Mdm2 Is Required for Survival and Growth of p53-Deficient Cancer Cells.

p53 deletion prevents the embryonic lethality of normal tissues lacking Mdm2, suggesting that cells can survive without Mdm2 if p53 is also absent. Here we report evidence challenging this view, with implications for therapeutically targeting Mdm2. Deletion of Mdm2 in T-cell lymphomas or sarcomas lacking p53 induced apoptosis and G2 cell-cycle arrest, prolonging survival of mice with these tumors. p53-/- fibroblasts showed similar results, indicating that the effects of Mdm2 loss extend to pre-malignant cells. Mdm2 deletion in p53-/- cells upregulated p53 transcriptional target genes that induce apoptosis and cell-cycle arrest. Mdm2 deletion also increased levels of p73, a p53 family member. RNAi-mediated attenuation of p73 rescued the transcriptional and biological effects of Mdm2 loss, indicating that p73 mediates the consequences of Mdm2 deletion. In addition, Mdm2 deletion differed from blocking Mdm2 interaction with p53 family members, as Nutlin-3 induced G1 arrest but did not activate apoptosis in p53-/- sarcoma cells. Our results indicate that, in contrast to current dogma, Mdm2 expression is required for cell survival even in the absence of p53. Moreover, our results suggest that p73 compensates for loss of p53 and that targeting Mdm2 in p53-deficient cancers has therapeutic potential. ©2017 AACR

First Order Premelting Transition of Vortex Lattices

Vortex lattices in the high temperature superconductors undergo a first order phase transition which has thus far been regarded as melting from a solid to a liquid. We point out an alternative possibility of a two step process in which there is a first order transition from an ordinary vortex lattice to a soft vortex solid followed by another first order melting transition from the soft vortex solid to a vortex liquid. We focus on the first step. This premelting transition is induced by vacancy and interstitial vortex lines. We obtain good agreement with the experimental transition temperature versus field, latent heat, and magnetization jumps for YBCO and BSCCO.Comment: revised version replaces 9705092, 5 pages, Latex, 2 postscript figures, defect line wandering is included, 2 step melting is propose

Rotational 3D Printing of Sensor Devices using Reactive Ink Chemistries

This paper charts progress in three key areas of a project supported by both UK government and UK industry to manufacture novel sensor devices using rotary 3D printing technology and innovative ink chemistries; (1) the development of an STL file slicing algorithm that returns constant Z height 2D contour data at a resolution that matches the given print head setup, allowing digital images to be generated of the correct size without the need for scaling; (2) the development of image transformation algorithms which allow images to be printed at higher resolutions using tilted print heads and; (3) the formulation of multi part reaction inks which combine and react on the substrate to form solid material layers with a finite thickness. A Direct Light Projection (DLP) technique demonstrated the robustness of the slice data by constructing fine detailed three dimensional test pieces which were comparable to identical parts built in an identical way from slice data obtained using commercial software. Material systems currently under investigation include plaster, stiff polyamides and epoxy polymers and conductive metallic’s. Early experimental results show conductivities of silver approaching 1.42x105 Siemens/m.Mechanical Engineerin

The effects of minimal tillage, contour cultivation and in-field vegetative barriers on soil erosion and phosphorus loss.

Runoff, sediment, total phosphorus and total dissolved phosphorus losses in overland flow were measured for two years on unbounded plots cropped with wheat and oats. Half of the field was cultivated with minimum tillage (shallow tillage with a tine cultivator) and half was conventionally ploughed. Within each cultivation treatment there were different treatment areas (TA). In the first year of the experiment, one TA was cultivated up and down the slope, one TA was cultivated on the contour, with a beetle bank acting as a vegetative barrier partway up the slope, and one had a mixed direction cultivation treatment, with cultivation and drilling conducted up and down the slope and all subsequent operations conducted on the contour. In the second year, this mixed treatment was replaced with contour cultivation. Results showed no significant reduction in runoff, sediment losses or total phosphorus losses from minimum tillage when compared to the conventional plough treatment, but there were increased losses of total dissolved phosphorus with minimum tillage. The mixed direction cultivation treatment increased surface runoff and losses of sediment and phosphorus. Increasing surface roughness with contour cultivation reduced surface runoff compared to up and down slope cultivation in both the plough and minimum tillage treatment areas, but this trend was not significant. Sediment and phosphorus losses in the contour cultivation treatment followed a very similar pattern to runoff. Combining contour cultivation with a vegetative barrier in the form of a beetle bank to reduce slope length resulted in a non-significant reduction in surface runoff, sediment and total phosphorus when compared to up and down-slope cultivation, but there was a clear trend towards reduced losses. However, the addition of a beetle bank did not provide a significant reduction in runoff, sediment losses or total phosphorus losses when compared to contour cultivation, suggesting only a marginal additional benefit. The economic implications for farmers of the different treatment options are investigated in order to assess their suitability for implementation at a field scale

The appearance, motion, and disappearance of three-dimensional magnetic null points

