Increased interactions and engulfment of dendrites by microglia precede Purkinje cell degeneration in a mouse model of Niemann Pick Type-C.

Niemann Pick Type-C disease (NPC) is an inherited lysosomal storage disease (LSD) caused by pathogenic variants in the Npc1 or Npc2 genes that lead to the accumulation of cholesterol and lipids in lysosomes. NPC1 deficiency causes neurodegeneration, dementia and early death. Cerebellar Purkinje cells (PCs) are particularly hypersensitive to NPC1 deficiency and degenerate earlier than other neurons in the brain. Activation of microglia is an important contributor to PCs degeneration in NPC. However, the mechanisms by which activated microglia promote PCs degeneration in NPC are not completely understood. Here, we are demonstrating that in the Npc1nmf164 mouse cerebellum, microglia in the molecular layer (ML) are activated and contacting dendrites at early stages of NPC, when no loss of PCs is detected. During the progression of PCs degeneration in Npc1nmf164 mice, accumulation of phagosomes and autofluorescent material in microglia at the ML coincided with the degeneration of dendrites and PCs. Feeding Npc1nmf164 mice a western diet (WD) increased microglia activation and corresponded with a more extensive degeneration of dendrites but not PC somata. Together our data suggest that microglia contribute to the degeneration of PCs by interacting, engulfing and phagocytosing their dendrites while the cell somata are still present

Simultaneous large optical and piezoelectric effects induced by domain reconfiguration related to ferroelectric phase transitions

Electrical switching of ferroelectric domains and subsequent domain wall motion promotes strong piezoelectric activity; however, light scatters at refractive index discontinuities such as those found at domain wall boundaries. Thus, simultaneously achieving large piezoelectric effect and high optical transmissivity is generally deemed infeasible. Here, it is demonstrated that the ferroelectric domains in perovskite Pb(In1/2Nb1/2)O3 Pb(Mg1/3Nb2/3)O3-PbTiO3 domain-engineered crystals can be manipulated by electrical field and mechanical stress to reversibly and repeatably, with small hysteresis, transform the opaque poly-domain structure into a highly transparent mono-domain state. This control of optical properties can be achieved at very low electric fields (less than 1.5 kV cm−1) and is accompanied by a large (>10000 pm V−1) piezoelectric coefficient that is superior to that of linear state-of-the-art materials by a factor of three or more. The coexistence of tunable optical transmissivity and high piezoelectricity paves the way for a new class of photonic devices

A three dimensional model of muckpile formation and grade boundary movement in open pit blasting

Formulation and case studies of a three dimensional kinematic model are presented. The in situ overburden geometry can be simulated accurately and various initiation patterns of blasts can be modelled. The overburden geometry, hole patterns and explosive distribution are all explicit model inputs. Because the effect of explosive properties, rock mass condition and inter-row delay are very difficult to measure in terms of blast performance, these are represented in the model by control parameters which are left for calibration using field data. The output of the model is a three dimensional muckpile shape of any cross section and a contour map of grade distribution within the muckpile. Two case studies are presented which have shown that the model is a valuable tool for optimizing production blasting as well as for controlling grade dilution during blasting

The solar O i λ 7773 triplet - II. Analysis using line inversion techniques

Profiles of the O i λ 7773 triplet obtained at a spatial resolution ∼ 0.5″ are analyzed using spectral line inversion techniques. Inferences are made about departures from LTE, convective velocity fields, and solar temperature fluctuations

An Inversion Technique for the Determination of Velocity Fields from Spectral Line Profiles

Studies of solar absorption line profiles obtained at high spatial and spectral resolution have usually been content to extract one parameter (the frequency shift in the core of the line) from each profile to describe the velocity field. However, attempts have been made to obtain the variation of velocity with depth in the solar atmosphere either by simultaneous observation of the frequency shift in the cores of several lines with different excitation potentials or by measuring the bisector-shift in a single line profile as described by Kulander and Jefferies (1966). In the first method it is necessary to assign a depth of formation to the core of each line used while in the second method a depth of formation has to be assigned to each point in the line profile. Parnell and Beckers (1969) have discussed the problems involved in assigning a depth on formation and in particular they have shown that when a velocity field is present the concept of depth of formation is dependent of the velocity field. In this contribution we describe a method of determining the velocity field from a single line profile which does not suffer from the problems associated with methods based on the concept of depth of formation.</jats:p

The solar O i λ 7773 triplet - I. Spatially resolved profiles

The reduction of observations of the O i λ 7773 triplet obtained at high spatial resolution (∼0.5″) at two disk positions is described. Two sets of triplet profile data are presented at each disk position. One set represents data taken from ∼0.5″ regions centered on the brightest granules, while the other set represents data taken from ∼0.5″ regions centered on the cooler infalling intergranular material