Gravity Drainage Prior to Cake Filtration

During the initial stages of a Buchner funnel or specific resistance test, gravity drainage occurs prior to application of the pressure differential. Some allow time for a small cake to form by gravity drainage. Filtrate data from the gravity drainage period can be used to determine constitutive properties of the cake under a hydrostatic pressure gradient. The constitutive properties that define the structure of the cake include the permeability and porosity as functions of the applied stress. Equations governing the drainage rate during a gravity filtration experiment assuming a constant and a non-constant average cake permeability and cake porosity were developed. Numerical solutions were shown predicting the gravity drainage rate given known constitutive relationships. Also, a procedure was shown illustrating how constitutive relationships could be determined using gravity drainage data

Stabilizing the Retromer Complex in a Human Stem Cell Model of Alzheimer's Disease Reduces TAU Phosphorylation Independently of Amyloid Precursor Protein.

Developing effective therapeutics for complex diseases such as late-onset, sporadic Alzheimer's disease (SAD) is difficult due to genetic and environmental heterogeneity in the human population and the limitations of existing animal models. Here, we used hiPSC-derived neurons to test a compound that stabilizes the retromer, a highly conserved multiprotein assembly that plays a pivotal role in trafficking molecules through the endosomal network. Using this human-specific system, we have confirmed previous data generated in murine models and show that retromer stabilization has a potentially beneficial effect on amyloid beta generation from human stem cell-derived neurons. We further demonstrate that manipulation of retromer complex levels within neurons affects pathogenic TAU phosphorylation in an amyloid-independent manner. Taken together, our work demonstrates that retromer stabilization is a promising candidate for therapeutic development in AD and highlights the advantages of testing novel compounds in a human-specific, neuronal system

Photon-number-resolution with sub-30-ps timing using multi-element superconducting nanowire single photon detectors

A photon-number-resolving detector based on a four-element superconducting nanowire single photon detector is demonstrated to have sub-30-ps resolution in measuring the arrival time of individual photons. This detector can be used to characterize the photon statistics of non-pulsed light sources and to mitigate dead-time effects in high-speed photon counting applications. Furthermore, a 25% system detection efficiency at 1550 nm was demonstrated, making the detector useful for both low-flux source characterization and high-speed photon-counting and quantum communication applications. The design, fabrication and testing of this detector are described, and a comparison between the measured and theoretical performance is presented.Comment: 13 pages, 5 figure

ACTH Prevents Deficits in Fear Extinction Associated with Early Life Seizures

Objective: Early life seizures (ELS) are often associated with cognitive and psychiatric comorbidities that are detrimental to quality of life. In a rat model of ELS, we explored long-term cognitive outcomes in adult rats. Using ACTH, an endogeneous HPA-axis hormone given to children with severe epilepsy, we sought to prevent cognitive deficits. Through comparisons with dexamethasone, we sought to dissociate the corticosteroid effects of ACTH from other potential mechanisms of action. Results: Although rats with a history of ELS were able to acquire a conditioned fear learning paradigm and controls, these rats had significant deficits in their ability to extinguish fearful memories. ACTH treatment did not alter any seizure parameters but nevertheless was able to significantly improve this fear extinction, while dexamethasone treatment during the same period did not. This ACTH effect was specific for fear extinction deficits and not for spatial learning deficits in a water maze. Additionally, ACTH did not alter seizure latency or duration suggesting that cognitive and seizure outcomes may be dissociable. Expression levels of melanocortin receptors, which bind ACTH, were found to be significantly lower in animals that had experienced ELS than in control animals, potentially implicating central melanocortin receptor dysregulation in the effects of ELS, and suggesting a mechanism of action for ACTH. Interpretation: Taken together, these data suggest that early treatment with ACTH can have significant long-term consequences for cognition in animals with a history of ELS independently of seizure cessation and may act in part through a CNS melanocortin receptor pathway

Sensitizing properties of proteins:executive summary

The scope of allergy risk is diverse considering the myriad ways in which protein allergenicity is affected by physiochemical characteristics of proteins. The complexity created by the matrices of foods and the variability of the human immune system add additional challenges to understanding the relationship between sensitization potential and allergy disease. To address these and other issues, an April 2012 international symposium was held in Prague, Czech Republic, to review and discuss the state-of-the-science of sensitizing properties of protein allergens. The symposium, organized by the Protein Allergenicity Technical Committee of the International Life Sciences Institute’s Health and Environmental Sciences Institute, featured presentations on current methods, test systems, research trends, and unanswered questions in the field of protein sensitization. A diverse group of over 70 interdisciplinary scientists from academia, government, and industry participated in the symposium. Experts provided overviews on known mechanisms by which proteins in food may cause sensitization, discussed experimental models to predict protein sensitizing potential, and explored whether such experimental techniques may be applicable in regulatory settings. Three accompanying reviews address critical factors and methods for assessing allergic sensitization: 1) food-and protein-related factors; 2) host-specific factors and 3) screening methods, i.e., the ability of experimental models to predict the sensitizing potential of proteins and whether such models are applicable within regulatory settings

X-Ray flares in Orion Young Stars. II. Flares, Magnetospheres, and Protoplanetary Disks

We study the properties of powerful X-ray flares from 161 pre-main sequence (PMS) stars observed with the Chandra X-ray Observatory in the Orion Nebula region. Relationships between flare properties, protoplanetary disks and accretion are examined in detail to test models of star-disk interactions at the inner edge of the accretion disks. Previous studies had found no differences in flaring between diskfree and accreting systems other than a small overall diminution of X-ray luminosity in accreting systems. The most important finding is that X-ray coronal extents in fast-rotating diskfree stars can significantly exceed the Keplerian corotation radius, whereas X-ray loop sizes in disky and accreting systems do not exceed the corotation radius. This is consistent with models of star-disk magnetic interaction where the inner disk truncates and confines the PMS stellar magnetosphere. We also find two differences between flares in accreting and diskfree PMS stars. First, a subclass of super-hot flares with peak plasma temperatures exceeding 100 MK are preferentially present in accreting systems. Second, we tentatively find that accreting stars produce flares with shorter durations. Both results may be consequences of the distortion and destabilization of the stellar magnetosphere by the interacting disk. Finally, we find no evidence that any flare types, even slow-rise flat-top flares are produced in star-disk magnetic loops. All are consistent with enhanced solar long-duration events with both footprints anchored in the stellar surface.Comment: Accepted for publication in ApJ (07/17/08); 46 pages, 14 figures, 2 table