N.A.M. acknowledges support from NASA grants NNX11AB61G, NNX12AB25G, and NNX15AF43G; NASA contract NNM07AB07C; and NSF SHINE grants AGS-1156076 and AGS-1358342 to SAO. C.E.P. acknowledges support from the St Andrews 2013 STFC Consolidated grant.While theoretical models and simulations of magnetic reconnection often assume symmetry such that the magnetic null point when present is co-located with a flow stagnation point, the introduction of asymmetry typically leads to non-ideal flows across the null point. To understand this behavior, we present exact expressions for the motion of three-dimensional linear null points. The most general expression shows that linear null points move in the direction along which the magnetic field and its time derivative are antiparallel. Null point motion in resistive magnetohydrodynamics results from advection by the bulk plasma flow and resistive diffusion of the magnetic field, which allows non-ideal flows across topological boundaries. Null point motion is described intrinsically by parameters evaluated locally; however, global dynamics help set the local conditions at the null point. During a bifurcation of a degenerate null point into a null-null pair or the reverse, the instantaneous velocity of separation or convergence of the null-null pair will typically be infinite along the null space of the Jacobian matrix of the magnetic field, but with finite components in the directions orthogonal to the null space. Not all bifurcating null-null pairs are connected by a separator. Furthermore, except under special circumstances, there will not exist a straight line separator connecting a bifurcating null-null pair. The motion of separators cannot be described using solely local parameters because the identification of a particular field line as a separator may change as a result of non-ideal behavior elsewhere along the field line.Publisher PDFPeer reviewe

Octahedral Tilt Instability of ReO_3-type Crystals

The octahedron tilt transitions of ABX_3 perovskite-structure materials lead to an anti-polar (or antiferroelectric) arrangement of dipoles, with the low temperature structure having six sublattices polarized along various crystallographic directions. It is shown that an important mechanism driving the transition is long range dipole-dipole forces acting on both displacive and induced parts of the anion dipole. This acts in concert with short range repulsion, allowing a gain of electrostatic (Madelung) energy, both dipole-dipole and charge-charge, because the unit cell shrinks when the hard ionic spheres of the rigid octahedron tilt out of linear alignment.Comment: 4 page with 3 figures included; new version updates references and clarifies the argument

The 24-h Movement Compositions in Weekday, Weekend Day or Four-Day Periods Differentially Associate with Fundamental Movement Skills

The aim of this study was to investigate the relationship between weekday, weekend day and four-day physical activity (PA) behaviours and fundamental movement skills (FMS) in British preschool children from a low socio-economic status background using compositional data analysis (CoDA). One hundred and eighty-five preschool children aged 3–4 years provided objectively assessed PA and sedentary behaviour (SB) data (GENEActiv accelerometer) and FMS (TGMD-2). The association of 24-h movement behaviours with FMS was explored using CoDA and isotemporal substitution (R Core Team, 3.6.1). When data were considered compositionally (SB, light PA (LPA), moderate and vigorous PA (MVPA)) and adjusted for age, BMI and sex, the weekday-derived composition predicted total motor competence (r2 = 0.07), locomotor (r2 = 0.08) and object control skills (r2 = 0.09); the weekend day-derived composition predicted total motor competence (r2 = 0.03) and object control skills (r2 = 0.03), the 4-day-derived composition predicted total motor competence (r2 = 0.07), locomotor (r2 = 0.07) and object control skills (r2 = 0.06) (all p < 0.05). Reallocation of 5 min of LPA at the expense of any behaviour was associated with significant improvements in total motor competence, locomotor and object control skills; for weekend-derived behaviours, MVPA was preferential. Considering movement behaviours over different time periods is required to better understand the effect of the 24-h movement composition on FMS in preschool children

Undernutrition and stage of gestation influence fetal adipose tissue gene expression

Funded by the Scottish Government’s Rural and Environment Science and Analytical Services Division (RESAS), including the Strategic Partnership for Animal Science Excellence (SPASE) and the U.S. National Institutes of Health (HD045784). None of the authors had any financial or personal conflicts of interest.Peer reviewedPostprin

A spatially-restricted Younger Dryas plateau icefield in the Gaick, Scotland: reconstruction and palaeoclimatic implications

Considerable research has been conducted in Scotland to reconstruct Younger Dryas glaciers and palaeoclimatic conditions, but our understanding remains incomplete. In this contribution, we examine the Gaick, a dissected plateau that extends over ∼520 km 2 in the Central Grampians, Scotland. The extent and style of Younger Dryas glaciation in the Gaick has been repeatedly contested, although a model of extensive plateau icefield glaciation has become generally accepted. This is despite well-documented issues with key elements of the plateau icefield reconstruction. We synthesise the results of recent geomorphological mapping in the Gaick and recognise a distinct morphostratigraphic signature in the upper parts of the western catchments. This differs markedly from sediment-landform associations in other parts of the area, and we argue this provides a strong indication of spatially-restricted Younger Dryas (∼12.9–11.7 ka) glaciation in the Gaick. Our interpretation is independently supported by glacierisation threshold analysis, which implies that the eastern Gaick was unable to nourish Younger Dryas ice. We therefore contest the accepted paradigm of extensive Younger Dryas glaciation in this area. Based on the geomorphological evidence and glacier surface profile modelling, we reconstruct a ∼42 km 2 plateau icefield that yields an equilibrium line altitude of 751 ± 46 m. Using this value, a sea-level precipitation value of 826 ± 331 mm a −1 is inferred for the Younger Dryas, which suggests considerably drier conditions than at present. Using recalculated glacier-derived precipitation estimates from Scotland, we present regional climate analysis that corroborates arguments for a strong west-east precipitation gradient across Scotland