftitox (Ontak®) or agalsidase beta (Fabrazyme®). The second is the opportunity to use protein toxin architecture to reach targets that are not normally accessible. This may be achieved by grafting regulatory domains from multiple species to form synthetic proteins, engineered to do multiple jobs. Examples include access to the nucleocytosolic compartment. Herein the use of synthetic proteins for drug delivery has been reviewed