Origin of intermittent accretion-powered X-ray oscillations in neutron stars with millisecond spin periods

We have shown previously that many of the properties of persistent accretion-powered millisecond pulsars can be understood if their X-ray emitting areas are near their spin axes and move as the accretion rate and structure of the inner disk vary. Here we show that this "nearly aligned moving spot model" may also explain the intermittent accretion-powered pulsations that have been detected in three weakly magnetic accreting neutron stars. We show that movement of the emitting area from very close to the spin axis to about 10 degrees away can increase the fractional rms amplitude from less than about 0.5 percent, which is usually undetectable with current instruments, to a few percent, which is easily detectable. The second harmonic of the spin frequency usually would not be detected, in agreement with observations. The model produces intermittently detectable oscillations for a range of emitting area sizes and beaming patterns, stellar masses and radii, and viewing directions. Intermittent oscillations are more likely in stars that are more compact. In addition to explaining the sudden appearance of accretion-powered millisecond oscillations in some neutron stars with millisecond spin periods, the model explains why accretion-powered millisecond oscillations are relatively rare and predicts that the persistent accretion-powered millisecond oscillations of other stars may become undetectable for brief intervals. It suggests why millisecond oscillations are frequently detected during the X-ray bursts of some neutron stars but not others and suggests mechanisms that could explain the occasional temporal association of intermittent accretion-powered oscillations with thermonuclear X-ray bursts.Comment: 5 pages, 1 figure; includes additional discussion and updated references; accepted for publication in ApJ

Electron Accumulation and Emergent Magnetism in LaMnO3/SrTiO3 Heterostructures

Emergent phenomena at polar-nonpolar oxide interfaces have been studied intensely in pursuit of next-generation oxide electronics and spintronics. Here we report the disentanglement of critical thicknesses for electron reconstruction and the emergence of ferromagnetism in polar-mismatched LaMnO3/SrTiO3 (001) heterostructures. Using a combination of element-specific X-ray absorption spectroscopy and dichroism, and first-principles calculations, interfacial electron accumulation and ferromagnetism have been observed within the polar, antiferromagnetic insulator LaMnO3. Our results show that the critical thickness for the onset of electron accumulation is as thin as 2 unit cells (UC), significantly thinner than the observed critical thickness for ferromagnetism of 5 UC. The absence of ferromagnetism below 5 UC is likely induced by electron over-accumulation. In turn, by controlling the doping of the LaMnO3, we are able to neutralize the excessive electrons from the polar mismatch in ultrathin LaMnO3 films and thus enable ferromagnetism in films as thin as 3 UC, extending the limits of our ability to synthesize and tailor emergent phenomena at interfaces and demonstrating manipulation of the electronic and magnetic structures of materials at the shortest length scales.Comment: Accepted by Phys. Rev. Let

HPLC Plasma Assay of a Novel Anti-MRSA Compound, Kaempferol-3-O-Alpha-L-(2 \u27\u27,3 \u27\u27-di-p-coumaroyl)rhamnoside, from Sycamore Leaves

Methicillin-resistant Staphylococcus aureus (MRSA) is a serious pathogen that is resistant to current antibiotic therapy. Thus, there is an urgent need for novel antimicrobial agents that can effectively combat these new strains of drug-resistant superbugs . Recently, fractionation of an extract from Platanus occidentalis (American sycamore) leaves produced an active kaempferol molecule, 3-O-alpha-L-(2 ,3 -di-p-coumaroyl)rhamnoside (KCR), in four isomeric forms; all four isomers exhibit potent anti-MRSA activity. In order to further the preclinical development of KCR as a new antibiotic class, we developed and validated a simple analytical method for assaying KCR plasma concentration. Because KCR will be developed as a new drug, although comprising four stereoisomers, the analytical method was devised to assay the total amount of all four isomers. In the present work, both a plasma processing procedure and an HPLC method have been developed and validated. Mouse plasma containing KCR was first treated with ethanol and then centrifuged. The supernatant was dried, suspended in ethanol, centrifuged, and the supernatant was injected into an HPLC system comprising a Waters C18, a mobile phase composing methanol, acetonitrile, and trifluoroacetic acid and monitored at 313 nm. The method was validated by parameters including a good linear correlation, a limit of quantification of 0.27 μg/mL, and high accuracy. In summary, this method allows a rapid analysis of KCR in the plasma samples for pharmacokinetics studies

Formation polarity dependent improved resistive switching memory characteristics using nanoscale (1.3 nm) core-shell IrOx nano-dots

Improved resistive switching memory characteristics by controlling the formation polarity in an IrOx/Al2O3/IrOx-ND/Al2O3/WOx/W structure have been investigated. High density of 1 × 1013/cm2 and small size of 1.3 nm in diameter of the IrOx nano-dots (NDs) have been observed by high-resolution transmission electron microscopy. The IrOx-NDs, Al2O3, and WOx layers are confirmed by X-ray photo-electron spectroscopy. Capacitance-voltage hysteresis characteristics show higher charge-trapping density in the IrOx-ND memory as compared to the pure Al2O3 devices. This suggests that the IrOx-ND device has more defect sites than that of the pure Al2O3 devices. Stable resistive switching characteristics under positive formation polarity on the IrOx electrode are observed, and the conducting filament is controlled by oxygen ion migration toward the Al2O3/IrOx top electrode interface. The switching mechanism is explained schematically based on our resistive switching parameters. The resistive switching random access memory (ReRAM) devices under positive formation polarity have an applicable resistance ratio of > 10 after extrapolation of 10 years data retention at 85°C and a long read endurance of 105 cycles. A large memory size of > 60 Tbit/sq in. can be realized in future for ReRAM device application. This study is not only important for improving the resistive switching memory performance but also help design other nanoscale high-density nonvolatile memory in future

?2-Microglobulin Amyloid Fibril-Induced Membrane Disruption Is Enhanced by Endosomal Lipids and Acidic pH

Although the molecular mechanisms underlying the pathology of amyloidoses are not well understood, the interaction between amyloid proteins and cell membranes is thought to play a role in several amyloid diseases. Amyloid fibrils of ?2-microglobulin (?2m), associated with dialysis-related amyloidosis (DRA), have been shown to cause disruption of anionic lipid bilayers in vitro. However, the effect of lipid composition and the chemical environment in which ?2m-lipid interactions occur have not been investigated previously. Here we examine membrane damage resulting from the interaction of ?2m monomers and fibrils with lipid bilayers. Using dye release, tryptophan fluorescence quenching and fluorescence confocal microscopy assays we investigate the effect of anionic lipid composition and pH on the susceptibility of liposomes to fibril-induced membrane damage. We show that ?2m fibril-induced membrane disruption is modulated by anionic lipid composition and is enhanced by acidic pH. Most strikingly, the greatest degree of membrane disruption is observed for liposomes containing bis(monoacylglycero)phosphate (BMP) at acidic pH, conditions likely to reflect those encountered in the endocytic pathway. The results suggest that the interaction between ?2m fibrils and membranes of endosomal origin may play a role in the molecular mechanism of ?2m amyloid-associated osteoarticular tissue destruction in DRA

The structural basis of rubisco phase separation in the pyrenoid

Approximately one-third of global CO2 fixation occurs in a phase-separated algal organelle called the pyrenoid. The existing data suggest that the pyrenoid forms by the phase separation of the CO2-fixing enzyme Rubisco with a linker protein; however, the molecular interactions underlying this phase separation remain unknown. Here we present the structural basis of the interactions between Rubisco and its intrinsically disordered linker protein Essential Pyrenoid Component 1 (EPYC1) in the model alga Chlamydomonas reinhardtii. We find that EPYC1 consists of five evenly spaced Rubisco-binding regions that share sequence similarity. Single-particle cryo-electron microscopy of these regions in complex with Rubisco indicates that each Rubisco holoenzyme has eight binding sites for EPYC1, one on each Rubisco small subunit. Interface mutations disrupt binding, phase separation and pyrenoid formation. Cryo-electron tomography supports a model in which EPYC1 and Rubisco form a codependent multivalent network of specific low-affinity bonds, giving the matrix liquid-like properties. Our results advance the structural and functional understanding of the phase separation underlying the pyrenoid, an organelle that plays a fundamental role in the global carbon cycle

Hematopoietic Cell Transplantation in Patients With Primary Immune Regulatory Disorders (PIRD): A Primary Immune Deficiency Treatment Consortium (PIDTC) Survey.

Primary Immune Regulatory Disorders (PIRD) are an expanding group of diseases caused by gene defects in several different immune pathways, such as regulatory T cell function. Patients with PIRD develop clinical manifestations associated with diminished and exaggerated immune responses. Management of these patients is complicated; oftentimes immunosuppressive therapies are insufficient, and patients may require hematopoietic cell transplant (HCT) for treatment. Analysis of HCT data in PIRD patients have previously focused on a single gene defect. This study surveyed transplanted patients with a phenotypic clinical picture consistent with PIRD treated in 33 Primary Immune Deficiency Treatment Consortium centers and European centers. Our data showed that PIRD patients often had immunodeficient and autoimmune features affecting multiple organ systems. Transplantation resulted in resolution of disease manifestations in more than half of the patients with an overall 5-years survival of 67%. This study, the first to encompass disorders across the PIRD spectrum, highlights the need for further research in PIRD management

Analysis of Mice Lacking DNaseI Hypersensitive Sites at the 5′ End of the IgH Locus

The 5′ end of the IgH locus contains a cluster of DNaseI hypersensitive sites, one of which (HS1) was shown to be pro-B cell specific and to contain binding sites for the transcription factors PU.1, E2A, and Pax5. These data as well as the location of the hypersensitive sites at the 5′ border of the IgH locus suggested a possible regulatory function for these elements with respect to the IgH locus. To test this notion, we generated mice carrying targeted deletions of either the pro-B cell specific site HS1 or the whole cluster of DNaseI hypersensitive sites. Lymphocytes carrying these deletions appear to undergo normal development, and mutant B cells do not exhibit any obvious defects in V(D)J recombination, allelic exclusion, or class switch recombination. We conclude that deletion of these DNaseI hypersensitive sites does not have an obvious impact on the IgH locus or B cell development